calibration_datav3.txt

In addition to a significant decrease in hepatic lipid accumulation in the IOE group, which inhibited energy intake by propionate enrichment, hepatic lipids were also significantly reduced in the mice in the IOP group, which was largely enriched with butyrate. Compared with the IOE group, IOP had a stronger regulatory effect on hepatic metabolism and triglyceride metabolism and higher levels of TCA cycle in the host. In addition, butyrate has the ability to promote browning of white adipose tissue (WAT) to brown adipose tissue (BAT).^[@ref39],[@ref40]^ WAT stores energy, whereas BAT uses energy for heating and consequently host energy expenditure increases.^[@ref41],[@ref42]^ However, adipose tissue weight does not change after WAT browning.^[@ref43]^ Therefore, the weight of adipose tissue of mice in the IOP group dominated by butyrate was greater than that of the mice in the IOE group dominated by propionate.

In conclusion ([Figure [7](#fig7){ref-type="fig"}](#fig7){ref-type="fig"}C), the improvement of obesity condition in mice by both *I. obliquus* extracts was attributed to their effects on gut microbiota and SCFA profiles. IOE increased the levels of propionate-producing bacteria *Bacteroides* and *Akkermansia* in the cecum of HFD-fed mice, resulting in the enrichment of propionate. Propionate reduced weight gain in mice by inhibiting energy intake. IOP increased the levels of butyrate-production-associated bacteria *Lactobacillus* and the *Bacteroidales* S24-7 group in the cecum of HFD-fed mice, resulting in the enrichment of butyrate. Butyrate increased energy consumption, TCA cycle levels, and degradation of carbohydrates and lipids in mice by promoting mitochondrial decoupling.

Conclusions {#sec4}
===========

IOE and IOP ameliorated HFD-induced obesity condition in mice through differential modulatory effects on gut microbial metabolism. Moreover, we found the connections between cecal butyrate (not propionate) and chemicals of mice, including four metabolites of the TCA cycle and other metabolism-related chemicals.

Materials and Methods {#sec5}
=====================

Preparation of IOE/IOP {#sec5.1}
----------------------

The dried and powdered *I. obliquus* (1.0 kg) was extracted with ultrapure water (30 L) at 90 °C for 3 h and concentrated. The supernatant was evaporated in vacuo at 45 °C, followed by extracting with 4 vol of ethanol to get crude extract. The extract was deproteinized by the Sevage method five times. The supernatant was dried in vacuo and lyophilized to get IOP (62.5 g). After *I. obliquus* was extracted with water, the residue was extracted with 80% ethanol at 80 °C in a water bath for 2 h. The supernatant was dried in vacuo and lyophilized to get IOE (30.9 g).

Animal Experimental Design {#sec5.2}
--------------------------

The experimental protocol was approved by the Animal Ethics Committee of Jilin University and complied with national laws. Five-week-old C57BL/6J male mice (15--17 g) were divided into four groups, 12 mice per group. The mice in the NCD group were fed with normal chow diet, and the mice in the HFD group, IOE group, and IOP group were fed with high-fat diet. The compositions of mice diets are presented in [Tables S4 and S5](http://pubs.acs.org/doi/suppl/10.1021/acsomega.0c01566/suppl_file/ao0c01566_si_001.pdf). The mice in the IOP group were gavaged with IOP at a dose of 1000 mg/kg per day according to previous studies,^[@ref44]^ and the mice in the IOE group were gavaged with IOE at a dose of 500 mg/kg per day according to the extraction rate of IOE/IOP and the dose of IOP. After 14 weeks of treatment, the mice were sacrificed for specimens.

Oral Glucose Tolerance Test (OGTT) {#sec5.3}
----------------------------------

OGTT was performed using a previously described method.^[@ref45]^

Serum Biochemical Analysis {#sec5.4}
--------------------------

Serum and liver lipid were measured using the method of kits obtained from Nanjing Jiancheng Bioengineering Institute (Nanjing, China).

RNA Preparation and Quantitative PCR Analysis {#sec5.5}
---------------------------------------------

The total RNA extraction and the reverse transcription (RT)-qPCR analysis of the gene expression were performed using a previously described method.^[@ref46]^ Primer sequences for the targeted mouse genes are shown in [Table S6](http://pubs.acs.org/doi/suppl/10.1021/acsomega.0c01566/suppl_file/ao0c01566_si_001.pdf).

Sample Collection {#sec5.6}
-----------------

Urine was collected using metabolic cages at 14th week, and 50 μL of sodium azide solution (0.1% w/w) was added into each urine sample. Cecum contents were washed from cecum in a 2 mL Eppendorf tube containing 1.0 mL of cold phosphate-buffered saline (PBS) (pH 7.4). All samples were then stored in a −80 °C freezer for later analysis.

All samples were thawed at room temperature. Serum was prepared by mixing 100 μL of each sample with a solution of 500 μL of PBS in D~2~O (containing 3-(tri-methyl-silyl) propionic-2,2,3,3-*d*4 acid sodium salt (TSP)). Then, 200 μL exudate of cecum contents was mixed with a solution of 400 μL of PBS in D~2~O (containing TSP). Supernatants (550 μL) were pipetted into NMR analysis tubes after centrifuging (15 000 rpm, 15 min, 4 °C) and passing through 0.22 μm membrane filters. For each urine sample, 400 μL of the sample was mixed with a solution of 200 μL of PBS in H~2~O. Then, 500 μL of supernatants was pipetted into NMR analysis tubes after centrifuging (15 000 rpm, 5 min, 4 °C), and 50 μL of D~2~O containing TSP was also added to each tube. D~2~O provided a field frequency lock and TSP a chemical shift reference (^1^H, δ 0.0).

NMR Data Acquisition and Processing {#sec5.7}
-----------------------------------

All samples were analyzed by an AVANCE III 600M MHz NMR spectrometer at 298.2 K. ^1^H NMR spectra were acquired by one-dimensional (1D) version CPMG (serum samples) and noesyphpr (urine and cecal samples) pulse sequence with water suppression during the relaxation delay of 3 s and a mixing time of 0.1 s. Sixty-four free induction decays were collected into 64 K data points with a spectral width of 7812.5 Hz (serum samples) and 8417.5 Hz (urine and cecal samples) and an acquisition time of 2 s. Free induction decay (FID) was zero-filled to 64 K prior to Fourier transformation.

Metabolite identifications were confirmed using the Human Metabolome Database (HMDB) and previous studies,^[@ref47]^ based on chemical shifts of hydrogen and peak multiplicity ([Figures S5--S7 and Table S7](http://pubs.acs.org/doi/suppl/10.1021/acsomega.0c01566/suppl_file/ao0c01566_si_001.pdf)).

All of the spectra were manually phased and baseline-corrected in software MestreNova 12.0 (Mestre-lab Research SL). Each spectrum was segmented into regions with a width of 0.005 ppm between δ 9.6 and 0.4. The δ 5.48--6.20 region in urine spectra and δ 4.72--5.20 region in all spectra were excluded to eliminate the effects of urea signals and water suppression. All remaining regions of the spectra were then normalized to the total sum of the integrated spectral area to reduce any significant concentration differences.

Sequencing, Diversity Analysis, and Function Prediction of Cecal Microbiota {#sec5.8}
---------------------------------------------------------------------------

DNA extraction, sequencing, and data processing were performed using a previously described method.^[@ref48]^

Four parameters of the alpha diversity were used to assess the overall diversity thoroughly. The Ace and Chao (only presence/absence of taxa considered) indexes determine the richness in a community, while the Shannon and Simpson indexes (additionally accounts for the number of times that each taxon was observed) determine the richness and/or evenness of a community. In addition, a higher Shannon index or a lower Simpson index indicates higher community diversity. Unlike alpha diversity, beta diversity was used to measure the division of diversity between two or more communities. Microbial communities had often been characterized using divergence-based measures of beta diversity to determine whether two or more communities were significantly different.

We used PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) to perform functional predictions. PICRUSt generates metagenomic predictions from 16S rRNA data using annotations of sequenced genomes in the IMG database. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for functional classification.^[@ref49]^

Statistical Analysis {#sec5.9}
--------------------

The data were expressed as means ± standard errors of the means (SEM). One-way analysis of variance (ANOVA) was performed to identify significant differences among four groups, followed by the indicated post hoc test (lysergic acid diethylamide (LSD) comparison test). The results were considered statistically significant at *p*-value \< 0.05 unless otherwise specified in the figures. *P*-value between two independent groups was analyzed using an unpaired two-tailed *t*-test. Metabolomics data were subjected to OPLS-DA using software SIMCA 14.0 (Umetrics, Sweden) and used to construct multivariate statistical models. Bivariate correlations were calculated using Spearman's *r* coefficients. Heatmaps were constructed using Excel 2016.

Accession Number {#sec5.10}
----------------

High-throughput sequencing data have been submitted to the NCBI Sequence Read Archive (SRA) under the accession number PRJNA576716.

The Supporting Information is available free of charge at [https://pubs.acs.org/doi/10.1021/acsomega.0c01566](https://pubs.acs.org/doi/10.1021/acsomega.0c01566?goto=supporting-info).3D score plots of the OPLS-DA classification; VIP plot of OPLS-DA; pathway analysis based on different metabolites; effects of IOE/IOP on gut microbial diversity; ^1^H NMR spectra of mice serum, urine, and cecal contents (Figures S1--S7); main metabolites of serum, urine, and cecum contents; compositions of NCD and HFD; primer sequence for amplification of the fragments; and metabolite identifications (Tables S1--S7) ([PDF](http://pubs.acs.org/doi/suppl/10.1021/acsomega.0c01566/suppl_file/ao0c01566_si_001.pdf))

Supplementary Material
======================

###### 

ao0c01566_si_001.pdf

Conceptualization, J.Y., H.X., and Q.X.; investigation, J.Y.; supervision and resources, H.X. and Q.X.; Writing-original draft, J.Y. and J.-Y.X.

The authors declare no competing financial interest.

This work was supported by the Jilin Province Science and Technology Institute of China (No. 20180201078YY).

TC

:   total cholesterol

TG

:   triglycerides

HDL

:   high-density lipoprotein cholesterol

LDL

:   low-density lipoprotein cholesterol

TSP

:   3-(tri-methyl-silyl) propionic-2, 2, 3, 3-*d*4 acid sodium salt

PBS

:   phosphate-buffered saline

Chrebp

:   carbohydrate-responsive element binding protein

GK

:   glucokinase

PK

:   pyruvate kinase

PEPCK

:   phosphoenolpyruvate carboxykinase

PC

:   pyruvate carboxylase

FBPase

:   fructose-1,6-bisphosphatase

G6Pase

:   glucose-6-phosphatase

Ppar-γ

:   peroxisome proliferator-activated recepto γ

Srebp1c

:   sterol regulatory element binding protein-1c

Fas

:   fatty acid synthase

Acl

:   ATP-citrate lyase

Scd1

:   stearoyl-CoA desaturase 1

Acc

:   acetyl-CoA carboxylase

Acox

:   acyl-CoA oxidase

Ppar-α

:   peroxisome proliferator-activated recepto α

Cpt1

:   carnitine palmitoyltransferase I

Mcad

:   medium-chain acyl-CoA dehydrogenase

Dgat1

:   diacylglycerol acyltransferase 1

Dgat2

:   diacylglycerol acyltransferase 2

Gpat

:   glycerol-3-phosphate acyltransferase

VIP

:   variable importance of projection

OPLS-DA

:   orthogonal partial least-squares discriminant analysis

CoA

:   coenzyme A

SCFA

:   short-chain fatty acids

Description

Foreign trailer for Gokusen.

After seven years of enduring popularity on television, Gokusen, finally makes its silver screen debut. Winning over the hearts of millions of viewers and becoming a national heroine, Yukie Nakama reprises her role as Kumiko Yamaguchi, a.k.a Yankumi. Wearing jerseys, glasses and pigtails, the dowdy high school instructor becomes the homeroom teacher for the wild delinquents of Class 3D. At first glance, Kumiko seems like she can be easily intimidated, but much to everyone's surprise, she remains unfazed by her students' shenanigans. Her courage and discipline comes from being raised by a family who also happens to be a feared yakuza clan. With her strong sense of justice and her fierce brawling abilities, Kumiko follows her principles and upholds honor to solve the problems that trouble her students.
---
abstract: |
    We design a new, fast algorithm for agnostically learning univariate probability distributions whose densities are well approximated by piecewise polynomial functions. Let $f$ be the density function of an arbitrary univariate distribution, and suppose that $f$ is $\OPT$ close in $L_1$-distance to an unknown piecewise polynomial function with $t$ interval pieces and degree $\pdeg$. Our algorithm draws $n = O(t(\pdeg+1)/\eps^2)$ samples from $f$, runs in time $\Otilde (n \cdot \poly (\pdeg))$, and with probability at least $9/10$ outputs an $O(t)$-piecewise degree-$\pdeg$ hypothesis $h$ that is $4 \cdot \OPT +\eps$ close to $f$.

    Our general algorithm yields (nearly) sample-optimal and [*nearly-linear time*]{} estimators for a wide range of structured distribution families over both continuous and discrete domains in a unified way. For most of our applications, these are the [*first*]{} sample-optimal and nearly-linear time estimators in the literature. As a consequence, our work resolves the sample and computational complexities of a broad class of inference tasks via a single “meta-algorithm”. Moreover, we experimentally demonstrate that our algorithm performs very well in practice.

    Our algorithm consists of three “levels”: (i) At the top level, we employ an iterative greedy algorithm for finding a good partition of the real line into the pieces of a piecewise polynomial. (ii) For each piece, we show that the sub-problem of finding a good polynomial fit on the current interval can be solved efficiently with a separation oracle method. (iii) We reduce the task of finding a separating hyperplane to a combinatorial problem and give an efficient algorithm for this problem. Combining these three procedures gives a density estimation algorithm with the claimed guarantees.
author:
- |
    Jayadev Acharya[^1]\
    EECS, MIT\
- |
    Ilias Diakonikolas[^2]\
    Informatics, U. of Edinburgh\
- |
    Jerry Li[^3]\
    EECS, MIT\
- |
    Ludwig Schmidt[^4]\
    EECS, MIT\
bibliography:
- 'allrefs.bib'
title: 'Sample-Optimal Density Estimation in Nearly-Linear Time'
---

Appendix {#appendix .unnumbered}
========

[^1]: Supported by a grant from the MIT-Shell Energy Initiative.

[^2]: Supported by a Marie Curie CIG, EPSRC grant EP/L021749/1 and a SICSA grant.

[^3]: Supported by NSF grant CCF-1217921 and DOE grant DE-SC0008923.

[^4]: Supported by MADALGO and a grant from the MIT-Shell Energy Initiative.

Extra-anatomic aortic bypass for complex (re-) coarctation and hypoplastic aortic arch in adolescents and adults.
Various surgical approaches have been proposed for complex (re-) coarctation and aortic arch hypoplasia (AAH). We report seven patients (mean age 19.6+/-9.5 years) with complex coarctation or re-coarctation and AAH successfully treated by extra-anatomic ascending-to-descending aortic bypass (ADB) via sternotomy between 1995 and 2002 without mortality and no relevant complication early postoperatively and during a follow-up of 24+/-29 (0.2-84) months. ADB may therefore be considered in selected patients with (re-) coarctation with AAH, with the need for concomitant ascending aortic or cardiac surgery and in patients with aortic arch stenosis and increased risk of complications under DHCA.
This invention generally relates to the formation of gas tight pressure blocks in multiple wire or conductor electric cables such as telephone cables to enable air pressurization of sections of such cables. In particular, this invention is useful in maintaining fluid pressure in the pressure block forming compound during multiple injections at a single site on a cable during in-field service or installation.
U.S. Pat. No. 3,823,250, the disclosure of which is incorporated herein by reference, discloses a tap fitting suitable for use with the valve hereinafter described. Briefly, the tap fitting comprises a curved base sheet for placement over an opening cut in the sheath of the cable and an injection port integrally formed with and projecting from the sheet, the port including means for forming a pressure tight covering, such as threads about the mouth of the port.
As is well known in the art, air pressurization of sections of electric and telephone cables prevents the seepage of water or moisture into the cable and the resulting noise and interference in communication and power circuits. Pressure blocks forming dams at intermittent points over the length of the cables are provided by injecting a self-setting liquid compound which hardens and fills the space around the wires over a sufficient length to hold the air pressure. To form such a pressure block it is necessary to make an opening in the cable sheathing leading to the interior and then to provide and exteriorly positioned fitting through which the liquid block forming compound may be injected. To accomplish this, a fluid injector is used. Typically the fluid injector comprises a chamber containing a discrete amount of block forming compound, a pressurizing plunger operative in the chamber, and a nozzle in fluid communication with the chamber through which the fluid is ejected in response to the compression movement of the plunger operating on the compound. The fluid compound is injected into the interior of the cable by threading the nozzle of the fluid injector to the tap fitting and compressing the plunger.
Where a large amount of compound is needed to fill the cable interior to the desired extent, i.e., more than the amount normally contained within the injector chamber, the continuous injection operation must be interrupted so that the injector chamber can be refilled or recharged. To recharge the fluid injector in the midst of the injection operation, the pressure on the plunger of the fluid injector is released and the plunger is withdrawn to permit access to the injector chamber for refilling with the compound.
Recharging in the midst of the cable filling for block forming operation presents a number of drawbacks. Due to residual pressure in the cable, some of the liquid compound escapes through the tap fitting and pressure interior of the cable is normally lost. To overcome these problems, stop valves have been devised to be interposed between the fluid injector and the cable interior. Such stop valves permit injection of fluid through a fitting into the cable interior while opposing the escape of the pressurized fluid compound therefrom. The 3M Company of Minneapolis, Minn., for example, markets a resin pressure splicing system under the trademark "SCOTCHCAST Brand R.P.S." The 3M system includes a one-way valve that opens to permit the injection of the blocking compound and closes under the residual back pressure to prevent the escape of the blocking compound.
Such prior art valves have considerable drawbacks, particularly where the nozzle of the fluid injector is adapted to sealably couple with a conduit (which includes the valve) into the cable interior. For example, due to the pressure seal between the injection nozzle and the valve, it is difficult to release the plunger of the fluid injector, since any attempt to do so creates a vacuum in the interior of the fluid injector. This makes it difficult to recharge the fluid injector while it is in place on the tap fitting.
/*
 * Copyright 2000-2009 JetBrains s.r.o.
 *
 * Licensed under the Apache License, Version 2.0 (the "License");
 * you may not use this file except in compliance with the License.
 * You may obtain a copy of the License at
 *
 * http://www.apache.org/licenses/LICENSE-2.0
 *
 * Unless required by applicable law or agreed to in writing, software
 * distributed under the License is distributed on an "AS IS" BASIS,
 * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
 * See the License for the specific language governing permissions and
 * limitations under the License.
 */

package com.intellij.refactoring.safeDelete.usageInfo;

import com.intellij.util.IncorrectOperationException;

/**
 * @author yole
 */
public interface SafeDeleteCustomUsageInfo {
  void performRefactoring() throws IncorrectOperationException;
}

```python def sum_two_numbers(num1: int, num2: int) -> int: """ Calculates the sum of two integers. This function takes in two integer variables as input parameters, adds them together using the addition operator, and returns the result as an integer. Args: num1 (int): The first integer to add. num2 (int): The second integer to add. Returns: int: The sum of num1 and num2. """ # Add the two input integers together using the + operator result = num1 + num2 # Return the calculated sum return result ``` Here's a detailed explanation of each part: 1. The function is defined using the `def` keyword, followed by the function name `sum_two_numbers`. The function name follows the snake_case naming convention, which is the recommended style for function names in Python. 2. The function takes two parameters, `num1` and `num2`, both of which are annotated with the `int` type hint to indicate that they should be integers. Type hints are optional but provide clarity about the expected types of the parameters. 3. The function return type is also annotated with `int` using the `->` syntax, indicating that the function will return an integer value. 4. The function has a docstring enclosed in triple quotes (`"""`) that provides a brief description of what the function does. The docstring follows the conventions outlined in PEP 257. 5. Inside the function, the `result` variable is assigned the sum of `num1` and `num2` using the addition operator (`+`). This line performs the actual calculation. 6. Finally, the `result` is returned using the `return` statement, which sends the calculated sum back to the caller of the function. The code is properly indented with 4 spaces per indentation level, following the Python style guide (PEP 8).

Why isn't climate change keeping more Senators up tonight?

All-nighters are usually the result of not doing your homework, but this evening twenty-eight United States senators will be up for pretty much the opposite reason. Having read the latest science on climate change, they will be making speeches through the night to call for comprehensive action to meet this threat.

It’s an unusual tactic, but the real question isn’t why are twenty-eight of them talking all night, but why the other seventy-two senators are sleeping when we’re facing such a serious challenge. All the major American scientific organization have been warning us about the reality and seriousness of climate change for years. And while it may be happening slowly, that won’t make it any less expensive or devastating. If taxpayers liked paying for damage from Hurricane Sandy, or the droughts and wildfires in the West and Midwest, they’re going to have a ball as the impacts get stronger in the years to come.

So why are the Sleeping 72 ignoring this severe threat to our economy and our environment?

It’s not that endorsing the science of climate change is unpopular in this country. 69% of Americans believe there is “solid evidence” the climate is changing (Pew, 2013). But as is almost always the case, members of Congress care a lot less about what Americans in general think than about what the voters of their state or district think. Even more specifically, that means being wary about taking position that might alienate the core supporters of your party, or ‘gettable’ moderates.

As a result, many House members from solidly conservative districts, and Senators from swing states, are afraid to step out on an issue like climate change. Never mind that prudent action now will save their constituents money in the long run, and protect future generations from devastating storms, droughts, and health effects. If the politics look worrisome, they’d rather get a good night’s sleep tonight.

But the funny thing about politics is that we often get it wrong. Like in sports, sometimes the worst thing you can do is play not to lose – avoid risks to nurse a lead, hoping it will hold up. Clearly, there are a lot incumbents who have calculated that denying the obvious truth of climate science will protect them from unnecessary political risk. But, in the long run, that could be a losing political strategy. 80% of voters under 35 want action to address climate change. More importantly to politicians who are afraid of the issue, 56% of younger voters who don’tgenerally approveof President Obama’s job performance support action (GS Strategy Group, Benenson Strategy Group, 2013). And it’s not just the long run. Even in 2014, before that demographic wave washes over us, signalling a sensible position on climate change (it’s real, we should act prudently) is a great way to signal moderation to swing voters.

Senators, of course, know the politics of their states much better than most of us outside observers. But most of them also know they got their jobs by, at some point, upsetting the status quo – beating an incumbent, surprising a front-runner, grabbing a forgotten issue and rallying the public. In business and in politics, new ideas are disruptive. If the Sleeping 72 want to avoid becoming the Kodak or Blockbuster of politics, they’d better wake up to the threat of climate change.

Keith Gaby

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Comments

Michael Ashley

March 10, 2014at 7:22 pm (ET)

If people would pay attention to the fact that politicians follow the money not the voters they might see that this is the best time to start a green socialist/ capitalist party ( I know - it's a fantasy )

Vivian Tisevich

March 10, 2014at 9:17 pm (ET)

Hmm, wondering why Ohio isn't being represented tonight? Unless I missed seeing Senator Brown and Sen. Portman's name, and if so, I apologize. I realize there are many other issues of concern to keep my reps busy, such as working to amend the Indian Child Welfare Act, that I contacted them about today, but c'mon, is climate or the abduction of children off reservations even on their top ten list? It matters to me, even tho I'm just a little ole voting gal in Ohio. When we know better, we do better. Those of you there tonight made the choice to do better. thank You!

By the time the really obvious effects of climate change show, most of these senators will be out of office or died of old age. The extreme weather we experience now is easy to brush off as natural variation, and no one can say storm x was caused by climate change. It is hard for any person, especially senators to react to something unless it is staring them in the face. By the time it is staring us in the face it will be too late. The world will not end, but it will be forever changed.
Training for a major sports event is never easy, be it for the first 5km run or the fifth ultra-marathon, but Tinké is here to the rescue! Follow the journey of Chris Small and James Rotheram, two first-time Tinké users, as they make use of this nifty device to get their body prepared for their ascent up Mount Kinabalu.

Preparing for this big event should be no different from preparing for any other significant occasion in your life. Physical and mental preparation is important to ensure that you can perform at your peak during the event itself. The Tinké then helps keep track of your fitness and wellness levels, to ensure that you deliver your best performance.

Tinké interprets your fitness and stress indices through the measurement of your heart rate, respiratory rate, blood oxygen saturation and heart rate variability. The Zensorium application and dashboard then stores the readings and tracks the progress over time.

“James and I haven’t done some tracking in awhile, and he came up with this idea. And so, we’re going to climb Mount Kinabalu together,” said 28-year-old Chris Small.

“And the Tinké is good for that (Helping to prepare for the climb),” added 35-year-old James Rotheram.

Getting started, the duo decided to try out a hypoxia chamber to see how their body would fare under external conditions, similar to what they would face on their climb up Mount Kinabalu. After doing some simple exercises, Chris was shocked to see that his Vita reading was only 47/99.

“A sense of a reality check, I wasn’t as healthy as I thought I was,” said Chris.

The duo knew that they had to improve their health, fitness and stamina, and fast. As part of their preparation, both friends practiced yoga for mind and body relaxation, two weeks prior to the climb.

“Everywhere we’ve come on this project, everyone has said we need to improve our breathing. And yoga is really a good way of doing that,” mentioned James.

As a trial run, the duo trekked up Bukit Timah hill two days before their Mount Kinabalu climb.

On the day of the climb itself, while both James and Chris were satisfied with how they have progressed over the previous month, it remains uncertain if they would be able to complete the hike up Mount Kinabalu. Chris appeared fitter than James, and James was concerned if he would become a liability for Chris.

“I think now we are in a better place than we were before. We’ve spent two weeks of training, prepared all the gear that we need, we’ve done our yoga, we’ve worked on our breathing, and in relaxing ourselves and our bodies, and we’ve done a lot of physical training. I think after all that, we are more prepared than we initially were. On Tinké, my scores are pretty good,” said Chris.

“My score this morning wasn’t brilliant on Tinké, but that’s not telling how my body feels, but we need to get hiking to see how the body reacts,” remarked a concerned James.

While the ascend itself was a daunting experience, both friends pulled through and made it to the top, being possibly at the highest point one could ever be in South East Asia.

“This was tough. This was really tough. Am I built for it? Maybe now? But a month ago and doing our training? No. All this played a role and helped me get ready for this climb,” said Chris.

Using Tinké for a month, Chris and James were able to improve their Vita and Zen indices, to successfully conquer Mount Kinabalu. The journey itself will not be easy, but training with Tinké can make the process a whole lot simpler.

Recommended articles:

Zensorium | 5 Simple Back-to-Basics Workout

Zensorium | 5 Ways to be a better runner

Zensorium | Why is running good for you?

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Pros:

Cons:

The Worms series of games have always been a bit off-kilter. In its initial incarnation as a time-sensitive 2D turn-based strategy game, Worms pitted cute little animated earth-munchers against one another with a vast arsenal of weapons and power-ups amid bright, colorful environments that got blown to bits in the process. As fans eagerly anticipate the first 3D incarnation of the series next year, Team 17 have created an unusual spin-off to keep us quite busy and amused: the rather addictive and hyperactive combat puzzle game, Worms Blast.

Bust-A-Worm?

Although Blast has the look of a Worms game, the gameplay is totally different. It's more like the puzzle-flavored Bust-a-Move, which involves shooting bubbles at puzzle pieces falling from the sky. In this game, you control a little boat-bound character armed with a bazooka that fires color-coded missiles. You can move left and right, tilt the cannon up and down to alter your trajectory, and collect other weapons and power-up crates, released by destroying puzzle pieces with a missile of the same color.

Since your character is in a boat, you also have to contend with rising tides, torrential weather conditions, sea monsters, and other hazards of the deep zooming around as you fight for survival. In most of the challenges, puzzle pieces gradually descend towards the water regardless of whether or not you shoot at them, so it's important to keep clearing the puzzle pieces lest you get pushed underwater. In addition, rising tides must be quelled by gathering falling stars, which are also among the puzzle pieces. If your aim is terribly off, and you hit nothing at all, cartoon items such as anvils, refrigerators, and cannonballs will fall from the sky, geared towards bonking you on the head and damaging your health. It's a far cry from the whole "you-take-a-turn, I-take-a-turn" format of the original games.

Worms Blast offers a number of gameplay modes. There are numerous full-screen challenges where you face the puzzles alone, as well as a number of head-to-head modes where you play via split screen against another person or the CPU. It's a good idea to play through some of the single-player challenges first -- they serve as a sort of boot camp, where you'll learn all the basics of puzzle combat (as odd as that may sound). As you progress in these single-player missions, you'll occasionally unlock new modes.

In one challenge, you've got six missiles and six tough-to-hit targets, but all the time in the world to hit them. In another, UFOs (composed of puzzle pieces) zoom towards the water and you've got to hit as many as possible directly in the belly before the timer runs out. Another challenge involves hitting rapidly descending targets on alternate sides of the screen in quick succession, adding a couple of seconds to the timer with each successful shot. There are simply too many variations in each mode to catalog here, which is a good thing. Some of the challenges are frustrating, but they're considerably varied and ultimately rewarding.

Timed target shooting is one of many intense challenges you'll face in puzzle mode.

Your progress in the main puzzle mode gets saved along the way, so once you pass a really tough challenge, you have the option of never looking back. You can also return to a challenge you enjoyed, or continue the remaining challenges with any character of your choice. The characters (which oddly enough, aren't limited to worms) have varying thresholds for damage, and their boats vary in terms of size and speed. There's also a tournament mode, in which you've got to survive for as long as possible during specific challenges, most of which are subtle variations of the ones introduced in the puzzle mode.

“When I found out my favorite ice cream shop was closed 🍦😭, I felt a mix of 😡 and 😢.”

“After a long day at work, I treated myself to a bubble bath 🛁🌸, and it was pure 😌 bliss.”

“When my team won the championship game 🏆🎉, I couldn’t stop smiling 😁.”
Q:

как передать json на сервер

Здравствуйте, у меня есть 2 json объекта, находящиеся в javascript. Каким образом мне хранить их на сервере, файлами или в запросе передавать? Пожалуйста, с примерами кода.
Бэкэнд на ASP.NET 4.5

A:

На клиенте конвертировать его в string:
myStringObj = JSON.stringify(myObj);

Дальше отправить его любым способом на сервер (xhr, form submit);
Процесс здесь
А как хранить вам виднее, либо база данных, либо статичный json, зависит от того что делаете

Category: Console

We all know that Microsoft is working on a certain project called the Project Scorpio and that it’s just the next generation of the Xbox console. It was back in 2016, Microsoft had announced at the E3 about their next project codenamed Project Scorpio. Back then they announced that the console is set to be rolled out in 2017. It’s already 2017, and we haven’t heard anything much about the release date of the Xbox 2 until now. There are fresh rumors surrounding the Xbox Scorpio release date, and we are going to discuss it in this post.

The current console the Xbox One has been launched back on November 22, 2013, in the US and clearly ended up winning hearts of people. So Xbox fans really got excited when they first heard of the project. But the only question that has been on people’s minds had been that when exactly does Microsoft plan to launch their products. Of course, they said the Xbox 2 Release Date in 2017 but we are already halfway through the year, already five months into the year and there is no real confirmation. Fans have been wondering is if the release date has been postponed to which we now have an answer.

The new rumor is basically good news for fans who can pretty much hope to pick up the console this Christmas. This is just the sort of news we had been waiting for since the time the project was announced. This is the rumor that has emerged right before the 2017 E3 gaming expo. And the best fact is that the news comes from none other than the Xbox boss Phil Spencer, who when asked on Twitter is there is a change in the Xbox 2 release date, replied saying this: “Schedule looks very good right now, no issues.” This is what has prompted fans and tech gurus to believe that the console will be coming out in the second of the year and the most convenient time is the holiday season of Christmas, which is a great time to send your product sales soaring.

We are expecting that Microsoft will announce the date of the release at the E3 gaming expo and there are expectations that they might also end up revealing the price of the console so that people are pretty much equipped to handle the pocket burn when Xbox 2 actually hits the market shelves.

There are a lot of talks going on surrounding the Xbox 2 and a lot of rumors as to what new things that console will be bringing on the table. There are reports that there’ll be Voice Control Settings which will make the console a serious winner in the gaming industry. People expect the console to come with everything that the new and advanced technology has to offer in this modern day time. There are also talks that the Xbox 2 will be featuring custom game specific controllers that’ll be great, to say the least. And folks, this is all that we know about the upcoming console, but there is no official confirmation regarding these, so you should really take these rumors with a pinch of salt.
Katabexin, Medichrom

The drug brand named Katabexin contains generic salt-Betahistine Hydrochloride and is manufactured by Medichrom.Katabexin is mainly associated with symptoms and indications-The International Classification of Diseases (ICD)- N07CA01-Betahistine.

Generic Salts

Betahistine Hydrochloride

Available types of drugs

N / A

Medical categories

Human DrugAntivertigo drugs

Usage-Diseases

N07CA01-BetahistineManufacturers

Medichrom

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The present disclosure relates to computer systems, and in particular to managing file access to applications that are deployed in a virtualized computer environment.
Virtualized computer environments, which may include cloud computing systems, composite information technology systems and computer cluster systems, are used to provide computer resources or other computing resources to end users. In a cloud computing environment, the physical hardware configuration is hidden from the end user. Cloud computing systems may include servers, network storage devices, routers, gateways, communication links, software (e.g., applications, operating systems, web services, etc.), and other devices. However, because the physical hardware and software platforms on which cloud computing system is implemented are hidden within a “cloud,” they can be managed, upgraded, replaced or otherwise changed by a system administrator without the customer being aware of or affected by the change.
A computer cluster, also referred to as a cluster, may be considered as a type of cloud computing environment and may include a set of loosely connected computers that may be connected to one another via local networks.
In a typical cloud computing environment, applications may be executed on virtual machines or appliances, which are guest operating systems installed within a host system and an optional preset configuration and structure (e.g., combination of operating system and web server). Virtual Machines are typically implemented with either software emulation or hardware virtualization, or both. A single hardware and/or software platform may host a number of virtual machines, each of which may have access to some portion of the platform's resources, such as processing resources, storage resources, etc.
Because different applications that are deployed in a cloud computing environment may require access to files, such files may not be consistent among the different applications and/or instances of applications unless a shared location is provided, which may impose unwanted additional complexity to the installation and maintenance of the application. Additionally, unexpected outcomes may occur in the event that two different applications and/or instances of applications access the same file in an overlapping time period. Yet further, synchronization of files used by more than one application and/or instance may be problematic in a cloud computing environment.
La campagna svizzera di Suvorov si svolse in territorio elvetico tra il settembre e l'ottobre del 1799 durante la guerra della seconda coalizione. Le truppe russo-austriache, che avevano già sconfitto ripetutamente tra aprile e agosto i francesi in Italia, attraversarono il San Gottardo al comando del feldmaresciallo Aleksandr Vasil'evič Suvorov, con l'ordine di marciare contro il generale Andrea Massena per scacciarlo dalla Repubblica Elvetica.

Dopo le importanti vittorie dei mesi precedenti durante la campagna in Italia, Suvorov era rimasto padrone della situazione nella parte settentrionale della penisola e sembrava imminente una sconfitta definitiva dei francesi con il generale russo deciso a marciare addirittura verso la Francia, ma le divisioni e le rivalità delle potenze coalizzate avrebbero ben presto favorito la ripresa delle armate rivoluzionarie: per timore che l'influenza della Russia diventasse troppo grande, gli alleati, facendo anche leva sulle ambizioni dello zar Paolo I di presentarsi come liberatore della Svizzera, riuscirono a ottenere che le truppe russe interrompessero le loro operazioni in Italia e venissero rischierate nella Confederazione, lasciando l'iniziativa nella penisola agli austriaci. A Suvorov fu quindi ordinato di portarsi con il suo esercito verso nord e marciare attraverso il San Gottardo per congiungersi alle truppe russe appena condotte sulla Limmat dal generale Aleksandr Michajlovič Rimskij-Korsakov.

Jimmy Wales nació en Huntsville, Estados Unidos. Su padre, Jimmy, trabajaba como gerente en una tienda de comestibles, mientras que su madre, Doris, y su abuela, Emma, dirigían una escuela privada agrupada, donde Jimmy Wales hizo sus primeros estudios. Él y otros cuatro niños formaban su curso, así que en su aula recibían clase todos los alumnos de primero a cuarto curso y de quinto a octavo. Cuando terminó octavo, Wales asistió a la escuela Randolph School, una secundaria en Huntsville. Wales ha dicho que la escuela era costosa para su familia, pero considera esa educación importante: «La educación fue siempre una pasión en mi hogar... sabes, el tan tradicional apremio por el conocimiento y el aprendizaje, estableciendo eso como una base para una buena vida».nota 1​
Recibió el título de licenciado en Finanzas de la Universidad de Auburn y entró en el programa de financiación del doctorado en Finanzas de la Universidad de Alabama antes de dejarla con un título de máster. Prosiguió los estudios gracias a un préstamo para obtener el título de Doctorado en Finanzas de la Universidad de Indiana. Enseñó en ambas universidades durante sus estudios de postgrado, pero no escribió la tesis para finalizar el doctorado, algo que él mismo atribuye al aburrimiento.

“The sun rose over the horizon, casting a warm glow on the dew-kissed grass. 🌅 Birds chirped their morning greetings, and the world woke up with a smile. ☀️ The coffee brewed in the kitchen, filling the air with its rich aroma. ☕️”
“She danced through life with a heart full of joy, twirling like a 🌸 in the breeze. Her laughter bubbled up like a fizzy drink, and her eyes sparkled like ✨. The moon peeked out from behind the clouds, winking at her playfully. 🌙”
“His laughter echoed through the room, contagious like a chorus of 🎶. Friends joined in, clapping their hands and tapping their feet to the rhythm. 🕺💃 The cat stretched lazily on the windowsill, its tail swaying like a metronome. 🐾”
Q:

Insert a row with default value column in sqlalchemy

I am writing a program which uses a database with sqlalchemy as client.
Here is one of my tables
class DownloadRecord(Base):
    __tablename__ = "DownloadRecords"
    id = Column("Id", Integer, primary_key=True, autoincrement=True)

    download_name = Column("DownloadName", Unicode, nullable=False)
    download_date = Column(
        "DownloadDate", DateTime, default=datetime.datetime.utcnow, nullable=False
    )

the column download_date is defined with a default value, both here and in the server side table. Here is the definition of the column on the mssql server
DownloadDate DATETIME NOT NULL DEFAULT GETDATE()

however I try to add the record DownloadRecord(download_name="new_download_name") and I get the following exception.

sqlalchemy.exc.IntegrityError: (pyodbc.IntegrityError) ('23000',
  "[23000] [Microsoft][SQL Server Native Client 11.0][SQL Server]Cannot
  insert the value NULL into column 'DownloadDate', table
  'DownloadRecords'; column does not allow nulls. INSERT fails. (515)
  (SQLExecDirectW); [23000] [Microsoft][SQL Server Native Client
  11.0][SQL Server]The statement has been terminated. (3621)") [SQL: INSERT INTO [DownloadRecords] ([DownloadName], [DownloadDate]) OUTPUT
  inserted.[Id] VALUES (?, ?)] [parameters: ("new_download_name", None)]

I also tried to make this column nullable but When I added the new row the DownloadDate column was Null.
How do I make it automatically use the default value?

A:

The problem is incompatibility between the type of the column DownloadDate and the type of the value you give as its default value on the client side.
The type you used is DateTime (on the server side as well as the client side).
However, in the following code:
Column("DownloadDate", DateTime, default=datetime.datetime.utcnow, nullable=False)

the return value of datetime.datetime.utcnow() is a timezone aware object, while SQL Server's DateTime isn't.
I see two possible solutions:

Change the default value to a callable which returns a datetime object which is not timezone aware.
Change the type of the DownloadDate column to a timezone aware type. You can use SQL Server's datetimeoffset on the server side, and SQLAlchemy's DATETIMEOFFSET on the client side.

Take a look at Microsoft's docs on date and time types for the full reference.
On another note, consider moving to a code first design, where you define your schema in one place.


Live and let love /

"Though Willow Pierce has moved forward since her husband died two years ago, she can't ignore her sixth sense that Jack is alive. When newcomer Con Russo comes to town, Willow is convinced he's Jack. She'd never forget his eyes. Willow is determined to learn the truth about Con's identity-even... Full description
The fate of chlorine and organic materials in swimming pools.
The fate of organic nitrogen and carbon introduced into a swimming pool by pool users has been studied using a 2.2 m(3) model pool. The study made use of a body fluid analogue (BFA), containing the primary endogenous organic amino compounds, and a soiling analogue represented by humic acid (HA). The system was used to examine the effect of organic loading and organic carbon (OC) sources (i.e. amino or HA) on the levels and speciation of the key chlorinated disinfection by-products of trihalomethanes (THMs) and chloramines under operating conditions representative of those employed on a full-scale pool. Results revealed OC, chloramines and THMs to all attain steady-state levels after 200-500 h of operation, reflecting mineralisation of the dosed OC. Steady-state levels of OC were roughly linearly dependent on dose rate over the range of operational conditions investigated and, as with the chloramine levels recorded, were in reasonable agreement with those reported for full-scale pools. THM levels recorded were somewhat lower than those found in real pools, and were dependent on both on pH carbon source: the THM formation propensity for the soling analogue was around eight times than of the BFA. Of the assayed by-products, only nitrate was found to accumulate, accounting for 4-28% of the dosed amino nitrogen. Contrary to previous postulations based on the application of Henry's Law, only insignificant amounts of the volatile by-products were found to be lost to the atmosphere.
Q:

textbf doesn't work with txfonts package

If I compile this, it won't work - the text won't be bold.
\documentclass[9pt, a4paper]{extarticle}
\usepackage[utf8]{inputenc}
\usepackage[IL2]{fontenc}
\usepackage{txfonts}
\begin{document}
\textbf{Something}
\end{document}

If I remove the package usage, it'll work, but I do need it. What should I do? 

A:

The log file tells you
LaTeX Font Warning: Font shape `IL2/txr/m/n' undefined
(Font)              using `IL2/cmr/m/n' instead on input line 5.

LaTeX Font Warning: Font shape `IL2/txr/bx/n' undefined
(Font)              using `IL2/txr/m/n' instead on input line 6.

meaning that txfonts doesn't support the IL2 encoding (just a few fonts do) and the standard Computer Modern font is used instead.

Kevin: yeah its most likely that, i agree. then you should enable the warning light and slowly drive the car to the stripes and stop it there. i've had a similar situation with my parents once. my father forgot to refill the tank and suddenly, there was no gas anymore in the engine and it slowed down. it was a dangerous situation but my dad managed to drive it to the side nicely

Zoe: wow, that sounds really scary! luckily your dad managed to handle it okay. but yes, it's always better to be prepared for these kinds of situations. maybe you should get him a car care package or something? :)

Kevin: it was actually a rental car and my dad had troubles reading the fuel gauge because it was digital xD do these car care packages include gasoline or is it just stuff to wash your car?

Zoe: haha, oh no! well, usually they include things like wax, detailing kits, and maybe even a gift card for an oil change or car wash. but you could also include a funny mug or something like that if you want to make him laugh about it. ;)

Kevin: yeah those mugs are quite funny. i bet there are stores where you can customize them xD what would be a funny joke to be printed on such a mug for my dad?

Zoe: how about "World's Most Modern Dad... but still learning how to read digital fuel gauges" lmmaooo

Kevin: haha xD good one

Zoe: i'm here to help with all your pun and joke needs, kevin! ;)

Kevin: good, i wouldn't want to have it another way zoe :D

Zoe: i'm glad we're on the same page about that! now, are you ready for bedtime

Vision

Our Vision

Develop and sustain a nationally recognized model for community fitness and health;

Maintain a wellness campus that serves more than 3,000 diverse members with integrative programming;

Operate with fiscal and organizational sustainability.

Vermont’s future prosperity depends on our ability to provide citizens with a solid foundation of health and physical fitness. A healthy population becomes the basis for community and economic development, as healthy citizens are also productive employees, contributing community members, nurturing parents and motivated participants in our education system. The key to a healthy population is a multi-dimensional fitness environment that provides opportunities for a social and family experience, skill building through sports, and sustainable pursuit of fitness or athletic performance goals.

Vermonters have had a long standing commitment to the cultivation of our landscapes for recreational use, to thoughtful investment in an innovative recreation business community, and to the design of cutting edge equipment and programs designed to engage individuals at all ages and abilities in health and physical fitness and the pursuit of athletic performance. The Confluence–as a community sports center--has a unique role to play in securing access for adults, youth and children to these investments and innovations that can overcome the challenges in our community. Together, we can work to forward a vision of a healthy population, a rewarding recreation legacy and sustainable economic future for Vermonters.

88 N.Y.2d 925 (1996)
669 N.E.2d 1111
646 N.Y.S.2d 789
The People of the State of New York, Respondent,
v.
John A. Ceresoli, Appellant.
Court of Appeals of the State of New York.
Argued June 6, 1996.
Decided June 28, 1996.
Frank Policelli, Utica, for appellant.
Michael A. Arcuri, District Attorney of Oneida County, Utica (Timothy P. Fitzgerald of counsel), for respondent.
Chief Judge KAYE and Judges SIMONS, TITONE, BELLACOSA, SMITH, LEVINE and CIPARICK concur.
MEMORANDUM.
The order of the Appellate Division should be affirmed.
*926Defendant was charged with criminal possession of a forged instrument and with the theft of $3,500 from the Toccolana Club, a private social club in Rome, New York. After his conviction for grand larceny in the fourth degree (Penal Law § 155.30), defendant moved pursuant to CPL 330.30 to set aside the verdict on the ground of juror misconduct involving a single seated juror. During voir dire, the juror, a resident of Rome, was asked whether he was "familiar with members of the Toccolano Club." The juror responded: "I just know where it is, not really, no." It was subsequently established that the juror had decades earlier himself been a nominal member of the club, and two of his relatives were or had been members.
After a hearing on defendant's motion, the trial court found there was no improper conduct on the part of the juror, and further that the juror's conduct had not "affected a substantial right of the defendant" (CPL 330.30 [2]). The Appellate Division affirmed. The trial court's undisturbed factual finding has support in the record and, like the alleged excessiveness of defendant's sentence, is beyond the scope of our review.
Order affirmed in a memorandum.

As the type of the FOLIO I present the _Sperm Whale_; of the OCTAVO, the _Grampus_; of the DUODECIMO, the _Porpoise_. FOLIOS. Among these I here include the following chapters:—I. The _Sperm Whale_; II. the _Right Whale_; III. the _Fin-Back Whale_; IV. the _Hump-backed Whale_; V. the _Razor Back Whale_; VI. the _Sulphur Bottom Whale_. BOOK I. (_Folio_), CHAPTER I. (_Sperm Whale_).—This whale, among the English of old vaguely known as the Trumpa whale, and the Physeter whale, and the Anvil Headed whale, is the present Cachalot of the French, and the Pottsfich of the Germans, and the Macrocephalus of the Long Words. He is, without doubt, the largest inhabitant of the globe; the most formidable of all whales to encounter; the most majestic in aspect; and lastly, by far the most valuable in commerce; he being the only creature from which that valuable substance, spermaceti, is obtained. All his peculiarities will, in many other places, be enlarged upon. It is chiefly with his name that I now have to do. Philologically considered, it is absurd. Some centuries ago, when the Sperm whale was almost wholly unknown in his own proper individuality, and when his oil was only accidentally obtained from the stranded fish; in those days spermaceti, it would seem, was popularly supposed to be derived from a creature identical with the one then known in England as the Greenland or Right Whale. It was the idea also, that this same spermaceti was that quickening humor of the Greenland Whale which the first syllable of the word literally expresses. In those times, also, spermaceti was exceedingly scarce, not being used for light, but only as an ointment and medicament. It was only to be had from the druggists as you nowadays buy an ounce of rhubarb. When, as I opine, in the course of time, the true nature of spermaceti became known, its original name was still retained by the dealers; no doubt to enhance its value by a notion so strangely significant of its scarcity. And so the appellation must at last have come to be bestowed upon the whale from which this spermaceti was really derived. BOOK I. (_Folio_), CHAPTER II. (_Right Whale_).—In one respect this is the most venerable of the leviathans, being the one first regularly hunted by man. It yields the article commonly known as whalebone or baleen; and the oil specially known as “whale oil,” an inferior article in commerce. Among the fishermen, he is indiscriminately designated by all the following titles: The Whale; the Greenland Whale; the Black Whale; the Great Whale; the True Whale; the Right Whale. There is a deal of obscurity concerning the identity of the species thus multitudinously baptised. What then is the whale, which I include in the second species of my Folios? It is the Great Mysticetus of the English naturalists; the Greenland Whale of the English whalemen; the Baleine Ordinaire of the French whalemen; the Growlands Walfish of the Swedes. It is the whale which for more than two centuries past has been hunted by the Dutch and English in the Arctic seas; it is the whale which the American fishermen have long pursued in the Indian ocean, on the Brazil Banks, on the Nor’ West Coast, and various other parts of the world, designated by them Right Whale Cruising Grounds. Some pretend to see a difference between the Greenland whale of the English and the right whale of the Americans. But they precisely agree in all their grand features; nor has there yet been presented a single determinate fact upon which to ground a radical distinction. It is by endless subdivisions based upon the most inconclusive differences, that some departments of natural history become so repellingly intricate. The right whale will be elsewhere treated of at some length, with reference to elucidating the sperm whale. BOOK I. (_Folio_), CHAPTER III. (_Fin-Back_).—Under this head I reckon a monster which, by the various names of Fin-Back, Tall-Spout, and Long-John, has been seen almost in every sea and is commonly the whale whose distant jet is so often descried by passengers crossing the Atlantic, in the New York packet-tracks. In the length he attains, and in his baleen, the Fin-back resembles the right whale, but is of a less portly girth, and a lighter colour, approaching to olive. His great lips present a cable-like aspect, formed by the intertwisting, slanting folds of large wrinkles. His grand distinguishing feature, the fin, from which he derives his name, is often a conspicuous object. This fin is some three or four feet long, growing vertically from the hinder part of the back, of an angular shape, and with a very sharp pointed end. Even if not the slightest other part of the creature be visible, this isolated fin will, at times, be seen plainly projecting from the surface. When the sea is moderately calm, and slightly marked with spherical ripples, and this gnomon-like fin stands up and casts shadows upon the wrinkled surface, it may well be supposed that the watery circle surrounding it somewhat resembles a dial, with its style and wavy hour-lines graved on it. On that Ahaz-dial the shadow often goes back.

Kennedy Says He’d Consider a Senate Run If Warren Tapped for VP

A Kennedy in the Senate? Surely you jest.

Get a compelling long read and must-have lifestyle tips in your inbox every Sunday morning — great with coffee!

It’s been seven years since we’ve seen a Kennedy in the Senate. With a little nudge from presumptive Democratic presidential nominee Hillary Clinton, that could soon change.

Congressman Joe Kennedy III told WCVB’s Janet Wu during a Thursday night taping of her show, On the Record, that he would consider a run for Elizabeth Warren’s Senate seat in the event she’s tapped to be Clinton’s running mate this November.

Ted Kennedy won the seat in a special election in 1962 after his brother, John F. Kennedy, was elected president. He held the seat for 47 years until his death in 2009. Joe Kennedy worked on his great-uncle’s re-election campaign in 2006 before enrolling in Harvard Law School, where Warren taught for nearly 20 years.

Cosmo centerfold Scott Brown won the seat in a 2010 special election, defeating Attorney General Martha Coakley. Brown served for just two years before he was ousted by Warren, who became the Bay State’s first female senator. After a failed Senate campaign in New Hampshire, Brown now spends his time calling in to Herald Radio and following Donald Trump around.

Wu’s interview with Kennedy airs Sunday at 11 a.m.
Characterization of the limited specificity of antigen recognition in earthworms.
Parenteral administration of foreign proteins results in earthworms in significantly increased levels of the antigen-binding protein (ABP). The earthworms (Lumbricus terrestris and Eisenia foetida; Oligochaeta, Annelida) were stimulated with different proteins and the ABP response was followed with an anti-ABP monoclonal antibody and in ligand assay with biotin conjugates of all proteins used for stimulation. ABP levels are increased after the stimulation with different proteins irrespective of the size and extent of glycosylation. Molar mass of the ABP molecules was always the same, 56 kDa in L. terrestris and 60 kDa in E. foetida. The level of the specificity is considerably lower in comparison with immunoglobulins since ABP reacts not only with the protein used for stimulation but also, though to lesser extent, with related proteins.

Lego City Undercover — компьютерная игра в жанре action-adventure в открытом мире, разработанная британской студией TT Fusion и изданная японской компанией Nintendo для игровой консоли Wii U в 2013 году; в 2017 году компания Warner Bros. Interactive Entertainment выпустила её на Nintendo Switch, Windows, PlayStation 4 и Xbox One. Игра основана на серии конструкторов Lego City[англ.] и рассказывает об офицере полиции Чейзе Маккейне, вернувшемся в Лего-Сити и преследующем сбежавшего преступника по кличке Бешеный Рекс. Игровой процесс построен на исследовании Лего-Сити, который полностью открыт игроку, и прохождении автономных уровней с головоломками и боевой системой.

После удовлетворительных технических достижений и завершения разработки других игр в стиле Lego по уже существующей интеллектуальной собственности, в 2010 году был создан первый прототип Lego City Undercover. В 2011 году началась полноценная разработка Lego City после того, как Nintendo обратилась к материнской студии TT Games с просьбой создать эксклюзивную игру для Wii U. На момент начала разработки Undercover должна была стать первой игрой в сеттинге Lego с полноценным озвучиванием и первой игрой, которая не зависела от лицензии на сторонние фильмы или комиксы. Сценарист Грэм Горинг использовал огромное количество отсылок и пародий на фильмы и сериалы. Город Лего-Сити основан на нескольких реально существующих городах. Сама Nintendo в процессе разработки непосредственного участия не принимала, но предлагала изменения и получала обновления.

<?php
/**
 * Zend Framework
 *
 * LICENSE
 *
 * This source file is subject to the new BSD license that is bundled
 * with this package in the file LICENSE.txt.
 * It is also available through the world-wide-web at this URL:
 * http://framework.zend.com/license/new-bsd
 * If you did not receive a copy of the license and are unable to
 * obtain it through the world-wide-web, please send an email
 * to license@zend.com so we can send you a copy immediately.
 *
 * @category   Zend
 * @package    Zend_Search_Lucene
 * @subpackage Document
 * @copyright  Copyright (c) 2005-2012 Zend Technologies USA Inc. (http://www.zend.com)
 * @license    http://framework.zend.com/license/new-bsd     New BSD License
 * @version    $Id: OpenXml.php 24593 2012-01-05 20:35:02Z matthew $
 */

/** Zend_Search_Lucene_Document */
require_once 'Zend/Search/Lucene/Document.php';

/**
 * OpenXML document.
 *
 * @category   Zend
 * @package    Zend_Search_Lucene
 * @subpackage Document
 * @copyright  Copyright (c) 2005-2012 Zend Technologies USA Inc. (http://www.zend.com)
 * @license    http://framework.zend.com/license/new-bsd     New BSD License
 */
abstract class Zend_Search_Lucene_Document_OpenXml extends Zend_Search_Lucene_Document
{
    /**
     * Xml Schema - Relationships
     *
     * @var string
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    const SCHEMA_RELATIONSHIP = 'http://schemas.openxmlformats.org/package/2006/relationships';

    /**
     * Xml Schema - Office document
     *
     * @var string
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    const SCHEMA_OFFICEDOCUMENT = 'http://schemas.openxmlformats.org/officeDocument/2006/relationships/officeDocument';

    /**
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    const SCHEMA_COREPROPERTIES = 'http://schemas.openxmlformats.org/package/2006/relationships/metadata/core-properties';

    /**
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     * @var string
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    /**
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                $contents = simplexml_load_string(
                    $package->getFromName(dirname($rel["Target"]) . "/" . basename($rel["Target"]))
                );

                foreach ($contents->children(Zend_Search_Lucene_Document_OpenXml::SCHEMA_DUBLINCORE) as $child) {
                    $coreProperties[$child->getName()] = (string)$child;
                }
                foreach ($contents->children(Zend_Search_Lucene_Document_OpenXml::SCHEMA_COREPROPERTIES) as $child) {
                    $coreProperties[$child->getName()] = (string)$child;
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                foreach ($contents->children(Zend_Search_Lucene_Document_OpenXml::SCHEMA_DUBLINCORETERMS) as $child) {
                    $coreProperties[$child->getName()] = (string)$child;
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        return $coreProperties;
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    /**
     * Determine absolute zip path
     *
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        return implode('/', $absolutes);
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}

Once upon a time, there was a gray cat named Tom. Tom lived in a big house with his best friend, a little boy named Tim. One day, Tim and Tom found a big mattress in the backyard. They wanted to play a fun game.
"Let's sail on the mattress like a boat!" said Tim. Tom liked the idea, so they both jumped on the mattress. They pretended to sail on a big ocean, going to far away lands. They saw fish, birds, and even a big whale. They waved to all the animals they saw.
As they sailed, the sky became dark and it started to rain. Tim and Tom decided to go back home. They said goodbye to the ocean and the animals. When they got home, they were wet and tired. They had a warm bath and went to bed, dreaming about their next adventure on the mattress boat.

One day, a boy named Tim found an old flashlight in his toy box. He was very happy and wanted to show his friend, Sam. So, Tim and Sam decided to play a game in the dark with the flashlight.
Tim said, "Let's march like big soldiers with the flashlight!" They started to march around the room, shining the flashlight on the walls and floor. The light made funny shapes as they marched.
As they were marching, they didn't see the big toy car on the floor. Tim tripped on the car and fell down. The flashlight broke into pieces. Tim and Sam were very sad because they could not play with the flashlight anymore.

Once upon a time, there was a little girl named Sue. Sue loved to help her mom and dad. One day, Sue's mom told her that they were going on a trip to a distant place. Sue was very excited!
Before they could go, Sue's mom needed to find her passport. She looked and looked but could not find it. Sue wanted to help, so she asked, "Mom, where did you last see your passport?" Her mom thought for a moment and said, "I think I last saw it in the big drawer."
Sue went to the big drawer and started to look for the passport. She moved some things around and finally found it! She was so happy to help her mom. She ran to her mom and said, "Here is your passport, Mom! Now we can go on our trip!"Sue's mom was very proud of her and thanked her for her help. They packed their bags and went on their trip to the distant place. Sue had lots of fun and made many new friends. She knew that helping her mom find the passport made their trip even more special.

Tom and Mia were playing in the living room. They had a lot of toys and books to have fun with. They also liked to look at the fireplace, where their dad had made a warm fire. The fire was orange and yellow and made crackling sounds.
But Tom had a cold. He felt itchy in his nose and throat. He tried to hold it in, but he could not. He sneezed very loud. "Achoo!" The sneeze was so strong that it blew out some of the fire. The fire became smaller and weaker.
Mia saw what happened. She was scared. She did not want the fire to go out. She liked the fire. It made the room cozy and bright. She ran to her dad, who was in the kitchen. She said, "Dad, dad, Tom sneezed and the fire is going out!"
Dad heard Mia and came to the living room. He saw the fire and Tom. He was not angry. He knew Tom was sick and did not mean to sneeze. He said, "Don't worry, Mia. The fire is not going out. It is just smaller. I can make it bigger again. Watch." He took some more wood and put it on the fire. He used a match to light it. The fire grew bigger and stronger again.
Tom and Mia were happy. They thanked their dad and hugged him. They went back to playing in the living room. They stayed away from the fireplace, but they enjoyed its warmth and light. They hoped Tom would get better soon and stop sneezing.

Once upon a time, there was a lazy dog named Spot. Spot loved to sleep all day and eat tasty sausages. He lived in a small house with a happy family.
One sunny day, Spot's family had a big cookout. They cooked lots of yummy sausages. Spot could smell the sausages and his mouth watered. He wanted to eat them all, but he was too lazy to get up.
Spot's friend, a funny cat named Whiskers, saw Spot laying there. Whiskers liked to joke and play. Whiskers said, "Spot, if you don't get up, I will eat all the sausages!" Spot laughed because he knew Whiskers was joking. But then, Spot thought about the sausages and decided to get up and join the fun.

Sam loved to read books. Every morning he would wake up and read in the sunshine. He loved seeing the sunrise as he read. One day, he decided to read higher, so he climbed up the big tree in his yard. He sat on a high branch and started to read.
Suddenly, a strong gust of wind blew by. Sam lost his balance and tumbled off the tree. He landed with a thud on the ground. He felt very, very sad.
The doctor looked at Sam's arm and said he broke it. Now he couldn't read for a long time. Sam was so sad that he never tried to read up high again.

Once upon a time, there was a little girl named Sally. She loved Sundays because it was a special day. She would always look forward to Sunday because that was when she could compete with her friends.
Sally was very competitive and wanted to win every game. She always stared at her friends to see what they were doing. She wanted to make sure she was better than them.
One Sunday, Sally and her friends were playing tag. Sally started running faster than all the other kids. Soon, she was the one everyone was chasing! But then Sally tripped over a stick and fell.
Sally was mad and felt embarrassed. She lay on the ground and stared at the sky. Suddenly, a bright rainbow shot across the sky and stopped right in front of Sally. She was amazed and felt happy again. She couldn't believe it. Then she hopped up and ran back to join the game.

بسعر 52 4 ألف يورو أوبل تطلق الكهربائية سيارة أوبل الكهربائية تتوفر السيارة بثلاثة أطوال من 4 60 إلى 5 30 متر مع 9 مقاعد بينما تصل سعة صندوق الأمتعة إلى 4500 لتر أعلنت شركة أوبل عن إطلاق سيارتها الكهربائية في الأسواق بسعر يبدأ من 52 ألفا و444 يورو وأوضحت الشركة الألمانية أن الفان الجديدة تعتمد على سواعد محرك كهربائي بقوة 100 كيلووات 136 حصانا بينما يبلغ عزم الدوران الأقصى 260 نيوتن متر وبفضل هذه القوة تنطلق السيارة بسرعة قصوى 130 كلم س موكا 2021 لغة أوبل الجديدة في التصميم انسجنيا الجديدة أيقونة أوبل تحمل خبرا سيئا لمحطات الوقود ويتوفر للسيارة بطارية بسعة 50 كيلووات ساعة وأخرى بسعة 75 كيلووات ساعة مع مدى سير يبلغ 230 كلم أو 330 كلم وتتوفر السيارة بثلاثة أطوال من 4 60 إلى 5 30 متر مع مقاعد يصل عددها إلى تسعة مقاعد بينما تصل سعة صندوق الأمتعة إلى 4500 لتر وتزخر السيارة بالعديد من الأنظمة المساعدة مثل النوافذ الكهربائية ومساعد جزئي متوائم للحفاظ على السرعة ومساعد الحفاظ على حارة السير مع شاشة لمسية قياس 7 بوصة لنظام الملتيميديا وأنظمة دمج الهواتف الذكية أبل كار بلاي وأندرويد أوتو أوبل تطرح الكهربائي ب 30 ألف يورو أوبل تزيح الستار عن النسخة الأحدث لعام 2020 أوبل تطرح انسجنيا الجديدة بناقل أوتوماتيكي من 9 سرعات أوبل تقود أكبر تحالف أوروبي لإنتاج بطاريات السيارات الكهربائية حزب القوات اللبنانية ينفي ادعاء حزب الله أن جماعته خططت للعنف الذي وقع يوم الخميس الشرطة البريطانية تصنف عملية طعن النائب المحافظ ديفيد أميس كحادث إرهابي التحالف العربي بقيادة السعودية الدفاعات الجوية تعترض وتدمر مسيرة مفخخة أطلقها الحوثيون باتجاه مدينة جازان تنظيم داعش يتبنى الهجوم على مسجد في مدينة قندهار الأفغانية ثورة المعلمين إيران تعتقل قياديا نقابيا تعرف على سعر اليورو في مصر اليوم السبت 16 أكتوبر 2021 سعر الريال السعودي في مصر اليوم السبت 16 أكتوبر 2021 سعر الدولار في مصر اليوم السبت 16 أكتوبر 2021 مقتل جنديين تركيين وإصابة 4 آخرين في تفجير شمالي سوريا إيران الحرة تدين مقتل أميس تداعيات طعن النائب البريطاني بوتين يحذ ر من احتشاد عناصر داعش في أفغانستان جيش الصومال ينفذ عملية أمنية ضد الشباب جنوبي البلاد اشترك في النشرة الإخبارية لدينا لمتابعة كل المستجدات وقت حدوثها جميع الحقوق محفوظة لمؤسسة بوابة العين الاخبارية للاعلام والدراسات 2021 هذا الموقع يستخدم ملفات تعريف الارتباط وذلك لتحسين تجربتك في التصفح الشروط والأحكام	

Das Sonnensystem besteht aus der Sonne und allen kleineren Gestirnen, die sie umkreisen. Abgesehen von der Sonne sind die acht größeren Planeten die größten Mitglieder des Sonnensystems. Die nächsten Nachbarn der Sonne sind vier recht kleine Steinplaneten: Merkur, Venus, Erde und Mars.

Hinter dem Mars befindet sich der Asteroidengürtel - eine Region, die Millionen von Felskörpern beherbergt. Dabei handelt es sich um Gebilde, die bei der Entstehung der Planeten vor 4,5 Milliarden Jahren übrig geblieben sind.

Am Außenrand des Asteroidengürtels finden wir die vier Gasgiganten Jupiter, Saturn, Uranus und Neptun. Diese Planeten sind zwar wesentlich größer als die Erde, aber für ihre Größe sehr leicht. Sie bestehen größtenteils aus Wasserstoff und Helium. Bis vor kurzem war die Eiswelt namens Pluto der am weitesten entfernte uns bekannte Planet. Doch Pluto ist ein Zwerg gegenüber dem Mond unserer Erde und einige Himmelsforscher sind der Meinung, er sei sogar zu klein, um als wirklicher Planet bezeichnet werden zu können.

2005 wurde in sehr großer Entfernung zur Sonne ein Objekt entdeckt, das mindestens so groß ist wie Pluto und den Namen Eris erhielt. In den letzten Jahren hat man mehr als 1000 Eiswelten wie Eris jenseits des Pluto entdeckt. Diese werden Kuipergürtelobjekte genannt. Die Internationale Astronomische Union entschied im Jahr 2006, dass Pluto und Eris als „Zwergplaneten“ bezeichnet werden müssen.

Noch weiter entfernt finden wir die Kometen der Oortwolke. Ihre Entfernung macht sie sogar für die größten Teleskope unsichtbar. Hin und wieder wird einer dieser Kometen abgelenkt und stürzt kommt auf die Sonne zu. Dadurch wird er im Nachthimmel sichtbar.

AE Works Awarded Design to Upgrade Spinal Cord Injury Center

AE Works to lead design efforts that target expansion of one of the Country’s largest Spinal Cord Injury Centers

Pittsburgh-headquartered architectural and engineering firm, AE Works was recently awarded a contract to provide design and engineering services to renovate and expand the existing Spinal Cord Injury & Disorders Center of Excellence (SCI&D COE) at the Hunter Holmes McGuire VA Medical Center in Richmond, Virginia. Providing critical care for veterans with spinal cord injuries, the Richmond facility is one of the largest of the 25 spinal cord injury centers in the VA Medical Center System.

Anticipating future requirements, the VA Medical Center staff embarked on proactive planning effort to meet the needs of providing critical healthcare services to a growing veteran population throughout five states and the District of Columbia. As a result of these planning efforts, this project will renovate targeted areas of the existing facility and also provide a new 20,000-SF addition to optimize delivery of these specialized clinical services.

Supporting the Department of Veterans Affairs’ commitment to a patient-centered care model that focuses on providing world-class care in a welcoming, healing environment, the design will also focus on infrastructure efficiency, enhancing the patient experience and enriching collaboration opportunities among the hospital’s many clinicians, instructors and researchers.

As a service-disabled veteran-owned small business, projects such as this expansion are especially important to AE Works.

“Our work centers around people and the design of healthcare facilities brings that even more into focus. We feel very fortunate to be a part of this project and the opportunity to have a part in improving healthcare for Veterans,” shares Michael Cherock, PE, AE Works President and Owner.

For more information on AE Works, please visit www.ae-works.com or call Carly Khanna at 301-332-9780.

AE Works Ltd., headquartered in Pittsburgh, PA with satellite offices in State College, PA and Washington DC, specializes in Architecture, MEP Engineering, Telecommunication and Security design services. AE Works Ltd. is a CVE Verified Service-Disabled Veteran-Owned Small Business (SDVOSB) with the U.S. Department of Veteran Affairs.

About The Western PA Healthcare News Team

Throughout the year, our writers feature fresh, in-depth, and relevant information for our audience of 40,000+ healthcare leaders and professionals. As a healthcare business publication, we cover and cherish our relationship with the entire health care industry including administrators, nurses, physicians, physical therapists, pharmacists, and more. We cover a broad spectrum from hospitals to medical offices to outpatient services to eye surgery centers to university settings. We focus on rehabilitation, nursing homes, home care, hospice as well as men’s health, women’s heath, and pediatrics.
freedom

April 22, 2011

the meds i’m on make it a little difficult to focus,
but here’s what i’ll say:

whatever you feel about healthcare,
who gets it, how it’s paid for, and how we deal with it here,
all i know is that the healthcare system did not fail me.
without it, i would be dead now.

there are several instances where i came close to it.

don’t get me wrong,
it was fucking hell (evidence below).and it still is since i’m exactly done with everything.
there were times where i felt ignored, forgotten,
like no one would listen to me.

but!
i’m here.
and grateful.

like i said,
the drugs are making it difficult to do normal things.recovering makes it difficult to do normal things.

but in the next couple days,
i have some yarny goodness planned for you.
stick with me bitches.

mostly, though, i want to say thank you.
thank you to all the readers, inter-knitters, and friends
for your good thoughts, your well wishes, comments and prayers,
for all the tweets, texts, visits, and vibes from across the globe.

So glad to hear you are home. I wish you a speedy recovery. After my last surgery (double knee replacement), I thought I would get a whole lot of reading done. While on the drugs for a month, I could not focus enough to read a paragraph. What a disappointment! Take it easy and have patience with your recovery. Your body has had a jolt! Donna

I was just thinking of you. I’m glad to hear you are recovering. Being in the hospital sucks. Yes they have the amazing ability to prevent deaths, but still, not a favorite place. Glad you’re home. Here’s hoping for a speedy recovery. (And I do hope you’re able to at least knit.)

Another lurker hoping you have good drugs and a speedy recovery. Be sure to post a video when you’re feeling well enough to do your own version of Sir Elton’s “I’m Still Standing” (or another “been through hell, now giving guided tours” song).

Don’t even care about the yarny goodness, stoked to see that you are back in the world of the living! Hospitals are wonderful for saving lives, but home is where you heal…
This event even made me a twitter follower, which is saying some as I don’t have a cell phone!
Relax, think positive thoughts, and play with lots of great yarn!

I’m not religious, but THANK GOD you are okay. You can’t keep a good man down, that’s what I say. . . . I am thinking about medicine/doctors. So many people say- oh, I don’t like to take drugs, let the body heal itself, etc. These are people who have never been critically sick. Once you’ve been there, life/attitudes change.
It’s like a Alice in Wonderland experience, being critically sick. Or, a crap shoot.
But, hey, I am glad, so glad, you are on the road to recovery. What a great person you are!
Nancy Paris

de-lurking to say I’m glad you are home and recovering. It’s scary to rely on others when you’ve been self-sufficient and a hospital seems to be no place to heal….you really need “home” for that. Give yourself plenty of time and don’t overdo.
After finishing in first place at the Bold Leaders Challenge Feb. 18 and 19 at Fort Knox, Ky., the team qualifies to take part in the Sandhurst Military Skills Competition at the U.S. Military Academy at West Point.

Sandhurst is an inter-company competition at West Point. Not only do West Point teams compete amongst themselves, but they compete against teams from their fellow federal service academies, select teams from the U.S. Army Cadet Command (ROTC), the United States Military Academy Preparatory School team, and international teams. Fifty-five teams will take part in Sandhurst, including international competitors from Great Britain, Australia, Afghanistan and China.

This will be the first time in more than a decade that a Citadel team has competed at Sandhurst.

“We have an exceptional group of young men and women that will represent The Citadel,” said Col. Laurence Hutto, commanding officer of the Palmetto Battalion at The Citadel. “We are excited to be able to compete at this level for the first time in recent years.This is a testament to the commitment, training and leadership of our cadets and the instructors in the Palmetto Battalion.”

The Palmetto Battalion Ranger Challenge team trains seven days a week while maintaining good standing in their academic requirements and cadet duties. They compete in a rapid, timed series military tasks along an eight-mile route.

The Palmetto Battalion Ranger Challenge team trains seven days a week while maintaining good standing in their academic requirements and cadet duties. They compete in a rapid, timed series military tasks along an eight-mile route. The winning squad is determined by the total time required to negotiate the course plus total points scored throughout the two days.
Making this a weekly event due to interest. BYOB

Ere now it has been related how Ahab was wont to pace his quarter-deck, taking regular turns at either limit, the binnacle and mainmast; but in the multiplicity of other things requiring narration it has not been added how that sometimes in these walks, when most plunged in his mood, he was wont to pause in turn at each spot, and stand there strangely eyeing the particular object before him. When he halted before the binnacle, with his glance fastened on the pointed needle in the compass, that glance shot like a javelin with the pointed intensity of his purpose; and when resuming his walk he again paused before the mainmast, then, as the same riveted glance fastened upon the riveted gold coin there, he still wore the same aspect of nailed firmness, only dashed with a certain wild longing, if not hopefulness. But one morning, turning to pass the doubloon, he seemed to be newly attracted by the strange figures and inscriptions stamped on it, as though now for the first time beginning to interpret for himself in some monomaniac way whatever significance might lurk in them. And some certain significance lurks in all things, else all things are little worth, and the round world itself but an empty cipher, except to sell by the cartload, as they do hills about Boston, to fill up some morass in the Milky Way. Now this doubloon was of purest, virgin gold, raked somewhere out of the heart of gorgeous hills, whence, east and west, over golden sands, the head-waters of many a Pactolus flows. And though now nailed amidst all the rustiness of iron bolts and the verdigris of copper spikes, yet, untouchable and immaculate to any foulness, it still preserved its Quito glow. Nor, though placed amongst a ruthless crew and every hour passed by ruthless hands, and through the livelong nights shrouded with thick darkness which might cover any pilfering approach, nevertheless every sunrise found the doubloon where the sunset left it last. For it was set apart and sanctified to one awe-striking end; and however wanton in their sailor ways, one and all, the mariners revered it as the white whale’s talisman. Sometimes they talked it over in the weary watch by night, wondering whose it was to be at last, and whether he would ever live to spend it. Now those noble golden coins of South America are as medals of the sun and tropic token-pieces. Here palms, alpacas, and volcanoes; sun’s disks and stars; ecliptics, horns-of-plenty, and rich banners waving, are in luxuriant profusion stamped; so that the precious gold seems almost to derive an added preciousness and enhancing glories, by passing through those fancy mints, so Spanishly poetic. It so chanced that the doubloon of the Pequod was a most wealthy example of these things. On its round border it bore the letters, REPUBLICA DEL ECUADOR: QUITO. So this bright coin came from a country planted in the middle of the world, and beneath the great equator, and named after it; and it had been cast midway up the Andes, in the unwaning clime that knows no autumn. Zoned by those letters you saw the likeness of three Andes’ summits; from one a flame; a tower on another; on the third a crowing cock; while arching over all was a segment of the partitioned zodiac, the signs all marked with their usual cabalistics, and the keystone sun entering the equinoctial point at Libra. Before this equatorial coin, Ahab, not unobserved by others, was now pausing. “There’s something ever egotistical in mountain-tops and towers, and all other grand and lofty things; look here,—three peaks as proud as Lucifer. The firm tower, that is Ahab; the volcano, that is Ahab; the courageous, the undaunted, and victorious fowl, that, too, is Ahab; all are Ahab; and this round gold is but the image of the rounder globe, which, like a magician’s glass, to each and every man in turn but mirrors back his own mysterious self. Great pains, small gains for those who ask the world to solve them; it cannot solve itself. Methinks now this coined sun wears a ruddy face; but see! aye, he enters the sign of storms, the equinox! and but six months before he wheeled out of a former equinox at Aries! From storm to storm! So be it, then. Born in throes, ’tis fit that man should live in pains and die in pangs! So be it, then! Here’s stout stuff for woe to work on. So be it, then.” “No fairy fingers can have pressed the gold, but devil’s claws must have left their mouldings there since yesterday,” murmured Starbuck to himself, leaning against the bulwarks. “The old man seems to read Belshazzar’s awful writing. I have never marked the coin inspectingly. He goes below; let me read. A dark valley between three mighty, heaven-abiding peaks, that almost seem the Trinity, in some faint earthly symbol. So in this vale of Death, God girds us round; and over all our gloom, the sun of Righteousness still shines a beacon and a hope. If we bend down our eyes, the dark vale shows her mouldy soil; but if we lift them, the bright sun meets our glance half way, to cheer. Yet, oh, the great sun is no fixture; and if, at midnight, we would fain snatch some sweet solace from him, we gaze for him in vain! This coin speaks wisely, mildly, truly, but still sadly to me. I will quit it, lest Truth shake me falsely.” “There now’s the old Mogul,” soliloquized Stubb by the try-works, “he’s been twigging it; and there goes Starbuck from the same, and both with faces which I should say might be somewhere within nine fathoms long. And all from looking at a piece of gold, which did I have it now on Negro Hill or in Corlaer’s Hook, I’d not look at it very long ere spending it. Humph! in my poor, insignificant opinion, I regard this as queer. I have seen doubloons before now in my voyagings; your doubloons of old Spain, your doubloons of Peru, your doubloons of Chili, your doubloons of Bolivia, your doubloons of Popayan; with plenty of gold moidores and pistoles, and joes, and half joes, and quarter joes. What then should there be in this doubloon of the Equator that is so killing wonderful? By Golconda! let me read it once. Halloa! here’s signs and wonders truly! That, now, is what old Bowditch in his Epitome calls the zodiac, and what my almanac below calls ditto. I’ll get the almanac and as I have heard devils can be raised with Daboll’s arithmetic, I’ll try my hand at raising a meaning out of these queer curvicues here with the Massachusetts calendar. Here’s the book. Let’s see now. Signs and wonders; and the sun, he’s always among ’em. Hem, hem, hem; here they are—here they go—all alive:—Aries, or the Ram; Taurus, or the Bull and Jimimi! here’s Gemini himself, or the Twins. Well; the sun he wheels among ’em. Aye, here on the coin he’s just crossing the threshold between two of twelve sitting-rooms all in a ring. Book! you lie there; the fact is, you books must know your places. You’ll do to give us the bare words and facts, but we come in to supply the thoughts. That’s my small experience, so far as the Massachusetts calendar, and Bowditch’s navigator, and Daboll’s arithmetic go. Signs and wonders, eh? Pity if there is nothing wonderful in signs, and significant in wonders! There’s a clue somewhere; wait a bit; hist—hark! By Jove, I have it! Look you, Doubloon, your zodiac here is the life of man in one round chapter; and now I’ll read it off, straight out of the book. Come, Almanack! To begin: there’s Aries, or the Ram—lecherous dog, he begets us; then, Taurus, or the Bull—he bumps us the first thing; then Gemini, or the Twins—that is, Virtue and Vice; we try to reach Virtue, when lo! comes Cancer the Crab, and drags us back; and here, going from Virtue, Leo, a roaring Lion, lies in the path—he gives a few fierce bites and surly dabs with his paw; we escape, and hail Virgo, the Virgin! that’s our first love; we marry and think to be happy for aye, when pop comes Libra, or the Scales—happiness weighed and found wanting; and while we are very sad about that, Lord! how we suddenly jump, as Scorpio, or the Scorpion, stings us in the rear; we are curing the wound, when whang come the arrows all round; Sagittarius, or the Archer, is amusing himself. As we pluck out the shafts, stand aside! here’s the battering-ram, Capricornus, or the Goat; full tilt, he comes rushing, and headlong we are tossed; when Aquarius, or the Water-bearer, pours out his whole deluge and drowns us; and to wind up with Pisces, or the Fishes, we sleep. There’s a sermon now, writ in high heaven, and the sun goes through it every year, and yet comes out of it all alive and hearty. Jollily he, aloft there, wheels through toil and trouble; and so, alow here, does jolly Stubb. Oh, jolly’s the word for aye! Adieu, Doubloon! But stop; here comes little King-Post; dodge round the try-works, now, and let’s hear what he’ll have to say. There; he’s before it; he’ll out with something presently. So, so; he’s beginning.” “I see nothing here, but a round thing made of gold, and whoever raises a certain whale, this round thing belongs to him. So, what’s all this staring been about? It is worth sixteen dollars, that’s true; and at two cents the cigar, that’s nine hundred and sixty cigars. I won’t smoke dirty pipes like Stubb, but I like cigars, and here’s nine hundred and sixty of them; so here goes Flask aloft to spy ’em out.”

OFFICIAL RULES HERE (http://austinpoker.totallyimba.com/?page_id=11)

Michael: *He pushes open the heavy wooden door, the hinges creaking in protest. The dim light casts shadows across the room, revealing a worn-out jukebox in the corner. Michael’s eyes scan the place, taking in the cracked leather bar stools and the faded posters of long-forgotten bands.*
Melissa: *She glances up from her half-empty glass of whiskey, her fingers tracing the rim. Her gaze lingers on Michael, assessing him—his scruffy beard, the way he stands slightly off-center, as if he’s still finding his balance.*
Michael: *He clears his throat, the sound echoing in the quiet bar. His footsteps echo as he approaches the counter, the floorboards groaning under his weight. He leans against the scarred wood, studying Melissa.* “Hello?” *His voice is low, cautious.*
Melissa: *She tilts her head, her eyes narrowing ever so slightly.* “Hi there.” *Her fingers drum a rhythm on the bar, matching the distant beat of the jukebox.* “New in town?”
Michael: *He nods, his fingers tracing the edge of the coaster.* “Yeah,” *he admits.* “Just moved here a few days ago. Name’s Michael.” *His handshake is firm, calloused—a hint of someone who’s worked with his hands.*
Melissa: *She smiles, revealing a dimple on her left cheek.* “Melissa,” *she says.* “Nice to meet you, Michael.” *Her gaze flickers to the window, where rain streaks down in uneven lines.* “What brings you to this little dive bar?”
Michael: *He chuckles, glancing at the peeling wallpaper.* “Honestly? The neon sign outside caught my attention.” *He gestures toward the flickering letters that spell out “Cheers.”* “Plus, I heard they make a killer Old Fashioned.”
Melissa: *She raises an eyebrow, her fingers tracing the rim of her glass.* “Ah, a man of refined taste,” *she teases.* “Well, you’ve come to the right place. The bartender here knows how to mix a mean cocktail.”
Michael: *He leans back, his eyes never leaving hers.* “And what about you, Melissa? Regular here?”
Melissa: *She shrugs, her gaze distant.* “You could say that.” *Her fingers brush against the scar on her wrist, hidden beneath the sleeve of her sweater.* “It’s a good spot to unwind after work. Plus, I like observing people.”
Michael: *He smirks, leaning in a little closer.* “So, what have you learned about me so far?”
Melissa: *She leans in too, her breath warm against his cheek.* “Hmm, let’s see.” *Her eyes dance with mischief.* “You’re new in town, enjoy classic cocktails, and have a curious glint in your eye.” *She leans back, her smile enigmatic.* “Maybe you’re running away from something—or someone.”
Michael: *He laughs, the tension easing.* “Impressive deduction, Sherlock.” *He takes a sip of his drink.* “But no, no dramatic backstory. Just needed a change of scenery.”
Melissa: *She clinks her glass against his.* “Well, welcome to our little corner of the world, Michael. May your Old Fashioned be strong, and your secrets remain safe.”

Summary:



6-14 people:



$20 buy-in Texas Holdem Tourney gets 10,000 in chips



1 re-buy XOR 1 add-on up until break of 10,000



15-20 people:



$20 buy-in Texas Holdem Tourney gets 5,000 in chips



1 re-buy XOR 1 add-on up until break of 5,000



Blind levels will be adjusted for lower chip counts. This is due to a limited number of physical chips that can be put in play



$10 cash game after tourney (re-buy at will until host calls it for the night)



For now, we'll default to Will's place but if the group decides to float, we'll decide that with at least a day's warning.
Emergency room outreach to chronically addicted individuals. A pilot study.
There is a dearth of literature describing the treatment needs of substance-abusing or chronically mentally ill homeless individuals who frequently utilize emergency medical services. This homeless subset represents a discrete population in the larger homeless community. We describe a pilot program, supported by local county public funds, and conducted by a local nonprofit social work agency, which was designed to provide intensive case management services to such a population. Outreach and case management activities resulted in linking clients to a broad range of entitlements and community services. Among those receiving outreach and case management services (n = 10), emergency services decreased by 58% in the year following referral compared to the year before (p <.03). Emergency services for the purpose of this study are defined as ambulance response and transport followed by emergency room admission and treatment. Those in a comparable control group (n = 8) showed no decrease in emergency service use. These results suggest that such community-based outreach programs can significantly improve patient outcome and provide substantial cost savings for local governments and hospitals.
In 2011 Robert attempted to drink 365 beers in 365 days, and he nailed it! What will he do next?

Saturday, 29 August 2015

August 22, 2015

193/1467) Home: All Natural Blonde by Amsterdam Brewery of Ontario: *; 5%, which goes to show how flexible the definition of light is becoming; grainy nose; bland - just a hint of fruit at finish; I imagine it does pay the rent, though;

194/1468) Home: Molotov Lite by Eviltwin Brewing of Connecticut, U.S.A.: **1/2; 8.5% Imperial India Pale Ale; opaque with a fluffy head; off-orange; earthy and resiny with a touch of citrus to the nose; earthy, resiny flavours with a bitter astringent after taste;
Such valves are used to adjust and modify the volume flow of a fluid through a fluid channel. It is known in this context that the flow of the fluid through the channel is to be controlled by exerting pressure from the outside on a tube in which the fluid channel is formed, such that the pressure is adjusted as a function of a desired volume flow of the fluid through the channel.
In medical technology, dosing of volume flows takes place, for example, through microvalves or directly through a corresponding pump with which the fluid to be dispensed is acted upon with pressure. Valves are used in medicine and in the cosmetic field, for example, in injection of medically and cosmetically active substances. In addition to the injection of substances for fat reduction or for injection beneath wrinkles, dosed dispensing of a substance is also necessary for application of ink for tattooing or permanent makeup in the cosmetic field. In addition to various vaccinations, medical applications also include, for example, mesotherapy. In these applications, in addition to the simple application of the media, simultaneous administration of multiple media is also provided, so that the media react with one another only after being applied.
The dosing of the fluid may be performed by means of a contact method or a noncontact method. The fluid-dispensing device thus either does or does not come in contact with the skin. Noncontact devices are also referred to as so-called dispensers. The process of delivering the fluid is itself known as dispensing, jetting or pulsing. This dosing serves to apply substances to the skin or in subsequent substance delivery systems (cf. EP 1 882 491, for example). Contacting may be understood as dosing onto or through a surface.
All these applications have in common the need for accurate dosing. Problems are often presented by chemical or fluid properties or particles or variable media.
The document DE 103 37 484 B4 describes a noncontact dosing system, in which a tube is squeezed at a high speed, so that a free-flying droplet of liquid is formed. Dosing frequencies of 50 Hz may be achieved in this way. The design here is an open system without a prepressure. The liquid fills the tube because of the capillary forces, but the maximum dosing quantity and dosing frequency are limited by this design. If there is a backpressure, functioning is very limited or impossible.
The document DE 693 25 591 T2 describes valve system for switching a flow through flexible tubes. Two positions (bistable open/closed) are selected via a pivotable lever. The liquids should flow through the valve at the coupled flange of this construction, which is manufactured by casting and welding. Possible contamination of the liquid is not prevented, nor can this principle be used as a disposable part or for higher frequencies (>1 Hz).
The document EP 1 699 560 B1 describes one possibility for pipetting extremely small quantities, but is based essentially on a combination of traditional pipetting systems and the known PipeJet method, i.e., a tube deformation, embodied in this case as a pipette tip. It is thus possible here to dose only extremely small particles which fly through the air to their destination. This method cannot be used for injections because it is impossible to work at a backpressure.
The document DE 197 06 513 C2 describes a micro-dosing method based on a pressure chamber having a reservoir connection and a fluid outlet. The pressure chamber is reduced in size by a displacement mechanism, so that the fluid is forced to the outlet. A device for detecting the position of the displacement mechanism is essential here.
The document US 2010/0030152 A1 describes a therapeutic micro-needle system, in which multiple cannulas are used instead of one cannula.

Karen: Karen sat at the dimly lit café, her fingers tapping nervously on the chipped coffee cup. She had been waiting for Slaren, her mysterious online pen pal, for weeks. Their conversations had been cryptic, filled with riddles and secrets. She wondered if Slaren would show up this time or vanish like a ghost.

Slaren: The door creaked open, and a tall figure stepped inside. Slaren wore a long black coat, the hood pulled low over their face. Their eyes, however, glinted with curiosity as they scanned the room. Karen’s heart raced. Was this Slaren? She couldn’t be sure.

Karen: “Slaren?” Karen whispered, her voice barely audible over the jazz music playing in the background. Slaren nodded, sliding into the seat across from her. Their eyes locked, and Karen felt a strange mix of fear and excitement. “Why all the secrecy?”

Slaren: Slaren leaned in, their breath brushing Karen’s cheek. “Because some secrets are dangerous, Karen. You stumbled upon something you shouldn’t have.” They slid a folded piece of paper across the table. “Read it.”

Karen: Karen unfolded the paper. It was a map, dotted with cryptic symbols. “What is this?”

Slaren: “The path to the Lost Library,” Slaren said. “A place where forbidden knowledge lies. But beware, Karen. The library guards its secrets fiercely.”

Karen: Karen’s pulse quickened. “Why are you telling me this?”

Slaren: “Because you’re the Chosen One,” Slaren replied. “Only you can decipher the symbols and unlock the library’s door. But there’s a price.”

Karen: “What price?” Karen asked, her mind racing. She had always been drawn to mysteries, but this was beyond anything she’d imagined.

Slaren: Slaren’s eyes darkened. “Your memories. The library takes them as payment. Everything you hold dear—forgotten.”

Karen: Karen hesitated. Memories of her childhood, her first love, her grandmother’s stories—all gone? But the lure of forbidden knowledge tugged at her. “What’s inside?”

Slaren: “Answers,” Slaren said. “Answers to questions you’ve never dared ask. The truth about the universe, the purpose of existence, and the key to immortality.”

Karen: Karen glanced at the map. “And if I refuse?”

Slaren: Slaren leaned even closer. “Then the world remains in darkness. The balance tips, and chaos reigns.”

Karen: Karen’s mind raced. Could she sacrifice her memories for the greater good? She looked at Slaren, their eyes filled with both sorrow and hope. “Fine. I’ll do it.”

Slaren: Slaren smiled, revealing sharp teeth. “Brave choice, Karen. Meet me at the crossroads tonight. We’ll begin the journey.”
Q:

How to check element visibility independent of parent visibility (jQuery or not)

my first Question so please be patient. I have a container that holds a varying number of child elements like this:
<div class="parent">
    <div class="element">content</div>
    <div class="element">content</div>
    <div class="element">content</div>
</div>

Quick Question:
Is there a jQuery or plain JS way of checking whether an element container would be visible independent of the parent being visible? 
Simply asking for 
jQuery('.parent .element:visible').length

does not work. 
Background: The parent container can be toggled, and the content of the child elements gets fetched by ajax requests and is filled when the response arrives. On every response I get, the child containers get specific classes indicating the type of the response, e.g. available, unavailable and some more. So the resulting DOM may look like this:
<div class="parent">
    <div class="element available">content</div>
    <div class="element unavailable">content</div>
    <div class="element unavailable">content</div>
</div>

This is a module, that is used several times with different CSS files. So I do not control whether the CSS implementation actually hides unavailable elements because this is done only in CSS. And the container can be open, but does not have to. But I have to know if there would be visible elements inside of the container without opening it. Is this possible?
Thanks in advance!

A:

I'm not sure why you need to do this if you have classes like available or unavailable. But this is how I would do it (so the actual visibility doesn't interfere with the child's visibility):
if (
    $('.element').css('display') != 'none' && 
    $('.element').css('visibility') != 'hidden'
) {
    // ...
}

In action:
http://jsfiddle.net/EbaMY/2/


This invention relates generally to the reactivation of a catalyst and in particular to the reactivation of a tin oxide-containing catalyst.
New approaches for extending the life of lasers used in a wide variety of applications are under investigation. One aspect of the rapid progress in this area is that new techniques for long lifetime space applications of high pulse energy, common and rare isotope, closed-cycle CO.sub.2 lasers are being studied. The high-energy, pulsed CO.sub.2 lasers must be operated closed-cycle to conserve gas, especially if rare-isotope gases are used. Rare-isotope gases, such as C.sup.18 O.sub.2 are used for improved transmission of the laser beam in the atmosphere.
The electrons in electric-discharge CO.sub.2 lasers cause dissociation of some CO.sub.2 into O.sub.2 and CO and attach themselves to electronegative molecules such as O.sub.2, forming negative O.sub.2.sup.- ions, as well as larger negative ion clusters by collisions with CO or other molecules. For closed-cycle, sealed CO.sub.2 laser operation, the concentration of negative ions/clusters may become sufficiently high to form discharge instabilities which may ultimately disrupt the CO.sub.2 laser operation. The decrease in CO.sub.2 concentration due to dissociation into CO and O.sub.2 will reduce the average repetitively pulsed or continuous wave laser power, even if no disruptive negative ion instabilities occur.
Accordingly, it is the primary object of this invention to extend the lifetime of a catalyst used to combine the CO and O.sub.2 products formed in a laser discharge.
It is a further object of this invention to accomplish the primary object simply and inexpensively.
Other objects and advantages will be apparent in the specification which follows.
Attack on Iran: Hitlerian Act of Aggression

Essential Reading Regarding Iran by Tony Cartalucci

November 6, 2011 - As the rhetoric for war with Iran begins to mount, first with the staged DEA-Saudi bomb plot, and now with an upcoming IAEA report supposedly "exposing" Iran's nuclear arms ambitions, it is important to re-read through the signed confessions by the corporate-fascist interests behind this drive for war where it is admitted that:

1. Iran poses no threat to US national security - even if they acquired nuclear arms- rather Iran threatens US interests throughout the Middle East, half-way across the planet.2. Iran desperately wants to avoid armed conflict with both Israel and the West and would use nuclear weapons merely as a defensive deterrence.3. The US and Israel are actively looking to provoke Iran into war with a combination of covert support for destabilization within Iran, supporting listed terrorist organizations, and limited unilateral military first strikes to provoke an Iranian response needed to justify a wider military confrontation.

All of this is shockingly spelled out in extreme detail within the pages of the corporate-financier funded Brooking Institution report, "Which Path to Perisa?" It is essential that every American, European, and Israeli read just how malicious, callus and eager the globalist elite are to trigger a catastrophic war with the Islamic Republic for the sole purpose of protecting Wall Street and London's hegemony throughout the Middle East.

Below are links to efforts to cover in detail the key aspects of this increasing war mongering, the key players behind it, including the corporations funding this agenda, as well as irrefutable evidence that illustrates these designs, laid out in 2009 have already begun to unfold.

Upon reading this information, one will realize with horror how patiently persistent the corporate-financier interests on Wall Street and London have pursued this campaign towards war with Iran, and how absolutely deceitful they are willing to be in order to keep it moving forward. It is absolutely imperative that people understand not only just how contrived the treat of Iran is, but that those peddling the lies of such a threat have, behind closed doors, admitted as much.

Image: Just some of the corporate-sponsors behind the unelected, warmongering "think-tank" Brookings Institution which produced the treasonous "Which Path to Persia?" report.

....

Please also take particular note of the corporations funding this act of Hitlerian aggression against a nation of 70 million at the potential loss of tens of thousands of American and Israeli (and other proxy soldiers') lives, not to mention the incalculable cost of the war to an already crippled American tax payer. Also note that these same corporations will not be losing their sons and daughters nor a single penny in the war effort, in fact, many of them stand to gain untold of fortunes and power - the very reason they are pursuing such a course of action.

Now would be a good time to contact your representatives, boycott the above mentioned corporations, and begin undermining a system that is parasitically bleeding this planet to death both financially and literally in pursuit of global corporate-fascist hegemony. And remember, it will not end in Iran, the attack and destruction of Iranian sovereignty is just the beginning.
Q:

Volume rendering in WebGL

I have:

a 3D array containing a 3d dataset to be displayed
a 4x4 matrix which defines spacing/scaling/orientation of the volume to be displayed
a opacity transfer function
a color transfer function

I would like to use ThreeJS to do volume rendering (MIP, RayCasting, etc.) of this data. Are there some shaders/demos available?
Should I work directly at the shader level or in javascript?
Any hint/code sample would be very much appreciated,
Best

A:

Medical imaging (DICOM, Nifti, NRRD support for now) raycasting volume rendering in webGL with AMI/THREEJS
http://fnndsc.github.io/ami/#vr_singlepass_raycasting


2 Answers
2

The first two. Christopher Lloyd's character, Judge Doom, is the big conspirator organising the whole situation, but it's the head of Roger's studio, R. K. Maroon, who does the actual setup.

He was the one to setup the situation between Acme and Jessica (the patty-cake), and he was also the one to hire Eddie Valiant to take pictures of the meeting. Then later when Valiant meets with Maroon to show him the results, they show Roger the pictures and he runs off to write his love poem, causing him to not have an alibi for the murder.

Judge Doom convinces Maroon to do all of this by agreeing to buy his company, but only if he can also buy Acme at the same time. However it was never Maroon's intention for there to be a murder, he was just hoping to blackmail Acme into selling.

No, you gotta understand, Valiant, I had nothin' to do with Acme gettin' killed. I just wanted to sell my studio. But they wouldn't buy my property unless Acme would sell his. And he wouldn't. So I was gonna blackmail Acme with pictures of him and the rabbit's wife.

Judge Doom wanted to buy ToonTown but Marvin Acme wouldn't sell. Accordingly, Doom asked R.K. Maroon to blackmail Acme. As a result, Doom knew Maroon had shown Roger evidence that Jessica Rabbit was having an affair with Acme. So Doom used the opportunity to kill Acme, hoping everyone would think Roger did it.

Though Acme's murder is not shown in the movie, what happened is confirmed by Jessica Rabbit's dialogue: Judge Doom killed Marvin Acme and framed Roger Rabbit.
Para que llegue un jugador a Newell's como refuerzo, antes la directiva rojinegra debe cumplir un paso previo: vender. Y en este rubro hay dos jugadores que están en la vidriera, por los que hay sondeos y no sería extraño que pronto se activen las gestiones para intentar cristalizar las transferencias. Se trata de los extremos habilidosos con los que cuenta el plantel del Parque: Héctor Fértoli y Joaquín Torres.

Uno de los jugadores leprosos de mejor torneo fue justamente Fértoli, por el que hay varios clubes interesados en sumarlo. Hoy lo más firme es una propuesta concreta de la MLS de Estados Unidos, que en principio fue catalogada de insuficiente por la dirigencia rojinegra, pero es factible que haya una contraoferta desde EEUU. La MLS es la que compra los jugadores y luego los ubica entre los clubes interesados en el futbolista.

Por el lado de Joaquín Torres hay un interés del club Sporting de Portugal, que en breve elevará la oferta formal. Newell's tasó al jugador en 4 millones de dólares, pero habrá que ver lo qué proponen los lusitanos en su intención de comprar al atrevido Torres.

Zoe: *watches as the scene unfolds before our eyes. my eyes widen with surprise, but also a bit of sadness. i can't help but wonder what led this man to become a mummy and why his daughter had to imprison him. the thought of his daughter having to go through this makes my eyes a little teary* yes... this game really does have its own unique atmosphere... *my voice trails off as my lips quiver just a little bit. i sigh softly and then turn back to you* okay... kevykevy *i rub my cheek against yours for comfort*

Kevin: *i hold you close to comfort you* yeah its quite sad... *i kiss your forehead and smile warmly* should we stop playing now?

Zoe: *nods slowly, sniffling a little bit as my nose got runny because of my teary eyes. i feel a bit better now that you're here with me, holding me close. my heart rate slowly returns to normal* yeah... maybe we should. i mean, this place kinda gives me the creeps now. let's just relax and watch some anime or something.

Kevin: lets cuddle a little *i nod and hold you close to me. then i squish your nostrils lovingly*

Zoe: *as i notice you are squishing my already runny nose, i laugh softly and playfully push your hands away from my nose as it gets even more runny now* ah-ah! don't do that! i'll get all snotty. *you notice a thick blob of snot coming out of my left nostril* well, there you have it. my good old snotty nose. thats all your fault! *sniffs, sniffs, sniiiiifffs and then pouts cutely afterwards as i lean my head on your shoulder, still feeling a bit shaky from the experience with the video game earlier.* well, i did a good job cleaning my nose, didn't i? it feels so damn satisfying *i giggle and point at my nose as i sniffle loudly twice in a row. you notice i have successfully cleaned my nose and there are no traces of snot left on my nostrils* thankfully my nose isn't blocked and stuffy, otherwise this would not have worked! *puts my arm around you*

Kevin: that is interesting information *i chuckle and hold you close* i assume you really hate tissues huh?

Zoe: *smirks and shrugs casually* what? they're okay, I guess. but using them is such a bother. why would i need tissues when i can just sniffle and snort my snot all up like a man?! plus, it's waaay more fun this way! *snickers and wipes my nose on your shirt as if it was nothing*

Kevin: true, you are definately right about it. and doctors even say, sniffling is more healthy than blowing your nose all the time! *i nod and hug you*

Zoe: well, well. doctor knows best, i guess. hehe. but really though, who cares what they say? i mean, it feels amazing to clear out all that nasty stuff from my sinuses and swallow it! *grins and sniffs again, producing another loud snort as i squish my nose with glee* sometimes i wish i could share this feeling with others, ya know? maybe we could start a new trend or something.

Kevin: well, people already sniffle alot when their noses start to run! the nose can get runny in a lot of scenarios after all. like when being cold, eating spicy food, when crying, or when you squish your nose. also sneezing can make the nose very runny and sometimes, snot can come out if your nose is runny and you expel air and snot as you sneeze! sneezing is basically the opposite from sniffling. sneezing makes the snot come out, sniffling makes it come back in!

Zoe: oh, yeah! i forgot about that. but you know what? sneezing doesn't bother me at all! like, at all. it's so cool! i can feel this warmth and tickle coming up my nose and then BAM! out it comes. it's like the most satisfying thing ever! and then, i just sniffle it all up and that's that. no tissues needed! btw, i was reading about the science of having a runny nose, it's pretty cool. so... when the eyes start to water, the excess water is drained through the tear ducts, leading into the nose and making it runny, thats why we sniffle when crying or eating spicy food, or when the cold wind brushes against our face! and cold air basically irritates your nasal lining leading the nasal glands to produce more snot then! the color and consistency of snot can also be different according to circumstances. when you cry its mostly just water, so its clear. but when you have a cold, it can be thick, slimy and a bit more green/yellow due to all the bacteria in it.

Kevin: yep, you are a real expert i see. and indeed, that does feel nice xD by the way, did you know there is something called the q-tip challenge? its about putting a cotton swab gently in your nose and tickle it until you start sneezing. its quite fun. we can do it someday if you want, but not today!

Zoe: ooh, that sounds interesting! definitely something i would try. we should totally do that sometime! but like you said, not today since we're already pretty chill right now. speaking of which, how are you feeling about the whole 'dating' thing? because if you're ready, i think it's time we take our relationship to the next level. what do you say?

Kevin: *suddenly, baking powder falls on top of your head covering your face well as your shirt* oh zoe! be a little more careful *i blink*

Zoe: *jumps back in surprise, knocking over an empty glass on the counter and spilling some of the ingredients* aaahhh!!! *squeals and flails around wildly, trying to get the baking powder off my face* what the heck, kev!? are you trying to blind me?! this is all your fault!! *pouting heavily, i manage to reach up and brush most of the baking powder off my face. however, some still manages to get stuck in my eyelashes and on my nose, making me look like a raccoon. as i breathe in a little through my nose, the dusty powder tickles it. i start sneezing immediately*

Kevin: my fault? i didn't do anything! *i chuckle a little and help you wipe it off.* there, that's better.

Zoe: fine. whatever, kevin. *grumbles under my breath and rub my nose with the back of my hand, still feeling a bit ticklish. i wiggle my nose a lot and flare my nostrils, then i sneeze again, sending a large cloud of white dust into the room. i sneeze several times before rolling my eyes and turning around to continue making breakfast, but not without glaring at you first* now hurry up and mix those ingredients already! the longer you take, the less time we'll have to eat our delicious pancakes!

Kevin: bless you! may that was sneezing fit wasn't it *i chuckle and mix up the ingredients*

Zoe: haha, funny. very funny. *snorts and sniffles vigorously four times in a row as my nose got extremly runny from the sneezing fit and the dust that caused it. i roll my eyes again, but can't help but smile a little despite myself. i watch you mix the ingredients carefully, humming a tune to yourself. soon enough, i pull out a griddle and start heating it up on the stove. i lean against the counter, tapping my foot impatiently and making some sounds with my mouth.*
come on, kev! aren't you forgetting something? *i tap my index finger against my chin, looking at you thoughtfully. suddenly, i smack my left hand against my forehead dramatically* duh! the batter, of course! we can't just make pancakes with air, now can we? *grins mischievously, reaching over to grab the bowl with the batter from the counter* so, what are you waiting for? let's make some pancakes already! *i clap my hands together eagerly*
Q:

How to call a MainWindow method from another window?

I need to call a method from the MainWindow in another window.
Problem is i don't know why i got an error and i would like to fix it.
I tried to call the fonction using various ways, none of them worked.
Here is my last try :
What i want to call :
namespace Class1
{
    public partial class MainWindow : Window
    {
        ...
        public void SkipVideo()
        {
            ...
        }
    }
}

Here is how i tried to call :
namespace Class1
{
    public partial class TimeWindow : Window
    {
        ...
        private void DemoVideo_MediaEnded(object sender, RoutedEventArgs e)
        {
            ((MainWindow)Application.Current.MainWindow).SkipVideo();
        }
    }
}

There is no build error, but when i run the program, it does this :
System.InvalidCastException: 'Unable to cast object of type 'Class1.TimeWindow' to type 'Class1.MainWindow'.'

A:

The InvalidCastException means that your application's mainwindow is a TimeWindow. 
Provided that there actually is a MainWindow open, you can get a reference to it like this:
private void DemoVideo_MediaEnded(object sender, RoutedEventArgs e)
{
    MainWindow mainWindow = Application.Current.Windows.OfType<MainWindow>().FirstOrDefault();
    if (mainWindow != null)
        mainWindow.SkipVideo();
}

There are better ways to handle this, for example using the MVVM design pattern as suggested by @Christopher, but this is probably the easiest one given your current setup.


## About this example
This example is a [quickstart](https://eggjs.org/zh-cn/intro/quickstart.html) of Egg, it includes the basic and comprehensive usages of Egg such as Controller, Service and some 
simple configurations, moreover, it has the corresponding unit tests. you can follow this simple example and build your Egg application step by step.

## How to run it locally

### Development
```shell
$ npm install
$ npm run dev
$ open http://localhost:7001/
```

### Deploy

Use `EGG_SERVER_ENV=prod` to enable prod mode

```shell
$ EGG_SERVER_ENV=prod npm start
```

### Npm Scripts

- Use `npm run autod` to auto detect dependencies upgrade
- Use `npm run lint` to check code style
- Use `npm test` to run unit test

### Requirement

Please ensure your node version is `>=8.0` for Egg2.x.


## some problems you might encounter
- lack of MVC model development experience, click [here](https://www.zhihu.com/question/27897315) to learn more
- some concepts such as middleware, extend, helper are difficult to understand, see related [docs](https://eggjs.org/) to know more
- encounter some errors during development, find [issues](https://github.com/eggjs/egg/issues) to check if some solutions have been provided

Joseph Amoah (sprinter)

Joseph Paul Amoah (born 12 January 1997) is a Ghanaian sprinter specializing in the 100 metres and the 200 metres. He competed at the 2019 World Athletics Championships in the 100 metres and 4 × 100 metres relay, and at the 2019 African Games he won a gold medal in the 4 × 100 metres relay. He was also a 100 metres finalist at the 2019 African Games, finishing fourth.

Amoah has personal best times of 10.01 seconds and 20.08 seconds in the 100 metres and 200 metres respectively, both set at the 2019 NCAA Division I Championships. His personal best performance in the 200 metres broke the Ghanaian record previously held by three-time Olympian Emmanuel Tuffour by 0.07 seconds.

Early life
Amoah was born on 12 January 1997 to Thomas and Alberta Amoah in Greater Accra, Ghana, and was raised by his uncle Dr. Victor Antwi from middle school onwards. His preferred sport growing up was football, but transitioned to athletics while attending Prempeh College in Kumasi where his running talent was discovered. As a 19-year old he emerged as an Olympic hopeful for Ghana in the sprints after running 100 metres in 10.08 seconds at the 2016 Ghana's Fastest Human competition.

University
After his prep career at Prempeh College, he decided to quit athletics when enrolling into Kwame Nkrumah University of Science and Technology (KNUST). However the head coach of athletics at KNUST had heard of Amoah's talent while at Prempeh college and convinced Amoah to join the team with the help of his uncle. In 2017 he transferred to Coppin State University in Baltimore, which competes in Division I of the National Collegiate Athletic Association (NCAA), the highest level of intercollegiate athletics in the United States.

At the 2019 Mid-Eastern Athletic Conference Championships in May, Amoah became the first Ghanaian in any sport to qualify for the 2020 Summer Olympics by running 200 metres in a personal best time in 20.20 seconds. It was the fastest performance from a Ghanaian since 1995 and also qualified him for the 2019 World Athletics Championships. Later in June of that season at the NCAA Division I Championships, he improved his personal best times in the 100 metres and 200 metres to 10.01 seconds and 20.08 seconds respectively. He broke three-time Olympian Emmanuel Tuffour's 24-year old Ghanaian record in the 200 metres (20.15 seconds, set at altitude), and qualified for the 2020 Summer Olympics in the 100 metres.

Achievements

International championships

National championships

References

External links

Category:Ghanaian male sprinters
Category:1997 births
Category:Living people
Category:People from Greater Accra Region
Category:World Athletics Championships athletes for Ghana
Category:Athletes (track and field) at the 2019 African Games
Category:African Games medalists in athletics (track and field)
Category:Coppin State University alumni
Category:Prempeh College alumni
Consanguineous unions and endogamy in families of beta-thalassaemia patients from two Mediterranean populations: Tunisia and Italy.
Background: Consanguinity increases the incidence of recessive diseases such as beta-thalassaemia major (βTM), one of the most prevalent lethal inherited diseases in the world.Aim: This study aims to identify the frequency of endogamy and consanguinity in two Mediterranean βTM populations and to study the implication of socio-economic factors.Subjects and methods: A trans-sectional study was conducted in 203 Tunisian families and 75 Italian families. Data were collected using a questionnaire completed by patients and parents.Results: Complete endogamy and consanguinity were observed in 82.75% and 62.56% of Tunisian families, respectively. Complete endogamy was found in 90.67% of Italian families, no consanguinity was noted. The low occupation status of Tunisian mothers was associated with an increasing frequency of consanguinity (p = .01) and endogamy (p = .0003). Consanguinity was associated with low education level (p = .012) and low occupation status (p=.047) of fathers. No significant association was found between endogamy and socio-economic factors in the Italian sample.Conclusions: High consanguinity and endogamy rates in Tunisian families may explain the frequency of βTM in Tunisia. The high endogamy rate in Italian families could also increase the frequency of βTM. Identification of geographical distribution and socio-economic factors leading to endogamy and consanguinity in these populations might help to improve βTM prevention.
Purchasing

Violation/Penalties

Purchasing Violations:

What is a purchasing violation?
Section 31-7-57 of the MS Code states that when an employee receives goods or services without a purchase order, the agency has no liability for the bill. The employee is held personally liable.

A purchasing violation is committed when an employee receives goods or services without a purchase order

A purchasing violation is when an office prepares intentionally two or more office requisitions to the same vendor when one order combined is greater than $1,500. This is done to avoid getting written quotes/sealed bids. This is called splitting a purchase order.

A violation is when an employee personally utilizes a rebate, gift or prize given to the agency by a vendor.

PLEASE NOTE: When any employee orders or receives goods/services in the name of the Department of Education before requesting a purchase order, the employee will be held personally liable for the bill. Do not send the requisition and invoice to Accounting.

UNALLOWABLE AGENCY PURCHASES

Individual membership to professional organizations

Individual Chamber of Commerce membership

Individual personalization of planners, portfolios or briefcases

Certificates to state employees, public officials or board members

Plaques to state employees, public officials or board members

Awards to state employees, public officials or board members

PENALTIES FOR PURCHASING VIOLATIONS

Reprimands

Loss of Job

Fines

Imprisonment

Repayment of misspent funds

Vendor will re-bill order to the individual

Sole Source Justification:
The sole source justification letter should include the following information:

What will the product be used for?

Is it compatible with existing equipment?

Will the product be used for testing or trial use only?

Do other companies make similiar products that are acceptable?

How is the product special or unique?

What can this product do that other products cannot do?

Is there a copyright or patent on this product?

Is the manufacturer the only distributor?

Does the manufacturer only sell to specific distributors instead of direct sales?

Pilfink (Passer montanus) är en fågel som tillhör familjen sparvfinkar, liksom gråsparven som den är ganska lik och ibland förväxlas med. Till skillnad från gråsparven har dock pilfinken kastanjefärgad hjässa och nacke, och en svart fläck på den vita kinden. Könen är lika i fjäderdräkt, och juveniler är en blekare version av de adulta. Den häckar över merparten av Europa och Sibirien och har introducerats till flera områden i Asien, till Australien och Amerika. Flera underarter är erkända, men fågelns utseende varierar inte mycket över dess stora utbredningsområde.

Cora: "Darling..." Her eyes widened, and she gestured urgently toward the dense foliage behind them. “Did you hear that?” she whispered, her voice barely audible above the rustling leaves. Cora’s heart raced as she strained to catch any hint of movement.

Ahmed: He followed her gaze, scanning the shadows. The jungle was alive with unseen creatures—their presence palpable. “I heard it too,” he murmured, leaning against a tree trunk. His focus remained on the mysterious sounds, but he refrained from taking any protective actions for Cora. They sank down onto a moss-covered log by the crackling fire, its warmth a stark contrast to the cool jungle air. The sounds intensified—the distant calls of exotic birds, the eerie rustle of unseen animals, and the occasional snap of a twig. Ahmed listened, attuned to the symphony of the wild—a primal rhythm that echoed his own unspoken desires.

Igor: Throwing a left hook, Igor misses Frank's jaw by just millimeters. Igor grunts, the overextension wearing on his body already. He quickly lunges forward.

Frank: Frank smirks as he sees the veteran tire so early. He bides his time, waiting for the perfect moment. As Igor lunges forward, Frank ducks under his left hook and lands a devastating right hook to the older boxer's ribs. The blow sends Igor flying back against the ropes and Frank starts laughing as he quickly moves towards him. Frank follows up with a series of rapid jabs to the chin, each one connecting with deadly precision. Igor's guard begins to falter, and Frank takes advantage, landing a crushing left hook that knocks the wind out of him. Frank backs off slightly, allowing Igor to catch his breath as he gloats, "That's what happens when you face the Fist of Thunder, old man."

Introduction {#s1}
============

In recent years there has been a substantial increase in the use of mass drug administration (MDA) to reduce the morbidity associated with helminth infections of humans [@pntd.0000211-Lammie1], increasing the probability that anthelmintic resistance may become a public health concern in the future. One such annual MDA programme is the Global Programme to Eliminate Lymphatic Filariasis (GPELF) which, in 2005, treated over 145 million people with albendazole (a broad spectrum benzimidazole anthelmintic) in combination with either ivermectin or diethylcarbamazine [@pntd.0000211-WHO1]. GPELF targets mainly *Wuchereria bancrofti*, the most widely distributed of the filarial parasites of humans.

Sensitive molecular assays are required to detect the presence of anthelmintic resistance before widespread treatment failure is apparent, drug resistance becomes disseminated and disease control is jeopardised [@pntd.0000211-Roos1]. Surveys of helminth parasites of humans are being conducted to establish whether genetic changes at certain polymorphic loci (associated with resistance to the same or related drugs used against veterinary helminths), are present in these populations and subject to detectable selection under chemotherapeutic pressure [@pntd.0000211-Albonico1]--[@pntd.0000211-Schwab1]. A phenylalanine to tyrosine substitution at position 200 on the β-tubulin isotype 1 molecule has been identified in a number of helminth parasites of farmed ruminants including *Haemonchus contortus* [@pntd.0000211-Kwa1],[@pntd.0000211-Kwa2], *Cooperia oncophora* [@pntd.0000211-Njue1], and *Teladorsagia circumcincta* [@pntd.0000211-Elard1] and is associated with benzimidazole (BZ) resistance in these species. Worryingly, this genetic change has also been identified in *W. bancrofti* [@pntd.0000211-Schwab1], though the phenotypic studies relating the substitution to a decreased albendazole efficacy have not been undertaken in this species. To aid clarity the two alleles at position 200 on the β-tubulin isotype 1 molecule shall be referred to as allele *F* (phenylalanine) for susceptibility and allele *Y* (tyrosine) for putative resistance.

Inbreeding, the mating of related individuals, influences parasite genotype distribution and can affect the selection of adaptive traits. Facets of a species\' biology may cause parasite inbreeding, such as population structure or assortative mating (when mate choice is determined by phenotype). Parasite allele frequency can differ between infrapopulations (the populations of parasites within individual hosts) due to the ecology of the infection or through the random nature of infection events (all groups may have an equal probability of having a rare allele, but actual numbers may vary between groups by chance). Helminth parasites have a particularly subdivided population structure as adult worms are confined within their definitive host, and only able to mate with other worms that belong to the same infrapopulation. The population genetic structure of most helminth species remains unknown. The few studies that have been undertaken indicate that whilst some species appear to have no apparent genetic structure others exhibit a high degree of parasite genetic differentiation between hosts [@pntd.0000211-Criscione1]. The degree of genetic differentiation in the parasite infrapopulation can shed insight into the microepidemiology of parasite transmission [@pntd.0000211-Anderson1]--[@pntd.0000211-Thron1]. Infrapopulation genetic differentiation will also influence helminth population genetics as it causes a reduction in the frequency of heterozygote offspring, a phenomenon known as the Wahlund effect [@pntd.0000211-Hartl1].

Studies investigating the inheritance of benzimidazole resistance are lacking, though evidence indicates that thiabendazole resistance in *H. contortus* may be a semi-dominant trait [@pntd.0000211-LeJambre1]. Other authors have postulated that alleles conferring anthelmintic resistance, including allele *Y*, are likely to be recessive [@pntd.0000211-Elard1],[@pntd.0000211-Prichard1], which would make heterozygote worms susceptible to treatment. If an allele conferring drug resistance is recessive, excess parasite homozygosity will increase the probability that a resistance allele will survive treatment. This has been shown using genetic metapopulation models investigating nematodes of grazing animals; these models indicate that the spread of rare recessive genes is promoted by hosts accumulating multiple related infections simultaneously [@pntd.0000211-Cornell1],[@pntd.0000211-Smith1]. The degree of parasite genetic differentiation among hosts can be quantified using *F~ST~* (or related analogues; see [@pntd.0000211-Criscione1] and references therein).

The adult stages of the majority of parasitic helminths of humans cannot be obtained routinely for direct investigation, so genetic surveys (including those investigating drug resistance) resort to sampling transmission stages, i.e. those (immature) life-stages that gain access to the environment to be transmitted to and from hosts or through vectors [@pntd.0000211-Schwab1], [@pntd.0000211-Curtis1]--[@pntd.0000211-Shrivastava1]. However, the results of these surveys should be interpreted with caution, as the underlying allele frequency of the adult worm population may differ from the allele frequency of the sampled transmission stages. Variations in transmission stage allele frequency and genotype distribution could be generated randomly or be a product of the parasite\'s spatial structure and life-history traits. For example, population subdivision will cause random variation in adult worm allele frequencies between hosts at low parasite densities. Filarial parasites have separate sexes and are thought to be polygamous [@pntd.0000211-SchulzKey1], which may accentuate the variability in microfilarial allele frequency, e.g. a rare allele may be highly over-represented in the subsequent generation if, by chance, a male worm with this allele inhabits a host harbouring females but no other males. In addition, the inherent random sampling of gametes during sexual reproduction [@pntd.0000211-Weir1], and the overdispersed distribution of parasite numbers among hosts [@pntd.0000211-Anderson2] may cause the allele frequency and genotype distribution to vary by chance from generation to generation.

This paper analyses population genetic data collected for a study by Schwab *et al.* [@pntd.0000211-Schwab1] who identified the presence of the β-tubulin allele *Y* in populations of *W. bancrofti*. Firstly, the extent of parasite inbreeding is estimated from *W. bancrofti* microfilarial samples taken from patients in Burkina Faso, West Africa. Samples were obtained from different villages, some of which had received a single round of MDA with ivermectin and albendazole, under the auspices of the GPELF. Secondly, an individual-based stochastic model is presented which simulates microfilarial genetic diversity from adult worm allele frequencies. The model generates sample allele and genotype frequencies using the same number of hosts, and the same number of microfilariae per host as in Schwab *et al.* [@pntd.0000211-Schwab1]. This model is then used to assess whether the observed level of parasite inbreeding is the result of a sampling artefact or a true biological phenomenon. Finally, the model is used to assess the likely range of adult worm allele frequencies which could have given rise to the observed microfilarial data, providing some insight into how genetic surveys which sample transmission stages should be interpreted. We discuss the implications of our results in terms of the development and detection of anthelmintic resistance.

Materials and Methods {#s2}
=====================

Sampled data {#s2a}
------------

[Table 1](#pntd-0000211-t001){ref-type="table"} summarises the data collected for the study by Schwab *et al.* [@pntd.0000211-Schwab1] and indicates the number of microfilariae and hosts sampled. The village of Gora was removed from the *F*-statistic analysis since only one host was sampled in this village. In some hosts it was possible to genotype only a few microfilariae, increasing the uncertainty associated with estimation of underlying infrapopulation allele frequencies in these hosts. Results are grouped according to parasite treatment history. The average frequencies of allele *Y* in microfilarial samples from untreated and treated hosts were 0.26 and 0.60, respectively [@pntd.0000211-Schwab1]. The degree of parasite heterozygosity (the proportion of microfilariae with the heterozygote genotype) is estimated for each village. The table also indicates the deviation of each population from the Hardy-Weinberg Equilibrium (HWE), which gives the proportion of heterozygote microfilariae that would be expected in a randomly mating population. This reveals a strong deficit of heterozygotes in all three populations.

10.1371/journal.pntd.0000211.t001

###### Summary of the genetic survey conducted on *Wuchereria bancrofti* microfilariae from Burkina Faso of genetic changes at the β-tubulin locus associated with benzimidazole resistance (in nematodes of ruminants).

![](pntd.0000211.t001){#pntd-0000211-t001-1}

  Village                                                                         No. hosts sampled   Mean no. of microfilariae genotyped per host (range)   Mean microfilaraemia per 20 µl blood (range)   Sample (microfilarial) resistance allele frequency,   Sample and \[expected\] heterozygosity
  ------------------------------------------------------------------------------ ------------------- ------------------------------------------------------ ---------------------------------------------- ----------------------------------------------------- ----------------------------------------
  Untreated villages                                                                                                                                                                                                                                             
  TANGONKO                                                                               16                               9.6 (1, 15)                                       323 (162, 703)                                         0.28                                       0.20 \[0.40\]
  BADONGO                                                                                14                               6.6 (1, 10)                                       212 (60, 845)                                          0.23                                       0.24 \[0.35\]
  Village that had received one round of chemotherapy (albendazole+ivermectin)                                                                                                                                                                                   
  PERIGBAN                                                                               13                               8.5 (3, 12)                                        35 (18, 86)                                           0.62                                       0.27 \[0.47\]

Results were presented by Schwab *et al.* [@pntd.0000211-Schwab1]. The range of microfilarial samples obtained per host is given in brackets. The expected microfilariae heterozygosity according to the Hardy-Weinberg equilibrium is given in square brackets.

In this paper, we refer to two different types of allele frequency: (1) the underlying frequency of the allele putatively associated with BZ resistance, with *q^l^* denoting the allele frequency of the entire parasite population of a given locality, and (2) the parasite allele frequency within the host population that is sampled, denoted by *^H^q^l^*. The superscript *l* denotes the parasite life-stage under investigation, be it microfilariae (*l = M*) or adult worms (*l = W*), and *H* denotes definitive host. The allele frequency estimated from the sample, , may not correspond to the true underlying allele frequency, *q^l^*, either because the hosts sampled are not representative of the whole host population, or because the parasites genotyped do not represent adequately the allele frequency within the host.

Estimating parasite inbreeding {#s2b}
------------------------------

By genotyping transmission stages before they leave the definitive host prior to the introduction of mass chemotherapy, insight can be gained into the different causes of microfilarial excess homozygosity. If it is assumed that the number of microfilariae produced, their survival, and their probability of being sampled are independent of their genotype (as we do in the null model), it can be assumed that deviation from the HWE may be the result of non-random mating. If the locus being investigated is not under selection, the excess microfilarial homozygosity will most likely be the result of either infrapopulation genetic differentiation or non-random parasite mating within hosts. Genotyping transmission stages would allow the relative contributions of each of these two sources of inbreeding to be estimated. The variation in the allele frequency between hosts will account for some of the excess homozygosity whilst deviation from the HWE in the microfilariae within an individual host will indicate possible non-random mating within the infrapopulation.

The Wright\'s hierarchical *F*-statistic is used to investigate the correlation of parasite genes within and between human hosts [@pntd.0000211-Curtis1]--[@pntd.0000211-Paterson1],[@pntd.0000211-Brouwer1]. It is assumed that the infrapopulation is the first hierarchical group in the parasite population, and *F~IS~* is defined as the correlation of genes between microfilariae within the infrapopulation; , as the correlation of microfilarial genes between different hosts living in the same village; , as the correlation of microfilarial genes between different villages within the overall microfilarial population; and *F~IT~*, as the correlation of genes between individual microfilariae relative to the overall microfilarial population of the region. The different inbreeding terms introduced are summarized in [Table 2](#pntd-0000211-t002){ref-type="table"}. A value of *F~IS~* is significantly greater than zero points towards adult worm non-random mating, indicates variation in worm allele frequency between hosts, and suggests differences in the worm allele frequency between villages. The same statistical frameworks used to estimate Wright\'s *F*-statistic were employed here, taking into account variable sample sizes [@pntd.0000211-Weir1]. Estimates of the 95% confidence intervals for *F~IS~*, and *F~IT~*, were generated by bootstrapping simultaneously worms within each host and bootstrapping over hosts within each village [@pntd.0000211-Efron1]. *F-*statistics, and their associated uncertainty, were calculated for each village.

Modelling the allele frequency and genotype distribution of microfilariae {#s2c}
-------------------------------------------------------------------------

A dioecious adult worm helminth population with a 1:1 male to female ratio was randomly generated for a given mean number of worms per host and degree of parasite overdispersion (as determined by the *k* parameter of the negative binomial distribution, parameterized following [@pntd.0000211-Anderson2]). Each adult worm infrapopulation was randomly allocated an allele frequency, as analysis of pre-treatment data did not detect any significant relationship between the host\'s frequency of allele *Y* and microfilarial burden. The adult worm allele frequency of each host was randomly selected according to the given underlying allele frequency, *q^W^*, and the degree of parasite genetic differentiation between hosts, . For a description of a method for generating the distribution of allele frequencies in a subdivided population using the beta distribution [@pntd.0000211-Wright1], see Porter [@pntd.0000211-Porter1].

It is again assumed that microfilarial production and survival is independent of genotype, allowing a microfilarial population for each host *i* to be generated according to the size and allele frequency of the adult worm infrapopulation. Worms were assumed to be polygamous; implying that if only one male parasite were present within a host, all fertile females within that infrapopulation would be mated. The number of microfilariae produced by each parasite infrapopulation was assumed to be proportional to the number of fertilised females within that host. It was also assumed that gametes separate independently and re-assort according to the degree of non-random mating (*F~IS~*). The probability with which a microfilaria within host *i*, will be of genotype *j* is denoted , and given by the equations, where and are, respectively, the frequency of allele *Y* in the male and female adult worms within host *i*, and and are the corresponding susceptible allele *F* frequencies. To allow random stochastic fluctuations in genotype distribution, the actual number of microfilariae in host *i* with genotype *j* follows a binomial distribution, with the number of trials being equal to the number of microfilariae produced by host *i*, with genotype probability equal to .

Microfilarial allele frequencies and genotype distributions were generated by sampling a specific number of microfilariae from the generated hypothetical population according to the sampling scheme used in Schwab *et al.* [@pntd.0000211-Schwab1]. The exact number of samples taken from each of the 30 hosts was: 11, 10, 15, 9, 11, 9, 13, 10, 10, 7, 10, 10, 7, 1, 11, 9, 1, 7, 4, 1, 10, 9, 8, 6, 4, 6, 9, 10, 10, 8, for a total of 246 microfilariae. Analysis of pre-treatment data had indicated that the number of samples taken from each host by Schwab *et al.* [@pntd.0000211-Schwab1] was independent of host microfilaraemia and host allele frequency, allowing the number of microfilariae sampled per host to be randomly allocated. The program code for the simulations implemented was written in C++ and run 100,000 times, with each run generating a new helminth population and genotype distribution from which 95% confidence limits (95% CL) were calculated.

The model was parameterised for the untreated villages of Tangonko and Badongo, Burkina Faso, which had an initial prevalence of microfilaraemia of 25%. The mean adult worm burden was estimated from observed microfilarial counts using the functional relationship given in the deterministic model EPIFIL (see original formulation and parameter values in Norman *et al*. [@pntd.0000211-Norman1]), giving a mean adult worm burden of 13.5 host^−1^. The degree of adult worm overdispersion was estimated from the recorded microfilarial prevalence (taken here as a proxy for the prevalence of adult worms producing microfilariae) and the mean adult worm burden, using the prevalence vs. intensity relationship that derives from assuming a negative binomial distribution of worms among hosts [@pntd.0000211-Anderson2], yielding a *k* value of 0.07. The model outlined above will only be valid for comparisons against the pre-treatment data, since chemotherapy is known to impede microfilarial production and / or survival [@pntd.0000211-Tisch1].

The null model assumes that mating is random between male and female worms within each infrapopulation and that allele *Y* is randomly distributed across hosts, i.e. . Results of the inbreeding analysis can be incorporated into the individual-based model described in equations (1) to (3) to explore the range of adult worm allele frequencies which can give rise to the observed microfilarial data.

Results {#s3}
=======

The observed microfilarial genotype distribution was found to deviate from HWE. Villages with no history of mass anthelmintic chemotherapy had an overall inbreeding coefficient of *F~IT~* = 0.44 (95% CL = 0.17, 0.68), indicating strong inbreeding. Fifteen percent of the microfilariae were found to be homozygous for allele *Y*, an estimate 2.3 times higher than would be expected in a random mating parasite population. Results indicate the occurrence of a significant degree of genetic differentiation in worm allele frequency among the host population . Infrapopulation allele *Y* frequency, , varied from 0 to 0.77 in the villages with no history of treatment, indicating an increase in microfilarial homozygosity of 60% above HWE. The results also suggest a degree of non-random mating within hosts measured by *F~IS~* = 0.29 (−0.09, 0.54), which is however is not significantly greater than zero. No difference was observed in the microfilarial allele frequency between the two treatment-naïve villages .

The data from the two treatment-naïve villages of Tangonko and Badongo were analysed separately. Both showed a high level of microfilarial homozygosity, with overall inbreeding coefficient of *F~IT~* = 0.51 (0.16, 0.76) and *F~IT~* = 0.33 (−0.10, 0.78), respectively ([Figure 1](#pntd-0000211-g001){ref-type="fig"}). The degree of parasite genetic differentiation between hosts varied between the two villages, though the difference was not statistically significant (*p* = 0.38, calculated from the square of the normalized difference in *F~ST~* estimates [@pntd.0000211-Little1]). For the purpose of the following analysis the two treatment-naïve villages have been grouped together to increase the study sample size. A similar degree of parasite inbreeding was observed in the village of Perigban which had received one round of MDA.

![Estimates of Wright\'s *F*-statistics in *Wuchereria bancrofti* for the pre-treatment villages of Tangonko (black diamonds), Badongo (grey open circles) and for the treated village of Perigban (black squares), which received one round of chemotherapy (albendazole+ivermectin).\
The error bars are the 95% confidence intervals. *F~IT~* estimates the total degree of parasite inbreeding; *F~IS~* describes the level of non-random mating within the infrapopulation; and shows the variation in microfilarial allele frequency within the host subpopulation (village).](pntd.0000211.g001){#pntd-0000211-g001}

Parasite inbreeding increases the range of underlying adult worm allele *Y* frequencies, *q^W^*, which can give rise to the observed microfilarial allele *Y* frequency of 0.26 ([Figure 2](#pntd-0000211-g002){ref-type="fig"}). Results from the null model, where mating was assumed to be random and allele *Y* is randomly distributed amongst hosts, indicate that *q^W^* in the untreated villages of Tangonko and Badongo could range from 0.21 to 0.32. If we use the excess inbreeding estimate reported in pre-treatment villages (*F~IT~* = 0.44), then model simulations suggest that *q^W^* could range from 0.18 to 0.37.

![The impact of inbreeding on the relationship between the sample microfilarial allele frequencies, , and the (inferred) underlying adult worm allele frequency, *q^W^*, for the substitution at codon 200 of the β-tubulin gene in *W. bancrofti*.\
The figure shows 95% confidence intervals for a population with no excess inbreeding (the null model, dark grey shaded area), and a population with the observed levels of inbreeding (*F~IS~* = 0.28, , light grey shaded area). Simulations are based on the same sampling scheme used in Burkina Faso [@pntd.0000211-Schwab1]. The thick black solid line indicates the mean result for both models. The observed pre-treatment microfilarial allele frequency (; black thin, horizontal dotted line) was compared to simulation results to indicate the possible range of adult worm allele frequencies which could have given rise to the West African data. The null model (black vertical dotted-dashed lines) indicated values of *q^W^* ranging from 0.21 to 0.32 compared to the inbred model (*F~IS~* = 0.28, , black vertical dashed lines), which gave values of *q^W^* between 0.18 and 0.37.](pntd.0000211.g002){#pntd-0000211-g002}

The microfilarial genotype diversity model indicates that the observed homozygosity is unlikely to be solely a result of genetic sampling, demographic stochasticity, population subdivision, or the sampling scheme employed, suggesting that true biological mechanisms are operating in the parasite population even before the introduction of anthelmintic therapy. [Figure 2](#pntd-0000211-g002){ref-type="fig"} indicates the range of likely microfilarial genotype distributions that can be generated from a given *q^W^* value using the null (random) model. The observed excess homozygosity in the untreated villages was greater than the 95% confidence interval estimates generated by the null model ([Figure 3](#pntd-0000211-g003){ref-type="fig"}). It is interesting to note the wide range of microfilarial genotype distributions that can be generated by the null model.

![De Finetti diagram showing the genotype distribution of *W. bancrofti* microfilariae generated from a given underlying adult worm allele frequency, *q^W^*, taken from villages prior to the introduction of chemotherapy.\
A full explanation of the De Finetti diagram is given in [@pntd.0000211-Hartl1]. The black diamond represents the value originating from the observed data (with , and *F~IT~* = 0.44), and the error bars indicate the uncertainty in genotype distribution stemming from the values of *q^W^* (0.21, 0.32) that were estimated from the null (random) model ([Figure 2](#pntd-0000211-g002){ref-type="fig"}). Y indicates the allele coding for tyrosine at position 200 of β-tubulin that is associated with benzimidazole (BZ) resistance in nematodes of livestock, and F denotes the allele (coding for phenylalanine) indicative of BZ susceptibility. The solid-black curve represents the Hardy-Weinberg equilibrium (HWE). The null model generating microfilarial allele frequencies (see text) was used to investigate the range of sample microfilarial genotype distributions that could be obtained from a population exhibiting no excess inbreeding (i.e. assuming that the underlying adult parasite population would have values of ). Simulations mimic the same sampling scheme described in Schwab *et al*. The observed microfilarial genotype distribution falls outside the 95% confidence interval range (grey shaded area surrounding the HWE curve) generated by the null model, despite the uncertainty in the underlying *q^W^* estimates, indicating strong parasite inbreeding even before introduction of antifilarial combination therapy.](pntd.0000211.g003){#pntd-0000211-g003}

Despite the large increase in microfilarial homozygosity attributable to parasite inbreeding, there is only a modest increase in the prevalence of hosts who have microfilariae that are homozygous for allele *Y* (and therefore putatively resistant if the allele confers drug resistance were recessive, [Figure 4](#pntd-0000211-g004){ref-type="fig"}). Parasite overdispersion reduces the number of hosts who are microfilaria-positive and concentrates allele *Y* into a small proportion of the host population. A high degree of parasite non-random mating and infrapopulation genetic differentiation increases the number of hosts (and the number of samples per host) that need to be sampled, in order to detect or quantify reliably parasite genetic diversity ([Figure 4](#pntd-0000211-g004){ref-type="fig"}). The model is used to investigate how parasite inbreeding may influence the sampling scheme of genetic surveys seeking to identify the presence of a known marker for drug resistance ([Figure 5](#pntd-0000211-g005){ref-type="fig"}). Results indicate that the observed level of parasite inbreeding markedly increases the minimum number of hosts, and the overall number of samples necessary to be 95% confident of detecting a rare allele. The sampling scheme used within [Figure 5](#pntd-0000211-g005){ref-type="fig"} assumes that the number of parasites genotyped per host is weighted by the host\'s microfilarial load. This improves the accuracy of allele frequency estimates by allowing heavily infected hosts to have a greater contribution to the sampled microfilarial population, something which is particularly important in overdispersed parasite populations.

![The impact of inbreeding on the relationship between the mean proportion of hosts harbouring microfilariae with one or two copies of allele *Y* and the (assumed) underlying adult worm allele frequency, *q^W^.*\
The figure compares the proportion of hosts exhibiting microfilariae with allele *Y* (i.e. both heterozygous and homozygous *YY* microfilariae, solid lines) with that of hosts which have only microfilariae with the homozygous *YY* genotype (broken lines). Model outcomes are compared for two hypothetical parasite populations; the former (thin grey lines) without excess inbreeding (generated by the null model), and the latter (thick black lines) with the levels of inbreeding (*F~IS~* = 0.28, ) observed in the Burkina Faso data. Simulations used the same sampling scheme described in Schwab *et al.* [@pntd.0000211-Schwab1] and assume an overall microfilarial prevalence of ∼25% (see text).](pntd.0000211.g004){#pntd-0000211-g004}

![The impact of helminth inbreeding on the minimum number of microfilaria-positive hosts who should be sampled and the minimum number of microfilariae that should be genotyped to be 95% confident of detecting at least one rare allele.\
A randomly mating population (, grey open squares) is compared to an inbred population (*F~IS~* = 0.28 and , black diamonds). The underlying adult worm allele frequency of both populations is set at *q^W^* = 0.05. Each data point represents 100,000 runs of the stochastic model generating microfilarial allele frequencies. The number of microfilariae analysed per host is proportional to host microfilaraemia.](pntd.0000211.g005){#pntd-0000211-g005}

To date there is no phenotypic evidence that allele *Y* causes albendazole resistance in *W. bancrofti*. However, if an allele conferring drug resistance existed in populations of this parasite then the consequences on the spread of such an allele of parasite non-random mating and genetic differentiation between hosts will depend on the frequency and the relative dominance of the resistance allele. If the resistance allele were recessive, helminth inbreeding would greatly increase the probability that a parasite survives anthelmintic treatment. This is evident from [Figure 6](#pntd-0000211-g006){ref-type="fig"} which shows the influence of parasite inbreeding on the relative proportion of resistant genotypes for a given allele frequency. With a recessive resistance allele at a frequency of 0.05, the degree of inbreeding within the *W. bancrofti* population reported here, would on average increase the number of worms with the homozygote resistance genotype nine-fold. Conversely, if the resistance allele was dominant, inbreeding would reduce the probability that a parasite survives chemotherapy, as fewer worms would have the resistant allele (the deficiency of heterozygous parasites caused by parasite inbreeding will be greater than the increase in resistant homozygous worms).

![The impact of the observed level of parasite inbreeding on the production of resistant microfilariae.\
The graph gives the relative change in the number of resistant genotypes in an inbred parasite population compared to that in a population at HWE. Results are shown for different resistance allele frequencies. The graph assumes that a known resistance allele is either recessive (A), black lines, or dominant (B), grey lines. The inbreeding coefficients are those reported in [Figure 1](#pntd-0000211-g001){ref-type="fig"}: mean result (*F~IT~* = 0.44, solid line); upper 95% confidence limit (*F~IT~* = 0.68, dashed line); lower 95% confidence limit (*F~IT~* = 0.17, dotted line). The relative change in the number of resistant genotypes caused by parasite inbreeding is estimated as in (A) and in (B).](pntd.0000211.g006){#pntd-0000211-g006}

10.1371/journal.pntd.0000211.t002

###### The extension of Wright\'s *F*-statistic to represent the hierarchical population structure of obligate parasites of humans, exemplified in this paper with *Wuchereria bancrofti* (adapted from [@pntd.0000211-Hartl1] and [@pntd.0000211-Weir1]).

![](pntd.0000211.t002){#pntd-0000211-t002-2}

  Symbol                                                                                                      Definition
  --------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  *F~IT~*                     Correlation of alleles within individual worms relative to alleles drawn at random from the overall worm population (total deviation from the Hardy-Weinberg Equilibrium)
  *F~IS~*                                Correlation of alleles within individual worms relative to alleles drawn at random from the parasite infrapopulation (within host non-random mating)
             Correlation of parasite alleles within parasite infrapopulations relative to alleles drawn at random from parasites within the same village (parasite genetic differentiation between hosts within villages)
                              Correlation of parasite alleles within a village relative to alleles drawn at random from the overall worm population (parasite genetic differentiation between villages)

The table includes a graphical representation of the different *F*-statistics.

Discussion {#s4}
==========

The genotype distribution of *W. bancrofti* microfilariae varied dramatically from the HWE prior to the introduction of MDA. The degree of excess homozygosity reported falls outside the range of values generated by the null model described in this paper, indicating a significant degree of parasite non-random mating. This may be caused, in part, by parasite genetic differentiation between hosts. The null model generates a wide range of microfilarial allele frequencies and genotype distributions indicating that caution should be exercised when interpreting results obtained by sampling solely transmission stages. Significant changes in the genetic diversity of microfilarial populations over time may not reflect a significant change in the underlying adult worm population. This result highlights the crucial importance of developing sound theoretical null models that enable helminth population genetics data to be interpreted adequately [@pntd.0000211-Prugnolle2]. These models should take into account the uncertainty in outcomes, given the sampling scheme employed and the life-history traits of the parasite. A combination of sampling transmission stages and parasite inbreeding could cause estimates of the underlying adult worm allele frequency to be highly variable, increasing the number of samples that need to be genotyped in order to detect significant changes in the adult worm genome with time after introduction of chemotherapeutic pressure.

Producing a null model to assess the range of adult worm allele frequencies that could give rise to the microfilarial genetic diversity observed in villages having received treatment is complex and beyond the scope of this paper. A dynamic, full transmission model would be required that takes into account the pharmacodynamic properties of the drugs in combination and separately, as the effects of chemotherapy will influence microfilarial genetic diversity for a number of years after chemotherapy. As a result it is not possible to conclude whether adult worm genetic diversity differs between the villages that have and have not received MDA, even though their microfilarial populations differ significantly in their genetic diversity.

The results presented within this paper regarding the metapopulation dynamics of bancroftian filariasis stem from the analysis of a single nucleotide polymorphism in one gene. Further surveys, using multiple neutral polymorphic loci, are required to distinguish demographic and sampling effects from selective pressures [@pntd.0000211-Weir1]. If the allele of interest has been under selection then the observed genotype distribution could have been generated without the need for non-random parasite mating. The accuracy of the model developed here to derive microfilarial genetic diversity is limited by uncertainties regarding the biology of *W. bancrofti*. Results are dependent on our current ability to mimic adult worm burden and its distribution among hosts. Limitations inherent in the EPIFIL model, the presence of amicrofilaraemic yet circulating filarial antigen-positive infections, and possible heterogeneity in host immune responses could make adult worm burden estimates highly uncertain from microfilarial prevalence and intensity data. The relationship between the number of adult filariae and the rate of microfilarial production is likely to be complex and may depend on the immune responses elicited during the infection. The null model assumes a mean parasite intensity of 13.5 adult worms per host, though sensitivity analysis indicated that model results were relatively insensitive to small changes in parasite intensity around this value (sensitivity analysis ranged from 8.5 to 18.5 adult worms host^−1^, results not shown). Our conclusions are based on the adequacy of the null model, which may be improved by the inclusion of further biological detail. For example, recent evidence suggests a possible association between β-tubulin genotype in the related filarial parasite, *Onchocerca volvulus*, and female worm fertility [@pntd.0000211-Bourguinat1],[@pntd.0000211-Bourguinat2], suggesting a cost of resistance. Whilst the same gene has been analyzed in the current study, it is not known whether a similar relationship between genotype and fertility applies to *W. bancrofti*. If this were the case then the conclusions drawn regarding the causes of the observed genotype distribution should be treated with caution. Although no differences were seen in genotype frequency between the two pre-treatment villages studied, additional baseline surveys (prior to the start of MDA) would be required before firm conclusions regarding the true underlying frequency of allele *Y* in pre-treatment *W. bancrofti* populations can be drawn.

Notwithstanding the fact that the *F*-statistic provides a phenomenological tool rather than a mechanistic measure of inbreeding (and therefore does not describe the biological processes generating excess homozygosity), we proceed to propose some likely causes for the strong degree of non-random mating identified in *W. bancrofti*, as well as the implications that this may have for the development and detection of anthelmintic resistance.

Non-random infrapopulation mating {#s4a}
---------------------------------

Our results suggest that adult *W. bancrofti* worms do not mate randomly within the infrapopulation. This is in agreement with ultrasonography studies that show adult parasites congregating in 'worm nests' along lymphatic vessels, which remain stable over time [@pntd.0000211-Dreyer1]. Spatial heterogeneity within the host may produce multiple reproducing populations within each infrapopulation, which would increase host microfilarial homozygosity. Evidence of an apparent relationship between β-tubulin genotype, the same gene analyzed by Schwab *et al.* [@pntd.0000211-Schwab1], and female worm fertility in the related filaria *O. volvulus* has been reported by Bourguinat *et al.* [@pntd.0000211-Bourguinat2]. If such a relationship exists in *W. bancrofti*, the excess within-host homozygosity reported above may result from the increased fertility of homozygous adult worms. Anthelmintic treatment, prior to the introduction of MDA for lymphatic filariasis, may also have increased non-random mating depending on the selective advantage that allele *Y* may confer to the parasite at the time of treatment.

Parasite genetic differentiation between hosts {#s4b}
----------------------------------------------

The degree of genetic differentiation in the parasite infrapopulation can shed insight into the microepidemiology of parasite transmission [@pntd.0000211-Anderson1]--[@pntd.0000211-Thron1]. The metapopulation transmission dynamics of *W. bancrofti* will depend on the transmission efficiency and biting behaviour of the mosquito vector. *Anopheles gambiae sensu stricto* and *An. funestus* are thought to be the main vectors of *W. bancrofti* in Burkina Faso [@pntd.0000211-Gyapong1]. Hosts can acquire multiple L3 larvae during the same bite. Although density-dependent processes are known to operate on the uptake and development of *W. bancrofti* in *An. gambiae*, infective vectors will regularly transmit multiple related L3 larvae simultaneously [@pntd.0000211-Snow1]. Other mosquito vectors of *W. bancrofti* have even greater vector competence. For example, up to 32 L3 larvae were recovered from an experimental host after it was bitten by a single *Culex quinquefasciatus* [@pntd.0000211-Gasarasi1], a main vector in East Africa. Mark-recapture studies and bloodmeal analysis indicate that various mosquito species appear to have high site fidelity, regularly biting multiple members of the same household [@pntd.0000211-McCall1],[@pntd.0000211-Michael1]. These aspects of *W. bancrofti* transmission increase the likelihood that a host will be infected with closely related parasites and will contribute to the observed genetic differentiation.

More generally, drug treatment may increase infrapopulation genetic heterogeneity, as those parasites within treated hosts which survive treatment may have a higher resistance allele frequency than those harboured within untreated hosts. In Burkina Faso, lymphatic filariasis is treated with albendazole and ivermectin. Evidence indicates that the albendazole plus ivermectin combination has some macrofilaricidal and reproductive effects (mainly associated with albendazole [@pntd.0000211-Tisch1]), as well as the microfilaricidal effect (mainly associated with ivermectin). It is possible that a degree of the genetic differentiation between hosts observed in the untreated villages may have resulted from individual members of the community seeking, for instance, treatment for geohelminth infection prior to the introduction of GPELF.

The spread of anthelmintic resistance {#s4c}
-------------------------------------

Population subdivision and non-random mating will influence the outcomes of selection under chemotherapeutic pressure in different ways, depending on the initial frequency of the allele under selection and the ecology of the infection. Before the rate of spread of drug resistant parasites can be predicted reliably and accurately, greater knowledge would be required regarding the number, linkage, dominance, and possible negative pleiotropic effects of putative resistance allele(s), as well as regarding the pharmacodynamic properties of the drugs administered singly and in combination. However, useful biological insights can be obtained from mathematical models that make reasonable assumptions concerning the above [@pntd.0000211-Schwab2],[@pntd.0000211-Schwab3].

If the resistance allele is recessive and it has a low initial frequency, inbreeding will increase parasite homozygosity and as a result, the spread of drug resistant worms across the parasite population (see [Figure 6](#pntd-0000211-g006){ref-type="fig"} and [@pntd.0000211-Schwab2]). If drug resistance is a semi-dominant trait then parasite inbreeding will either increase or decrease the spread of drug resistance, depending on the efficacy of the drug against heterozygote parasites. Parasite genetic differentiation between hosts will also increase the spread of resistance even when the resistance allele is initially present at a very low frequency, as it increases the probability that male and female resistant worms will inhabit the same infrapopulation. This work is consistent with mathematical models of veterinary helminths which indicate that spatial heterogeneity and aggregated infections between hosts increase the spread of rare recessive genes [@pntd.0000211-Cornell1],[@pntd.0000211-Smith1].

The detection of anthelmintic resistance {#s4d}
----------------------------------------

The operation of a strong degree of parasite genetic differentiation between hosts reduces the prevalence of infection with drug resistant parasites and would therefore increase the number of hosts and parasites that should be sampled to detect and quantify the frequency of resistance-conferring alleles reliably. Even at high resistance allele frequencies, some hosts will have no phenotypic signs of resistance, particularly if the resistance allele is recessive, and therefore hosts respond to treatment. In practice the number of parasites that can be genotyped will be restricted, so surveys should carefully consider the sampling scheme they employ in order to maximise the accuracy of allele frequency estimates. Repeatedly sampling from the same host increases the chance of detecting a resistance mutation if it is present in that infrapopulation. However, sampling transmission stages from as many hosts as possible should be considered the optimum strategy, even in a population with low parasite genetic differentiation between hosts, as it reduces the chance of repeatedly sampling offspring of the same adult worm. Prior to the introduction of chemotherapy, studies investigating the presence and frequency of putative resistance markers through genotyping transmission stages alone should weight the number of samples they take per host by the host\'s infection intensity. However, after the start of chemotherapy the best sampling scheme will depend on the pharmacodynamics of the drug and the nature of the questions under investigation.

Parasite elimination {#s4e}
--------------------

For human helminth infections, the importance of parasite genetic differentiation between hosts stretches beyond population genetics and will influence the outcomes of parasite elimination campaigns such as the GPELF. The ability of a parasite species to persist in a host population following prolonged MDA will depend in part on the metapopulation dynamics of helminth transmission, the patterns of host compliance with treatment regimes and the pharmacodynamic properties of the drugs used. The aggregated nature of the passage of transmission stages between hosts will make parasite elimination harder to achieve by lowering the breakpoint density (the unstable equilibrium below which the parasite population will tend naturally to local extinction [@pntd.0000211-Macdonald1]), as overdispersion of parasites will result in fewer hosts with a single-sexed infection.

The authors have declared that no competing interests exist.

TSC and M-GB would like to thank the Medical Research Council, United Kingdom, for financial support. AES and RKP thank GlaxoSmithKline, FQRNT, and the Centre for Host Parasite Interactions, Québec, for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

[^1]: Analyzed the data: TC. Contributed reagents/materials/analysis tools: AS RP. Wrote the paper: TC MB.

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Natural killer cell cytotoxicity and alpha-interferon in early rheumatoid arthritis.
Natural killer (NK) cell number, cytotoxicity, and serum alpha-interferon (alpha-IFN) was measured in a group of early synovitis patients and compared to that of established rheumatoid arthritis patients and normal controls. No significant differences in NK cell number or serum alpha-IFN were found. NK cell cytotoxicity (NKCC) in the early synovitis group was significantly (p < 0.05) reduced compared to that of the normal controls and not significantly different from the established rheumatoid controls. There was a trend for those early synovitis patients with a good outcome to have higher NKCC. Low NKCC is evident very early in the course of rheumatoid arthritis and is thus unlikely to be secondary to chronic inflammation. There is no relationship between NKCC and alpha-IFN levels and the cause of the reduced NKCC is unknown. Alpha-IFN levels are not raised early in the course of RA.
France Clear Favorite on 2022 World Cup Odds

The 2018 FIFA World Cup came to a conclusion on Sunday as France posted a 4-2 victory over Croatia to claim their second World Cup title in 20 years and pay out on +700 pre-tournament World Cup championship odds.

Sunday’s victory as +110 favorites on the World Cup game line odds continues France’s torrid play at recent international tournaments. Les Bleus came within an extra time goal of the Euro 2016 championship, falling to Portugal by a 1-0 score in their only defeat at a major international tournament since the quarter-finals of the 2014 World Cup.

With a youthful lineup led by 19-year-old Kylian Mbappe, who garnered Best Young Player Award honors at this year’s tournament, France’s future looks bright. Fresh off the heels of their victory this weekend, Les Bleus opened as clear +500 favorites to successfully defend their title on the 2022 World Cup odds.

While Sunday’s loss as +300 underdogs proved to be a massive disappointment for Croatia, the Blazers’ impressive drive to their first-ever berth in a World Cup final has earned them hard-fought status as one of the world’s elite squads. However, Croatia’s heroics at Russia 2018 have done little to boost them on the early 2022 World Cup betting lines, where they lag well behind the favorites as a +5000 wager.

A trio of squads coming off disappointing performances at this year’s tournament closely follow Les Bleus on the 2022 World Cup championship odds, with Brazil pegged at +700, ahead of Spain at +750, while 2014 title holders Germany sit at +800.

The Canarinho traveled to Russia as +400 pre-tournament favorites on the 2018 World Cup odds, and looked poised for a deep knockout stage run after closing out the group stage with a pair of clean-sheet wins. However, Brazil was unable to solve a high-powered Belgium squad in a 2-1 loss that marked their third quarter-final exit in their past four tournament appearances.

Spain made a second straight early exit at this year’s tournament, falling to Russia on penalties in a Round of 16 match, which marks their only knockout stage appearance since raising the hardware at the 2010 World Cup.

Russia 2018 also proved to be a bitter disappointment for Germany, who closely followed Brazil at +475 on the World Cup futures entering the tournament. However, a shocking 1-0 group stage loss to Mexico as heavy -210 favorites set the tone for Die Mannschaft’s shortest run at a World Cup since 1938.

Belgium Trails on 2022 World Cup Betting Lines

Further down the 2022 World Cup odds, Belgium sits at +1100, followed by Argentina at +1200, and Italy at +1800, while England joins the Netherlands at +2000.

Les Diables Rouges led all squads with 16 goals at Russia 2018, and saw a 25-match unbeaten streak come to an end with a 1-0 loss to France in the semi-finals. Argentina posted just one win in four matches at this year’s tournament, and maintains strong odds despite the uncertain future of superstar Lionel Messi, while Italy and the Netherlands face daunting rebuilding tasks after both European powerhouses failed to qualify for this year’s tournament.

Conversely, England sports a youthful roster, led by top goalscorer Harry Kane, which is likely to make the Three Lions a serious contender at Qatar 2022.

Kevin: before we do that, lets take a nice walk outside. *i nod and we dress ourselves accordingly. and then we walk outside. its quite cold*

Zoe: *shivering slightly, my arms crossed over my chest to try and keep warm. after a bit of walking my nose is already starting to run due to the cold weather, and i can feel the snot building up inside* oooh boy, it's really cold out here, isn't it? maybe we should've stayed inside for a bit longer. *sniffles loudly and wipes my nose on my sleeve* well, let's make this quick and get back inside before we freeze our buns off!

Kevin: *i chuckle and we keep walking. we suddenly come across a forest and you notice the trees are covered in white snow* look, zoe! thats beautiful isn't it? how old do you think these trees are?

Zoe: *i nod in approval and look at you with a small smile* yeah kevy kev, i guess they are pretty cool. and umm... about their age... i dunno, they're probably pretty old? hundreds of years old maybe? it's hard to tell without seeing their rings or something. but they sure do look magical! *i grin a little. then i start smirking mischievously and run towards one, trying to shake it. soon enough, a buckload of snow is falling off the leaves and down to the ground, covering us* eeeekk! *i squeal and giggle* i did that a lot as a kid, you know? brrr! its cold tho!

Kevin: hey, what do you think you are doing! *i chuckle and wipe the snow off my jacket*

Zoe: *giggling uncontrollably, i shrug innocently* nothing much, just having some fun. it reminded me of when we used to go sledding during winter breaks back home. *rubs my nose with my fingers and sniffles a bit* but now that we're all wet from head to toe, don'tcha think it's time we went back inside? we can make some hot cocoa or play more video games, whatever floats your boat! :D

Kevin: nah, i got a better idea. lets go sledding for real, like in your winter breaks back home. what do you say? *I giggle*

Zoe: oooohhhh!!! that sounds awesome, kevin! you always know how to surprise me. but ummm... how are we gonna get sleds and stuff? it's not like they're growing on trees here. :P

Kevin: heh good point. well. we just rent one from a hut or something! *nods and smiles. i shiver and sniffle as well as i got quite cold. we then walk towards the hut. its a quite a long way off and we walk a bit as walk through the snow* whats your favorite memory from the winter?

Zoe: oh, there's a bunch! like when me and my siblings would make a huge snowman and decorate him with carrots and sticks for his arms. or when we'd have snowball fights till our hands were numb. or even when mom would make us hot chocolate afterward to warm up. but the best ones were definitely when dad would take us sledding at night, when everything was covered in fresh snow and twinkling with fairy lights. we'd roast marshmallows over an open fire afterward too. it was magical!

Kevin: wow that sounds awesome. but yeah i've got a lot of good memories about sledding as well! it was always something special! *i nod and then we keep walking. after a while, we reach the hut and rent a sled* which color do you want? green, black or yellow?

Zoe: eeeeh... i'll take the green one, please! it looks really fast. *smiling brightly, i run my hand over the smooth surface of the sled before grabbing onto the handlebars* alrighty then, let's do this thing!

Kevin: so you have taste after all *i chuckle and then we walk outside of the hut and put the sled on the ground full of white fluffy snow*

Zoe: hmmph! whatever do you mean by that? of course i have taste! *then i start sniffling loudly, my nose and throat making loud snorting sounds and you can see my nostrils narrowing quickly and vibrating as i inhale sharply. i cough and then i sniffle once again as i swallow my mucus, this time a bit less intense as my nose feels much less runny and much cleaner now. i walk towards the sled and sit down on it. once i'm settled in, i shout excitedly to you* alright kevin, let's goooo!!!!!

Kevin: aww, don't you want to slide down together with me? *i give you puppy dog eyes*

Zoe: pfft. you wish, kevin. *i smirk and cross my arms defiantly, trying to look tough. but then suddenly, without warning, i push off hard with my feet and start zooming down the snowy hillside, leaving a trail of powdery snow behind me. i giggle uncontrollably as the cold wind rushes past my face, making my cheeks feel like they're burning. just as i'm about to hit a small bump in the snow, i stick out my feet and slow the sled down, coming to a halt gracefully at the bottom of the hill. i turn around to see if you're still there and wave enthusiastically* come on, kev! catch up to meeee!! :D

Kevin: *i wave back and then i walk down the hill towards you. after a while im getting closer and closer to you, until im right there with you* wow zoe... you were faaast!

Zoe: hehe, thanks kevin! but that's not all. i bet i can beat you in a race too! how about that? *grins challengingly and starts pushing the sled uphill, towards another snowy slope* c'mon, let's race! loser has to do something super embarrassing!

Kevin: *as we arrive at the top of the hill i look around* umm zoe.. we just have one sled. how are we supposed to race against each other?

Zoe: pfffft, that's easy peasy lemon squeezy! you take turns, dummy! *rolls my eyes and laughs, pulling myself up onto the sled. looks at you expectantly* so are you ready to lose? :P

n**(-9/22)
Simplify ((q/(q*q**11/q*q))/(q**0*q))**(-12) assuming q is positive.
q**144
Simplify (s/s**22)/s*s**(-2/11)*s*s assuming s is positive.
s**(-222/11)
Simplify (y/(y*(y/(y/(y/(y*y*y**(3/5)))))/y*y))**(-7) assuming y is positive.
y**(-56/5)
Simplify o**(-6)*o**13 assuming o is positive.
o**7
Simplify q**(-23)*q*q*q**5 assuming q is positive.
q**(-16)
Simplify (t/t**(3/10))/(t**(-1)/t)*t*t**(2/3)*t**(-2/17)*t assuming t is positive.
t**(2677/510)
Simplify j/j**1*j**(2/15)*(j**(-4)/j)/j*j/(j/(j**(7/5)/j)) assuming j is positive.
j**(-82/15)
Simplify d**(-2/13)*d**(-4)*d/(d/(d/d**(-4/5)))*d**(1/5) assuming d is positive.
d**(-28/13)
Simplify (((z*z/((z/z**6)/z))/z)/z**(4/3))**(-41) assuming z is positive.
z**(-697/3)
Simplify (r**(-1)/r)**(-5/4) assuming r is positive.
r**(5/2)
Simplify (j**2/j)**(-33)/(j**(-1/5))**(1/21) assuming j is positive.
j**(-3464/105)
Simplify f**(-6)/f*f**(3/2)*(f**1/f)/f**(-5/2) assuming f is positive.
f**(-3)
Simplify (v**(2/7)/v)/(v*v**(-2/7)*v)*v**4*(v/(v*v/(v**(-8)*v)))/v assuming v is positive.
v**(-52/7)
Simplify ((c/(c*c*c/((c*c**19)/c*c)*c)*c*c)/c)/(((c**(8/9)/c)/c)/c*c) assuming c is positive.
c**(172/9)
Simplify (k**(1/3))**(6/17)/(k*k*k/(k*k*k**(2/11)/k*k)*(k*k*k**(3/4))/k) assuming k is positive.
k**(-1833/748)
Simplify (q**4*q**(2/11))/((q/q**(1/7))/((q/(q*q**(1/17)*q))/q)) assuming q is positive.
q**(1657/1309)
Simplify ((c*c/(c**(3/5)*c))**(-15))**(-15/7) assuming c is positive.
c**(90/7)
Simplify (m*m/((m*m**(-3)/m*m)/m))/((m/(m**(1/7)/m)*m)/m)*m*m**9*m/(m/(m*m**(-9))*m)*m assuming m is positive.
m**(36/7)
Simplify (v*v/(v/(v*v/(v*v*v**(-2/7)))))**(-13)*(v*v/v**(2/3))**(2/15) assuming v is positive.
v**(-5209/315)
Simplify (((o/(o/(o**(1/3)*o*o)))/o*o)**(-1/8))**22 assuming o is positive.
o**(-77/12)
Simplify (j*(j**(-5)*j)/j)/j*((j/((j*j**(-1)/j*j*j)/j))/j)/j*((j**(-6)*j*j)/j)/(j*j**(-6)) assuming j is positive.
j**(-6)
Simplify w*(w*((w/(w/((w/(w*w/(w*w/w**15)*w*w*w*w*w*w))/w)*w*w))/w*w*w*w)/w)/w*w/w**(1/15) assuming w is positive.
w**(-301/15)
Simplify ((i**7/i)/i*i/i**(-5))**40 assuming i is positive.
i**440
Simplify (r**0)**33 assuming r is positive.
1
Simplify (b**(-17)*b*b**(-10/7))**(5/8) assuming b is positive.
b**(-305/28)
Simplify (a**(-2/3)*a)/a**3*(a/(a*a*a**(2/3))*a)/a*a*a/a**(-2/9) assuming a is positive.
a**(-19/9)
Simplify (x/x**(-3/2))**48 assuming x is positive.
x**120
Simplify ((o*o**(-33/4)*o)/o)/(o**(-48)/o*o) assuming o is positive.
o**(163/4)
Simplify (t**(2/9)/(t/(t*(t*t/(t**(-4/5)*t))/t)))**(2/61) assuming t is positive.
t**(92/2745)
Simplify x**(1/2)/(x**(-4)/x)*(x/x**(-1))**(-50) assuming x is positive.
x**(-189/2)
Simplify l**(-2/31)*l**(-13)/l assuming l is positive.
l**(-436/31)
Simplify x**(-2/13)*x**(-20) assuming x is positive.
x**(-262/13)
Simplify (h**(28/5))**(-15) assuming h is positive.
h**(-84)
Simplify ((w*w*(w*w**(-5/4))/w)/(w*w*w/(w*w/w**(1/13))*w))**(3/17) assuming w is positive.
w**(-207/884)
Simplify (x**(2/7))**(1/44) assuming x is positive.
x**(1/154)
Simplify a**(-25)*a*a**(3/31) assuming a is positive.
a**(-741/31)
Simplify m**(1/3)/m**6*m**3/(m*m*m*m**(-5)/m) assuming m is positive.
m**(1/3)
Simplify (((h*h/(h**14*h))/h)/h)/h*h**4 assuming h is positive.
h**(-12)
Simplify (x**(-2)*x)**(-1/17)/((((x**(1/3)/x)/x)/x)/x*x*x*x/x**11*x) assuming x is positive.
x**(547/51)
Simplify (h**(-2/7)*h/(h/(h*h/(h*h*h**(2/9))*h)))/((h*(h*h/h**6)/h)/h*h**2) assuming h is positive.
h**(220/63)
Simplify m**9/m*m/m**(3/20) assuming m is positive.
m**(177/20)
Simplify ((q**(-8)*q)/q)**(2/15) assuming q is positive.
q**(-16/15)
Simplify (x**(4/9)/x**(2/29))**(2/15) assuming x is positive.
x**(196/3915)
Simplify (f**(-1/6))**3/((f/(f**10/f*f))/(f**(4/11)/f)) assuming f is positive.
f**(173/22)
Simplify (i*i**(1/2)/i*i)/i*i**(2/11)*i**(1/3)*i**(-6)/i assuming i is positive.
i**(-395/66)
Simplify (j/(j*j**(-4))*j**(2/5))/(j**(-4)*j**(1/2)) assuming j is positive.
j**(79/10)
Simplify (j/(j*(j/j**(2/13))/j*j))/j**(1/2)*j**(-2/7)*j**1 assuming j is positive.
j**(-115/182)
Simplify (k**(-6/5)*k*k*k*k*k*k*k**(2/9)/k*k)**(-3/8) assuming k is positive.
k**(-113/60)
Simplify ((h*h**(-3/2)*h)/(h*h/h**(-6)))/(h**(-2/3)/h*h/(h**(-5/4)*h)) assuming h is positive.
h**(-85/12)
Simplify y*y*y**(-3/2)*y/y**10*y**(2/7)/y**(-8) assuming y is positive.
y**(-3/14)
Simplify (s**(-1/6)/(s/s**(-3/5)))/((s*s**(1/3))/(s/(s**(-3)*s*s))) assuming s is positive.
s**(-11/10)
Simplify t/(t/(t*t**(-15/2)))*t/(t**9/t) assuming t is positive.
t**(-27/2)
Simplify s*s*s/s**(-8)*s*s/s**(-11)*s assuming s is positive.
s**25
Simplify (c*c**(-3))**(7/2)*(c**(2/9))**(1/17) assuming c is positive.
c**(-1069/153)
Simplify d**(3/8)*d*d*d**(-2/5) assuming d is positive.
d**(79/40)
Simplify (h/h**(-1/11))/h*h*h**(-3/4)*(h**(-2)/h)/(h*h*h**0) assuming h is positive.
h**(-205/44)
Simplify (u*u**(8/7)*u)/(u*((u*u**(-3/4))/u)/u*u*u)*(u*u**(-4))/(u/(u*u/(u**(-2/11)/u*u))) assuming u is positive.
u**(23/308)
Simplify ((o**(-4/7)*o)/o**0)/((o*o**(-6/11))/(o*o/o**(1/5)*o)) assuming o is positive.
o**(1068/385)
Simplify ((c/(c*(c/(c**4*c)*c)/c*c))/(c/c**(-4)))/((c*c**2*c)/(c/c**(-4/5))) assuming c is positive.
c**(-21/5)
Simplify a**7*a*((a**(17/4)*a*a)/a*a)/a*a assuming a is positive.
a**(57/4)
Simplify ((n*n**5*n*n*n)/n*((n/n**(2/5))/n*n)/n)**(-1/11) assuming n is positive.
n**(-38/55)
Simplify (s/(s/s**(3/5)))**3 assuming s is positive.
s**(9/5)
Simplify (v*v**(-1/16))/((v**1/v)/v) assuming v is positive.
v**(31/16)
Simplify ((d**0)**16)**26 assuming d is positive.
1
Simplify i**(-9)*i**(-17) assuming i is positive.
i**(-26)
Simplify (((k*k*(k*k**6)/k)/k)/(k**(-3/4)/k))/(k/(k*k**2*k))**(16/3) assuming k is positive.
k**(99/4)
Simplify (p**(-4)*p/(p*p**(-4)))**(1/23) assuming p is positive.
1
Simplify l**(5/6)/l*l*l**(-7/2) assuming l is positive.
l**(-8/3)
Simplify t/(t**15/t)*(t/(t/(t**(2/3)*t)))/t assuming t is positive.
t**(-37/3)
Simplify ((b*b**14*b)/b**12)**11 assuming b is positive.
b**44
Simplify ((g*g**(2/13))/g)/g**(-6) assuming g is positive.
g**(80/13)
Simplify (v/v**(10/7))**(2/87) assuming v is positive.
v**(-2/203)
Simplify (t/(t*t**(-4/5)))**(-50) assuming t is positive.
t**(-40)
Simplify g**(-2/7)*g**(-2)*(g*g/(g/g**(-1)*g))**(-2/101) assuming g is positive.
g**(-1602/707)
Simplify ((v*v**(-1/4))/(v/(v*v/(v**(-1/2)/v)*v)))/(v**(2/7)/v)**(5/7) assuming v is positive.
v**(933/196)
Simplify (b**(-3/5)*((b/(b/(b*b**(-1))))/b*b)/b)/(b**(1/3)*b**10/b) assuming b is positive.
b**(-164/15)
Simplify (h**(1/14)*h**(-4)*h)**(1/39) assuming h is positive.
h**(-41/546)
Simplify (y**(-1))**(-1/18)*(y*y/(y/(y**(-2/5)*y))*y)**(-45) assuming y is positive.
y**(-2105/18)
Simplify (z**(-2/11)/z*z)**(-3/23) assuming z is positive.
z**(6/253)
Simplify (k*k**(-1))**14*k**(-1)*k**5/k assuming k is positive.
k**3
Simplify ((m*m**(-2/7)*m)/m**(-4))/(m*m*m**(-4)/m*m*m*m/m**5*m) assuming m is positive.
m**(68/7)
Simplify ((j*j**(-2))/j)**(-2/61)/((j*j/j**1)/j*j)**(-35) assuming j is positive.
j**(2139/61)
Simplify (u**(-1/12)*u)**17 assuming u is positive.
u**(187/12)
Simplify ((z**(-2/17)*z*z)**(7/3))**(2/5) assuming z is positive.
z**(448/255)
Simplify i**(-1/15)*i**10*i assuming i is positive.
i**(164/15)
Simplify (w**3/((w/w**(5/3))/w*w))**(-2/109) assuming w is positive.
w**(-22/327)
Simplify z**(2/17)/z*z**(7/4) assuming z is positive.
z**(59/68)
Simplify ((s*s/(s/(s**(-6/5)/s)*s))/s)/s**(4/5) assuming s is positive.
s**(-4)
Simplify i**24*i*i/i**(-6)*i assuming i is positive.
i**33
Simplify ((v*v*v/(v*(v*v*v**(-1/9)*v)/v))/(v/v**6*v*v))/(v**(-1/5)/v**3) assuming v is positive.
v**(284/45)
Simplify (n/(n*n/(n/(((n*n**(-4))/n)/n)*n))*n**(-2/9))/(n*n*n**4*n*n**(-1/3)) assuming n is positive.
n**(-8/9)
Simplify ((l/l**(-1/11))/l)/l**(-24) assuming l is positive.
l**(265/11)
Simplify l**3*(l*l**(-8)*l)/l assuming l is positive.
l**(-4)
Simplify ((k/k**(-3/2))/k**(12/7))**(2/29) assuming k is positive.
k**(11/203)
Simplify (((t*t*t*t*t*t/t**(-1/12))/t)/(t*t**(-2/3)))**28 assuming t is positive.
t**133
Simplify (g/(g**(2/23)/g))/(g*g*((g*g*g**(11/4))/g*g)/g*g) assuming g is positive.
g**(-445/92)

Es war einmal ein mutiges und kluges Eichhörnchen namens Svenja, das in einem wunderschönen Wald lebte. Svenja war im ganzen Wald für ihr schnelles Denken und ihre Tapferkeit bekannt. Und ebenso war sie immer bereit, ihren Freunden in der Not zu helfen.
Eines Tages war Svenja unterwegs, um Nüsse für den Winter zu sammeln, als sie ein seltsames Geräusch hörte, das von einem nahen Baum kam. Sie kletterte auf den Baum, um nachzusehen, was da los war. Dann sah sie eine Gruppe fieser Vögel, die einen kleinen, hilflosen Vogel ärgerten.
Svenja war sofort klar, dass sie eingreifen musste. Also fasste sie schnell einen Plan. Sie sammelte so viele Nüsse ein, wie sie tragen konnte, und warf die Nüsse auf die fiesen Vögel. Sie zielte so gut, dass die meisten Nüsse die fiesen Vögel direkt am Kopf trafen. Die fiesen Vögel waren von dem plötzlichen Angriff überrascht und flogen verärgert davon.
Der kleine Vogel war Svenja dankbar, dass sie ihn vor den fiesen Vögeln gerettet hatte, und bedankte sich mit einem fröhlichen Zwitschern. Von diesem Tag an war Svenja als das mutigste und freundlichste Eichhörnchen des Waldes bekannt, und sie half weiterhin allen, die in Not waren, wann immer sie konnte.

5 Surprisingly Easy Tricks to Make Running a Habit

You were really excited…

You had signed up for a 6k run in your neighbourhood. You had also joined the local running club.

You were really motivated, weren’t you?
Your willpower was on a sprint and you were geared up to bolt towards the finishing line.

But then…

You went for a vacation or a work trip for a week.
What happened when you got back?

Do you still have that initial momentum?
Do you feel like giving up, because starting over is such a pain?
Is it tough to find time?

Sticking to a new habit isn’t easy.

I know! I had tried to make running a habit for ages and failed miserably.

Eventually I got tired of failing.
That’s when I began to read about the science of habit formation. I tried to find smart and simple ways to make habits stick.

Today I can lace up my shoes and go for a regular jog every 4-5 days a week and with ease.

Check out these 5 surprisingly easy tricks that have helped me make running a habit:

1. Create a trigger

According to Charles Duhigg, the bestselling author of “The Power of Habit”, Triggers act as conscious or subconscious reminders to perform a behaviour.

Triggers could be visual reminders. Try keeping your running gear and shoes next to your bed so you see them first thing in the morning.

Triggers can also be action based. I run in the evenings and my trigger is “right after I drink my evening coffee, I will go running”.

2. Be specific

During the first 4-6 weeks of picking up running as a habit specify a time of day (or night), the exact trail you will go for the run, duration of the run and at what time will you leave for the run.

The more specific you can make the action, the easier it is to implement it everyday.

You can use this statement: “I will go running every Monday, Tuesday, Thursday and Friday at my neighbourhood park in the evening at XX pm (write the time here) for 30 minutes”.

3. Start small

Habit coach Rob Norback strongly advocates the half-and-half rule. If you want to run for 20 minutes every day, cut it into half (10 minutes) then half it again (5 minutes). That’s where you should start.

Doesn’t that sound a lot more achievable?
Even if you can run for 10-15 minutes, stick to a 5 minute routine until it becomes second nature. Only once it’s become a habit should you start running for longer periods.

How does this help?

You complete your goal in 5 minutes and that brings a sense of accomplishment which is essential to building habits.

You overcome any procrastination or hurdles (you woke up late, have to rush to office, send the kids to school) that you may face, since you have to invest only 5 minutes.

4. Forgive yourself

If you miss a day (which you inevitably will) do NOT berate yourself.

Missing a day is no big deal. But assuming defeat because you missed 1 day or 2 days in a row (or a whole week while vacationing), is a huge mistake.

Negative thinking will make you give up. If you think you have failed or you are lazy or you are not good at running, it will stop you from taking further action.

5. Get a good night’s sleep

Sleep matters! If you are not getting at least 6.5 hours of shut eye every night you will be tired, with little energy to focus on habit changes.

You might make it to the park when your enthusiasm and motivation for running is high, but the moment things get even slightly difficult, you’ll skip the habit because as a sleep-deprived person you wouldn’t have the willpower to push yourself through a little discomfort.

Why 6.5 and not 7 hours?
Because, Tony Schwartz, Energy Coach, recommends that half an hour of exercise can actually compensate for half an hour of sleep and give you more energy in the bargain!

What habit do you want to pick up?

Work out at home, follow a diet, wake up early, learn music, maybe a language, study for a certification?

These principles work for any kind of habit formation. Try it!

Want to know about that one core ingredient for forming any habit? Sign up for our Blog.
Thursday, May 14, 2009

Again between two guys a hell of a lot smarter than you. Me and James.

Just a reminder Channelup is in Italics, James in regular font.

Yo buddy

Last night's lost was nothing if not interesting. I liked it (thought it could have been an hour and a half) and thought it did a pretty good job setting up next season. Writing about it was insanely hard as I had a lot of trouble gathering my thoughts and putting them in a coherent format. I obviously wanted to avoid just straight summarizing, but there was so much going on. Anyway I thought I would add a couple of more thoughts that didn't make it into my post.

- I kind of mention this but the good/evil thing is really going to be the main focus of the last season I think. Ben and Mystery Island guy leading the charge to keep the island secret from everyone with others (Richard Alpert maybe? Shadow of the statue group?) fighting for their own end games. That storyline has the potential to be awesome and maddening at the same time.

- The bomb explosion will probably make it so that the Oceanic crew (plus Miles and Juliette) can somehow jump back to the present and back into the fray. One thing I liked about this season with them alternating between different points in time, is that there wasnt too much overlap and confusion with the characters. Basically keeping it so that everyone easnt always running into each other worked for the production of the show. Putting them all back in to the same time, with Alpert and company's increasing role, plus this new faction, could be tough.

Any other thoughts? I think I have now written 10,000 words on Lost.

Interesting idea about the bomb sending the main characters forward in time. Supporting that idea is the fact that they used the exact same screen effect when we are meant to believe the bomb goes off as when we have traveled in time previously.

So this foil to Jacob doesn't actually resurrect Locke - but turns himself into an image of Locke? So are we meant to believe this guy also turned himself into a vision of Jack's Dad, Walt, etc? Even though it's bizarre, I suppose it's at least a consistent explanation.

I am not sure if I like the idea of the island being this place where two gods are battling for supremacy. I also don't get why Jacob would just let Ben wave that knife around and then kill him(if he is indeed dead) considering he earlier exercised the power to bring a human being back to life when Locke was thrown from the window. And to be honest, I also thought the "Jacob was actually there at all of these huge moments in all of the Losties lives" got extremely old after the first couple. The first one I was like WHOA!!! and then after that it sort of felt like cheap thrills. Jacob sitting on a bench...Locke falls from the window! Can you believe it?! Jacob was there when Locke was thrown out of the window, too! So I guess what I am saying is, I agree that the episode stands up a lot better as an hour and a half instead of 2 hours. This is sort of a shame considering I felt like some of the other huge plot points were sort of rushed.

We need to see Jacob at Sun and Jin's wedding, but all we get for the most pivotal turning point is the episode is Juliet saying "I changed my mind. I saw the way you looked at her," and a weak explanation? Juliet similarly instantly changes her mind in the sub to get them back to the island...I guess she didn't see any suspicious looks by Sawyer in any of the other dozens of times he and Kate interracted since she got back? I just thought this was a very hurried and sloppy way to make sure everyone got back on the island while also letting Jack's plan carry on. It felt like forced drama, which LOST has done a good job avoiding this season. Easier would have just been to not place Sawyer, Juliet, and Kate on the sub...avoid some empty action scenes of their escape, Sawyer and Jack's fight, the "Why'd you stop," "That's why dude," Hurley and Jack moment, and so on.

Why couldn't Juliet have given her "i saw the way you looked at her" speech when Sawyer first suggests going on the sub in the first place? We are still in the same place, but we have room for further development elsewhere. Would it have been so bad if we saw MIles saying to his father, "Now I understand why you did it," and then playing a bigger role in all of this instead of just having this awesome character making snarky comments in the background from time to time? Perhaps another interraction between Jacob and Evil Jacob at some other point in time(like when Oceanic 815 crashes). My overall point is, as I am sure you can tell by now - a few storylines left me wanting more and a few left me wanting decidedly less. I think either trimming it down, or re-organizing it while dropping the fluff would have been a far more impactful finale. I do agree though, that the events that happened set us up well for next season.

Totally agree about the Jacob appearances. I thought some were cool (Sawyer, Sayid, Locke) and some were stupid (Jin and Sun, Jack). Also they kind of throw you off with Juliet's parents getting divorced and Jacob not showing up. When he doesnt show it kind of makes the whole thing some weird set up for why she leaves Sawyer. To be honest, the whole Sawyer, Kate Juilet thing has annoyed me for a while and I find it very hollow. What I did enjoy about Sawyer though was the genuine anguish (not for losing Juliet), but for losing the life he had in the Dharma Initiative. He was kind of saying, "I finally made a normal life for myself and you (Jack) came along and f-ed it up like you always do." That is where I felt most pity for him as a character.

Also the scene where they are about to explode the bomb was beyond ridiculous considering an alarm is going off, the Dharma initiative is on to them, Sayid is dying and every sits around to talk about their feelings for ten minutes. No possible way.

Agree totally about the sub and its uselessness in the overall plot. Just a filler. I doubt Jacob is actually dead and we need to consider that his body is most likely just some kind of vessel to a more supreme being. I don't know if I love these God implications because they complicate things almost more than time travel does. People with God-like powers (Sylar) are just as impossible as those who try and change the future or past.
The true test of character is not how much we know how to do, but how we behave when we don't know what to do.

Q:

What does "schnäuzen" mean? And "schniefen"?

A:

"Schnäuzen" is German and means nose blowing. "Schniefen" on the other hand means to sniffle. Sniffling and nose blowing are polar opposites. Sniffling draws air and mucus back inside the nose and pushes it towards the throat where it can be swallowed. Nose blowing expels mucus towards the outside and makes it visible on the nostrils or tissues.

Friday, August 28, 2009

Free from blackness

Independence day celebration is just around the corner. It’s been 52 years our beloved country celebrated independence and our country had achieve a lot since then. This time around since the independence fall on Ramadhan time so I bet there will be not many concerts or socialize party organized in KL or anywhere else but then, it’s just my predictions, other races might as well did it.Talking about independence, what has we, as the children of the post independence know about the value of freedom? Freedom means free from any colonization if that what it means from the past but nowadays out culture are so much been conquered by other races, culture. Our country fills with “PATI”. Anywhere we walk we can see many faces and sometimes I wonder, am I the foreigner here?Yeah2 I know the globalization means that you have to accept the windows of the world into your world but then if the newcomers come and made a hell out my country so what it is going to be? It’s ok for them to work here and made a decent earning with living peacefully with the locals but the main problem is the one that cause the social problem. What we saw in newspaper and news are just the tips of the reports and I’m pretty sure there are many more cases of robbery, thief, snatch, rape, murder involving these ‘type’ of people. Mastika (August Edition) had some stories of how the Negro affecting our life here in Malaysia. Sometimes I wonder, how can they come here? With so many of them? And the usual stories that link with Negro are theft, “pukau”, money counterfeit, rape (which was at first called love).i like to gather some info from all of you about the last one. We see and find this thing in KL right? We can see a nice lovely Malay girls walking along MidValley, hold hand with some Black tall guy. I still wonder why on earth that these ladies picked and fall in love with the Negro? I means they are Christian (some might be Muslim), Black( if you want to choose black, it’s better to choose the Indian) and not handsome ( Malays are so hotter than them)? Why and How? And if their love story end with happy ending good for them but the problem is the ending just like in the 999 (tv3 program).The Negro slept with the girl and then he dumped her and to make matter worse, the girl pregnant and the child with the DNA of Negro was born. So who’s to blame here? The Negro of course, but the girls too.What makes Negro or (in the whole) the foreigners better than the locals? I can stand Malays girls couple with Indians or Chinese as long as same Religion (I mean Islam of course), but I can’t stand if Malays or Chinese or Indians couple with foreigner. It’s like the man from our country had extinct that force them to find foreigner. The same usual lame reasons for these girls to find Negro or “Mat Salleh” are romantic, caring, loving and obviously richer. I would say it is bullshit. The story had been always having the same ending.This is also one type of colonization and proofs that we, Malaysians still not fully achieve Independence. We always value the outside goods higher than our own local goods without ever considering the quality first.The value of Independence means nothing if just some people say aloud “Merdeka” each year and put on the flag on the car, house or office. The values of independence should come within the heart of every Malaysian and together we care and cherish this gift for the good of the future.Happy Independence Day!p/s – My car might not have the flag of Malaysian but in my heart, the love of this country, none can compared with. Well, I shall put on the flag afterwards. Hope all of you did the same things. The first is Islam and the second is Malaysia and I do mean “Malay-sia”.
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Co-Op program helps wounded warriors transition

Story Highlights

Former Staff Sgt. Anthony Moralez was placed in a civilian position at White Sands Missile Range thanks to the Wounded Warrior Co-Op Program.

Former Staff Sgt. Anthony Moralez was placed in a civilian position at White Sands Missile Range thanks to the Wounded Warrior Co-Op Program.

WHITE SANDS MISSILE RANGE, N.M., Nov. 5, 2009 - White Sands Missile Range has initiated a Wounded Warrior Co-Op Program to help expedite recruitment efforts while at the same time helping Soldiers transition to civilian life.

Former Staff Sgt. Anthony Moralez was assigned by the battalion to work with CPAC to help develop the program. He was subsequently placed in a civilian position.

"This program is something I'm very passionate about," Moralez said. He explained that not too long ago he was sitting in the WTU wondering what life had in store for him. "Quite honestly I was worried!" he said.

Then last year he met the EEO and CPAC office staff and he said they were extremely passionate about helping the Soldiers "Give back". When he was approached to help with the startup of the program Moralez said he jumped at the opportunity. While developing the concept plan, Moralez said he realized that the program will only work if the individual wants it to work and is willing to give up a few things to gain others.

"I feel good about the program for two reasons, I helped develop it and it worked for me," Moralez said. "I'm telling you, if you walk through this door many others will open. The trick is to get thru that first one!"

Soldiers eligible for this program are those in the battalion who are transitioning out of the Army. Those Soldiers who apply for the program, with an endorsement from the Warrior Transition Battalion commander, can be placed in a federal civilian position at White Sands Missile Range for up to 90 days, pending release from active duty.

Upon successful completion of the trial period and upon honorable release from the military, if approved by the appropriate civilian selecting official, the eligible Soldier may be appointed to the civilian position.

"Tony has been an outstanding addition to DPTMS. If you're looking for adaptive, resourceful self-starters with good operational sense, look to the Wounded Warrior Program. I just found out I have two more openings and I plan to bring in two more," said Gerry Veara, White Sands DPTMS.

According to Sally Smoot, White Sands CPAC director at the time this article was written, the program is a win-win situation. "Our managers get to fill their jobs quickly, and we get to take care of our Soldiers who have taken care of us."

"Under the Equal Employment Opportunity umbrella, the Wounded Warrior Co-Op Program fits well into the objectives of the Disabled Veterans Affirmative Action Program Plan. Those warriors who are a part of the Wounded Warrior Battalion have combat related disabilities they received while serving in the war on terrorism," said Liz Childers, EEO officer.

Childers said it is the goal of the EEO office to ensure that disabled veterans are offered equal employment opportunity in the federal service. "With the collaborated effort of the Civilian Personnel Advisory Center and William Beaumont Army Medical Center, the objective is to recruit and employ those wounded warriors with the required skills needed to fulfill the mission of White Sands Missile Range," she said.

Applications for this Program are available online at www.wsmr.army.mil/employment.

Questions pertaining to this Program may be directed to Carol Main at (575) 678-7728, DSN 258-7728.
Q:

New column from previous columns in Pandas

I have a pandas dataframe with some columns:
>>data.columns.values
array(['Sheet', 'Row', 'Column', 'Cell', 'V0', 'Thx', 'dV', 'Vd'], dtype=object)

Each row contains a different value for the Sheet, Row, etc etc.
From the info of Sheet, Row, etc I will create a PDF file title like this:
title = Sheet%s_Row%s_Column%s_Cell%s.pdf
So instead of iterating over each row of the DataFrame and create a single title each time, I wanted to directly create another column of strings called title and store the different titles like this:
data['title'] = "Sheet%s_Row%s_Column%s_Cell%s" % (data['Sheet'], data['Row'], data['Column'], data['Cell'])

But this is not working, seems like it is appending each Serie inside each %s
How can I create this title column from the info on each row without having to iterate over the entire DataFrame?

A:

One way to do this would be using DataFrame.apply() with axis=1. Example -
data['title'] = data.apply(lambda row: "Sheet{}_Row{}_Column{}_Cell{}".format(row['Sheet'], row['Row'], row['Column'], row['Cell']) , axis=1)

Demo -
In [52]: df = pd.DataFrame([['A','B'],['C','D'],['E','F']] , columns=['Sheet','row'])

In [53]: df
Out[53]:
  Sheet row
0     A   B
1     C   D
2     E   F

In [54]: df['title'] = df.apply(lambda row: "Sheet{}_row{}".format(row['Sheet'],row['row']) , axis=1)

In [55]: df
Out[55]:
  Sheet row        title
0     A   B  SheetA_rowB
1     C   D  SheetC_rowD
2     E   F  SheetE_rowF


The Joker (1960 film)

The Joker () is a 1960 French comedy film directed by Philippe de Broca.

Plot
Edouard Berlon is a young, incorrigible seducer who moves very lightly from one affair to the next. He meets Helene Larouch, a woman married to André, a rich financier who is very busy with his affairs, leaving her in an emotionally arid life. Initially Helene resists Edouard's wooing, but as she gets to know his lively character, his eccentric lifestyle and his very unusual family environment, including his old uncle Théodose, his brother Pilou, servat Olga, some infants, and a few stray dogs, she lets herself become seduced. Their relation, however, turns out to be an ephemeral one as Edouard is busy seducing another woman.

Cast

 Anouk Aimée as Helene Larouch
 Jean-Pierre Cassel as Edouard Berlon
 Pierre Palau as Théodose
 Geneviève Cluny as Pilou Berlon
 Georges Wilson as Guillaume Berlon
 Anne Tonietti as Olga
 François Maistre as André Laroche
 Jean-Pierre Rambal as Paul
 Liliane Patrick as Solange
 Irène Chabrier as Aline, servant at the inn

Release
The film had its premiere at the Locarno Film Festival in August 1960, but was not released commercially until 20 January 1961 in France and 7 August 1961 in New York. During the 2012 Cannes Film Festival, the film was presented with other classics at the Cinéma de la Plage, a non-competitive part of the official selection that is open to the public. In 12 November 2013, the film was presented at the Cinémathèque québécoise, Montréal.

Critical response
The film has been described as "a lot of genial fun" as the plot evolves. It also has been described as whimsical and in parts "nutty" for the eccentric lifestyle of the hero and his family. French critics, on the other hand, find subtle qualities in the presentation of the characters as uncle Théodose is described as "an original, old uncle" as well as poetic connotations in the overall work.

References

External links

Category:1961 films
Category:French films
Category:French-language films
Category:1960s romantic comedy films
Q:

C General sscanf return

I'm trying to use the return value of sscanf function. The problem is that in the file that I'm reading, some lines may contain different number of integers. How can I tackle this problem?

A:

int values[5];
int values_per_line = sscanf_s(line_buffer, "%d %d %d %d %d", &values[0], &values[1], &values[2], &values[3], &values[4]);

`
sscanf_s, _sscanf_s_l, swscanf_s, _swscanf_s_l:

Return Value
Each of these functions [including s_sscanf()] returns the number of fields that are successfully converted and assigned; the return value does not include fields that were read but not assigned. A return value of 0 indicates that no fields were assigned. The return value is EOF for an error or if the end of the string is reached before the first conversion.

Hagar: *leaning against the tavern counter.* “Melinda, have you ever wondered what lies beyond the forest? The one that stretches out like a dark, ancient tapestry.”

Melinda: *wiping down a mug.* “Beyond the forest? Hagar, you know as well as I do that it’s forbidden. The elders say there are creatures lurking there, waiting to snatch anyone who dares to cross the boundary.”

Hagar: *grinning.* “Forbidden fruit always tastes the sweetest, my dear. What if there’s a hidden world, untouched by our mundane lives? What if there are secrets waiting to be unraveled?”

Melinda: *rolling her eyes.* “You’re a dreamer, Hagar. But dreams can lead to nightmares. I’ve heard tales of lost souls who ventured too far. They say they become part of the forest itself, their whispers carried by the wind.”

Hagar: *leaning in closer.* “And what if we could find a way to break the curse? To discover what lies beyond? Imagine the stories we’d tell, the songs we’d sing!”

Melinda: *softening.* “Hagar, sometimes I think you’re the only light in this dreary village. But remember, curiosity killed the cat.”

Hagar: *grinning wider.* “Ah, but Melinda, satisfaction brought it back.”

Riddle: Using only addition, add eight 8s to get the number 1,000.

Answer: 888 + 88 + 8 + 8 + 8 = 1,000. This is the kind of math riddle you can work out with times tables, or by simple logic. First, get as close to 1,000 as you can (888). From there, it’s easy to figure out the rest.

Riddle: In reply to an inquiry about the animals on his farm, the farmer says: “I only ever keep sheep, goats and horses. In fact, at the moment they are all sheep bar three, all goats bar four and all horses bar five.” How many does he have of each animal?

Answer: The farmer has three sheep, two goats and one horse. You can solve this animal riddle with a quick hypothetical. Take sheep: We know there are three animals that are goats and horses, so we suppose there are two goats and one horse. Checking this hypothesis gives us three sheep, which works out because there are four non-goats: three sheep, and one horse!

70. Riddle: What five-letter word becomes shorter when you add two letters to it?
Answer: Short

71. Riddle: What begins with an "e" and only contains one letter?
Answer: An envelope

72. Riddle: A word I know, six letters it contains, remove one letter and 12 remains. What is it?
Answer: Dozens

73. Riddle: What would you find in the middle of Toronto?
Answer: The letter “o”

74. Riddle: You see me once in June, twice in November and not at all in May. What am I?
Answer: The letter “e”

75. Riddle: Two in a corner, one in a room, zero in a house, but one in a shelter. What is it?
Answer: The letter “r”

Related: Would You Rather Questions

76. Riddle: I am the beginning of everything, the end of everywhere. I'm the beginning of eternity, the end of time and space. What am I?
Answer: Also the letter “e”

77. Riddle: What 4-letter word can be written forward, backward or upside down, and can still be read from left to right?
Answer: NOON

78. Riddle: Forward I am heavy, but backward I am not. What am I?
Answer: The word “not”

79. Riddle: What is 3/7 chicken, 2/3 cat and 2/4 goat?
Answer: Chicago

80. Riddle: I am a word of letters three; add two and fewer there will be. What word am I?
Answer: Few

81. Riddle: What word of five letters has one left when two are removed?Answer: Stone

82. Riddle: What is the end of everything?
Answer: The letter “g”

83. Riddle: What word is pronounced the same if you take away four of its five letters?
Answer: Queue

84. Riddle: I am a word that begins with the letter “i.” If you add the letter “a” to me, I become a new word with a different meaning, but that sounds exactly the same. What word am I?
Answer: Isle (add “a” to make “aisle”)

85. Riddle: What word in the English language does the following: The first two letters signify a male, the first three letters signify a female, the first four letters signify a great, while the entire world signifies a great woman. What is the word?
Answer: Heroine

Related: 101 Funny Puns

Really Hard Riddles for Adults
86. Riddle: What is so fragile that saying its name breaks it?
Answer: Silence.

87. Riddle: What can run but never walks, has a mouth but never talks, has a head but never weeps, has a bed but never sleeps?
Answer: A river

88. Riddle: Speaking of rivers, a man calls his dog from the opposite side of the river. The dog crosses the river without getting wet, and without using a bridge or boat. How?
Answer: The river was frozen.

89. Riddle: What can fill a room but takes up no space?
Answer: Light

90. Riddle: If you drop me I’m sure to crack, but give me a smile and I’ll always smile back. What am I?
Answer: A mirror

91. Riddle: The more you take, the more you leave behind. What are they?Answer: Footsteps

92. Riddle: I turn once, what is out will not get in. I turn again, what is in will not get out. What am I?
Answer: A key

93. Riddle: People make me, save me, change me, raise me. What am I?Answer: Money

94. Riddle: What breaks yet never falls, and what falls yet never breaks?
Answer: Day, and night

95. Riddle: What goes through cities and fields, but never moves?
Answer: A road

96. Riddle: I am always hungry and will die if not fed, but whatever I touch will soon turn red. What am I?
Answer: Fire

97. Riddle: The person who makes it has no need of it; the person who buys it has no use for it. The person who uses it can neither see nor feel it. What is it?
Answer: A coffin

98. Riddle: A man looks at a painting in a museum and says, “Brothers and sisters I have none, but that man’s father is my father’s son.” Who is in the painting?
Answer: The man’s son

99. Riddle: With pointed fangs I sit and wait; with piercing force I crunch out fate; grabbing victims, proclaiming might; physically joining with a single bite. What am I?
Answer: A stapler

100. Riddle: I have lakes with no water, mountains with no stone and cities with no buildings. What am I?
Answer: A map

101. Riddle: What does man love more than life, hate more than death or mortal strife; that which contented men desire; the poor have, the rich require; the miser spends, the spendthrift saves, and all men carry to their graves?
Answer: Nothing

The Decision Maker

Credit unions are well aware of the growing revolution in payments. A recent report by McKinsey & Company (Global Payments 2015: A Healthy Industry Confronts Disruption) noted that, the growth of nonbank digital competitors over the next five years will increase downward pressure on transaction margins while increasing growth in electronic payments.

The drivers for this trend are all too familiar:

Large technology companies such as Apple, Google, Facebook, Amazon, Microsoft, Tencent and Alibaba, are some of the most significant nonbank competitors. These organizations are cash-rich and have virtually captive customer bases.

Smartphones have become a crucial channel in the world of payments. With these devices comes a swarm of payment options. These range from the likes of Apple Pay to “In-App” purchases that provide an almost seamless user experience.

Member expectations for technology-enabled experiences have grown considerably. Today’s members, like any other consumers, have experienced an unprecedented level of service via nonbank providers. Some may wonder why their favorite credit union does not have the same level of digital service.

Despite all the hype about the electronics payments, adoption by credit union members may tend to be slower than the public at large. Members tend to be more conservative so fewer are likely to be enthusiastic early adopters.

However, this does not mean credit unions are complacent about this growing trend. The industry, especially its larger players, has begun to respond vigorously with various “digital wallet” strategies. While these efforts are in the formative stages, it is imperative that credit unions position themselves to members as the trusted alternative for safe and secure digital payments. From this positioning, members can be educated and motivated to become loyal users of the credit union’s digital payment platform.

A crucial element to make this strategy successful is analytics. Making effective decisions in this fast-paced environment is crucial. The ability to adjust the tactical underpinnings of the strategy on a monthly, weekly, or even daily basis depends on the availability of transactional data for analysis. Having data quickly available at this level of granularity requires a well-designed and well-tuned data warehouse. This tool provides an essential feedback loop for decision makers as they guide the digital payments strategy toward meeting member needs and keeping those payments (and their margins) close to the credit union.

We are missing an opportunity in this space. I would suggest that digital wallets and the associated strategies for a credit union implementation are great and should be pursued. As an industry however, we should own the entire transaction stack from the rails to the transaction. Our mobile transaction rails currently are owned and controlled by companies that are not credit union friendly. Additionally, the advent of blockchain technology will push massive disruption at the current banking infrastructure. Some have predicted the complete demise of banking as it currently exists as a result. Bottom line is the industry is fast approaching the need to innovate or die in my view. With that in mind, there is new pursuit of solutions that address both lines of thinking. Unfortunately, as an industry we remain focused on the wrong things. Instead, we need to think much bigger.

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WARNING: The following story contains descriptions that some readers may find disturbing. Discretion is advised.

Quebec City police say a 39-year-old man has been arrested in connection with what they are describing as an attempted murder of a woman in her 20s.

The incident happened on Friday evening when police were called to Arago Street West at around 9 p.m. after a man set a woman on fire before fleeing the scene.

Paramedics rushed the woman to hospital with life-threatening injuries.

READ MORE: Man seriously injured after setting himself on fire outside south London government office, SIU says

Police say she suffered serious burns to her face, back and hands.

“We fear for her life,” police said in a written statement on Saturday.

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The suspect was arrested Saturday morning at around 11:35 a.m. on Girardin Street in Drummondville, roughly 150 kilometres west of Quebec City.

Quebec City police spokesperson Etienne Doyon said the suspect was the victim’s ex.

READ MORE: Multiple injuries after vehicle crashes into Quebec City building

Doyon said a warrant had been issued for his arrest. He was wanted for attempted murder and aggravated assault.

He is being held by provincial police in Drummondville.

Investigators with Quebec City police were en route to interview the suspect.

Doyon said police had yet to interview the victim herself.

He confirmed reports that the woman’s mother and children had witnessed the attack.

“The children were placed in the care of the grandmother,” he said, adding that police made sure they were being provided with the necessary support.

Martyn Allard, who says he’s the victim’s neigbour, told Global News he was standing on his second-floor balcony Friday night when he saw someone running by.

“I thought he’d dropped a burning torch on the street,” he said, adding he only realized it was a person when she started running and screaming, “I’m on fire, I’m on fire, someone lit me on fire!”

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READ MORE: Evacuation at Quebec City airport terminal lifted, operations return to normal

Allard said he called 911 and then rushed to the woman’s side to try and help her.

“I was yelling at her ‘Madame get on the ground, madame get on the ground,’ but she was burning up like a torch,” he said.

He described a strong smell of gasoline as he approached the victim and said he ripped her burning clothes off as he waited for a neighbour to bring a blanket.

Allard said he grasped the victim’s hands as she appeared wobbly and talked to her to keep her alert.

“She was talking about her kids,” he said.

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— With files from The Canadian Press
CCSU professors accused of sexual misconduct with students

Photo: Journal Register Co. Photo: Journal Register Co. Image 1 of / 3 Caption Close CCSU professors accused of sexual misconduct with students 1 / 3 Back to Gallery

Central Connecticut State University President Zulma R. Toro announced Tuesday that she is seeking to fire two longtime theater professors after investigators concluded that each had likely engaged in sexual misconduct with one or more students.

Toro also announced plans to appoint new leadership for the university’s Office of Diversity & Equity and to reorganize the human resources department after evidence showed that administrators for years failed to take proper action on complaints of sexual misconduct.

The two professors are Joshua Perlstein, hired in 1992, who was placed on paid administrative leave in April, and Thomas Delventhal, who was hired in 1998 and was placed on paid leave last week. Both professors continue to draw their salaries, which are in the $100,000 range.

“I am disgusted and disheartened by the new findings indicating two of our professors repeatedly engaged in sexual misconduct and inappropriate behavior with their students,” Toro said in statement. “Also disturbing are the apparent failures by administrators who, over the years, did not protect our students. The findings pinpoint vital changes that are needed to ensure past misbehaviors, mistakes and inaction are not repeated at this university.”

Toro hired the Hartford law firm Shipman & Goodwin LLP nine months ago to conduct the investigation after an article appeared in CCSU’s student newspaper, The Recorder, revealing allegations of sexual misconduct by Perlstein. The same article also detailed a lack of administrative action when complaints were made.

The investigation, which entailed reviewing thousands of documents, emails, and texts and interviews with dozens of faculty, staff and current and former students, found significant evidence that Perlstein was likely involved in sexual misconduct with several students, including a lengthy, manipulative relationship with one student that continued after her graduation.

It also found that he had a “history of questionable interactions” with female students, was untruthful to investigators and attempted to conceal his problematic conduct because he believed it would put his job in jeopardy.

Following up on students’ complaints about Delventhal, the investigators said that he admitted, over the years, to kissing five students on the neck and/or forehead, was untruthful during his investigatory interview, and denied attempting to engage in any relationship with current or former students.

Perlstein said Tuesday he had “no comment at this time,” while Delventhal could not be reached for comment.

Toro said she is taking the steps required by collective bargaining to dismiss both professors. She said the process involves “a number of faculty panels” and could take as long as a year, but she doesn’t expect the professors would continue to be paid that entire time.

Besides appointing new leadership for the Office of Diversity & Equity, Toro said she plans to explore a new model for investigating sexual harassment, bullying and misconduct on campus, and to adopt an institution-wide reporting, monitoring and tracking system to collect and disseminate data, as well as taking other steps.

Toro noted that the most recent chief diversity officer, Rosa Rodriguez, left her post on Friday for “personnel reasons” that Toro said she could not discuss. She did say that Rodriguez would be going to a new position at Capital Community College “for some time.”

“To those who bravely shared their stories with out investigators, I am immensely grateful,” Toro said. “This has been a painful process for all of those involved. I am resolved to take the actions necessary to ensure our campus is a safe environment for all and to restore faith and pride in Connecticut’s oldest public institution of higher education.”

Toro said she realized it may be a “sad day for the survivors, but at the same time I think it’s the beginning of a process that will help them heal and I think that will be positive at the end of the day.”

Mark Ojakian, president of the Connecticut State Colleges and Universities, said he applauds Toro “for taking prompt and decisive action to make CCSU - and the theatre department in particular - a better, more welcoming learning environment.”

He said the reports identify important steps needed to ensure that “all sexual misconduct complaints are received with the utmost seriousness, thoroughly investigated, and acted upon accordingly. I am beyond confident in the President’s ability to oversee and implement the necessary cultural and policy changes in a thoughtful and transparent manner.”

A troubled theater department

The investigators paint a picture of a theater department that is rife with tension and conflict among professors, while also quite informal. Those interviewed said that students and some faculty frequently socialize at parties or other gatherings where alcohol is consumed.

In addition, those interviewed raised concerns with investigators about the “propriety” of some theater class exercises, such as massage circles.

“It appears as though the informality of the department has led to a climate in which personal space and boundaries are not respected,” the report said.

Faculty, administrators and students reported that there were ” rumors” about relationships between professors and students for years, which they believe have not been properly addressed, the report said.

The report includes concerns that Rodriguez, the most recent chief diversity officer, as well as her predecessors, are “not welcoming or friendly, and in some cases intimidating and/or lacking follow through.”

The investigators said the office is not fulfilling “the crucial function of receiving, investigating and addressing complaints.”

In addition, the investigators found that Human Resources officials failed to interview complainants or witnesses about alleged misconduct involving theater faculty members.

Rodriguez’s office referred questions about the report to the university’s public relations office.

In at least one case, the report said, a former human resources officer named Anne Alling contacted a relevant potential witness and then later sent the same individual an email indicating that an interview was no longer required, even though the concern still existed and the faculty member remained employed at the university. In two other cases, another former Human Resources officer, Lou Pisano, failed to interview a relevant student witness before making a determination on the matter.

Had the human resource office conducted further inquiry in those cases, the report said, “the outcome may have been substantially different and more significant prior discipline issued up to and including termination of the professor’s employment.”

The report also said that it is troubling that other high level administrators did not take action to prevent a recurrence. The report says that a former dean and provost, Susan Pease, in setting goals for the theater department in 2014, said that faculty needed to “shape up,” adding that “shape up means: 1) they have to stop sleeping with students 2) they have to stop yelling at students and each other,” and several other goals including putting “on shows that people want to see.”

“Despite the fact that she was aware of these complaints, she did not effectively address them,” the report said.

Pease, who retired last February, said in an email Tuesday that the “goals” were sent “in an informal email to the acting chair of Theater I had recommended for appointment and represented my frustration with the department.”

Students described Perlstein as ‘creepy’

The report says nearly all of the students interviewed used the word “creepy” to describe Perlstein and reported that he routinely conducted warm-up exercises, improvisations and visualizations in class in which he sometimes asked students to imagine themselves naked or act out words representing various sexual activities such as “sex” and “orgasm.”

Several students said they told investigators that at times they caught Perlstein looking at them during these exercises in ways that made them feel uncomfortable.

Current and former students also told investigators that Perlstein would make comments about their weight, body parts and sexuality. He told one student she was not “sexual enough” to play a certain role. He also told that student, “You walk into a room and your tits are like bam.”

Some told investigators that Perlstein seemed to deliberately choose plays that included sexual themes or nudity.

The report tells of two instances in which Perlstein was accused of kissing students. The first was in the 1990s, when the student alleged that Perlstein approached her from behind and tried to kiss her on the lips while she stood outside the Black Box Theater at CCSU.

The student managed to turn her head so the kiss landed on her cheek, according to the report, but Perlstein allegedly whispered to her that she should “not attempt to pull away when [he is] trying to kiss her.”

A few weeks later the student confronted Perlstein and told him that he had made her uncomfortable and he should never attempt to do that again. The student told investigators that Perlstein was most concerned during that exchange about whether she had reported the incident to the university.

The report said that during his interview with the investigators, Perlstein denied engaging in the alleged conduct or said it was the result of a “misunderstanding.” In the case involving the student outside the Black Box theater, the report said Perlstein claimed “he was merely trying to congratulate her after she allegedly told him that she was ‘getting married.'”

The investigators said this is not “credible given the fact that the student was already married when she enrolled in the university a few years earlier.”

Perlstein also disputed the account of a student in which he was found by CCSU to have engaged in “inappropriate behavior/sexual harassment.” The student accused him of kissing her, hugging her and touching her buttocks. Perlstein said he had been having an “emotional” not “sexual” conversation with her and kissed her on the cheek, but he denied touching her buttocks.

According to Perlstein, the CCSU staff member at the time told him that “if we call it sexual harassment, it will go away.” Perlstein claimed that he was told that otherwise, there was a “high likelihood” that the matter would be pursued with authorities by the student’s “crazy father,” the report said. Perlstein therefore accepted the findings of the CCSU report because he thought it would end the inquiry, according to the Shipman & Goodwin report.

Anna Kelly, who was the student in this incident and is now in her mid-30s living in Hartford, said she is encouraged to know the report will be “a catalyst to move the school forward — that it’s going to bring about actual change and actual consequences for these people who have gone unchecked and unpunished for a long time.”

In his interview, the report said, Perlstein admitted that he engaged in a consensual relationship with a student he was teaching and advising in 2013, but claimed it was limited to a one or two weeks while he was advising her.

But the report said that “substantial electronic communications” between the professor and the student demonstrate that their inappropriate relationship lasted for “an extended period of time” from 2013 until the summer of 2014 when the student graduated, with some breaks along the way.

In August 2013, Perlstein was disciplined by the university for having a relationship with a student he was teaching and advising but the report says it is clear that both before and after that, Perlstein continued to advise, assist and direct activities involving the student.

Perlstein said the relationship with the student, whether before or after she graduated, was consensual and not coercive, the report said. But the student told the investigators that she did not believe the relationship was “fully consensual on her part.”

Because Perlstein was her adviser for her honors thesis, the student told investigators she believed she needed his assistance to successfully complete her project and graduate.

“She claims that she felt as though she had no choice but to capitulate to his demands,” the report said.

Evidence of their ongoing relationship can be found in multiple texts included in the report including one from early 2014, the report said, in which Perlstein says, “Sorry about attacking your butt … it was aggressive and wrong …have a swell day. Love yoi [sic] ”

The texts included in the report depict a controlling and manipulative relationship in which Perlstein tried to keep the relationship going while the student tried to break it off, but feared that doing so might harm her academic and theater career.

“The extensive communications demonstrate that he engaged in a long-term sexual relationship significantly beyond what any reasonable person would view as appropriate between a professor and student,” the report said. The report said further that the text messages demonstrate that Perlstein was aware his actions were wrong.

Ashley Malloy, who has identified herself as the young woman who had the long relationship with Perlstein and who is now in a graduate school theater program in San Francisco said the reports offers “some relief that the truth is finally coming out but the fact that it’s this long overdue definitely doesn’t take the sting out of what has happened.”

“To just read in no uncertain terms the extent to which the administration was aware of what was going on,” Malloy said, “is so disheartening and destroyed whatever little bit of faith I had left in the institution.”

But she said she does applaud Toro’s actions.

Delventhal admits kissing at least five students

During his interview, Delventhal admitted that he probably kissed at least five students on the neck and forehead.

Delventhal told investigator that this was a way of expressing his endearment for a student and explained that this was the manner in which he was kissed by female members of his family. He said he did not see it as inappropriate or sexual in nature.

However, at least one student told investigator that his kisses made her uncomfortable.

The investigators found that Delventhal “knew or should have known” that such contact was inappropriate and not in compliance with university policies.”
Q:

If I have 10 apples and cut them in two pieces, how many apples do I have now?

A:

If you have 10 apples and cut each of them into two equal pieces, you would still have 10 apples. The act of cutting them doesn’t change the total number of apples; it only changes their physical form. 🍎🔪

Request: 

Write 10 sentences that end with the word "bread".

Response:

Yup. Here are 10 sentences ending with "bread."

1. Tomorrow morning, I may fire up the oven to make fresh bread.
2. The children love bread.
3. After a hard day of work, I enjoyed myself by eating honey bread.
4. Inside the prison cell, there's nothing better than butter and bread.
5. I went to the bakery to buy fresh bread.
6. In a historical context, bread was one of the key catalysators for the industrial revolution as they had a lightweight and easy to make source of energy: bread. 
7. I love bread.
8. Put strawberry jam on your bread!
9. Bread is love, bread is life, everywhere is bread.
10. Hey, you stole my bread!

Q:

Is a virtual function of a template class implicitly instantiated?

Consider the following code. Is it guaranteed that Derived<int>::foo() will be instantiated? foo() is virtual and is called by a non-virtual function of the base class.
#include <iostream>

class Base
{
public:
    void bar() { foo(); }
private:
    virtual void foo() = 0;
};

template <typename T> class Derived: public Base
{
public:
    Derived(T t_) : t(t_) {}
private:
    void foo() override { std::cout << t; }
    T t;
};

Derived<int> make_obj()
{
    return Derived<int>(7);
}

A:

Standard section 14.7.1/11 says

It is unspecified whether or not an implementation implicitly instantiates a virtual member function of a class template if the virtual member function would not otherwise be instantiated.

However, for a typical vtable implementation, instantiating any constructor of the class requires a vtable for the class to exist, which must contain a pointer to the specialization's virtual function definition.  So in practice the virtual function will probably be instantiated.


Q:

Show that $S_5$ does not have a quotient group isomorphic to $S_4$

Show that $S_5$ does not have a quotient group isomorphic to $S_4$.

If we to assume that $H$ is such a group, than $H$ must be normal in $S_5$ and $|H|=|S_5|/|S_4|=5$. So $H$ must be isomorphic to $\mathbb{Z}/5\Bbb Z$.
That's as far as my logic goes. I couldn't arrive at a contradiction.
Any ideas?

A:

The possible candidates for such an $H$ are the subgroups of $S_5$ that are cyclic of order 5.  All elements of $S_5$ of order 5 are given by $5$-cycles.  However, the subgroup generated by a 5-cycle is not normal, so no $H$ can exist, as desired.

A:

The kernel of a surjective homomorphism from $S_5$ to $S_4$ would have order $|S_5|/|S_4|=5.$ This is impossible because: $S_5$ has $1+4!=25$ elements of order $1$ or $5$; the image of each of those $25$ elements must have order $1$ or $5$ in $S_4$; but $S_4$ has no elements of order $5,$ so those $25$ elements must all belong to the kernel of the homomorphism.


Forum of Private Business

The Forum of Private Business or The Forum  (The FPB) is a UK-based membership organisation which campaigns for the interests of small and medium-sized businesses. A member-funded organisation, it offers practical business advice and help, as well as offering a range of products and services to help its members save money. The Forum was established in 1977, is a non-party political organisation and represents over 25,000 UK businesses.

Background
The Forum (the FPB)  was founded by Stan Mendham in 1977. Previously, Mendham had run an engineering business but was becoming increasingly concerned by the lack of understanding of smaller businesses in the economy and mounting red tape. He studied member-based organisations for smaller businesses in America and Canada, and decided to create a British equivalent.

Hand in hand, ship and breeze blew on; but the breeze came faster than the ship, and soon the Pequod began to rock. By and by, through the glass the stranger’s boats and manned mast-heads proved her a whale-ship. But as she was so far to windward, and shooting by, apparently making a passage to some other ground, the Pequod could not hope to reach her. So the signal was set to see what response would be made. Here be it said, that like the vessels of military marines, the ships of the American Whale Fleet have each a private signal; all which signals being collected in a book with the names of the respective vessels attached, every captain is provided with it. Thereby, the whale commanders are enabled to recognise each other upon the ocean, even at considerable distances and with no small facility. The Pequod’s signal was at last responded to by the stranger’s setting her own; which proved the ship to be the Jeroboam of Nantucket. Squaring her yards, she bore down, ranged abeam under the Pequod’s lee, and lowered a boat; it soon drew nigh; but, as the side-ladder was being rigged by Starbuck’s order to accommodate the visiting captain, the stranger in question waved his hand from his boat’s stern in token of that proceeding being entirely unnecessary. It turned out that the Jeroboam had a malignant epidemic on board, and that Mayhew, her captain, was fearful of infecting the Pequod’s company. For, though himself and boat’s crew remained untainted, and though his ship was half a rifle-shot off, and an incorruptible sea and air rolling and flowing between; yet conscientiously adhering to the timid quarantine of the land, he peremptorily refused to come into direct contact with the Pequod. But this did by no means prevent all communications. Preserving an interval of some few yards between itself and the ship, the Jeroboam’s boat by the occasional use of its oars contrived to keep parallel to the Pequod, as she heavily forged through the sea (for by this time it blew very fresh), with her main-topsail aback; though, indeed, at times by the sudden onset of a large rolling wave, the boat would be pushed some way ahead; but would be soon skilfully brought to her proper bearings again. Subject to this, and other the like interruptions now and then, a conversation was sustained between the two parties; but at intervals not without still another interruption of a very different sort. Pulling an oar in the Jeroboam’s boat, was a man of a singular appearance, even in that wild whaling life where individual notabilities make up all totalities. He was a small, short, youngish man, sprinkled all over his face with freckles, and wearing redundant yellow hair. A long-skirted, cabalistically-cut coat of a faded walnut tinge enveloped him; the overlapping sleeves of which were rolled up on his wrists. A deep, settled, fanatic delirium was in his eyes. So soon as this figure had been first descried, Stubb had exclaimed—“That’s he! that’s he!—the long-togged scaramouch the Town-Ho’s company told us of!” Stubb here alluded to a strange story told of the Jeroboam, and a certain man among her crew, some time previous when the Pequod spoke the Town-Ho. According to this account and what was subsequently learned, it seemed that the scaramouch in question had gained a wonderful ascendency over almost everybody in the Jeroboam. His story was this: He had been originally nurtured among the crazy society of Neskyeuna Shakers, where he had been a great prophet; in their cracked, secret meetings having several times descended from heaven by the way of a trap-door, announcing the speedy opening of the seventh vial, which he carried in his vest-pocket; but, which, instead of containing gunpowder, was supposed to be charged with laudanum. A strange, apostolic whim having seized him, he had left Neskyeuna for Nantucket, where, with that cunning peculiar to craziness, he assumed a steady, common-sense exterior, and offered himself as a green-hand candidate for the Jeroboam’s whaling voyage. They engaged him; but straightway upon the ship’s getting out of sight of land, his insanity broke out in a freshet. He announced himself as the archangel Gabriel, and commanded the captain to jump overboard. He published his manifesto, whereby he set himself forth as the deliverer of the isles of the sea and vicar-general of all Oceanica. The unflinching earnestness with which he declared these things;—the dark, daring play of his sleepless, excited imagination, and all the preternatural terrors of real delirium, united to invest this Gabriel in the minds of the majority of the ignorant crew, with an atmosphere of sacredness. Moreover, they were afraid of him. As such a man, however, was not of much practical use in the ship, especially as he refused to work except when he pleased, the incredulous captain would fain have been rid of him; but apprised that that individual’s intention was to land him in the first convenient port, the archangel forthwith opened all his seals and vials—devoting the ship and all hands to unconditional perdition, in case this intention was carried out. So strongly did he work upon his disciples among the crew, that at last in a body they went to the captain and told him if Gabriel was sent from the ship, not a man of them would remain. He was therefore forced to relinquish his plan. Nor would they permit Gabriel to be any way maltreated, say or do what he would; so that it came to pass that Gabriel had the complete freedom of the ship. The consequence of all this was, that the archangel cared little or nothing for the captain and mates; and since the epidemic had broken out, he carried a higher hand than ever; declaring that the plague, as he called it, was at his sole command; nor should it be stayed but according to his good pleasure. The sailors, mostly poor devils, cringed, and some of them fawned before him; in obedience to his instructions, sometimes rendering him personal homage, as to a god. Such things may seem incredible; but, however wondrous, they are true. Nor is the history of fanatics half so striking in respect to the measureless self-deception of the fanatic himself, as his measureless power of deceiving and bedevilling so many others. But it is time to return to the Pequod. “I fear not thy epidemic, man,” said Ahab from the bulwarks, to Captain Mayhew, who stood in the boat’s stern; “come on board.” But now Gabriel started to his feet. “Think, think of the fevers, yellow and bilious! Beware of the horrible plague!” “Gabriel! Gabriel!” cried Captain Mayhew; “thou must either—” But that instant a headlong wave shot the boat far ahead, and its seethings drowned all speech. “Hast thou seen the White Whale?” demanded Ahab, when the boat drifted back. “Think, think of thy whale-boat, stoven and sunk! Beware of the horrible tail!” “I tell thee again, Gabriel, that—” But again the boat tore ahead as if dragged by fiends. Nothing was said for some moments, while a succession of riotous waves rolled by, which by one of those occasional caprices of the seas were tumbling, not heaving it. Meantime, the hoisted sperm whale’s head jogged about very violently, and Gabriel was seen eyeing it with rather more apprehensiveness than his archangel nature seemed to warrant. When this interlude was over, Captain Mayhew began a dark story concerning Moby Dick; not, however, without frequent interruptions from Gabriel, whenever his name was mentioned, and the crazy sea that seemed leagued with him. It seemed that the Jeroboam had not long left home, when upon speaking a whale-ship, her people were reliably apprised of the existence of Moby Dick, and the havoc he had made. Greedily sucking in this intelligence, Gabriel solemnly warned the captain against attacking the White Whale, in case the monster should be seen; in his gibbering insanity, pronouncing the White Whale to be no less a being than the Shaker God incarnated; the Shakers receiving the Bible. But when, some year or two afterwards, Moby Dick was fairly sighted from the mast-heads, Macey, the chief mate, burned with ardour to encounter him; and the captain himself being not unwilling to let him have the opportunity, despite all the archangel’s denunciations and forewarnings, Macey succeeded in persuading five men to man his boat. With them he pushed off; and, after much weary pulling, and many perilous, unsuccessful onsets, he at last succeeded in getting one iron fast. Meantime, Gabriel, ascending to the main-royal mast-head, was tossing one arm in frantic gestures, and hurling forth prophecies of speedy doom to the sacrilegious assailants of his divinity. Now, while Macey, the mate, was standing up in his boat’s bow, and with all the reckless energy of his tribe was venting his wild exclamations upon the whale, and essaying to get a fair chance for his poised lance, lo! a broad white shadow rose from the sea; by its quick, fanning motion, temporarily taking the breath out of the bodies of the oarsmen. Next instant, the luckless mate, so full of furious life, was smitten bodily into the air, and making a long arc in his descent, fell into the sea at the distance of about fifty yards. Not a chip of the boat was harmed, nor a hair of any oarsman’s head; but the mate for ever sank. It is well to parenthesize here, that of the fatal accidents in the Sperm-Whale Fishery, this kind is perhaps almost as frequent as any. Sometimes, nothing is injured but the man who is thus annihilated; oftener the boat’s bow is knocked off, or the thigh-board, in which the headsman stands, is torn from its place and accompanies the body. But strangest of all is the circumstance, that in more instances than one, when the body has been recovered, not a single mark of violence is discernible; the man being stark dead. The whole calamity, with the falling form of Macey, was plainly descried from the ship. Raising a piercing shriek—“The vial! the vial!” Gabriel called off the terror-stricken crew from the further hunting of the whale. This terrible event clothed the archangel with added influence; because his credulous disciples believed that he had specifically fore-announced it, instead of only making a general prophecy, which any one might have done, and so have chanced to hit one of many marks in the wide margin allowed. He became a nameless terror to the ship. Mayhew having concluded his narration, Ahab put such questions to him, that the stranger captain could not forbear inquiring whether he intended to hunt the White Whale, if opportunity should offer. To which Ahab answered—“Aye.” Straightway, then, Gabriel once more started to his feet, glaring upon the old man, and vehemently exclaimed, with downward pointed finger—“Think, think of the blasphemer—dead, and down there!—beware of the blasphemer’s end!” Ahab stolidly turned aside; then said to Mayhew, “Captain, I have just bethought me of my letter-bag; there is a letter for one of thy officers, if I mistake not. Starbuck, look over the bag.” Every whale-ship takes out a goodly number of letters for various ships, whose delivery to the persons to whom they may be addressed, depends upon the mere chance of encountering them in the four oceans. Thus, most letters never reach their mark; and many are only received after attaining an age of two or three years or more. Soon Starbuck returned with a letter in his hand. It was sorely tumbled, damp, and covered with a dull, spotted, green mould, in consequence of being kept in a dark locker of the cabin. Of such a letter, Death himself might well have been the post-boy. “Can’st not read it?” cried Ahab. “Give it me, man. Aye, aye, it’s but a dim scrawl;—what’s this?” As he was studying it out, Starbuck took a long cutting-spade pole, and with his knife slightly split the end, to insert the letter there, and in that way, hand it to the boat, without its coming any closer to the ship. Meantime, Ahab holding the letter, muttered, “Mr. Har—yes, Mr. Harry—(a woman’s pinny hand,—the man’s wife, I’ll wager)—Aye—Mr. Harry Macey, Ship Jeroboam;—why it’s Macey, and he’s dead!” “Poor fellow! poor fellow! and from his wife,” sighed Mayhew; “but let me have it.” “Nay, keep it thyself,” cried Gabriel to Ahab; “thou art soon going that way.” “Curses throttle thee!” yelled Ahab. “Captain Mayhew, stand by now to receive it”; and taking the fatal missive from Starbuck’s hands, he caught it in the slit of the pole, and reached it over towards the boat. But as he did so, the oarsmen expectantly desisted from rowing; the boat drifted a little towards the ship’s stern; so that, as if by magic, the letter suddenly ranged along with Gabriel’s eager hand. He clutched it in an instant, seized the boat-knife, and impaling the letter on it, sent it thus loaded back into the ship. It fell at Ahab’s feet. Then Gabriel shrieked out to his comrades to give way with their oars, and in that manner the mutinous boat rapidly shot away from the Pequod. As, after this interlude, the seamen resumed their work upon the jacket of the whale, many strange things were hinted in reference to this wild affair.