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“The port was used by infrastructure development company IL&FS to bring coal for its thermal power project near the port and by Tamil Nadu Electricity Board. However, there is hardly any traffic at present, leading to a cashflow problem,” a banker said.
In a regulatory filing, it said that traffic achieved in FY14 stood at 6.23 MT of multi cargo with 205 major cargo vessels as compared to 6.61 MT with 237 vessels handled in FY13, a drop of 5.75%. Karaikal Port Private Ltd (KPPL) is a subsidiary of Marg Ltd, a infrastructure and real estate developer along the Chennai IT corridor with interest ranging across various areas that include residential projects, commercial real estate projects, SEZs, ports, townships, IT parks and malls.
According to bankers, the rest of the debt is yet to be auctioned. “While Indian Bank has the maximum exposure of around Rs 405 crore, the bank is yet to sell it,” a source added. Banks like Oriental Bank of Commerce (OBC), Allahabad Bank, Punjab National Bank, United Bank of India and State Bank of Hyderabad have lend to Karaikal Port. Some private equity firms, including Standard Chartered Private Equity and Ascent Capital, have also invested in the company.
The company’s term loans of Rs 1,268 crore were restructured in FY13 with a two-year moratorium ending December 31, 2014 along with an additional funding of Rs 80 crore. In FY14 it reported a net loss of Rs 69 crore on the back of Rs 263 crore in revenues. The company’s debt stood at Rs 1,650 crore in FY14 (latest document available), from Rs 1,619 crore in the previous year.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
create message bubble and path on Google static maps
I am trying to create a static map url using google maps api which looks similar to following
It seems like I require to increase the zoom levels and add a path parameter to the url. I have tried to create url like following
http://maps.googleapis.com/maps/api/staticmap?scale=4&format=png32¢er=50.133751,4.833644&zoom=16&size=640x640&markers=color:red%7C50.133751,4.833644&sensor=false&path=color:blue|48.133751,4.833644|50.133751,4.833644&style=feature:road.local
But it is not giving required results, I need to create dynamic urls based on the addresses and lat/lng values provided. I somehow requires to rotate map in such a way so that it always have a vertical road in the middle so that I can draw a path over it. Additionally, I need a bubble which will show a fixed time to reach say 5/1 min.
I am not using any programming language as of now. I am trying to create these urls manually.
Thanks in advance.
EDIT : I don't need to rotate it now. Just wants to show a 1-5 min directions to the given latitude/longtitude/address value and for message bubble, I have created a static image which I can show as an overlay.
A:
Based on your specific needs to show a path and a time from 1 to 5 minutes I would recommend the following:
First of all you need to know that you have two possibilites concerning the label
Use the standard marker and add a label with a length of 1 and [A-Z], [0-9] (so just the time in your case...one to five)
Use a custom icon which already includes the label (in your case this is a option because you just have to create five images containing "2 min" or something)
For the first option I would take the center of two connected points and add a white marker with the label of the route duration like markers=color:white|label:1|52,5210924,13,39181335. Then you will have a white standard marker on your route like this.
For the second option you can change the marker position away from the path (depending on how your label image looks like) and add the image with the correct duration (1.png, 2.png, 3.png,...) like markers=icon:https//your.path/to/image.png|52,5210924,13,39228335. Like this you can include your own image, which would look like this (sorry for the bad image ;-)).
Adding a custom marker icon with a label (in the URL) is sadly not possible.
I think in your case (also when creating it manually) it would be fine to create 5 bubble images and add those as described to your static map. The faster and easier (but not so good looking) way would be the first option, because you could place it right on the path and don't have to create the bubble images.
|
{
"pile_set_name": "StackExchange"
}
|
/*
This software is provided 'as-is', without any express or implied warranty.
In no event will the authors be held liable for any damages arising from the use of this software.
Permission is granted to anyone to use this software for any purpose,
including commercial applications, and to alter it and redistribute it freely,
subject to the following restrictions:
1. The origin of this software must not be misrepresented; you must not claim that you wrote the original software. If you use this software in a product, an acknowledgment in the product documentation would be appreciated but is not required.
2. Altered source versions must be plainly marked as such, and must not be misrepresented as being the original software.
3. This notice may not be removed or altered from any source distribution.
*/
//Initial Author Jackson Lee, 2014
#include "b3GpuParallelLinearBvhBroadphase.h"
b3GpuParallelLinearBvhBroadphase::b3GpuParallelLinearBvhBroadphase(cl_context context, cl_device_id device, cl_command_queue queue) : m_plbvh(context, device, queue),
m_overlappingPairsGpu(context, queue),
m_aabbsGpu(context, queue),
m_smallAabbsMappingGpu(context, queue),
m_largeAabbsMappingGpu(context, queue)
{
}
void b3GpuParallelLinearBvhBroadphase::createProxy(const b3Vector3& aabbMin, const b3Vector3& aabbMax, int userPtr, int collisionFilterGroup, int collisionFilterMask)
{
int newAabbIndex = m_aabbsCpu.size();
b3SapAabb aabb;
aabb.m_minVec = aabbMin;
aabb.m_maxVec = aabbMax;
aabb.m_minIndices[3] = userPtr;
aabb.m_signedMaxIndices[3] = newAabbIndex;
m_smallAabbsMappingCpu.push_back(newAabbIndex);
m_aabbsCpu.push_back(aabb);
}
void b3GpuParallelLinearBvhBroadphase::createLargeProxy(const b3Vector3& aabbMin, const b3Vector3& aabbMax, int userPtr, int collisionFilterGroup, int collisionFilterMask)
{
int newAabbIndex = m_aabbsCpu.size();
b3SapAabb aabb;
aabb.m_minVec = aabbMin;
aabb.m_maxVec = aabbMax;
aabb.m_minIndices[3] = userPtr;
aabb.m_signedMaxIndices[3] = newAabbIndex;
m_largeAabbsMappingCpu.push_back(newAabbIndex);
m_aabbsCpu.push_back(aabb);
}
void b3GpuParallelLinearBvhBroadphase::calculateOverlappingPairs(int maxPairs)
{
//Reconstruct BVH
m_plbvh.build(m_aabbsGpu, m_smallAabbsMappingGpu, m_largeAabbsMappingGpu);
//
m_overlappingPairsGpu.resize(maxPairs);
m_plbvh.calculateOverlappingPairs(m_overlappingPairsGpu);
}
void b3GpuParallelLinearBvhBroadphase::calculateOverlappingPairsHost(int maxPairs)
{
b3Assert(0); //CPU version not implemented
}
void b3GpuParallelLinearBvhBroadphase::writeAabbsToGpu()
{
m_aabbsGpu.copyFromHost(m_aabbsCpu);
m_smallAabbsMappingGpu.copyFromHost(m_smallAabbsMappingCpu);
m_largeAabbsMappingGpu.copyFromHost(m_largeAabbsMappingCpu);
}
|
{
"pile_set_name": "Github"
}
|
Optimizing surgical backup for multiple simultaneous percutaneous transluminal coronary angioplasty procedures.
At busy interventional centers, it may be difficult to coordinate surgical backup for multiple simultaneous PTCA procedures. We sought to determine the actual risk of two simultaneous cases requiring surgery, and to identify a group in which multiple simultaneous PTCA procedures could be performed at low risk. We prospectively applied the ACC/AHA A/B/C lesion classification system and an empiric low/medium/high risk classification (based on patients' overall clinical picture) to 1,128 PTCA procedures over a 9 month period; 22 of these patients (1.9%) went directly from the catheterization laboratory to emergency CABG. The incidence of emergency CABG by groups was A-low 1/166, A-medium 1/71, A-high 0/22, B-low 1/116, B-medium 10/481, B-high 2/52, C-low 2/47, C-medium 3/88, and C-high 2/85. The patients were divided into two groups: minimal risk (A + B-low: 3/375 or 0.8%) and increased risk (B-med/high + C: 19/753 or 2.5%). The difference between the groups was significant using chi square with an alpha < 0.05. The risk of two cases requiring surgery at the same time was calculated as a function of the number of simultaneous PTCA procedures performed. Six or fewer minimal risk PTCA, one increased risk plus up to three minimal risk, and a maximum of two increased risk cases were found to have a risk of < 0.001. We conclude that it is possible to identify a group of patients with minimal risk, in whom multiple simultaneous procedures can be performed with a negligible probability of two cases requiring surgery at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Never miss a big story in Plymouth again with our daily newsletters Sign me up! Thank you for subscribing See our privacy notice Invalid Email
The British Army could be drafted in to help run local councils and calculate taxes in the event of a crash-out Brexit, according to new analysis of Operation Yellowhammer.
Snippets of the hush-hush Whitehall dossier, outlining UK planning in the event of No Deal, have been leaked to the public by the national media in recent months.
Now fresh scrutiny of a 'hard Brexit' - which some consider the worst case scenario - reveals how councils would be forced to quickly change the way they work.
According to Private Eye, thousands of civil servants working for local authorities up and down the country would be deployed to Westminster to cope with a swell in administrative duties to prevent chaos at the Dover and Irish borders and speed up port checks.
The British Army - including territorial volunteers - would then in turn be deployed to run town halls and perform civil servant duties; including but not limited to the delivery of everyday public services and sorting through council tax payments.
(Image: Britsih Army/MoD)
One military chief, according to the current affairs news magazine, is concerned troops lack 'basic literacy and numeracy' skills to carry out such functions.
"Quite how they would get on in calculating council tax, or providing adult social care and children's services, remains to be seen," Private Eye observed.
The revelations come after Plymouth City Council Labour boss, Councillor Tudor Evans, warned of a brutal economic shock in the event of No Deal.
His concerns came amid a request from Whitehall for local authorities to step in and help businesses hit by an EU exit.
Cllr Evans said the council had no additional funds to help - and has already been hammered with massive austerity cuts.
And he warned how ministers had failed so far to dish out £20million to authorities to cover Brexit-related costs.
No Deal Brexit - Will it actually happen?
Video Loading Video Unavailable Click to play Tap to play The video will start in 8 Cancel Play now
No Deal Brexit - the scenario where the UK fails to agree trade deal terms with Europe - could actually be taken off the table together, despite PM Boris Johnson's pledge to push it through if it meant delivering upon the result of the 2016 EU Referendum.
That's because the House of Lords today passed a Bill to thwart No Deal - which this week got through the Commons. It now needs Royal Assent for it to be enshrined in law.
But whether the Government will ignore it or not is anyone's guess - although it may be forced to challenge through the courts to get Brexit over the line on October 31.
The Tories may also trigger a General Election - which could determine the eventual outcome.
Alternatively, the Government could accept the end of No Deal - and subsequently request a further delay to Brexit, subject to EU approval.
Regardless, if no official deal with the EU is agreed by October 19, then the Prime Minister will be legally obliged to ask the EU for another extension to Brexit.
Boris' way around that, if he refused to plead for an extension, would be to go to the polls.
|
{
"pile_set_name": "OpenWebText2"
}
|
The organisers of the Dick Smith NRL Nines rugby league tournament to be held at Eden Park next month say the event will go ahead as scheduled.
However, Martin Sneddon, the chief executive of Duco Events - who have run the tournament since its inception two years ago - say his company are still owed money by the Australasian electronics company.
Duco Events has a five-year naming rights contract with Dick Smith, which today went into receivership.
Sneddon said his company would contact the receivers regarding the money owed for this year, and whether Dick Smith would continue to sponsor the event.
Dick Smith paid a sum to Duco Events every year for the naming rights.
"It will have no impact whatsoever on our ability to put on a great tournament on Waitangi Day," Sneddon said.
"We'll contact the receivers but they've got bigger things to worry about than us at the moment. We've got plenty of time to wait for the dust to settle. What's happened is a real shame because Dick Smith have been a great partner and supporter of the NRL Nines."
Dick Smith's sponsorship, along with support from, among others, Auckland Council's events arm ATEED, allows the organisers to offer a winner's cheque of $A500,000 ($NZ577,000) from the total prize pool of $A2.25 million.
All of the NRL's 16 clubs are contractually obliged to attend the two-day tournament, which starts this year on Waitangi Day, February 6.
The event will be held in Auckland until at least 2018, with other cities, most notably Sydney, also keen to host it.
|
{
"pile_set_name": "OpenWebText2"
}
|
Javadiyan S, Lucas SEM, Wangmo D, et al. Identification of novel mutations causing pediatric cataract in Bhutan, Cambodia, and Sri Lanka. Mol Genet Genomic Med. 2018;6:555--564. 10.1002/mgg3.406
1. INTRODUCTION {#mgg3406-sec-0005}
===============
Pediatric cataract (including congenital cataract) is an opacity of the ocular lens that is present at birth (congenital) or develops during childhood. Prevalence estimates range from 0.33 to 22.7 per 10,000 (Sheeladevi, Lawrenson, Fielder, & Suttle, [2016](#mgg3406-bib-0016){ref-type="ref"}) live births in populations across the world. It was previously thought that prevalence was around 10 times greater in low‐income economies than high‐income countries (Foster, Gilbert, & Rahi, [1997](#mgg3406-bib-0004){ref-type="ref"}), but more recent reviews suggest that this is not the case with high prevalence reported in many higher income countries (Sheeladevi et al., [2016](#mgg3406-bib-0016){ref-type="ref"}). Nonetheless, cataract is an important cause of childhood blindness globally and is one of the preventable and treatable conditions targeted by Vision 2020 programs (Gilbert & Foster, [2001](#mgg3406-bib-0006){ref-type="ref"}).
Around 25% of pediatric cataract is inherited (Shiels & Hejtmancik, [2007](#mgg3406-bib-0018){ref-type="ref"}) and over 100 genes have been reported for isolated pediatric cataract, with hundreds more for syndromic cataract (Shiels, Bennett, & Hejtmancik, [2010](#mgg3406-bib-0017){ref-type="ref"}). Cataract‐causing genes include structural proteins of the crystalline lens as well as transport molecules, signaling proteins, and transcription factors. Analysis of panels of cataract‐causing genes in patients with inherited cataract detect mutations in 60%--70% of patients (Gillespie et al., [2014](#mgg3406-bib-0007){ref-type="ref"}; Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}; Ma et al., [2016](#mgg3406-bib-0013){ref-type="ref"}), but these studies have been undertaken in cohorts of patients predominantly of European descent. Mutations in these same genes have been reported in patients from all over the world; however, large‐scale gene screening has not yet been undertaken in patients with pediatric cataract from developing countries.
Recently, surveys to document causes of childhood blindness have been undertaken in Bhutan (Farmer et al., [2015](#mgg3406-bib-0003){ref-type="ref"}), Cambodia (Sia et al., [2010](#mgg3406-bib-0019){ref-type="ref"}), and Sri Lanka (Gao et al., [2011](#mgg3406-bib-0005){ref-type="ref"}). These studies identified many children in attendance at schools for the blind in these countries, with cataract as the underlying cause of their visual impairment. We investigated the genetic causes of cataract in children with suspected or known inherited cataract through screening of 51 genes known to cause this disease, using the same methodologies as applied to Australian pediatric cataract patients (Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}).
2. MATERIALS AND METHODS {#mgg3406-sec-0006}
========================
2.1. Ethical compliance {#mgg3406-sec-0007}
-----------------------
Consent for each participant was obtained from parent, guardian, or other authorized persons in the first language of the patient or parent. The study was approved in Australia by the Human Research Ethics Committees of the University of Adelaide and Flinders University in South Australia. In Bhutan, permission to visit schools was granted by the respective ministries of Health in Bhutan. Approval was also obtained from the Research Committees at the National Referral Hospital, Thimphu, Bhutan. In Cambodia, permission to visit schools was granted by the Ministry of Health, Cambodia and approval was obtained from the National Ethics Committee for Health Research in Cambodia. In Sri Lanka, permission to visit the schools was granted by each principal and ethics approval was obtained from the Faculty of Medicine, University Of Peradenya Ethical Review Committee. The study adhered to the tenets of the Declaration of Helsinki.
2.2. Participant selection {#mgg3406-sec-0008}
--------------------------
Children under 16 years of age attending blind schools in Bhutan (Farmer et al., [2015](#mgg3406-bib-0003){ref-type="ref"}), Cambodia (Sia et al., [2010](#mgg3406-bib-0019){ref-type="ref"}), and Sri Lanka (Gao et al., [2011](#mgg3406-bib-0005){ref-type="ref"}) underwent an ocular examination and review of records as part of audits of the causes of childhood blindness in each community as described previously (Farmer et al., [2015](#mgg3406-bib-0003){ref-type="ref"}; Gao et al., [2011](#mgg3406-bib-0005){ref-type="ref"}; Sia et al., [2010](#mgg3406-bib-0019){ref-type="ref"}). While all children were examined at the time of recruitment, it was not possible to access historical medical records to determine age of onset, or to interview the family for a detailed history. The recruitment of additional family members was only possible if the family decided to attend the school on the day of the survey.
Patients were included in this analysis if they were observed to have bilateral pediatric (or congenital) cataract, with or without other ocular or systemic features. Patients with aniridia were excluded, even if cataract was also present. Where possible, additional affected and unaffected family members were also examined and recruited. Saliva was collected from each participant in the DNA saliva collection kit (Oragene DNA saliva collection kit) and extracted using prepIT L2P (DNA Genotek Inc., Ottawa, ON, Canada).
2.3. Screening of cataract genes {#mgg3406-sec-0009}
--------------------------------
Genes known to cause pediatric cataract in human or mouse were selected from the literature and the complete list is available in Table [S1](#mgg3406-sup-0002){ref-type="supplementary-material"}. Fifty‐one genes known to cause pediatric cataract were sequenced as described previously, (Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}), using identical sequencing, variant filtering, and functional prediction methods to allow direct comparison between studies. PCR primers to amplify coding, 3′‐ and 5′‐ untranslated regions of the 51 genes were designed with the Ion AmpliSeq Designer tool v1.22 (Life Technologies, <http://www.ampliseq.com>) and used to prepare amplicon‐based sequencing libraries with the Ion AmpliSeq library kit version 2.0. Sequencing was performed on an Ion Torrent PGM using The Ion PGM Sequencing 200 Kit v2 and an Ion 318 chip (Life Technologies). The final assay design consisted of a total of 1,216 amplicons ranging from 125 to 225 bp, covering 94.3% of the 154.1 kb target sequence.
Sequence alignment, variant calling, and annotation were performed as described previously (Siggs et al., [2017](#mgg3406-bib-0020){ref-type="ref"}). Briefly, reads were aligned to the human genome reference sequence 19 (hg19) and variants called using the Torrent Suite v3.6 tools and annotated with Ion Reporter v4.0.
Variants were prioritized for validation and further analyzed if they were predicted to be protein‐changing, and were absent or rare with minor allele frequency (MAF) \<1% in dbSNP137 (<https://www.ncbi.nlm.nih.gov/SNP/>), the Exome Aggregation Consortium (ExAC) (<http://exac.broadinstitute.org/>), and gnomAD (<http://gnomad.broadinstitute.org/>). In addition, identified variants were compared with an in‐house list of common sequencing errors previously detected with this gene panel (Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}).
2.4. Confirmation of variants {#mgg3406-sec-0010}
-----------------------------
Sanger sequencing was used to confirm the presence of variants meeting the filtering criteria and to assess segregation of mutations in families. Forward and reverse primer sequences were designed using Primer3 (Koressaar & Remm, [2007](#mgg3406-bib-0011){ref-type="ref"}; Untergasser et al., [2012](#mgg3406-bib-0021){ref-type="ref"}). PCR and sequencing was conducted as described previously (Siggs et al., [2017](#mgg3406-bib-0020){ref-type="ref"}). Sequence chromatograms of affected and unaffected individuals were compared to each other and the reference sequence (see Table [S1](#mgg3406-sup-0002){ref-type="supplementary-material"} for GenBank accession numbers) using Sequencher v.5 (GeneCodes Corporation, Ann Arbor, MI, USA).
Two detected variants in *GALK1* in proband WW1 could not be assessed by Sanger sequencing due to difficulties with primer design for fragments suitable for capillary sequencing. These two variants were confirmed using Sequenom iPLEX GOLD chemistry on an Autoflex Mass Spectrometer at the Australian Genome Research Facility, Brisbane, Australia.
2.5. Functional predictions {#mgg3406-sec-0011}
---------------------------
Each confirmed segregating novel mutation was assessed for a potential functional effect on the predicted protein sequence using SIFT (Kumar, Henikoff, & Ng, [2009](#mgg3406-bib-0012){ref-type="ref"}) (<http://sift.jcvi.org/>) and the HumDiv model of Polyphen‐2 (Adzhubei et al., [2010](#mgg3406-bib-0001){ref-type="ref"}) (version 2.2.2) (<http://genetics.bwh.harvard.edu.ezproxy.utas.edu.au/pph2/>). The conservation of each altered amino acid was calculated using PhyloP as implemented in Mutation Taster (<http://www.mutationtaster.org/>) and available through the University of California Santa Cruz (UCSC) genome browser. PhyloP values between −14 and +6 indicate conservation at individual nucleotides, ignoring the effects of neighboring nucleotides. Amino acid conservation across species was visualized using the Mutation Taster website. Variants were also assessed against the recommendations of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (Richards et al., [2015](#mgg3406-bib-0014){ref-type="ref"}).
All variants reported in this study have been submitted to the ClinVar database (<https://www.ncbi.nlm.nih.gov/clinvar/>; ClinVar accessions 3267773).
3. RESULTS {#mgg3406-sec-0012}
==========
Thirty‐three probands with pediatric cataract were screened for mutations in the 51 reported cataract‐causing genes.
The mean number of mapped reads per sample was 1,259,305 with 86% of reads on target. A mean of 892 reads was achieved per amplicon, with a coverage uniformity of 89%. Of all the amplicons, 93% and 88% were covered at least 20‐ and 100‐fold, respectively. The average coverage per gene is shown in Figure [1](#mgg3406-fig-0001){ref-type="fig"}. Of the 1,216 amplicons, 27 amplicons (2%) across 15 genes were covered \<20‐fold (Figure [S1](#mgg3406-sup-0001){ref-type="supplementary-material"}).
{#mgg3406-fig-0001}
A total of 4,844 variants were annotated with an average of 146 variants per individual. In total, 188 variants were absent or rare (Minor Allele Frequency \<1%) in publicly referenced databases including ExAC which contains 4,327 individuals from East Asian and 8,256 individuals from South Asian countries. Of the 188 variants, 90 were nonsynonymous exonic variants. Sixty‐five of these variants were removed due to their presence in our in‐house list of sequencing artifacts observed on the Ion Torrent platform with this gene panel. Of the remaining 25 variants, 24 variants were confirmed by Sanger sequencing in 12 probands (Table [1](#mgg3406-tbl-0001){ref-type="table"}) and one was a false positive. The clinical phenotype observed in each proband is described in Table [2](#mgg3406-tbl-0002){ref-type="table"}.
######
Rare coding variants detected in probands with pediatric cataract
Country Proband Inheritance Gene Position in hg19 Nucleotide change Protein change Phylop Seg MAF in Poly phen2 SIFT ACMG
----------- ----------- ------------------------------------------------ ------------------------------------------------ ------------------ --------------------- ---------------- -------- --------------- --------------- --------------- ------- ------ ----
Bhutan P1 AD *GJA8* chr1:147380921 c.839C\>G p.(Pro280Arg) 5.36 Yes 0 0 ProbD D US
E1 AD *GALE* chr1:24123216 c.766A\>G p.(Arg256Gly) 2.4 N/A 3.62 × 10^−5^ 2.55 × 10^−5^ Benign D US
WW1 AR *GALK1* chr17:73758836 c.742C\>T p.(Arg248Trp) 0.25 Yes 9.95 × 10^−5^ 1.14 × 10^−4^ ProbD D US
*GALK1* chr17:73759221 c.485C\>G p.(Thr162Arg) 1.34 Yes 4.16 × 10^−5^ 5.74 × 10^−5^ Benign D US
Cambodia BB16cat *GJA8* chr1:147380102 c.20T\>C p.(Leu7Pro) 3.3 N/A 0 0 ProbD D LP
PP50cat AD *MIP* [a](#mgg3406-note-0003){ref-type="fn"} chr12:56848301 c.97C\>T p.(Arg33Cys) 3.6 Yes 0 0 ProbD D LP
AD *COL4A1* chr13:110864795 c.356C\>G p.(Pro119Arg) 5.27 No 0 0 ProbD T US
AD *NSDHL* chrX:152037470 c.932T\>C p.(Val311Ala) 0.9 No 0 1.12 × 10^−5^ ProbD T US
SR11cat *PAX6* chr11:31823289 c.177G\>C p.(Arg59Ser) 1.79 N/A 0 0 ProbD T US
SR12cat AD *TDRD7* chr9:100245251 c.2533C\>G p.(Gln845Glu) 3.5 No 1.65 × 10^−5^ 4.07 × 10^−6^ ProbD D US
*COL4A1* chr13:110857844 c.900T\>A p.(Ser300Arg) 0.15 No 1.65 × 10^−5^ 1.62 × 10^−5^ Benign T US
Sri Lanka PCC10‐189 AR *GCNT2* [b](#mgg3406-note-0004){ref-type="fn"} chr6:10626784 c.1153C\>T p.(Arg385Cys) 1.51 Yes 0 4.06 × 10^−6^ ProbD D US
PCC01‐34 *HSF4* chr16:67201678 c.910G\>A p.(Glu304Lys) 0.9 N/A 1.53 × 10^−4^ 1.31 × 10^−4^ Benign T US
PCC10‐188 *EPHA2* [b](#mgg3406-note-0004){ref-type="fn"} chr1:16464671 c.987_988insT p.(Ser330Phefs\*51) -- N/A 0 8.32 × 10^−6^ -- -- --
*GCNT2* [b](#mgg3406-note-0004){ref-type="fn"} chr6:10626784 c.1153C\>T p.(Arg385Cys) 1.51 0 4.06 × 10^−6^ ProbD D US
*NHS* chrX:17743727 c.1438C\>T p.(Arg480Cys) 5.33 1.82 × 10^−4^ 1.75 × 10^−4^ ProbD T LB
PCC01‐97A *AGK* chr7:141255292 c.26G\>A p.(Arg9Gln) 2.47 N/A 1.11 × 10^−3^ 9.75 × 10^−4^ PossD D US
*TDRD7* chr9:100234592 c.1759G\>T p.(Asp587Tyr) 1.38 2.47 × 10^−5^ 1.81 × 10^−5^ ProbD D US
*PAX6* chr11:31815036 c.982G\>T p.(Ala328Ser) 6.22 0 0 Benign T US
*BFSP1* chr20:17479645 c.776G\>C p.(Cys259Ser) 3.99 1.48 × 10^−4^ 1.42 × 10^−4^ ProbD D US
*CRYBB1* chr22:27008146 c.186_188delGGT p.(Val63del) -- 0 0 -- -- --
PCC02‐105 AD *CRYGD* chr2:208986444 c.477_477delC p.(Thr160Argfs\*8) 0.75 Yes 0 0 -- -- --
*CRYGD* chr2:208986623 c.299G\>A p.(Gly100Asp) 4.96 No 0 0 ProbD D US
*VIM* chr10:17275680 c.719A\>T p.(Glu240Val) 5.2 No 1.65 × 10^−5^ 8.12 × 10^−6^ ProbD D US
ACMG, American College Medical Genetics and Association for Molecular Pathology recommendations; B, Benign; D, deleterious; ExAC, Exome Aggregation Consortium; gnomAD, Genome Aggregation Database PolyPhen2 symbols; LB, likely benign; LP, likely pathogenic; N/A indicates no additional family members available for segregation or inheritance analysis; PossD, possibly damaging; ProbD, probably damaging; Seg, segregation in additional family; SIFT symbols; T, tolerated; US, uncertain significance.
Mutation in MIP previously reported in a patient with congenital cataract.
Variant is homozygous in the proband.
John Wiley & Sons, Ltd
######
Observed phenotypes and potentially pathogenic rare coding variants detected in pediatric cataract genes in probands
Country Proband Causative gene(s) Phenotype Age at diagnosis Age at recruitment Sex Surgery
----------- -------------------------------- ------------------------------------------------------------------------------- ---------------------------------------------------------- ------------------ -------------------- ----- --------- -----
Bhutan P1 *GJA8* Congenital cataract with posterior capsule opacification Birth 16 F Yes Yes
E1 *Possibly GALE* Congenital cataract, amblyopia, retinal dystrophy Unknown 13 M Yes Yes
WW1 *GALK1* Congenital cataract of unknown etiology Unknown Not recorded F Yes Yes
Cambodia BB16cat *GJA8* Pediatric cataract Unknown -- --
PP50cat *MIP* Pediatric cataract Unknown M -- --
SR11cat *Possibly PAX6* Pediatric cataract Unknown -- --
SR12cat *None segregating* Pediatric cataract Unknown M -- --
Sri Lanka PCC10‐189 *Possibly GCNT2* Congenital cataract with nystagmus Birth Not recorded M No No
PCC01‐34 *None predicted* Pediatric cataract, no perception of light, minor phthisis, left corneal scar Birth 11 years M -- --
PCC10‐188 *EPHA2 or GCNT2* Pediatric cataract Birth Not recorded F Yes Yes
PCC01‐97A *Multiple; CRYBB1 most likely* Pediatric cataract, microphthalmos and pseudophakia Birth 6 years F Yes Yes
PCC02‐105 *CRYGD* Bilateral congenital cataract Unknown 7 years F No No
John Wiley & Sons, Ltd
3.1. Bhutanese probands {#mgg3406-sec-0013}
-----------------------
Of the five probands recruited, three had variants in the screened genes meeting the filtering criteria of rare and protein coding (Table [1](#mgg3406-tbl-0001){ref-type="table"}). A novel mutation was detected in proband P1 in *GJA8,* c.839C\>G, resulting in p.(Pro280Arg). The proband was described as having congenital cataract with posterior capsule opacification and has had surgery on both eyes (Table [2](#mgg3406-tbl-0002){ref-type="table"}). The same mutation was detected in the proband\'s affected sister (Figure [2](#mgg3406-fig-0002){ref-type="fig"}a) but the parents were not available for analysis. This variant is highly conserved and predicted to be damaging by both SIFT and Polyphen‐2 and is the most likely cause of disease in this family.
{#mgg3406-fig-0002}
Variant c.766A\>G resulting in p.(Arg256Gly) in *GALE* was detected in patient E1 (Figure [2](#mgg3406-fig-0002){ref-type="fig"}b). Along with pediatric cataract, amblyopia and retinal dystrophy were reported in this patient indicating the syndromic nature of the disease. No other family members were available for assessment. The variant is well conserved and is predicted to be damaging by SIFT, but benign by Polyphen‐2. It has been reported in ExAC with a minor allele frequency of 0.000036 and 0.000025 in gnomAD. It cannot be said with certainty if this variant is responsible for the disease in this proband.
Two variants in *GALK1* were detected in proband WW1, c.742C\>T coding for p.(Arg248Trp) and c.485C\>G, coding for p.(Thr162Arg) (Figure [2](#mgg3406-fig-0002){ref-type="fig"}c). Both of these variants were validated in the proband using MassArray genotyping due to technical infeasibility of Sanger sequencing. Both the variants are predicted to be deleterious by SIFT but only p.(Arg248Trp) is predicted to be damaging by PolyPhen‐2. However, these predictions do not take into account the combined presence of these very rare variants in the same patient with likely recessive inheritance. Neither variant was present in the proband\'s unaffected brother and together they likely account for autosomal recessive inheritance of cataract in this proband.
3.2. Cambodian probands {#mgg3406-sec-0014}
-----------------------
Fourteen probands from Cambodia were available for analysis and rare coding variants were observed in four patients.
Patient BB16cat had a novel variant in the well‐known cataract gene, *GJA8* (Figure [2](#mgg3406-fig-0002){ref-type="fig"}d). Variant c.20T\>C encoding p.(Leu7Pro) is well conserved and predicted to be pathogenic by multiple algorithms. No additional phenotypic information was available for this patient and family members were not available for genetic analysis, however, this mutation is highly likely to be the cause of the disease in this patient.
Patient PP50cat had a previously reported (Ma et al., [2016](#mgg3406-bib-0013){ref-type="ref"}) mutation in *MIP* c.97C\>T encoding p.(Arg33Cys). This well‐conserved variant is predicted to be pathogenic by both algorithms and segregates with cataract status in the pedigree (Figure [2](#mgg3406-fig-0002){ref-type="fig"}e). Variants were also detected in *COL4A1* and *NSDHL* (Table [1](#mgg3406-tbl-0001){ref-type="table"}), but did not segregate with cataract status in other family members, thus the *MIP* variant is the most likely cause of the disease in this family.
Proband SR11cat had a variant c.177G\>C, p.(Arg59Ser) in *PAX6* (Figure [2](#mgg3406-fig-0002){ref-type="fig"}f). The variant is novel, conserved, and is predicted to be pathogenic by PolyPhen‐2 but not SIFT. No detailed phenotypic information or additional family members were available for analysis. This variant may account for the disease, but requires further confirmation.
SR12cat had variants in two genes, *TDRD7* and *COL4A1*. Both variants are also reported in ExAC at low frequencies and neither segregated with the disease in the family (Figure [2](#mgg3406-fig-0002){ref-type="fig"}g). These variants are unlikely to be the cause of the disease in this family.
3.3. Sri Lankan probands {#mgg3406-sec-0015}
------------------------
Of the 14 available patients, rare coding variants of these genes were detected in five probands.
Proband PCC10‐189 was homozygous for the c.1153C\>T variant coding for p.(Arg385Cys) in *GCNT2*. The proband\'s affected brother (individual II:1) was also homozygous for this novel variant (Figure [2](#mgg3406-fig-0002){ref-type="fig"}h). No DNA was available from the parents, but neither was affected. This mutation likely represents the cause of the autosomal recessive cataract observed in these brothers.
The only variant detected in PCC01‐34 is a rare missense mutation in *HSF4* (Figure [2](#mgg3406-fig-0002){ref-type="fig"}i). Although this gene is well known to cause cataract, given that the variant is present in the population, is in a poorly conserved region of the protein and is predicted to be tolerated by both algorithms, this variant is unlikely to be the cause of the disease in this patient. No additional family members were available for segregation analysis.
Variants in three genes were detected in proband PCC10‐188, a rare variant in *NHS* and novel variants in *EPHA2* and *GCNT2,* both in the homozygous state (Figure [2](#mgg3406-fig-0002){ref-type="fig"}j). The cataract was present at birth in the proband and she had surgery in both eyes; however, no further details were available. Due to the nature of the mutation, the frameshift mutation in *EPHA2* c.987_988insT, p. (Ser330Phefs\*51) is highly likely to be the cause of the disease, although this is difficult to confirm in the absence of additional family members. The mutation in *GCNT2* in PCC10‐188 is the same novel homozygous mutation that was found segregating in PCC‐189 and his brother (p.(Arg385Cys)). The possibility that this is a novel population specific variant should be considered; however, it is the most likely cause of disease detected in proband PCC‐189 and his brother.
Proband PCC01‐97A displays rare coding variants in five different cataract genes (Table [1](#mgg3406-tbl-0001){ref-type="table"}). Three of the variants were rare in the population (in *AGK*,*TDRD7*, and *BFSP1*) and two (in *PAX6* and *CRYBB1)* were novel (Figure [2](#mgg3406-fig-0002){ref-type="fig"}k). Cataract in this patient was present at birth and was described as syndromic (with microphthalmos and pseudophakia). The syndromic nature of the phenotype implicates *PAX6*, however, multiple other variants may be contributing to the phenotype in this patient with bioinformatic predictions suggesting that all mutations except the one in *PAX6* are likely to be functional. Given that the variant in *CRYBB1* is completely novel and results in the deletion of a whole codon, it may be considered the most likely causative variant. No other family members were available for the study, limiting the ability to interpret the findings of multiple variants.
Three variants were detected in two genes in PCC02‐105; two novel variants in *CRYGD* and one rare variant in *VIM* (Table [1](#mgg3406-tbl-0001){ref-type="table"}). The frameshift mutation in *CRYGD,* c.477_477delC resulting in p.(Thr160Argfs\*8) was the only variant present in the proband and his three affected cousins (Figure [2](#mgg3406-fig-0002){ref-type="fig"}l) and as such is the probable cause of the disease in this family.
4. DISCUSSION {#mgg3406-sec-0016}
=============
Thirty‐three probands with pediatric cataract were recruited during audits of the causes of childhood blindness in three countries---Bhutan, Cambodia, and Sri Lanka. Rare, coding variants were identified in 12 probands; however, these variants are likely to explain the cause of the disease in only six of these patients (P1 and WW1 from Bhutan; BB16cat and PP50cat from Cambodia; PCC02‐105 and PCC10‐188 from Sri Lanka) with a further four possibly solved (E1 from Bhutan; SR11 from Cambodia; and PCC01‐97A and PCC10‐189 from Sri Lanka). This equates to a rate of 18% (6/33) of cataract patients from the region having disease‐causing mutations in known cataract‐causing genes, and 30% if the possibly solved cases are included. This is substantially lower than the rates of 60%--70% reported in case series of European descent (Gillespie et al., [2014](#mgg3406-bib-0007){ref-type="ref"}; Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}; Ma et al., [2016](#mgg3406-bib-0013){ref-type="ref"}). This difference remains evident even when compared with our previous study of Australian patients screened using the same gene panel, the same sequencing methodology, and the same variant filtering criteria, which found a success rate of 62% (Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}). Gene discovery for this disease has predominantly been undertaken in patients of European descent and it is clear from this study that there remain novel genes to discover for inherited pediatric cataract in non‐European populations. We can hypothesize that such genes contribute to a higher proportion of disease in these relatively understudied populations. Families with multiple affected family members and clear phenotypes such as SR12 will be important in identifying such genes.
Alternatively, it is possible that a portion of the patients included in this study have nongenetic cataracts. The recruitment strategies employed made it difficult to obtain thorough family histories for all patients and in several cases, the inclusion of a child was made at the discretion of the examining clinician based on the information to hand. Up to 25% of cataract is inherited (Shiels & Hejtmancik, [2007](#mgg3406-bib-0018){ref-type="ref"}) and the rate may be lower in areas without vaccination programs to prevent maternal rubella infection. This may mean that more children with this, or other nongenetic causes of cataract blindness, may have been inadvertently included in this study. Maternal rubella infection, however, does not account for the observations in this study. In 2012, Sri Lanka had a national rubella vaccination program, but Cambodia and Bhutan did not (Centres for Disease Control and Prevention, [2013](#mgg3406-bib-0002){ref-type="ref"}). We found the highest rate of causative mutations in Bhutan (two of five probands). The audit also reported no cases of measles/rubella induced vision loss in the Bhutanese school children (Farmer et al., [2015](#mgg3406-bib-0003){ref-type="ref"}). It remains to be determined how many of the probands with no detected mutations in this panel of genes have genetic forms of cataract and how many may be accounted for by environmental causes.
This study has thoroughly evaluated a large number of known cataract genes in a population which has not previously been studied to any extent, however, there are some limitations. The coverage of the target genes in this gene panel is high, but some regions could not be sequenced, either due to the inability to design amplicons in a given region, or the poor performance of some amplicons. A detailed assessment of the coverage and quality of sequencing using this panel on the Ion Torrent PGM has been published previously by our group (Javadiyan et al., [2017](#mgg3406-bib-0009){ref-type="ref"}). Furthermore, the bioinformatic analysis can have a profound effect on the ability to detect variants. The algorithms for sequence alignment, variant calling, and variant annotation are constantly improving and these data should be reanalyzed in the future to detect variants missed in the current pipeline. The guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (Richards et al., [2015](#mgg3406-bib-0014){ref-type="ref"}) classify most of the detected variants as variants of uncertain significance. This particular algorithm is designed to provide conservative findings in a clinical setting where results of genetic testing will be returned to patients and clinicians for use in the medical management of patients and genetic counseling of families. This necessarily requires caution when applying a label of pathogenic and only the highest levels of evidence are accepted. This tool reminds us to interpret the findings with caution and to seek additional evidence regarding the pathogenicity of these variants, but a classification of "uncertain significance" does not rule out a variant from being the true cause of disease.
This study has identified novel genetic mutations linked to pediatric cataract; p.(Pro280Arg) and p.(Leu7Pro) in *GJA8,* p.(Thr160Argfs\*8) in *CRYGD*, p.(Arg385Cys) in *GCNT2*, p.(Ser330Phefs\*51) in *EPHA2*, and very likely p.(Val62_Phe64del) in *CRYBB1*. This extends the known mutation spectrum for pediatric cataract. We also identified a recurrent mutation, p.(Arg33Cys) in *MIP*, segregating in a family from Cambodia. This mutation was previously reported de novo in a sporadic case of nonsyndromic bilateral congenital cataract (Ma et al., [2016](#mgg3406-bib-0013){ref-type="ref"}) and in a multigeneration Chinese family with total congenital cataract (Gu et al., [2007](#mgg3406-bib-0008){ref-type="ref"}).
Two novel variants were identified in the *CRYGD* gene in a family from Sri Lanka. The first, a frameshift mutation, p.(Thr160Argfs\*8), clearly segregates with disease in the family and is the most likely cause of the disease in this family. The proband (PCC02‐105) also carries a second novel variant in this gene, which is also predicted to be pathogenic, p.(Gly100Asp). This second variant is not present in any of the other affected family members and thus is not likely to be the primary cause of the disease. This highlights the need to treat the interpretation of variants identified in only one individual with extreme caution. In terms of this study, this is applicable to patient BB16cat with a mutation in *GJA8* as well as the *EPHA2* variant in Sri Lankan proband PCC10‐188 and the novel variants in *PAX6* and *CRYBB1* in PCC01‐97A. The novel variants in *EPHA2* and *CRYBB1* are a frameshift and a deletion, respectively. Both genes and types of mutations have a strong tendency to be pathogenic for cataract; however, the *CRYBB1* mutation occurs in the context of other possibly pathogenic variants and additional evidence is required to determine if these novel variants are in fact the cause of disease.
We further identified three genes with recessive mutations in cataract patients. Proband WW1 from Bhutan is compound heterozygous for two mutations in *GALK1*. His unaffected brother does not carry either mutation. The parents were not available for testing; thus, it is not definitively determined if these variants are inherited in *cis* or *trans*; however, recessive mutations in this gene have been reported in many families with cataract previously, both as homozygous and compound heterozygous variants (Shiels et al., [2010](#mgg3406-bib-0017){ref-type="ref"}). Both these variants are present at low rates in the ExAC database, consistent with a recessive inheritance pattern. The second recessive mutation identified in this cohort is in *GCNT2,* which is well known to cause recessive cataract (Shiels et al., [2010](#mgg3406-bib-0017){ref-type="ref"}). The novel homozygous variant, p.(Arg385Cys), was detected in two brothers from Sri Lanka (PCC10‐189 and his brother), as well as a third affected child (PCC10‐188), not reported to be related but attending the same school for the blind. The presence of this homozygous novel variant in two "families" from the same school in Sri Lanka suggests that these two families are consanguineously related but this cannot be definitively determined from the data generated for this study. PCC10‐188 also carries a homozygous mutation in *EPHA2* (p.(Ser330Phefs\*51)). This gene has been reported with this mode of inheritance in a family from Pakistan (Kaul et al., [2010](#mgg3406-bib-0010){ref-type="ref"}). This homozygous variant was not present in ExAC at the time of generating the data; however, it has subsequently been identified in two individuals in the gnomAD resource. The homozygosity in proband PCC10‐188 further suggests the consanguinity of the parents of this child, in addition to the *GCNT2* variant. Either mutation is likely sufficient to cause cataract in this child.
There has been just one report of association between the deficiency of *GALE* and pediatric cataract in a 5.5‐year‐old girl with autosomal recessive pediatric cataract (Schulpis et al., [1993](#mgg3406-bib-0015){ref-type="ref"}). Here, we report a missense variation, p.(Arg256Gly), in this gene in a proband from Bhutan with pediatric cataract, amblyopia, and retinal dystrophy (patient E1). Without additional family members, we cannot definitively determine a role for this variant in the disease; however, the variant has been reported at low frequency in public databases and is predicted by at least one algorithm to be benign. Coupled with the knowledge that this gene has only been reported previously in recessive disease, it seems unlikely that it is the sole cause of cataract and associated features in this proband.
We were able to determine the genetic cause in approximately 21% of pediatric cataract cases screened from three diverse Asian countries. It is probable that this mutation rate would be improved by more complete ascertainment of family members of affected probands. It is clear that while the known cataract genes do contribute to this disease in the Asian region and that novel variants exist in these populations, there is a clear need for further research to uncover the remaining genetic causes of the disease in this and other understudied regions.
CONFLICTS OF INTEREST {#mgg3406-sec-0018}
=====================
The authors have no conflicts of interest to declare.
Supporting information
======================
######
######
Click here for additional data file.
######
######
Click here for additional data file.
The authors acknowledge the support of Sight For All in undertaking this work and the contribution of the schools for the blind and the health departments in each country. This work was funded by grants from the Channel 7 Children\'s Research Foundation, the Ophthalmic Research Institute of Australia, and Centre for Excellence grant from the National Health and Medical Research Council of Australia (NHMRC). KPB is supported by an NHMRC Senior Research Fellowship and JEC by an NHMRC Practitioner Fellowship. SEML is supported by the Australian Government Research Training Program Scholarship and the Pennicott Foundation.
[^1]: These authors contributed equally to this work.
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EVEN as it tries to slow production down, America is still pumping three billion more cubic feet (85m cubic metres) of natural gas a day out of the ground than it can consume. The country has become so awash in the stuff since “fracking” (hydraulic fracturing of gas-bearing shale deposits) began barely five years ago that the price has plummeted from $8 per thousand cubic feet to $2. (A thousand cubic feet of natural gas contains roughly a million BTUs of energy.) Not that long ago, natural gas was a tenth of the price of oil in energy terms; now it is a 50th.
If the natural-gas companies go on producing at the current rate, all the storage reservoirs in America will be full by autumn. With nowhere left to put the stuff, its marginal price will fall to zero. Such a situation is unsustainable.
Extracting natural gas from tightly packed shale deposits costs around $5-6 per thousand cubic feet. Wells have to be sunk thousands of feet underground and then drilled horizontally through the gas-bearing formations for thousands of feet more. A slurry of water, quartz sand and chemical additives has then to be pumped into the well at high pressure, to fracture the shale and open fissures for the trapped gas to escape. And all the waste water has to be pumped back to the surface to be processed and stored, at considerable cost.
At today's spot prices for natural gas, producers are losing money hand over fist. Many could cease to exist as the industry is forced to contract. And consolidate it will. There are so many firms that the top ten producers account for less than half the market between them. The trouble is that fracking is almost too productive for its own good, and there is just too much shale gas out there. Only big companies with deep pockets will survive.
Back in 2000, America had enough accessible natural gas in the ground to provide a little more than 12 years of consumption. But once the country's shale deposits started to be tapped in earnest, reserves leaped to over a century's supply. And because output from existing wells is not tapering off as fast as initially expected, the actual reserves could wind up being double present estimates.
Such a bonanza ought to be a blessing. And one day it will be. But right now finding users to suck up all that excess natural gas is a headache.
With the United States importing more than half its oil (at over $1 billion a day), and transport accounting for two-thirds of the country's oil consumption, logically the biggest single market for natural gas ought to be motorists. If they could be enticed to switch from petrol to compressed natural gas (CNG)—as drivers in Brazil, Iran and Pakistan have done—America would no longer need to depend on foreign oil.
But do not count on it, even though there is much to like about CNG. For one thing, it is the cleanest burning of fossil fuels—producing significantly less carbon dioxide, nitrogen oxides and unburned hydrocarbons than petrol. Because it leaves no carbon deposits inside the engine, wear is reduced to a minimum and oil changes are required less often. At the equivalent of typically $2 a gallon, CNG is half the price Americans pay at the pump for petrol. It is also safer. If its pressurised container is ruptured, CNG does not pool on the ground, but disperses into the air. And with twice the ignition temperature of petrol, it is less likely to catch fire.
So, what is holding CNG back? One reason is that converting petrol engines to run on CNG is expensive. Conversion kits that meet Environmental Protection Agency (EPA) requirements cost anything from $6,000 to $16,000, depending on the vehicle. For another, the pressurised storage tank leaves little space for luggage in the vehicle's boot.
Only one car designed specifically to run on CNG, the Honda Civic GX, is commercially available in the United States. Compared with its petrol-engined LX sibling, the GX has significantly lower power, has similar fuel economy, and has a sticker price that is $7,000 higher. But it is cheaper to refuel. The GX is also squeaky clean, having the least polluting internal-combustion engine in production anywhere. In California, it has the enviable right—like electric vehicles and certain hybrids—to use the car-pool lanes with only the driver aboard.
CNG cars have other drawbacks that similarly plague electric vehicles—including range anxiety. Refuelling stations are few and far between. At the last count, America had little over 1,000 natural-gas stations compared with 120,000 petrol stations. Honda sells a home-refuelling appliance called Phill, which uses the domestic gas supply to recharge the GX's pressurised tank (equivalent to an eight-gallon petrol tank) in 16 hours, to give a typical range of around 200 miles (320km).
Lorries and buses are a much better proposition. Operating on fixed duty cycles and returning to base at the end of the working day, buses, delivery vans and waste-collection vehicles are ideal candidates for CNG. Indeed, the vast majority of America's fleet of 114,000 CNG vehicles are buses and other municipal vehicles.
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Clear Creek Bridge
The Clear Creek Bridge, in Butler County, Nebraska near Bellwood, Nebraska, was built in 1891. It is a Warren through truss bridge. It was listed on the National Register of Historic Places in 1992.
It is a single-span bridge. It was designed and built by the King Bridge Co. of Cleveland, Ohio; it was fabricated by the CRM Co.
Its 1991 National Register nomination noted that "the bridge's integrity has been diminished by later alterations, [but] this fact is mitigated by the structure's extreme rarity and age. Among Nebraska's oldest vehicular spans, the crossing continues to carry vehicular traffic." In 2010, the bridge was blocked off and no longer carried traffic.
It brings a township road over Clear Creek about northwest of Bellwood.
References
External links
Category:Bridges in Nebraska
Category:Warren truss bridges
Category:National Register of Historic Places in Butler County, Nebraska
Category:Buildings and structures completed in 1891
Category:King Bridge Company
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About Me
Tuesday, January 29, 2013
I know you can image today what I am going to bring you. Today I am bringing to Linux for free. Only from Technology Market. Everyone know what is Linux. Linux is a famous operating system in world. Most of companies use this operating system for their computers or laptops This operating system is really easy. Don't afraid to have this. And don't be late. Try this now.
Well the link is below. I don't waste time yours. I help you from this blog hot and fast.
By the way I forgot to say this too. Linux is a bulletproof Operating System for your computer. Linus is fast, stable and immune to virus and spyware. over 30 games, Firefox browser, flash video, image editor, Microsoft Office compatible. So simple. AND GRANDMA CAN USE IT. Don't wait. Get this now.
Saturday, January 26, 2013
"This is great. Rear change. Amazing. Wow." I am sure that you guys will tell like this words. Because this is absolutely amazing. Today I'm goint to show you a way to rich from affiliate marketing. Affiliate markenting..? What is that.
Affiliate marketing is very simple. It is working just like this. For example I want to sell my car for someone, I sell that for $100 000, then you come to me and you will find me a buyer for my car. So I will give $ 1000 for that. Wow. You owned $1000. That is affiliate marketing. I told you that is really easy. There are many companies for affiliate marketing. I will put some affiliate companies like that.
1. Clickbank
2. Clicksure
You can search for affiliate companies online. Go to the site and sign up. And do affiliate marketing. You will be get paid. and you will rich like Bil Gates.
This is the fun part. I will give you two big rear chance to earn with affiliate marketing. This a auto pilot way. I will put the links below. You have to follow the link and get the auto pilot. After that you can do anything in anytime. Because the auto pilot is working.
This is end of our post. I hope this was helped to you a little bit for increase your knowledge or your internet money career. I will be very pleased if you put a commet to me. thank you all. good luck guys.
Friday, January 25, 2013
Welcome back everyone. This is our second post. But we are not second for anyone. Let me introduce our future plans in Technology Market. This is our target. To help people what they looking from our blog. We basically help people from what they looking for. For example if you want to have something new software, we are here to help you. We have many goods for everyone. Every time. If u want something different things from us. Send us a message and we will give that right away.
This is not a normal or regular blog every time you see. We are different from others. So visit our blog... take anything from us... we are ready to serve to you...
Thursday, January 24, 2013
Welcome to Technology Market. Today we are beginning a new era of blogging history. Joining with us you can find something new something useful or something for education in this blog. We are ready to start our career. Are you ready to join with us for future. Lest do this. I would not write very big and long content. Because it would be boring for you or you will be get tired from it. So I write shortly and with some jokes. LOL. Well now your decision to stay with me and give support to me. Thank you all. STAY WITH US.
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The British Guide to Showing Off
The British Guide to Showing Off is a 2011 documentary film written and directed by Jes Benstock, which follows the build-up and execution of the twelfth Alternative Miss World - artist Andrew Logan's pastiche of the Miss World beauty pageant.
Synopsis
As well as charting the latest incarnation of the Alternative Miss World, the film studies the history of the show itself, which first took place in 1972 and has had a number of high-profile celebrities both entering and judging it.
Cast
The film features contributions from Brian Eno, Ruby Wax, Zandra Rhodes, Richard O'Brien, Nick Rhodes and Grayson Perry.
Reception
Variety wrote that the film was "Heartfelt and humorous" in its attention to the life of "eccentric" artist Andrew Logan and his creation of the "Alternative Miss World competition". They favorably compare director Jes Benstock's documentary to other works by artist Logan, calling it a "mixed-media collage" through its blending of archival footage and photos, its inclusion of commentary from the artist and his relatives, its inclusion of input from notables from the worlds of art, fashion, music and theater, and inventive animation.
Screen Daily, in speaking toward the film's study of artist Andrew Logan and his creation of the Alternative Miss World competition in 1972, wrote that the film is an "exuberant and joyous look into the life and work." They note that the film has a "simple structure" that ties together two aspects of Logan's life, his career as an alternative artist and creation of the Alternative Miss World competition, and Logan's 2009 search for a venue and the subsequent design and staging of the latter event.
The Guardian in describing the film wrote that: "The events are a very English combination of carnival, kids' dressing-up parties, drag balls and PoW camp shows." and "...this playful movie is partly a biography of the gay, ever-cheerful, Oxford-educated sculptor Andrew Logan and the extravagantly staged Alternative Miss World shows he's been putting on at various London venues since 1972."
References
External links
Category:British films
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So what. If the definition says that 1 shot per pull of trigger and since the trigger is moving back and fourth for each shot how would this not fit the definition.
Because it doesn't fit the definition as it has been and is interpreted by BATF and the courts. You can contact the BATF and get an official read directly from them if you wish.
From past rulings the BATF says that the key is that the SHOOTER must be what operates the trigger once for each shot. If a spring or or some other mechanism is what operates the trigger then it's not going to be legal.
The shooter must do something each time the gun fires--he must physically operate some part of the firearm by manually moving it a noticeable amount for each time a shot is discharged.
If you can make a single movement and then remain motionless while the gun continues firing then it doesn't matter how the mechanism accomplishes that operation--doesn't matter if the trigger moves each time the gun fires or stays motionless against your finger. The firearm is a machinegun if it fires more than one shot without your having to do anything other than move once.
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Union Luxembourg
Union Sportive Luxembourg, usually known as Union Luxembourg, was a football club, based in Luxembourg City, in southern Luxembourg. It is now a part of Racing FC Union Luxembourg.
History
Union Luxembourg was formed in 1925 as an amalgam of US Hollerich Bonnevoie and Jeunesse Sportive Verlorenkost. Although US Hollerich had been one of the top clubs in Luxembourg, winning five titles consecutively, by 1925, its success had dried up. From the merger until the Second World War, the club would win only one trophy: the championship in 1927.
In 1940, the Nazis renamed Union, along with all other clubs as part of the process of Germanisation. Between 1940 and 1944, Union's name would be Verein für Rasenspiele 08 Luxemburg. The end of occupation and reversion of moniker did little to change Union's success (or lack thereof); a solitary Luxembourg Cup was all that Union had to show for the first fifteen years of freedom after the war.
However, that all changed very swiftly, as Union hit its stride, beginning with another cup victory in 1959. Between 1959 and 1971, Union won two league titles and the Luxembourg Cup five times. Another barren spell followed; the 1970s and 1980s saw Luxembourg finish consistently in the top four in the league, but, in seventeen years, Luxembourg reached only two cup finals and finished in the two top just once.
Another sudden spike of success came at the end of the 1980s. Luxembourg won three National Division titles back-to-back between 1990 and 1992 and returned to the habit of European qualification. Nonetheless, as with so many clubs in Luxembourg during the 1990s and 2000s, Union could not withstand the pressure to consolidate. Union arranged a merger with CA Spora Luxembourg and CS Alliance 01 to form its modern form, Racing FC Union Luxembourg, to take effect after the 2004–05 season. As it happens, Union was relegated in 2004–05 (as was Spora), marking an unfitting end to one of Luxembourg's most successful clubs.
Honours
National Division
Winners (6): 1926–27, 1961–62, 1970–71, 1989–90, 1990–91, 1991–92
Runners-up (9): 1921–22, 1947–48, 1962–63, 1963–64, 1964–65, 1965–66, 1972–73, 1992–93, 1997–98
Luxembourg Cup
Winners (10): 1946–47, 1958–59, 1962–63, 1963–64, 1968–69, 1969–70, 1985–86, 1988–89, 1990–91, 1995–96
Runners-up (10): 1922–23, 1925–26, 1932–33, 1936–37, 1960–61, 1961–62, 1966–67, 1977–78, 1982–83, 1996–97
As US Hollerich Bonnevoie
National Division
Winners (5): 1911–12, 1913–14, 1914–15, 1915–16, 1916–17
Runners-up (2): 1909–10, 1917–18
European Competition
Union Luxembourg qualified for UEFA European competition 21 times.
UEFA Champions League
Qualifying round (1): 1971–72
First round (4): 1962–63, 1990–91, 1991–92, 1992–93
UEFA Cup Winners' Cup
Qualifying round (2): 1996–97, 1997–98
First round (8): 1963–64, 1964–65, 1969–70, 1970–71, 1978–79, 1984–85, 1986–87, 1989–90
UEFA Cup
Qualifying round (1): 1998–99
First round (5): 1965–66, 1966–67, 1973–74, 1988–89, 1993–94
Without having won a tie, Union won two matches against European opponents. The first came in 1970–71, against Turkish side Göztepe in the Cup Winners' Cup. Göztepe had won the first leg 5–0, but Union managed a 1–0 victory in the home leg (this was very limited revenge, as Göztepe had knocked Union out the previous year, too). Their second victory was over Bodø/Glimt of Norway, by one goal to nil, having losing the first leg 4–1. Union also managed draws against Botev Plovdiv and Djurgårdens IF in 1984–85 and 1989–90 respectively.
Managers
Bill Berry (1961–65)
René Noerdinger (1973–79)
Alex Pecqueur (1989–92)
Roland Schnit (1992–93)
Heinz Maas (1993)
Alex Pecqueur (1994–95)
Rachid Belhout (2001–03)
Jeannot Reiter (2003–05)
Category:Association football clubs established in 1925
Category:Association football clubs disestablished in 2005
Category:1925 establishments in Luxembourg
Category:2005 disestablishments in Luxembourg
fr:Racing FC Union Luxembourg
|
{
"pile_set_name": "Wikipedia (en)"
}
|
Q:
How to implement the android zoomview?
I want to implement the android-zoom-view (https://code.google.com/p/android-zoom-view/).
I added the jar to the buildpath. I created the following xml:
<?xml version="1.0" encoding="utf-8"?>
<pl.polidea.view.ZoomView xmlns:android="http://schemas.android.com/apk/res/android"
android:layout_width="fill_parent"
android:layout_height="fill_parent" >
<ImageView
android:id="@+id/webcam1"
android:layout_width="match_parent"
android:layout_height="match_parent"
android:layout_gravity="center"
android:layout_marginBottom="20dp"
android:scaleType="matrix" />
<ImageView
android:id="@+id/webcam2"
android:layout_width="wrap_content"
android:layout_height="wrap_content"
android:layout_gravity="center"
android:scaleType="matrix" />
</pl.polidea.view.ZoomView>
and added the following code to my activity:
View v = ((LayoutInflater) getSystemService(Context.LAYOUT_INFLATER_SERVICE))
.inflate(R.layout.zoomable_view, null, false);
v.setLayoutParams(new LinearLayout.LayoutParams(
LayoutParams.FILL_PARENT, LayoutParams.FILL_PARENT));
zoomView = new ZoomView(this);
zoomView.addView(v);
LinearLayout main_container = (LinearLayout) findViewById(R.id.LinearLayout1);
main_container.addView(zoomView);
what am I doing wrong?
I get the following error:
Caused by: android.view.InflateException: Binary XML file line #2: Error inflating class pl.polidea.view.ZoomView
A:
I added the following constructor to the ZoomView class and it works now at least for one imageview in the zoomview.
public ZoomView(final Context context, AttributeSet attr) {
super(context, attr);
}
|
{
"pile_set_name": "StackExchange"
}
|
Q:
$scope.push failing to update after entering same value in Angular (bug!)
I am new to Angular and I was trying my hands on a few functions. I found this strange behavior when I try to re-enter the same value.
<!-- HTML -->
<body ng-app="angular-test">
<div ng-controller="FormController">
<ul>
<li ng-repeat="name in names">{{name}}</li>
</ul>
<form ng-submit="addName()">
<input type="text" ng-model="newName">
<input type="submit" value="Add">
</form>
</div>
</body>
/*** Angular Code ***/
(function() {
var app = angular.module("angular-test", []);
app.controller("FormController",formController);
function formController($scope){
$scope.names = ['Israel','Agyeman','Prempeh','Osei','Apea'];
$scope.addName = function(){
$scope.names.push($scope.newName);
$scope.newName = '';
}
}
})(angular);
![A list generated from the existing model in the HTML page][1]
Israel
Agyeman
Prempeh
Osei
Apea
King
king
______________ [Add] (input form)
"King" was added through the add button so was "king" but as I typed "king" again it failed to update and does not update afterwards no matter what I insert. Any ideas as to what is causing this?
A:
Evening Israel,
You can't duplicate values in a repeater. To make it works, just add the following:
name in names track by $index
Or see it in action: http://codepen.io/anon/pen/xGzRKK
Hope it helps!
|
{
"pile_set_name": "StackExchange"
}
|
Radiolabelled compounds have uses in medical imaging and, in the case of 18F radiolabelled compounds, in Positron Emission Tomography (PET).
One family of radiolabelled compounds of particular, current interest are radiolabelled thymidines and, in particular, 3′-deoxy-3′-[18F] fluorothymidine (18FLT) for PET imaging especially in the field of oncology.
18FLT may be synthesized from 5′-O-(4′,4′-dimethoxytrityl) thymidine by nucleophilic substitution (with inversion of stereo chemistry) at the 3′ position using 18F as illustrated in scheme 1.
During this fluorination procedure, the elimination product d4T is often formed in high yield owing to competition between OH− and 18F− and is therefore the main impurity in this reaction. d4T tends to be formed at a much higher rate than 18FLT and may be present in a d4T:18FLT ratio of 100-10000:1. Separation of 18FLT and d4T may be problematic.
High performance liquid chromatographic separation of the two compounds may be achieved using different stationary phases, however HPLC is costly and complex and not a preferred purification method in a clinical environment such as a hospital.
HPLC methods can also be time consuming which is a particular problem with the use of radionuclides with short half lives (18F has a half-life of about 110 minutes). Another serious problem is that HPLC does not lend itself to use with commercially available synthesis modules which simplify the preparation and purification of radiolabelled compounds.
WO 2005/025519 describes a method and apparatus for the automated synthesis of 18FLT in which a separation procedure is performed using a Sep-Pak® C-18 solid phase extraction (SPE) column.
WO 2006/133732 also describes a method for the manufacture of [18F]-FLT in which a separation is performed using an Oasis® HLB SPE column.
Unfortunately, the SPE methods previously described for use in the manufacture of [18F]-FLT do not result in good enough separation and so are not always suitable for clinical use.
The present invention aims to address the problems mentioned above by providing a separation process which is relatively simple, less costly than HPLC, results in excellent separation and lends itself to use, especially, in a clinical environment.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
package com.phoenixnap.oss.ramlplugin.raml2code.github;
import org.junit.Test;
import com.phoenixnap.oss.ramlplugin.raml2code.rules.GitHubAbstractRuleTestBase;
import com.phoenixnap.oss.ramlplugin.raml2code.rules.Spring4ControllerDecoratorRule;
/**
* @author aleksandars
* @since 0.10.13
*/
public class Issue215RulesTest extends GitHubAbstractRuleTestBase {
@Test
public void optional_param_as_resource_level() throws Exception {
loadRaml("issue-215-1.raml");
rule = new Spring4ControllerDecoratorRule();
rule.apply(getControllerMetadata(), jCodeModel);
verifyGeneratedCode("Issue215-1Spring4ControllerStub");
}
@Test
public void optional_param_as_resource_part() throws Exception {
loadRaml("issue-215-2.raml");
rule = new Spring4ControllerDecoratorRule();
rule.apply(getControllerMetadata(), jCodeModel);
verifyGeneratedCode("Issue215-2Spring4ControllerStub");
}
@Test
public void two_optional_parms() throws Exception {
loadRaml("issue-215-3.raml");
rule = new Spring4ControllerDecoratorRule();
rule.apply(getControllerMetadata(), jCodeModel);
verifyGeneratedCode("Issue215-3Spring4ControllerStub");
}
}
|
{
"pile_set_name": "Github"
}
|
Background
==========
To date no standard treatment for recurrent ingunal hernias exists. Open or laparoscopic approaches were proposed with apposition of meshes with reknown advantages and limits\[[@B1]\]. Long term recurrence-rate, postoperative pain, fistulization or prosthetic infection risks remain open questions in this surgery. Aim of this work is to show results of our experience with the open anterior approach in local anesthesia\[[@B2]\] for recurrent inguinal hernia repair in old patients (Age\>75 yrs.).
Materials and methods
=====================
Between January1994 and December 2011, on a total of 3120 patients referred to us for inguinal hernias, 218 patients (6.9%) were submitted to inguinal hernioplasty for hernia recurrence. Twenty-nine (13.3%) of them were \<75 years old, with a middle age of 80.59 (range 75-89). The time for recurrence appearance was ranging from 3 to 191.5 months. Ten (34.4%) were recurrence after mesh implantation, while 19 (65.6%) were after traditional hernioplasty for direct suture. They were all affected by one or more comorbidities: Sixty patients (55.1%) by cardiovascular disease, 8 by respiratory disease (27.5%) , 3 by neuropathy (10.3%), 6 by metabolic one (20.7%). They underwent an inguinal hernioplasty by open anterior approach with prosthetic material (polypropylene) apposition in 26 patients (89.6) under local anesthesia, in 2 patients (6.9%) under spinal anesthesia and in 1 more patient (3.5%) under general anesthesia.
Results
=======
We repaired in 12 cases (41.3%) by apposition of a cilindric Lichtenstein's plug\[[@B3]\], in 6 cases (20.7%) with Trabucco's T1 plug, in 9 cases (31.1%) by performing a mesh and plug repair and in 2 cases (6.9%) with a "mesh only" repair. Only polypropylene mesh or plug were used\[[@B4]\]. No drainage was used. We registered no intraoperative and postoperative complications. Twenty-four patients (82.7%) were discharged within 24 hours. In a long-term telephonic, clinical and ecographic follow-up (middle value 107 months; range 16-220 months) we found 2 recurrences (\~7%). Those patients were again repaired through an open anterior approach. No mesh infections or fistulas, so like chronic pain cases were registered in our follow-up. Never was necessary to remove a plug or a mesh.
Conclusions
===========
The recurrent inguinal hernia repair in old patients (\>75 yrs), due to general aging of population and number of inguinal hernioplasties all over the world, is becoming a clinical entity of moderate impact on surgeon's daily activity (about 13% of inguinal hernioplasties for recurrences in our experience). Recurrent hernia in old patients is often present togheter with important comorbidities, expecially cardio-respiratory ones. An open anterior approach in local anesthesia shows advantages of really "mini-invasive" method, with reduction of surgical risks\[[@B5]\], in front of laparoscopic techniques in which general anesthesia is usually required. Other advantages are prompt reahabilitation, feasability in most of case in day surgery\[[@B6]\] setting and good long-term results about recurrence if compared with till today published literature's data. Additionally as our experience shows, in case of re-recurrence, patients are more prone to accept a new operation due to reduction of trauma of the first intervention.
In conclusion recurrent inguinal hernia repair requires an eclectic surgical approach, in old patients anterior approach with polypropylene mesh, or plug, or both apposition under local anesthesia seems to be effective, safe showing good long-term results and feasable in the big majority of patients in a day surgery setting. Laparoscopic approaches should be considered, in this special cohort of patients, as the very second choice.
|
{
"pile_set_name": "PubMed Central"
}
|
One of the best looking upgrades I’ve seen so far over the standard blu ray as far as colors and image “pop” go. Definitely my favorite looking Disney title so far that I’ve seen. The atmos track is at times very enveloping with its use of overheads and surrounds, especially during the storm scenes. There’s only a few times the bass really digs in but for a Disney title it was above average for both bass and atmos use. Just don’t forget to crank your receiver up a few notches like ever other Disney movie. Honestly I didn’t plan on watching this whole thing since it was more a purchase for the kiddos and I’ve seen it a couple times already, but the imagery and sound kept me entertained like the first time I saw it in theaters years ago. Wonderful addition.
|
{
"pile_set_name": "OpenWebText2"
}
|
definitely not alone. Experts on both sides of the political spectrum have been warning that it is very likely that...
|
{
"pile_set_name": "OpenWebText2"
}
|
Full Canyon Colorado River Rafting
Overview
Full Canyon trips cover both the Upper and Lower sections of the Colorado River. There are multiple exit points (river miles 188, 225 and 280) and trip durations offered by the many outfitters and their unique itineraries. Starting at Lee’s Ferry in magnificent Marble Canyon, you’ll see all of the canyon’s details including some of the best white water river rafting around. There are over 42 major rapids rated 5 or above on a 1-10 rating scale which make Colorado River rafting a unique experience for adventure seekers from all over the world.
Rapids include House Rock, Unkar, Hance, Sockdolager, Zoroaster, Lava Falls, Hermit and many others. Highlights include the turquoise blue waters at the confluence of the little Colorado river as well as Havasupai creek. The Redwall cavern is another remarkable attraction, and many amazing chasms and waterfalls on a full canyon river trip. This is the best of the best!
As the days pass you’ll get more and more comfortable in the Grand Canyon, arriving at a new campsite each late afternoon and dining river-side. Delicious food that will amaze, the most incredible views and sleeping under the stars are just a precursor to waking up to one of the most magnificent sunrises you’ll ever see. Not only will your qualified and talented river guides prepare gourmet meals, but they are also well versed in geology, wildlife, canyon lore and trained in first aid for emergency situations.
Each morning you will enjoy waking up to freshly brewed coffee and a hearty breakfast. After camp has been taken down and boats loaded, you will spend several hours on and off of the river with one or two side canyon hikes each day. Depending on your location on the river, some days you will hike more and travel less, and others travel more and hike less. Your guides, who each have their own specialty be it geology, history, canyon lore, etc. will entertain you with endless knowledge while you enjoy the views of the million year old rock walls surrounding you.
All of the meals are prepared for you, and all camping gear is included. While at camp you have your choice either sleeping inside a tent or under the stars on a comfortable cot or sleeping pad, with a warm sleeping bag & sheet. Dry bags are also supplied so you can protect your items from water.
At Trips End
Depending on the outfitter’s itinerary, there are multiple take out points with no hike-out responsibility. The Whitmore Wash (Helipad) at river mile 188 includes a short helicopter ride to Bar 10 Ranch. From there a charter plane will return you to either your starting point or Las Vegas. Diamond Creek Road at river mile 225 includes ground transport to Flagstaff or Las Vegas. Lake Mead at river mile 280 includes a jet-boat ride from river mile 240 arriving at 280 where ground transport will return you to Las Vegas or your starting point.
Transportation Options for Colorado River Rafting
Transportation: Meeting locations depend on itineraries which vary from one outfitter to the next. Return transportation also depends as some trips end at the South Rim, while others include transportation to Flagstaff.Las Vegas NV: Trip may start here or you may use as a hub and take a charter flight to Marble Canyon if trip begins thereMarble Canyon AZ: Fly to Las Vegas, Charter flight to Marble Canyon or Drive from Las Vegas to Marble Canyon (4.5 hours) or from Phoenix to Marble Canyon (4 hours)Page AZ: Fly into Page by way of Phoenix, or arrive in Phoenix and drive to Page 4.5 hoursFlagstaff AZ: Fly into Flagstaff, or drive from Phoenix via car or shuttle service (2-4 hours) or from Las Vegas via car or shuttle service (4-6 hours)
We are a FREE SERVICE supported by our outfitters at absolutely no additional cost to you
We are a team of highly experienced experts, having voyaged every route in every raft down the Colorado River in the Grand Canyon.
|
{
"pile_set_name": "Pile-CC"
}
|
Enzyme-linked immunosorbent assay for detection of antibodies to varicella zoster virus.
A sensitive enzyme-linked immunosorbent assay (ELISA) is described for detection of varicella zoster virus (VZV) IgG antibodies. The antigen consisted of a sonicated extract of VZV-infected human embryo cells. Goat antihuman IgG peroxidase conjugate was used to detect human IgG bound to viral antigen. The results have been compared with those obtained by the indirect peroxidase antibody to membrane antigen technique (IPAMA). Comparison of titers obtained by ELISA with those obtained by IPAMA in sera of 41 medical students, six chickenpox patients and six herpes zoster patients showed good agreement between the tests as to the presence or absence of antibody. ELISA was about 88 times more sensitive than IPAMA. The specificity and sensitivity of ELISA as compared to other serologic techniques for detection of antibody to VZV is discussed.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Chickpea ‘Crab’ Cakes
BY Rosane Oliveira, DVM, PhD
Our Chickpea ‘Crab’ Cakes are a plant-based version of this New England/Mid-Atlantic classic. The chickpea base is combined with artichoke hearts, hearts of palm, breadcrumbs (to thicken), and a variety of seasonings. Making them is as simple as mixing the ingredients together, forming into patties, and then baking them to golden brown perfection. To complement the yumminess, we also include a recipe for dairy-free Tartar Sauce.
Directions
Pulse artichokes, chickpeas and hearts of palm in food processor until mixed and chunky.
Place mixture in bowl and combine with 1/2 cup breadcrumbs, Old Bay seasoning, Dijon mustard, lemon juice, and black pepper.
Sprinkle 1/4 cup breadcrumbs on a plate. Form mixture into patties then coat each in breadcrumbs.
Place on baking sheet. Bake 30–40 minutes, flipping halfway through.
Mix together Tartar Sauce ingredients. Serve with crab cakes.
*Greek-style dairy-free yogurt can also be used.
Rosane Oliveira, DVM, PhD
Rosane Oliveira, DVM, PhD is Founding Director of UC Davis Integrative Medicine and Adjunct Assistant Professor at the Department of Public Health Sciences at the School of Medicine at the University of California Davis. Blending a life-long passion for food and nutrition with over 20 years of scientific experience in genetic research, Dr. Oliveira is devoted to educating people about how food and lifestyle choices can affect genetic expression–i.e. how genes are turned on and off and either cause disease or promote health. She is a native of Rio de Janeiro, Brazil and has lived in the US since 2003.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
Questions About Vectors and Deleting Memory Associated With Them
I wrote a program a few months ago using Vectors. I used the clear() member function to "reset" the vectors, assuming that it would not only clear the items in the elements out and reset the size data member, but that it would also give the heap back the memory that was being used with it previously. Well, I stumbled onto a post about vectors saying that this is not the correct way to get memory back from the Vector, as using clear() will not do it, but that one needed to use the swap method:
vector<MyClass>().swap(myVector);
I'm curious as to why we have to call the swap to delete the old memory? I assume this is more of a workaround, in that we are using the swap, but something else is happening. Is a destructor being called at all?
One last question, all of the articles that I've now read saying that clear() doesn't deallocate memory that that the objects are "destroyed." Can anyone clarify what is meant by that? I'm unfamiliar with the vernacular. I assumed that if an object was destroyed, it was cleared out and the memory was given back to the heap, but this is wrong, so is the word "destroy" referring to just wiping the bits associated with each element? I'm not sure. Any help would be greatly appreciated. Thanks.
A:
To answer the question, you need to separate the memory directly allocated by the vector from memory indirectly "owned" through the member objects. So for example, say MyClass is an object taking 1000 bytes, and then you work with a std::vector<std::unique_ptr<MyClass>>. Then if that vector has 10 elements, the directly allocated memory will typically be close to 10*8=80 bytes on a 64-bit system, whereas the unique_ptr objects indirectly own 10*1000=10000 bytes.
Now, if you call clear() on the vector, the destructor is called on each unique_ptr element, so the 10000 indirectly-owned bytes are freed. However, the underlying array storage isn't freed, so the 80+ bytes directly owned by the vector are still allocated. (At this point, the vector has a capacity() of at least 10, but a size() of 0.) If you subsequently call the vector's destructor, that will cause the storage array to be freed as well.
Now, if you execute
std::vector<std::unique_ptr<MyClass>>().swap(v);
let's break down what that does: first, a temporary vector object is created, which has no allocated array and a capacity() of 0. Now, the swap transfers the underlying array of v to the temporary vector, and swaps the null or empty array from the temporary vector into v. Finally, at the end of the expression, the temporary object goes out of scope so its destructor is called. That causes the destructors of any elements previously belonging to v to be called, followed by freeing the underlying array storage that previously belonged to v. So at the end of this, v.capacity() is 0, and all memory previously belonging to v is freed, whether it was directly allocated by v or indirectly belonged to it through the stored unique_ptr objects.
|
{
"pile_set_name": "StackExchange"
}
|
NOTICES
I think people who opt to come to Korea to study should have the right expectations. They should know that people in Korea generally do not converse well in English. Therefore I think it is quite reasonable for them to be prepared to learn Korean before deciding to come here. The steep learning curve for… Read more
Author: Hilola Hakimova One of the biggest problems for Muslim students in Korea, I think, is finding halal food. There are very few places in Daejeon where you can have halal food and most of them being off campus. In this article I will introduce you to some places where you can find halal food. Close… Read more
Sport complex is labeled as N3 as we take a look on the campus map HERE. It is on the north side, near the auditorium and futsal field. There are several facilities that can be used in the sport complex, such as badminton court, basketball court, volleyball court, stage, dance room, fitness center, running track,… Read more
Author: Edrick Kwek Imagine something out of its natural habitat; a fish out of water. Being in an entirely foreign land as is Korea to internationals form something that indeed is a close match to the analogy (although the existence of a slight difference distinguishes the two). Adaptability, an indispensable human trait is what makes… Read more
|
{
"pile_set_name": "Pile-CC"
}
|
Oculus Facebook deal could ignite equity crowdfunding - bernardlunn
http://bernardlunn.wordpress.com/2014/03/30/oculus-facebook-deal-will-accelerate-equity-crowdfunding-and-change-the-world/
======
aaronbrethorst
The Oculus founders got $2.4m of free seed funding via Kickstarter.
No they didn't. They took money for pre-orders.
I believe that the Oculus Facebook deal will accelerate the equity
Crowdfunding revolution.
I don't doubt this for a second, but I bet you that the vast majority of
people who are allowed to invest in startups through the JOBS equity
crowdfunding provisions are going to lose their shirts.
even if a lot of people who gave free funding to Oculus via
Kickstarter in return for a beta product and a T Shirt feel
a bit burned today.
Why should any of them feel burned? They spent money in order to get a t-shirt
or an Oculus DK1.
FWIW, the terms were clear, the folks who ponied up cash were
promised an early version of the product and got what “it said
on the tin”.
Yep, exactly.
Personally I think how millions of people make a living
[via crowd funding]...is more interesting than...the VR
Oculus story.
Citation needed on that "millions of people" figure, and what does this have
to do with equity? Do you really think that the next musician who funds their
first album through a Kickstarter is going to hand out equity to their
backers?
If Oculus had been in the Valley they would have easily got
Angel funding – and given 25% to those Angels.
Um, Oculus raised almost $100mm after their Kickstarter. I would be astonished
if they didn't give up at least 25% of the company across those two rounds.
Still, it's pretty cool that they were able to skip raising a seed round, and
I don't doubt that the founders retained more equity than they would have
otherwise.
Nobody wants a bunch of T Shirts plus being the first kid
on the block with a new toy for $500m of equity value.
If Oculus had sold equity instead of product pre-orders I don't believe for a
second that their Series A round would have worked out nearly as well. I'd
much rather walk into a meeting with a VC with 7,400+ pre-orders for my
expensive gadget tucked under my arm than a list of people who ponied up a
thousand bucks for a sliver of equity in my company.
However we are still in the really, really early days of
crowdfunding, the days when we have not yet moved from the
“first they laugh at you” phase.
Right, because the Indian independence movement is _exactly_ like
crowdfunding.
~~~
BrainInAJar
> Right, because the Indian independence movement is exactly like
> crowdfunding.
Grandiose, self-important valley startup wank talk. Like "disrupting the
market" by making another bullshit website or app.
~~~
dang
This is a truly awful comment that should never be on Hacker News at all, let
alone upvoted. This is not because of what it says about "the valley", but
because of its form. It could be about anything else and be just as bad.
Please don't post this sort of thing.
(Edit: I completely rewrote my comment here, because I'm still getting the
hang of this. Also, all these feedback comments I've been adding are an
experiment in comment quality and transparency. We're going to keep
experimenting until we find things that work. I doubt that this experiment is
going to work, because I'm getting tired of writing these, and some of you are
no doubt tired of reading them.)
~~~
tptacek
I think these comments are awesome, but I can't imagine having to write them
regularly.
The "I'm burying the story" stuff is especially useful.
~~~
dang
I'm going to keep writing them for a while while we brainstorm alternatives.
It's good to do things manually for a long time before you figure out how to
automate them. That's how I wrote my HN moderation software.
~~~
rdl
I especially love how you generally stick to criticizing the action vs. the
person -- sort of like "this comment isn't appropriate for HN; please do
better" vs. "please die".
(I was just going through all your comments after seeing one; this is really
becoming the new 'pg: "Please stop"')
~~~
tptacek
Someone needs to buy Paul Graham a baseball cap with those words embroidered
onto it.
------
philmcc
I -guess- each $300 backer could've received $150,000 of stock/cash...
...if this kickstarter happened 6 months from now, as an equity kickstarter.
The 6 month number is sort of arbitrary, but the SEC is currently evaluating
Regulation Crowdfunding. Title III of the JOBS act.
(for more info, here [https://blogs.law.harvard.edu/corpgov/2013/12/06/jobs-
act-ti...](https://blogs.law.harvard.edu/corpgov/2013/12/06/jobs-act-title-
iii-crowdfunding-moves-closer-to-reality/))
Regulation Crowdfunding will allow "funding portals"
(kickstarter/indiegogo/etc) to facilitate equity based crowdfunding, with a
limit of up to $1,000,000.
We'll pretend that Oculus at $1mm KS has the same destiny as Oculus as a
$2.4mm KS. [I think in an equity world, people would be less inclined to
invest after that wall is hit.]
We'll ALSO pretend (here's the bigger stretch) that the subsequent rounds of
financing at $16mm and $75mm somehow magically didn't affect the equity of the
seed round. [Hahaha, hilarious.]
If the KS had stated that the $1mm was to own 25% of the company (I bet
he'd've done more, but we'll go low) that means that each $300 backing is
equivalent to %0.0003 of $1mm.
%0.0003 of 25% equity is %.000075 of Oculus.
%.000075 of 2 billion dollars is $150,000.
[I think. %50 chance I mucked this math up at some point.]
~~~
bernardlunn
I was only suggesting that the people who pony up the early cash get some
token equity. Lets say give up 5% to enthusiastic early adopters who share
your passion rather than 25% to angels. If say the $300 netted you $3,000
bonus on exit, you can have a party and celebrate the founder's good fortune.
Its a win/win (founders get lower cost of capital than angel route, early
adopters make some cash. Methinks we will see more of this, but only time will
tell.
------
ig1
The big problem that equity crowd-funding faces is that the seed rounds of
most top-tier companies are already over-subscribed; that means the only
startups who'll end up raising on equity crowd-funding sites are those who
can't raise the money from good angels.
Given angel investing follows the power law with the majority of returns
coming from a small number of companies not having access to the top 10% of
the deals vastly reduces your chance of having a decent return.
~~~
backprojection
What if, rather than offering equity, crowdfunders got voting rights instead.
I feel that most of the outrage from the Oculus deal is that people feel
betrayed. They could almost not have picked a worse outfit to have been bought
by (rightly or wrongly, the point here is sentiment). If there had been a
shareholder-esque vote, I think it's unlikely the deal would have been
approved.
So maybe that could be the deal going forward - sure I'll put up $100 to fund
your project, but that comes at the cost of you not selling out in the future.
EDIT: Clearly the weight of your vote would be proportional to your
investment.
~~~
mattzito
This would be disastrous for startups - for $100 you get a say in what we do?
How deep does that go? Change of control events? That would basically mean
that a startup would have to disclose that they were in negotiations for
acquisition/investment/whatever, with whom, and for how much. That would
basically mean potential acquisitions would become public knowledge - it's
hard enough keeping them quiet when it's just the startup, their investors,
and the acquirer involved.
~~~
backprojection
Well your vote would be proportional to your investment, $100 out of $2.4M, in
this case.
> That would basically mean potential acquisitions would become public
> knowledge
That would kind of be the point, it would be about fairness. People may not
want to invest in a promising project that could change the world, just for it
to be bought up by the next FB/Google.
------
samstave
[https://news.ycombinator.com/item?id=7471344](https://news.ycombinator.com/item?id=7471344)
So I am not the only one who thinks this;
" __ _Personally, I think this illustrates a severe gap in how crowd-funding
works. 10K drops by an individual are no different than an angel investor.
There should be a chip-in-level for crowd-funding campaigns that require the
OP to provide some % equity into the project._ __"
------
fragsworth
Crowdfunding could be a powerful way to fight against monopolies.
For instance, if a town's population cares enough, they can decide on their
own to invest $500-1000 per person in a series of fiber cables (and get equity
for it), making the initial costs more appealing to everyone involved.
Then the crowdfunding participants would receive dividends on the lease
payments for the lines.
~~~
ianbishop
Isn't that what a traditional co-op is?
~~~
andygates
Offering equity as well as gadgets is an interesting spin on the co-op model.
It works well enough; generally it's chosen for something that doesn't want
explosive growth but instead is serving a community -- and that might not gel
with the "get rich" urges of some startup types.
------
mcphage
Is the problem that people had with the Facebook deal really just that they
didn't get a cut?
~~~
yaeger
That would be stupid of them as nowhere did it say that was even a
possibility.
As the article says, everyone got what it said on the tin. After they received
their shirts and the dev kit, the kickstarter campaign was done. Period.
The only people who like to make a stink now are people like this Notch fellow
who throw a tantrum cause they don't like the business model of the company
that acquired Oculus.
Completely ignoring the facts that as a tech company, facebook really does a
lot of good things. Open Sourcing inhouse technology. Backer of the open
hardware project to mention two examples.
They all be better served to stay quite until it becomes evident that facebook
backtracked from their original statements and starts to call the shot at
Oculus. But that is of course not how angry, emotional people act. On the
internet or in real life.
I for one would have pre ordered the DK2 last week if I had the money and I
would pre order it today. And I look forward to call a lot of people out on
their hypocrisy once the final product launches and I notice people who swore
they were boycotting this and who swore they were so done with Oculus suddenly
raving about how great this thing is.
------
tormeh
Crowd investment is already happening. Check out Seedrs. The companies are
mostly uninspiring, but that will hopefully change at some point.
~~~
onehp
There's wefunder too ([https://wefunder.com/](https://wefunder.com/)) who are
getting set up to allow unaccredited (lower net worth) investors once the JOBS
act goes through.
------
HelloMcFly
The font on that article is all over the place.
~~~
dadrian
Agreed, I couldn't concentrate enough to even read it because the font kept
changing.
------
siglesias
We already have "equity crowd funding." It's called an IPO.
------
hershel
The main problem with crowdfunding is prevention of scams. The SEC which is
responsible for implementing this bill,have an expensive list of
demands(papers, lawyers) for companies wanting to go that route, making the
whole process not worthy for companies.
Until a solution for this problem will be found, it's hard to see crowd-
funding becoming an option.
~~~
swalsh
What prevents scams on kickstarter?
~~~
squidfood
A scam where you don't get one product you ordered is a different order of
magnitude than one where you lose a long-term stake in a company.
(For Kickstarter, it's the same thing that prevents scams over any online
exchange really - nothing except you might go after someone for fraud).
~~~
smsm42
Yes, the former is much worse - you're immediately don't get a useful product,
instead of not getting a paper which may or may not bring you some money
somewhere in the future if 1000 things align right. Note that most sales of
product actually end up in product being sold, while most startups end up
failing and wiping their investors clean. That is without any fraud - just
plain statistics.
------
Jonovono
Saskatchewan just started allowing something like this to exist. No one has
taken advantage of it (from what I have heard). I am thinking of looking more
into it:
[http://www.fcaa.gov.sk.ca/SKEC](http://www.fcaa.gov.sk.ca/SKEC)
------
bashcoder
It's possible that new investment instruments, such as YC's Safe [0] which
removes the friction of convertible notes by offering warrants for future
equity, could facilitate this sort of thing.
[0] [http://blog.ycombinator.com/announcing-the-safe-a-
replacemen...](http://blog.ycombinator.com/announcing-the-safe-a-replacement-
for-convertible-notes)
~~~
bashcoder
My point being, the OP lists four methods by which he thinks crowdfunding can
work (pre-order plus reward, equity, debt, and donation).
Each method has its own set of concerns for regulatory issues, requirements
for qualified investors, upside potential, tax implications, etc.
My point is that there may be other possible options, and I point to Safe as a
good example of how VC can innovate and remove friction from raising startup
capital.
------
everyone
What language is this article written in?
------
notastartup
equity crowdfunding is a bad idea. it's an open invitation for government
regulation for something that works really well right now.
Next time you want to make a game on kickstarter and share the wealth with
"investors", you are going to be facing the SEC and fending off people's
lawsuits.
Not to mention people getting scammed appearing on News would ruin the whole
crowdfunding movement.
|
{
"pile_set_name": "HackerNews"
}
|
Q:
TP Link TD-W8968 how to view data statistics based on ip
I have a tp link modem and multiple device connected to it. I want to see which device is eating up all the bandwidth and crossing my data limit. How can I see that?
I have my mobile phone, pc, laptop, tablet all connected to it. If I can see which device used how much bandwidth or total data, I can judge by that.
Not sure if this is the right place to ask this question.
A:
The hardware version of your modem router is V3 where as you are checking the document of hardware V1. Please have a look on the document of V3 hardware. It seems that the feature is not available with hardware V3.
|
{
"pile_set_name": "StackExchange"
}
|
Artificial respiration has long been recognized as a method whereby one person can induce another, having stopped breathing, to respire. Heretofore, artificial respiration has included putting the person to receive artificial respiration on their back and tilting their head back to open the air passage to the lungs. Making sure the tongue is not obstructing the air passage, the person's nostrils are closed and the respiring person places his/her mouth over that of the person receiving artificial respiration and respiring air is blown into the person's mouth and lungs. Pulling back, the respiring air is exhaled from the lungs and mouth. This process is repeated until, for example, emergency assistance arrives.
If available, a person can artificially respire using a mouth and nose covering mask and a collapsible bag. Holding the mask over the person's nose and mouth the bag is collapsed and released to provide artificial respiration.
With diseases such as herpes, syphilis, acquired immunodeficiency syndrome (AIDS) and others, reluctance has been expressed by some to render artificial respiration. This is true since one must make intimate, mouth-to-mouth contact with the person who is to receive artificial respiration. Even if a bag respirator is available, it is often difficult to obtain a good seal about the nose and mouth for a proper respiration.
Hence, a need is seen for an inexpensive, efficient and compact device to assist in providing artificial respiration.
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
Fate of the residual distal and proximal aorta after acute type a dissection repair using a contemporary surgical reconstruction algorithm.
In this study, we evaluated the long-term results of our contemporary, standardized surgical management algorithm for repair of acute type A aortic dissections. Prior reports have analyzed heterogeneous techniques and populations. From 1993 to 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our aortic center. Hemiarch repair was performed in 97.7% (216 of 221), and total arch in 2.3% (5 of 221). Of these, 72.9% (161 of 221) underwent aortic valve resuspension, and 27.1% (60 of 221) had aortic root replacement. In-hospital mortality for a primary operation was 12.7% (28 of 221). Actuarial survival was 79.2% at 1 year, 62.8% at 5 years, and 46.3% at 10 years. Significant risk factors for decreased survival included prior stroke, cerebral malperfusion, and length of cardiopulmonary bypass. Freedom from proximal reoperation after aortic valve resuspension was 94.6% at 5 years and 76.8% at 10 years, with cardiac malperfusion as the main risk factor. Freedom from distal reoperation was 87.6% at 5 years and 76.4% at 10 years, with Marfan syndrome, age, and extent of dissection as significant risk factors for reoperation. In-hospital mortality was 18.2% (2 of 11) after proximal reoperation and 31.2% (5 of 16) after distal reoperation. We report improved long-term durability of our proximal root repair, with cardiac malperfusion as a significant risk factor. Marfan disease, younger age, and DeBakey type I dissection are risk factors for distal reoperation. To further improve long-term outcome, means to prevent progression of distal aortic disease need to be developed.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
In a large non-stick stockpot, heat a bit of vegetable oil in the pot. Lightly brown the venison in the pot.
Once the venison is browned, remove the meat from the pot, and set it aside. Cover the meat so it doesn't dry out.
Add the onions, celery, carrots, and potatoes to the stockpot. (You may need to add a bit more vegetable oil to the pot.) Lightly saute' the vegetables for about 5 minutes.
In a 6-quart crock-pot or slow-cooker, add the browned venison, cooked vegetables, beef broth, tomato sauce, bouillon granules, and the pepper. Cover, and cook on high for 3 hours.
After the 3 hours of cooking time, remove 2 cups of the broth, and add it to a 3-quart saucepan. At this point, add the thawed peas and well drained sliced mushrooms to the crock-pot, and cover the crockpot.
To the 3-quart saucepan, bring the broth to a boil, then add the 2/3 cup of barley, Cover the pan, reduce the heat to a simmer, and simmer the barley for 10 minutes. Be sure to stir the barley frequently, so it doesn't stick to the pan. The liquid/broth will be reduced and absorb the barley.
Now add the cooked barley into the crock-pot and stir. Ladle the stew into the bowls and serve.
|
{
"pile_set_name": "Pile-CC"
}
|
I have a meeting at EECC which is scheduled from 1130-130, but there is a
risk it will run long. 300 would be better.
Thanks for setting this up.
Kay
From: Kathleen Carnahan 01/29/2001 08:02 AM
To: Kay Mann/Corp/Enron@Enron, Fred Mitro/HOU/ECT@ECT, Rusty
Stevens/Corp/Enron@ENRON
cc:
Subject: Meeting with Herman Manis
Herman can meet with us at 2:00 today in his office EB 3394. Please let me
know if this time isa okay with you and I will call him to confirm it.
Thanks.
Kathleen
|
{
"pile_set_name": "Enron Emails"
}
|
/(-14))*(17 - 37)/(-80).
-1/14
Evaluate (310/186)/(5/(-4))*(-18)/4.
6
What is 4 + -7 + (9 - 22)?
-16
Evaluate -16*(18/(-4))/(-9).
-8
What is (-4)/(-10) + (8 - (-6 + (-1529)/(-110)))?
1/2
Evaluate (65/40 + 21/(-14))*(-3)/(-3).
1/8
What is the value of (2 + 2/(-24)*22)*(1 + 2)?
1/2
(-134)/16 + 108/192*(-8)/(-12)
-8
What is the value of 10/(-4) + (-99)/66 - (-10)/4?
-3/2
What is the value of 13/(-5)*(2 + -1)?
-13/5
Calculate 360/12*(-12)/20.
-18
What is 10/15 + 528/99?
6
Evaluate (-45288)/1368 + (-2)/(-19).
-33
What is the value of (-289 - -275 - 592/(-42))/(-2)?
-1/21
-9 + (-32)/20*(-150)/40
-3
What is (-15 + 0)*15/36*448/280?
-10
Evaluate 8/(-10)*25/70.
-2/7
What is the value of (-38)/(-133) + (-180)/42?
-4
What is the value of (18/(-10))/(94/470)?
-9
What is (0 - -3)/(-42 + 8260/196)?
21
Calculate (48 - 32 - 7) + -17.
-8
(-9)/12*688/258
-2
Evaluate 6 + -2 - (-18 - -32).
-10
Calculate (-161)/2*(-3462)/(-12117).
-23
What is the value of ((-21)/(-35))/(6/135)*(-42)/(-63)?
9
What is the value of 22 + 1/(19/(-34) + (-29)/(-493))?
20
Evaluate (30/5)/((-80)/160).
-12
-8 - 75/(-15) - (-1 - 0)
-2
Evaluate 3/4*(-1190)/255*36/21.
-6
Calculate -2 + 27/(-20) + 221/(-884).
-18/5
What is the value of (-4 + (-48)/(-18))/(-4)?
1/3
Evaluate (-28)/(-3*11/(-99)*(-6 + 0)).
14
Calculate 21 + -28 + 0/(-17).
-7
What is the value of 1002/(-1503)*(-153)/6?
17
Calculate 5681/(-247) + -3 + 52.
26
Evaluate (-924)/847 + (-40)/44.
-2
What is the value of 57/741*(-169)/(-195)?
1/15
Evaluate (50 + 15 + -31)/(-2).
-17
Evaluate 24/130*(3 + (-45)/90).
6/13
What is the value of ((-238)/(-2))/(120/(-16)) - (-8)/(-60)?
-16
Evaluate (-78)/378 + 14/(-63) + 0/8.
-3/7
Calculate ((-4576)/286)/((-4)/1)*2.
8
What is 0 - (-19 + 169/26 + (-3)/(-2))?
11
2600/(-108) + (-4)/(-54)
-24
What is 150/(-40)*28/(-70)?
3/2
(780/66)/2 + 37/((-296)/48)
-1/11
What is the value of (4 - (1 - 84/(-30))) + (-1)/(-5)?
2/5
What is (-5)/4 + 15810/(-11160)?
-8/3
Calculate (5 - 9)*((-68)/(-16) - 2).
-9
Calculate ((-12906)/16491)/((-1)/23).
18
Evaluate -3 + 7/(7 - 8) - -5.
-5
What is the value of 33/66*(15/27 - 1)?
-2/9
Calculate (-30)/3*((-8)/(-36) + (-7)/(-9)).
-10
What is (-170)/(-12) - 20/130*91?
1/6
What is (93/(-9) + 12)/((-2)/(-30)*5)?
5
What is 6/1 - ((-2088)/(-360) - (0 - 0))?
1/5
Evaluate -6 + 12/(-6) + 9 + (-9 - -8).
0
What is 16/9 - (23 - (8 + 3) - 10)?
-2/9
Calculate (-11 - (-30 - -15)) + (-10 - -18 - 1).
11
Evaluate 30/15 - (86/18 - (-10)/45).
-3
What is the value of 120/22*(-3729)/678?
-30
What is the value of (-365)/4745 + 10*2/(-78)?
-1/3
Calculate ((-2790)/(-84))/15 - (44/8 + -4).
5/7
What is the value of -8 + (44/(-3))/((-74)/111)?
14
Evaluate 4/24 + (-1792)/672.
-5/2
Evaluate 60/(-3) + 0 - (-39 - -49).
-30
What is (0 - 14) + (80/(-24))/((-8)/12)?
-9
Evaluate 5/((116/264)/(-29)*-15).
22
What is (4 - 516/30)*(-25)/15?
22
Calculate (1 - 0)/(10/(-2400)*-24).
10
What is 16/((-144)/(-45)) + -6?
-1
Calculate (-595)/(-34629)*42/(-35).
-2/97
What is 14/(-25)*-5*-5?
-14
What is -12 + -11 + 8 + 3/1?
-12
(72/252)/(((-2)/28)/((-9)/(-30)))
-6/5
Evaluate 10/(-3)*(-1232)/1760.
7/3
(-1)/40*-340*(0 - -2)
17
Calculate (-8)/(-12)*(8 - 2)*(-20)/(-16).
5
What is ((-104)/260)/((-12)/(-15))*66?
-33
What is the value of 304/(-532) - (1 - (-183)/(-112))?
1/16
What is the value of (-35)/((-1050)/60) + (-259)/140?
3/20
((6/4)/(13/(-39)))/((-6)/28)
21
152/(-198) + 2/9
-6/11
(-9)/8 + 558/240
6/5
Calculate (-4 + 3 + (-30)/(-38))/(1 + 1).
-2/19
Calculate ((-1578)/(-1315))/(1/(-15)).
-18
Calculate -69*((888/(-24))/(-111))/(0 - 1).
23
What is the value of 2296/(-144) - 2 - 20/360?
-18
Evaluate (-186)/(-403) - 536/1274.
2/49
Evaluate (1 + -21)*(6/(-32))/((-4)/16).
-15
Evaluate (3 + -2)/((-1)/((-9)/(-36))).
-1/4
Calculate (-7)/((-42)/24) + 3 + (-12395)/1776.
1/48
5274/3809 + (-2616)/1833
-2/47
Evaluate ((16/(-16))/(7/(-2)))/(3 - 4).
-2/7
Evaluate 6/3 - (54/45 + 130/(-25)).
6
Evaluate (275/50)/(33/192).
32
Evaluate 1/(6/(-16))*68/((-1224)/81).
12
136/(-22) - (-56)/308
-6
36/(-3) + 1030/85
2/17
What is 2 - 72/28*(-14)/3?
14
What is (-39)/(-21) + -1 - (-5 + (-1600)/(-266))?
-3/19
What is the value of 2/(-27) + (-124930)/8370?
-15
What is the value of ((-20)/12)/((-65)/78)?
2
Evaluate (-283 + 278)*4/(-500).
1/25
What is 8 + -3*871/312?
-3/8
What is the value of -581*(-7)/343 - 5/(-35)?
12
What is the value of -10 + (-2 + 1 - (-5355)/495)?
-2/11
35/1*(66/(-30))/(-11)
7
Calculate -112*(-32)/(-7360) + (-2)/(-5).
-2/23
What is (-65)/(2275/1260) - -39?
3
What is ((-247)/52 - -11)/5?
5/4
Evaluate ((-30)/(-48))/(-45*120/(-864)).
1/10
Calculate 1/4 - ((-5)/25 - 3857/140).
28
What is the value of 89/143 + 27/297*6/(-1)?
1/13
What is the value of (1/(-3))/(59/236)?
-4/3
What is (2 - 30) + 39420/1410?
-2/47
Evaluate (-665)/30 + ((-2100)/(-1470))/(12/(-7)).
-23
(-28)/35 + (-2502)/(-90)
27
Evaluate ((-1900)/7)/(-10) - 2*(-6)/14.
28
Calculate (-531)/(-4956)*(-14)/4.
-3/8
What is the value of -6*(-21)/(36540/10)?
1/29
Calculate (-17 - 2581/(-145))*-5.
-4
What is the value of ((-3)/(-9))/((-494)/(-28158))?
19
What is the value of 36/6 + -9 + -2*7/2?
-10
What is (-3)/2*16224/(-936)?
26
45/6 + (-221)/(-34)
14
What is (-66)/(-308)*(-315)/60?
-9/8
((-3)/3)/(2160/198 - 11)
11
Calculate 9828/(-693) - 24/(-132).
-14
Calculate 109/(-327)*(-2)/(-4).
-1/6
What is 62/(-120) - (10/(-145) - 315/1740)?
-4/15
4/((-48)/(-28)) + -2 + (-16)/(-24)
1
((-9)/(-42))/((-6)/(-8)) + (-7 - -7)
2/7
Calculate ((-78)/(-1690))/((-30)/100).
-2/13
What is the value of (152/36 - 4)/((-8 + -1)/(-9))?
2/9
What is the value of 15/12 - 49/((-588)/(-351))?
-28
((-18)/(-1188) - 7/(-42))/(-2)
-1/11
(22/10 - 1)/(-14 + (-5069)/(-370))
-4
Evaluate (1/(-2))/((-194)/(-6596)).
-17
What is (-4)/(10 + -2)*20*9/6?
-15
What is the value of 2/(-22 + 13536/612)?
17
Evaluate -1 + 75 + (-10440)/232.
29
What is 26/91 - 180/385 - (-39)/33?
1
Calculate ((-33)/6)/((-223)/(-446)).
-11
What is (-3)/(7/112*12)?
-4
Evaluate 3/((-1)/(6/(-3))) + 5.
11
Evaluate 2/(1*(-18)/9)*85/10.
-17/2
Evaluate (2*2/(-344))/(222/(-888)).
2/43
48/18*(150/220)/(-5)
-4/11
What is (-476)/68 + (390/55 - (-1 - -1))?
1/11
What is the value of (27/(-2))/(3*3/18)?
-27
((-52)/(-156))/((-5)/75) + -4
-9
What is 204/(-2907)*18/(-12)?
2/19
(-8)/(-16) + 1 + -6 + (-4416)/(-1152)
-2/3
Calculate (-582)/485*(-4)/(-8).
-3/5
Evaluate 16/(-7) + (-750)/(-2625).
-2
What is the value of (-10 - 190/(-20))/((-5)/(-2))?
-1/5
Evaluate 6/(-9) + -1*(-55)/33.
1
What is -93*(-30)/90 - 15?
16
Calculate ((-57)/475)/((-45)/(-75)).
-1/5
Evaluate (264/26)/(-2) + -13*60/(-156).
-1/13
Evaluate (-2)/(-25)*(19 + -29).
-4/5
Calculate (1 - -3) + 209/(-24) - (-84)/224.
-13/3
What is 2/((-112)/(-343)) + (-1 - (5 - 0))?
1/8
Calculate (0 + 2)/((-73)/438).
-12
740/(-5920) + (-1)/(-2)
3/8
Calculate 12 - 1079/91 - -2*(-25)/154.
-2/11
Calculate ((-250)/45)/5*(-10 + 228/30).
8/3
What is (-95)/57*(8/(-6))/((-208)/468)?
-5
What is 1023/(-77) - -25*9/(-315)?
-14
Calculate -3 - -13 - (1 - (-133)/(-19)).
16
Calculate (1/((-6)/12))/12 + (-1)/(-6).
0
Evaluate (-4)/(-24)*(48/(-20) + 20/50).
-1/3
Evaluate 4214/2580 + 2/(-15) + (-51)/26.
-6/13
What is the value of (9 - 4) + -9 - ((-400)/(-56))/(-2)?
-3/7
Evaluate (-320)/4080*(-3)/4.
1/17
Calculate (18 - 4 - 685/50) + (-323)/10.
-32
18/28 - (-28 + (-495)/(-18))
8/7
(18 + 0)*((-2)/(-4)*-1)/(-1)
9
((-171)/114)/((-1)/2)
3
6/(-16) - (-4221)/2680
6/5
370/35 + -3 + 72/21
11
Evaluate ((-52)/(-50))/13 + (-7270)/(-750)*-3.
-29
What is the value of ((-31407)/(-667) - 47) + -1 + 602/(-46)?
-14
Calculate (-87)/7 + -40 + (-22356)/(-567).
-13
Calculate (1/(-21))/(-5 - 363/(-77)).
1/6
Evaluate 112/294*2 - 6/9.
2/21
What is the value of (12/(-21) + (-936)/(-1344))/((-39)/(-572))?
11/6
Calculate -112*(-8)/32 + -12.
16
Evaluate 30/5*-1 + -5 + 129/12.
-1/4
Evaluate (-2794)/(-48895) + 593/35.
17
What is (-2)/(-7) - (-2055)/(-5754)?
-1/14
Calculate (2160/5)/18 - 10.
14
Calculate -13 + (-9849)/(-756) + 2/(-8).
-2/9
What is the value of (-108)/12 + 5 + 1/((-15)/(-57))?
-1/5
((-89)/(-10) - 128/320)/(27/(-18))
-17/3
What is 356506/193070 - (-2)/(-43)?
9/5
What is the value of (-21*273/(-588))/(9/12)?
13
Calculate (-19 + (-438)/(-24))/((30/(-56))/1).
7/5
Calculate 356/(-1869)*(-3)/(-2).
-2/7
What is the value of (16/(-28))/((-1900)/(-266))?
-2/25
Evaluate -9*(2/
|
{
"pile_set_name": "DM Mathematics"
}
|
---
abstract: 'The off-axis location of the Advanced Camera for Surveys (ACS) is the chief (but not sole) cause of strong geometric distortion in all detectors: the Wide Field Camera (WFC), High Resolution Camera (HRC), and Solar Blind Camera (SBC). Dithered observations of rich star cluster fields are used to calibrate the distortion. We describe the observations obtained, the algorithms used to perform the calibrations and the accuracy achieved.'
author:
- 'G.R. Meurer$^1$, D. Lindler$^2$, J.P. Blakeslee$^1$, C. Cox$^3$, A.R. Martel$^1$, H.D. Tran$^1$, R.J. Bouwens$^4$, H.C. Ford$^1$, M. Clampin$^3$, G.F. Hartig$^3$, M. Sirianni$^1$, & G. de Marchi$^3$'
title: Calibration of Geometric Distortion in the ACS Detectors
---
Introduction
============
Images from the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) suffer from strong geometric distortion: the square pixels of its detectors project to trapezoids of varying area across the field of view. The tilted focal surface with respect to the chief ray is the primary source of distortion of all three ACS detectors. In addition, The HST Optical Telescope Assembly induces distortion as does the ACS M2 and IM2 mirrors (which are designed to remove HST’s spherical aberration). The SBC’s optics include a photo-cathode and micro-channel plate which also induce distortion.
Here we describe our method of calibrating the geometric distortion using dithered observations of star clusters. The distortion solutions we derived are given in the IDC tables delivered in Nov 2002, and currently implemented in the STScI CALACS pipeline. This paper is a more up to date summary of our results than that presented at the workshop. An expanded description of our procedures is given by Meurer (2002).
Method
======
[**Observations**]{}. The ACS SMOV geometric distortion campaign consisted of two HST observing programs: 9028 which targeted the core of 47 Tucanae (NGC 104) with the WFC and HRC, and 9027 which consisted of SBC observations of NGC 6681. Additional observations from programs 9011, 9018, 9019, 9024 and 9443 were used as additional sources of data, to check the results, and to constrain the absolute pointing of the telescope.
The CCD exposures of 47 Tucanae were designed to well detect stars on the main sequence turn-off at $m_B = 17.5$ in each frame. This allows for a high density of stars with relatively short exposures. The F475W filter (Sloan g’) was used for the CCD observations so as to minimize the number of saturated red giant branch stars in the field. For the HRC two 60s exposures were taken at each pointing, while for the WFC which has a larger time overhead, only one such exposure was obtained per pointing. Simulated images made prior to launch, as well as archival WFPC2 images from Gilliland et al. (2000) were used to check that crowding would not be an issue. For calibrating the distortion in the SBC we used exposures of NGC 6681 (300s - 450s) which was chosen for the relatively high density of UV emitters (hot horizontal branch stars). The pointing center was dithered around each star field. For the WFC and HRC pointings, the dither pattern was designed so that the offsets between all pairs of images adequately, and non-redundantly, samples all spatial scales from about 5 pixels to 3/4 the detector size. For the SBC pointings, a more regular pattern of offsets is used augmented by a series of 5 pixel offsets.
[**Distortion model**]{}. The heart of the distortion model relates pixel position ($x,y$) to sky position using a polynomial transformation (Hack & Cox, 2000) given by: $$x_c = \sum_{m=0}^{k}\sum_{n=0}^{m} a_{m,n}(x - x_r)^n (y - y_r)^{m-n}\, , \hspace{0.5cm}
y_c = \sum_{m=0}^{k}\sum_{n=0}^{m} b_{m,n}(x - x_r)^n (y - y_r)^{m-n}$$ Here $k$ is the order of the fit, $x_r,y_r$ is the reference pixel, taken to be the center of each detector, or WFC chip, and $x_c,y_c$ are undistorted image coordinates. The coefficients to the fits, $a_{m,n}$ and $b_{m,n}$, are free parameters. For the WFC, an offset is applied to get the two CCD chips on the same coordinate system: $$X' = x_c + \Delta{x}{\rm (chip\#)}\, , \hspace{0.5cm}
Y' = y_c + \Delta{y}{\rm (chip\#)}.$$ $\Delta{x}{\rm (chip\#)},\Delta{y}{\rm (chip\#)}$ are 0,0 for WFC’s chip 1 (as indicated by the FITS CCDCHIP keyword) and correspond to the separation between chips 1 and 2 for chip 2. The chip 2 offsets are free parameters in our fit. $X',Y'$ correspond to tangential plane positions in arcseconds which we tie to the HST $V2, V3$ coordinate system. Next the positions are corrected for velocity aberration: $X =
\gamma X'$, $Y = \gamma Y'$, where $$\gamma = \frac{1 + {\bf u} \cdot {\bf v} / c}{1 - (v/c)^2}.$$ Here [**u**]{} is the unit vector towards the target and [**v**]{} is the velocity vector of the telescope (heliocentric plus orbital). Neglect of the velocity aberration correction can result in misalignments on order of a pixel for WFC images taken six months apart for targets near the ecliptic. Finally, we must transform all frames to the same coordinate grid on the sky $X_{\rm sky}, Y_{\rm sky}$: $$X_{\rm sky} = \cos \Delta \theta_i X - \sin \Delta \theta_i Y + \Delta X_i\, , \hspace{0.5cm}
Y_{\rm sky} = \sin \Delta \theta_i X + \cos \Delta \theta_i Y + \Delta Y_i$$ where the free parameters $\Delta X_i, \Delta Y_i, \Delta \theta_i$ are the position and rotation offsets of frame $i$.
[**Calibration algorithm**]{}. We use the positions of stars observed multiple times in the dithered star fields to iteratively solve for the free parameters in the distortion solution: fit coefficients $a_{m,n}, b_{m,n}$; chip 2 offsets $\Delta x{\rm (chip\, 2)}, \Delta
y{\rm (chip\, 2)}$ (WFC only); frame offsets $\Delta X_i, \Delta Y_i,
\Delta \theta_i$; and tangential plane position $X_{\rm sky}, Y_{\rm
sky}$ of each star used in the fit. The stars are selected by finding local maxima above a selected threshold. The centroid in a $7 \times 7$ box about the local maximum is compared to Gaussian fits to the $x, y$ profiles, if the two estimates of position differ by more than 0.25 pixels, the measurement is rejected as likely being effected by a cosmic ray hit or crowding. Further details of the fit algorithm can be found in Meurer et al. (2002).
[**Low order terms**]{}. Originally only SMOV images taken with a single roll angle were used to define the distortion solutions. The solution using only these data is degenerate in the zeroth (absolute pointing) and linear terms (scale, skewness). So we used the largest commanded offsets with a given guide star pair to set the linear terms. However, comparison of corrected coordinates to astrometric positions showed that residual skewness in the solution remained. Hence, as of November 2002, the IDC tables for WFC and SBC are based on data from multiple roll angles. The overall plate scale is set by the largest commanded offset. For the HRC, the linear scale is set by matching HRC and WFC coordinates, since the same field was used in the SMOV observations. The zeroth order terms (position of the ACS apertures in the HST $V2,V3$ frame) was determined from observations of an astrometric field.
Results
=======
-------- ------ ------------ -------- ----------- -------- ------------ ------------ -------
pixel
Camera chip size Filter Pointings $N$ rms(x) rms(y) Notes
\[arcsec\] \[pixels\] \[pixels\]
WFC 1 0.05 F475W 25 142289 0.042 0.045
WFC 2 0.05 F475W 25 103453 0.035 0.037
WFC 1 0.05 F775W 10 31652 0.050 0.056 2
WFC 2 0.05 F775W 10 33834 0.041 0.048 2
HRC 0.025 F475W 20 77433 0.027 0.026
HRC 0.025 F775W 13 31515 0.026 0.043 3
HRC 0.025 F220W 12 14715 0.112 0.108 3
SBC 0.03 F125LP 34 1561 0.109 0.094
-------- ------ ------------ -------- ----------- -------- ------------ ------------ -------
: Summary of fit results[]{data-label="t:res"}
The distortion in all ACS detectors is highly non-linear as illustrated in Fig. \[f:nonlin\]. We find that a quartic fit ($k=4$) is adequate for characterizing the distortion to an accuracy much better than our requirement of 0.2 pixels over the entire field of view. Table \[t:res\] summarizes the rms of the fits to the various datasets.
The WFC and HRC fits were all to F475W data as noted above. To check the wavelength dependence of the distortion we used data obtained with F775W (WFC and HRC) and F220W (HRC) from programs 9018 and 9019. We held the coefficients fixed and only fit the offsets in order to check whether a single distortion solution is sufficient for each detector. Table 2 shows that there is a marginal increase in the rms for the red data of the WFC, little or no increase in the fit rms for the red HRC data, but a significant increase in the rms using the UV data. An examination of the HRC F220W images reveals the most likely cause: the stellar PSF is elongated by 0.1". A similar elongation can also be seen in SBC PSFs. We attribute this to aberration in the optics of either the ACS M1 or M2 mirrors or the HST OTA (Hartig, et al., 2002). The aberration amounts to 0.1 waves at 1600Å, but is negligible relative to optical wavelengths, hence it is not apparent in optical HRC images. While it was expected that the same distortion solution would be applicable to all filters except the polarizers, recent work (by Tom Brown, STScI, and our team) has shown that at least one other optical filter (F814W) induces a significant plate scale change (factor of $\sim 4 \times 10^{-5}$). In the long term, the IDC tables will be selected by filter in the STScI CALACS pipeline.
While a quartic solution is adequate for most purposes, binned residual maps (Fig. \[f:resid\]) show that there are significant coherent residuals in the WFC and HRC solutions. These have amplitudes up to $\sim 0.1$ pixels. The small-scale geometric distortion is the subject of the Anderson & King contribution to this proceedings.
Hack, W., & Cox, C. 2000, ISR ACS 2000-11, STScI. Hartig, G. et al. 2002, in “Future EUV and UV Visible Space Astrophysics Missions and Instrumentation”, eds. J.C. Blades & O.H. Siegmund, Proc. SPIE, Vol. 4854, in press \[4854-30\]. Gilliland, R.L. et al. 2000, ApJ, 545, L47. Meurer, G.R. et al. 2002, in “Future EUV and UV Visible Space Astrophysics Missions and Instrumentation”, eds. J.C. Blades & O.H. Siegmund, Proc. SPIE, Vol. 4854, in press \[4854-30\].
|
{
"pile_set_name": "ArXiv"
}
|
Clinical pharmacology of flumazenil.
(1) Flumazenil is a highly specific benzodiazepine (BZ) antagonist. It exerts its effect by competitive interaction at the BZ receptor site. (ii) Flumazenil antagonizes all central BZ effects irrespective of its contiguity to the BZ administration. (iii) The pharmacological effect of flumazenil depends upon the number of BZ receptors that can be occupied by flumazenil according to the mass-action law. Receptor occupancy is determined by the affinity of the BZ for the receptor and the free BZ concentration near the receptor. (iv) The minimal effective dose of flumazenil is 0.2 mg. After extreme BZ overdose 1 mg may be needed. (v) The optimal dosing strategy starts with an initial dose of flumazenil 0.2 mg i.v. The administration of further low doses of 0.1 mg at 1-min intervals allows the interruption of the injection of flumazenil exactly at the stage of vigilance that is most convenient for the patient. (vi) The duration of effect depends upon the type and dose of the administered BZ, the dose of flumazenil, and the time interval between flumazenil and the BZ administration. (vii) The therapeutic or safety index is above 3000, which means that a 3000 times overdose is still tolerated.
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{
"pile_set_name": "PubMed Abstracts"
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[Results of measuring neutrons doses and energy spectra inside Russian segment of the International Space Station in experiment "Matryoshka-R" using bubble detectors during the ISS-24-34 missions].
The paper presents the results of calculating the equivalent dose from and energy spectrum of neutrons in the right-hand crewquarters in module Zvezda of the ISS Russian segment. Dose measurements were made in the period between July, 2010 and November, 2012 (ISS Missions 24-34) by research equipment including the bubble dosimeter as part of experiment "Matryoshka-R". Neutron energy spectra in the crewquarters are in good agreement with what has been calculated for the ISS USOS and, earlier, for the MIR orbital station. The neutron dose rate has been found to amount to 196 +/- 23 microSv/d on Zvezda panel-443 (crewquarters) and 179 +/- 16 microSv/d on the "Shielding shutter" surface in the crewquarters.
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{
"pile_set_name": "PubMed Abstracts"
}
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Emergency personnel enter the home at 8545 De Havilland Court on Oct. 19, 2014, after Eric Deffendall was found shot to death on the floor of the first-floor family room in the Vero Beach home. (FILE PHOTO)
SHARE Mark Deffendall Eric Deffendall
By Dan Garcia, Special to Treasure Coast Newspapers
VERO BEACH — A 41-year-old man who is claiming a "stand your ground" defense after fatally shooting his older brother in 2014 during a drunken fight in their Indian River Aerodrome home testified April 1 he simply can't remember any details of the shooting.
Mark E. Deffendall, who is charged with first-degree murder in the shooting death of Eric Deffendall, 42, testified he and his brother argued during a long night of drinking and drug use, but he could not recall details of the actual shooting.
Under questioning by Assistant State Attorney Chris Taylor, Mark Deffendall repeatedly testified "I don't remember" when asked to recall how the violence culminated on Oct. 19, 2014.
The hearing before Circuit Judge Cynthia L. Cox was the first of several pretrial hearings in which witnesses will testify for the defense and the prosecution. Cox will issue a ruling on whether the "stand your ground" defense applies in the case.
According to Florida's "stand your ground" law, a person may use deadly force in self-defense if he or she is in imminent threat of death or great bodily harm.
If Deffendall is successful in claiming a "stand your ground" defense, the charge of first-degree murder cannot be brought before a jury, and it would be dismissed.
However, Deffendall did not shed much light in the case by repeatedly claiming he could not remember critical details of the shooting.
Deffendall testified he and his brother fought frequently, but this time he said he feared for his life after they physically fought downstairs in their home, at 8545 De Havilland Court.
Both brothers previously had been arrested for DUI and battery and had frequently fought, "but this time it was different," Deffendall testified, because Eric Deffendall angrily followed him up the stairs after a fight downstairs.
Deffendall testified he feared for his life because his brother had not previously chased him up the stairs, where Mark Deffendall slept.
But Taylor asked Deffendall why he took the time to take a shower if he feared his brother would come upstairs and attack him.
"I don't recall," Deffendall testified Friday.
Deffendall said he grabbed his gun, a Russian 9 mm Makarov, because his brother also owned guns, but he admitted Eric Deffendall did not have a gun when he headed upstairs.
Under questioning by his lawyer, Assistant Public Defender Kiernan P. Moylan, Mark Deffendall said that before the shooting, the brothers fought in their Aerodome home after drinking and smoking cocaine.
Deffendall said "he (Eric Deffendall) grabbed me by the neck and slammed me over backward and started pummeling me. I had a gash in my head and my nose was busted."
Mark Deffendall was arrested at Indian River Medical Center in Vero Beach, where he had gone for treatment of cuts and bruises and an injury to his nose.
But Taylor asked Deffendall: "How big was the laceration? Does 1 centimeter sound correct? And your nose was not treated because your nose was not broken, correct?"
"I'm not sure," Deffendall replied.
Mark Deffendall testified he fired two shots as his brother was coming upstairs, but he does not know if he hit him as the victim retreated.
Prosecutors charged Deffendall with pursuing his brother into the living and dining rooms, shooting him four times.
"Was he facing down?" when Eric Deffendall was shot, Taylor asked.
"I don't recall," the defendant replied.
"What was going on in your mind when you shot your brother in the face point-blank?" Taylor asked.
"I don't remember," Deffendall replied.
"How many times did you shoot him downstairs?" Taylor asked.
"Are you asking me from my memory or from what I have read?" Deffendall said. "From my personal knowledge, I don't remember going into the living room."
Taylor asked Deffendall: "Do you know if you shot your brother at all?"
Deffendall's attorney called two witnesses who were boyhood friends of the Deffendalls and they recalled Eric Deffendall got the better of his brother in fights.
But one witness admitted he knew Eric Deffendall "in eighth grade."
|
{
"pile_set_name": "OpenWebText2"
}
|
When the TV presenter's post-match questions to Joachim Löw turned to the inevitable Erdogan question, the mood of the national coach changed. ARD's Alexander Bommes asked Löw for his thoughts on the whistles that greeted Ilkay Gündogan when he came off the bench during the second half of Germany's final game before the World Cup. Löw sighed, trying to stay calm after he'd cut a mean glance towards the whistling fans.
"We've talked a lot about it," Löw said, referring to the photo of Gündogan and fellow Germany player Mesut Özil with Recep Tayyip Erdogan. The coach stressed that the issue has been dealt with internally and that there is nothing else to discuss. "Now we must look forward. Only then will the topic be over, OK? "An understandable, but unrealistic, wish. This is an affair that won't disappear quietly.
DW Sport's Joscha Weber
Not because the media have to fill a summer hole, but because the fans are angry. While Özil is injured, Gündogan is booed in Leverkusen. The whistles of Germany's own fans followed Gündogan's every touch of the ball in Austria six days ago too, creating a tough situation for the player and a nightmare for the coach, who applauded Gündogan and provided his player with unwavering support. A completely understandable response by Löw. For a successful World Cup he needs the support of the fans and especially players to keep them focused on the pitch. But it looks as though this drama will follow the team to Russia, and this is partly of the DFB's own making.
Gündogan and Özil must apologize
Whatever made Özil and Gündogan pose alongside Erdogan for his campaign and to present him with a jersey with the inscription "For my president, respectfully", it has had fatal consequences. A crack has developed between the intimate relationship of Germans and their national team. Shortly after the release of the Erdogan photos, a majority in a representative survey in Germany even demanded the exclusion of Özil and Gündogan from the team over the matter. A meeting was quickly arranged with the German president, Frank-Walter Steinmeier. But, unlike the DFB, this was not enough. Many Germans still shake their heads over the two players who are supposed to represent Germany, but at the same time pose with a man who tramples on freedom of expression in his country, blocks political opponents and dissidents and, in many cases, abolished the rule of law. Large parts of the German public expect an apology, or at least a full explanation. But it is not forthcoming.
Ilkay Gündogan was jeered when he entered the game for Germany on Friday.
Erdogan's big coup
Turkey are not in the World Cup, but there's a feeling that Erdogan is going anyway in the shape of a shadow cast over the DFB. Already, he has been able to celebrate a big political coup. More than any demand for election campaigns in Germany, he managed with a few photos to drive a wedge in Germany, the country with the largest Turkish exile community. The persistent whistles against Turkish-born players are likely to push Turks living in Germany into Erdogan's arms. That is exactly what the incumbent will do before the presidential election in Turkey on 24 June. It is time to end this epidode sooner rather than later, so that Germany can look again towards the World Cup.
You can post a topic-related comment below this article.
|
{
"pile_set_name": "OpenWebText2"
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|
Centering,
grounding. Aligns energies, "stone of harmony." Stimulates circulation and
blood flow. This stone is an infection fighter and helps to strengthen
the lungs. It is a cubic lead structure that adds balance to the emotions
and the etheric body
Warning: Galena
is the principle ore of lead, and forms glistening silver cubes with almost
unnaturally perfect shapes. Although lead is normally extremely flexible,
the sulfur content of galena makes it extraordinarily brittle and reactive
to chemical treatment. Galena is capable of taking an equally heavy toll on
workers and amateur researchers who are exposed to it. Contact with
specimens may lead to lead dust exposure, while workers in mines face a high
risk of poisoning from contact with the mineral and the deadly dusts
released through production. Once extracted, the lead content from this
mineral poses environmental and health threats during treatment and
extraction. Galena has a cubic fracture, and if hit with a hammer, the
crystal will shatter into multiple smaller replicas of its original shape.
Let us make your custom made
Galena pendant, purchase a stone from above or send us one you have, then
choose your findings
$35.00
Choose Wire Or
Cap
These gem essences, and essential oils are
properly prepared by an expert and the healing properties are sent into the
essences without ever actually touching the water and oils. This
particular product, works well as an
INDIRECT ELIXIR, which means it does not actually touch the water, but rather is
prepared by a process that allows the stone's energies to be absorbed into
the liquid, and does not bring its poisonous attributes to the product.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
Is there a way in Sublime Text 2 to support JavaScript completion of objects/functions defined in other files?
If I am editing a .js file in Sublime Text 2 that makes use of a library defined in a separate .js file, is there a way to support tab completion of objects/functions defined in the external library file?
Something analogous to the following from Visual Studio:
/// <reference path="/js/some-library.min.js" />
which enables IntelliSense over the library/plugin code.
A:
I haven't tried it myself yet, but there's SublimeCodeIntel: https://github.com/Kronuz/SublimeCodeIntel#readme
The OP in this thread: http://www.sublimetext.com/forum/viewtopic.php?f=3&t=5319 seems to be complaining that it's pulling suggestions from outside the current file, which may mean it's doing what you want.
|
{
"pile_set_name": "StackExchange"
}
|
You may proceed to the site by clicking here, however some pages might not
work correctly.
Your browser does not support iframes.
LATEST VIDEOS
More Videos:
Cramer and Dicker: Downing of MH17 Has Coincidences Benefiting Putin and Russia's Economy
Written by: Daniel Dicker07/23/14 - 2:30 PM EDT
Tickers in this article:
APC BP PXD XEC XOM
NEW YORK (TheStreet) -- I was talking to Jim Cramer today about the downing of Malaysian airline flight 17 and the increasing tensions in Ukraine that are impacting upon the oil markets.
The strong Russian hand print on the tragedy strikes me as a coincidence that runs alongside a number of other facts that relate directly to the energy situation in Europe and the prices of oil worldwide.
A second round of U.S. sanctions directed at Russia focused ostensibly on the banks, but the prime bank targeted was Gazprombank, the financial arm of the largest Russian oil company. This round of sanctions was clearly directed against the Russian oil machine, the prime driver of the Russian economy.
Oil had been sinking slowly towards $100 a barrel before the plane was downed, and sub-$100 oil is an economic burden on the Russian petro-state, even more than the 7% drop in the price of the Russian stock market caused by the increasing sanctions.
While Europe cannot follow suit in applying sanctions on Russia because of Europe's dependence on Russian natural gas, there is a pro-EU government now sitting in Kiev that continues to reach out for support from Europe in fighting the Russian-backed rebels in the Eastern provinces.
The fact is that oil has strongly rallied since the airliner’s downing and Europe is again showing fear and forbearance in front of Russian natural gas, still representing 60% of the EU's demand.
If the downing of MH17 was a mistake -- and it still most likely was -- the results of the tragedy represent more than a few "happy" results for Vladimir Putin and his Russian thugs. A sobering thought, indeed.
I talk more about MH17 and the European oil markets with Jim in the video above.
At the time of publication the author had no position in any of the stocks mentioned.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
CVPixelBufferGetBytesPerRow() for CVImageBufferRef returns unexpected wrong value for 1080p video frame
I am developing an application doing real-time video processing using AVFoundation with back cameras of iDevices. The AVCaptureSession is configured with sessionPreset AVCaputeSessionPreset1920x1080 (full HD), video settings kCVPixelBufferPixelFormatTypeKey=kCVPixelFormatType_32BGRA and outputs sample buffers of type CMSampleBufferRef to a AVCaptureVideoDataOutput delegate. Video/Interface orientation portrait is used (means frames of size 1080x1920 are expected). On each arrival of a frame, a CVImageBufferRef is retrieved from the sample buffer for further access to it's raw bytes. When accessing CVPixelBufferGetBytesPerRow() of this CVImageBufferRef instance, I get the value 4352 which is totally unexpected in my opinion. My expectation is, that bytes per row reflects 4 bytes (BGRA) per pixel for the entire frame width (1080) resulting in the value 4320 (=1080*4bytes). With bytes per row = 4352, divided by 4bytes this would give a frame width of 1088. Does anyone have a clue why this is actually happening? I can't work with the expected width of 1080 when analyzing pixel-wise as it leads to distorted images (checked converting to UIImage and save to disk), I definitly need to work with 1088 as width so the image is straight and analysations give proper results - but this is weird.
As I am using the raw frame bytes for real-time analyzation and expect to use a width of 1080, this is very essential for me so I really appreciate help on this issue.
Devices used:
- iPod touch 5G with iOS 6.0.1
- iPhone 5S with iOS 7.0.2
Code excerpt:
- (uint8_t*) convertSampleBuffer: (CMSampleBufferRef) sampleBuffer {
CVImageBufferRef imageBuffer = CMSampleBufferGetImageBuffer(sampleBuffer);
size_t bytesPerRow = CVPixelBufferGetBytesPerRow(imageBuffer); // = 4352 (=1088*4)
.....
}
A:
Apple released "Technical Q&A QA1829 Understanding the bytes per row value returned by CVPixelBufferGetBytesPerRow" on 5/1/2014 which states that this is due to hardware alignment requirements. See the tech note for details.
|
{
"pile_set_name": "StackExchange"
}
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Vitamin D status is a biological determinant of health disparities.
In human beings, dark skin requires more exposure to ultraviolet light to synthesize the same amount of vitamin D as lighter skin. It is has been repeatedly shown that at the latitude of the United States there are vitamin D disparities related to skin color. Although inadequate vitamin D status and health disparities have been associated with many of the same diseases, neither nutrition policy nor public health policy in the United States currently recognizes any role at all for vitamin D as a determinant of health disparities. This study investigated the relationship between health, skin color, and vitamin D nutriture in the US population. The design is cross-sectional, correlational, and can be generalized to the population of the United States. We used data from 12,505 (unweighted) subjects (3,402 non-Hispanic blacks, 3,143 Mexican Americans, and 5,960 non-Hispanic whites), aged 13 years or older, from the continuous National Health and Nutrition Examination Survey 2003-2006. Self-rated health, a repeatedly validated indicator of objective health status, was used as a continuous measure of health. Using software appropriate for the complex survey design of the National Health and Nutrition Examination Survey, the study consisted of six regression models, one predicting vitamin D status and five predicting self-rated health. Controlling for the covariates sex, interview language, country of birth, tobacco use, age, body mass index, and leisure exercise as well as the socioeconomic variables education and family income, remaining disparities in self-rated health are greatly reduced or eliminated by controlling for serum 25-hydroxyvitamin D levels. We found that socioeconomic factors are the strongest determinant of skin-color based health disparities in the US population, but that it may not be possible to eliminate health disparities in the United States without eliminating the skin-color-related disparities in vitamin D nutriture.
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{
"pile_set_name": "PubMed Abstracts"
}
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Call Toll Free 1-866-777-2557
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If you or a loved one took the medication Xarelto® and suffered a serious internal bleeding injury or stroke, you may be entitled to financial compensation from the manufacturer. Please call us today for a free, no obligation case review. Call Toll Free 1-866-777-2557 or fill out our online contact form and a Union City California Xarelto Lawyer will get back to you as soon as possible to answer your questions. There are no legal fees or costs to you unless you receive financial compensation at the end of the case. Time is limited, so please call us today. We are also accepting cases if your loved one passed away after taking the medication.
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FAQ
As we all know, the blood in our bodies is a liquid. It's consists of red blood cells engineered to move oxygen, white blood cells which allow our bodies to overcome infections, plasma which houses the fluid and proteins/chemicals which help our bodily processes, and platelets that help the blood clot within the body. Blood clots arise at the areas it's necessitated just like if you have an injury to your body, a cut around the skin, and so forth.
Clots inside the veins, having said that, just isn't typical and may induce a number of unfavorable situations. Blood clots can build-up the moment the blood ceases moving for one explanation or another. We really need to check why blood clots build and then look at the indicators of blood clots. For you to stop blood clots from leading to a major problem, you will want to spot out the indications early so you can discard any complications they could cause.
Kinds of Blood Clots All Throughout the Circulatory System
You will find several sorts of blood clots that may perhaps be dangerous to your health. Written below are various variations which you ought to be on the lookout for.
Arterial thrombi
This is a blood clot jammed in the artery generated by plaque buildup stemming from atherosclerosis. The constricting of the blood vessel as well as the plaque buildup makes the blood to clot in an infrequent position. This could possibly result in a stroke, heart attack or peripheral artery disease
Venous thrombosis
This kind of blood clot shows up if the blood is at a standstill from inactivity in the body. When an individual is physically handicapped, the muscle groups aren't contracting, thus forcing the blood to begin to clot in the veins.
Blood clotting inside the heart
Whenever a person develops atrial fibrillation (unusual heart rhythms) the blood may gradually grow stagnant inside the walls of the atrium and acquire clots at some point. Clots can potentially show up inside the heart after a heart attack as well.
Warning Signs of Blood Clots
Indicators of the blood clots vary depending on the clot's setting. Many times, challenging blood clots amass within the extremities (e.g. the legs). The signs of the blood clots are commonly felt in the legs/arms that are impacted. You might possibly sustain some swelling, redness, discomfort/warmth in the suffering arm/leg.
In the instance that you end up with a clot inside the artery, the blood won't be able to arrive at a specific part of the body and the cells in that place should begin to perish. Ordinarily discomfort is the 1st indicator of an arterial clot. If for example the clot is forbidding blood from travelling to the heart, it induces a heart attack. In case the clot is keeping blood from entering the brain, it stimulates a stroke. If perhaps you are fighting with any of these blood clot symptoms, it's of great importance that you obtain medical help right away.
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Bell Attendant
A Bell Attendant is responsible for transferring and storing guest luggage and responding to guest requests in the hotel's continuing effort to deliver outstanding guest service and financial profitability.
What will I be doing?
As a Bell Attendant, you will be responsible for transferring and storing guest luggage and responding to guest requests in the hotel's continuing effort to deliver outstanding guest service and financial profitability. Specifically, you will be responsible for performing the following tasks to the highest standards:
* Greet and escort arriving and departing guests to and from their accommodations
* Retrieve and transport guest luggage
* Inspect guest rooms and acquaint guests with these rooms and their features
* Respond to guest inquiries and requests in a timely, friendly and efficient manner
* Organize and store luggage, as needed, according to guidelines
* Assist in the maintenance, appearance and functionality of equipment
EOE/AA/Disabled/Veterans
Requirements
What are we looking for?
Bell Attendants serving Hilton Brand hotels are always working on behalf of our Guests and working with other Team Members. To successfully fill this role, you should maintain the attitude, behaviors, skills, and values that follow:
Positive attitude and communication skills
Ability to work flexible hours
Ability to work under pressure
Ability to work on own and as part of a team
Commitment to respond to Guest requests and deliver high levels of service
Excellent grooming standards
It would be advantageous in this position for you to demonstrate the following capabilities and distinctions:
Previous experience as a Bell person
Previous experience working within a hotel
What will it be like to work for Hilton?
Hilton is the leading global hospitality company, spanning the lodging sector from luxurious full-service hotels and resorts to extended-stay suites and mid-priced hotels. For nearly a century, Hilton has offered business and leisure travelers the finest in accommodations, service, amenities and value. Hilton is dedicated to continuing its tradition of providing exceptional guest experiences across its global brands. Our vision to fill the earth with the light and warmth of hospitality unites us as a team to create remarkable hospitality experiences around the world every day. And, our amazing Team Members are at the heart of it all!
Work Permit:
Applicants who do not already have legal permission to work in the location of this job will not be considered.
Management Position: No
Description
A Bell Attendant is responsible for transferring and storing guest luggage and responding to guest requests in the hotel's continuing effort to deliver outstanding guest service and financial profitability.
What will I be doing?
As a Bell Attendant, you will be responsible for transferring and storing guest luggage and responding to guest requests in the hotel's continuing effort to deliver outstanding guest service and financial profitability. Specifically, you will be responsible for performing the following tasks to the highest standards:
* Greet and escort arriving and departing guests to and from their accommodations
* Retrieve and transport guest luggage
* Inspect guest rooms and acquaint guests with these rooms and their features
* Respond to guest inquiries and requests in a timely, friendly and efficient manner
* Organize and store luggage, as needed, according to guidelines
* Assist in the maintenance, appearance and functionality of equipment
EOE/AA/Disabled/Veterans
Requirements
What are we looking for?
Bell Attendants serving Hilton Brand hotels are always working on behalf of our Guests and working with other Team Members. To successfully fill this role, you should maintain the attitude, behaviors, skills, and values that follow:
Positive attitude and communication skills
Ability to work flexible hours
Ability to work under pressure
Ability to work on own and as part of a team
Commitment to respond to Guest requests and deliver high levels of service
Excellent grooming standards
It would be advantageous in this position for you to demonstrate the following capabilities and distinctions:
Previous experience as a Bell person
Previous experience working within a hotel
What will it be like to work for Hilton?
Hilton is the leading global hospitality company, spanning the lodging sector from luxurious full-service hotels and resorts to extended-stay suites and mid-priced hotels. For nearly a century, Hilton has offered business and leisure travelers the finest in accommodations, service, amenities and value. Hilton is dedicated to continuing its tradition of providing exceptional guest experiences across its global brands. Our vision to fill the earth with the light and warmth of hospitality unites us as a team to create remarkable hospitality experiences around the world every day. And, our amazing Team Members are at the heart of it all!
|
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}
|
Q:
Inverse limit of finite flat morphisms
Suppose that an inverse limit of finite flat morphisms $X_k\to S$ of qcqs schemes, with affine transition maps, is $X\to S$, such that a closed fiber of $X\to S$ is finite.
Is $X\to S$ finite?
A:
No (in general).
Take $S = \mathrm{Spec}(A)$ and $X_k = \mathrm{Spec}(A[T]/(T^2))$, with affine transition maps given by $T \mapsto f T$ for some $f \in A$. The limit $X$ is the spectrum of $A \oplus A[f^{-1}] T$ (with $T^2 = 0$). Then $X \rightarrow S$ is an isomorphism (hence finite) over the closed subscheme $V(f)$ of $S$, while $X \rightarrow S$ is finite if and only if $A \rightarrow A[f^{-1}]$ is finite.
To give a specific counterexample, just take $A = \mathbb{Z}$ and $f$ any integer $\geq 2$.
|
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android:fillColor="#FF000000"
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"pile_set_name": "Github"
}
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What a government shutdown could mean for WorkSource Pierce
TACOMA, Wash. – With the deadline looming for the federal government to either approve a 2018 budget or pass another Continuing Resolution, WorkForce Central is preparing for the possibility of a government shutdown – and what that might mean for the WorkSource Pierce service-delivery system.
As always, providing services to job seekers, workers and businesses remains our No. 1 priority. We remain hopeful that a resolution can be reached before the Friday, Jan. 19 deadline, and we believe our cash-on-hand capacity will allow us to withstand a brief shutdown without limiting or reducing services.
However, it is possible that a prolonged shutdown could force our service providers to limit services or put a hold on accepting new enrollees, as many of our services are federally funded. In the event of a shutdown, WorkForce Central and its contracted service providers would be limited to cash-on-hand, and would not be able to draw any new funding from federal sources.
“Any time our funding is limited, our priority is to ensure we continue serving job seekers, workers and businesses to the fullest extent of our capacity,” said Linda Nguyen, CEO of WorkForce Central. “If the federal government does shut down, we will continue to provide these services for as long as our cash-on-hand will allow. However, we are also preparing a contingency plan in the event of a shutdown that lasts longer than a few weeks, and will work to keep the Pierce County community informed about what those next steps will be.”
In the event of a shutdown, the WorkSource Pierce Job Center will remain open and fully operational from 8 a.m. to 5 p.m., Monday through Friday, until lack of funding requires a reduction in services. WorkForce Central will continue to evaluate its service-delivery capacity throughout any government shutdown, and will announce any future decisions about service-delivery reductions as soon as possible.
WorkForce Central strengthens the Pierce County economy by identifying skill gaps between jobseekers and employment opportunities, fostering data-driven decision making, and connecting workforce development partners into a cohesive, collaborative and effective network.
What a government shutdown could mean for WorkSource Pierce2018-01-182018-01-18/wp-content/uploads/2017/06/workforce-logo-colorrev_light.pngWorkForce Centralhttp://workforce-central.org/wp-content/uploads/2017/06/letterheadheader.jpg200px200px
|
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|
Q:
How to show post based on id in url with PHP
I'm building a simple page where I list all posts on.
I'm a bit stuck because it's some time ago I made something like this.
I want to show the specific post when clicking the link. Here's an image of what I mean:
The blue 'title' is a url.
I don't know how to link this to another page, where the post with the id in the url is shown.
My link looks like this:
<a class="posts" href="http://example.com/blog/<?php echo $row['id']; ?>"><?php echo $row['titel']; ?></a>
This obviously gives a 'Not Found' error message.
How can I do this? It's kinda hard, because it's some time ago I worked with this.
NOTE: I am using a .htaccess file to delete the .php extension from the url.
My urls look like:
http://example.com/home/blog
etc.
A:
RewriteEngine on
RewriteRule ^blog/([^/\.]+)/?$ blog.php?id=$1 [L]
Here, assuming your blog.php takes $_GET['id'], having the above in your .htaccess will route
/blog/69 to blog.php?id=69
|
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"pile_set_name": "StackExchange"
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|
Q:
How do I insert an array into a Google Doc using data from Google Sheets?
I am trying to pull a range of names from a Google sheet and place it into a Google Doc.In the spreadsheet, the last names("lastNames") come before the first names ("firstNames"), and both are in separate columns. I am trying to place the first and last names together into my doc with the first names first.
I used a for loop to put the first and last names together into an array ("fullNames"), and that part works just fine. When I used Logger.log, all the first names and last names are together in an array, with each full name separated by a common, just the way I wanted them to be.
What I can't figure out how to do is actually insert this new array into the body of the document. I am using the appendTable method, but every time I try to I get the following error: "The parameters (number[]) don't match the method signature for DocumentApp.Body.appendTable."
What changes do I have to make to my code to actually place my new array into my google doc?
function namePusher() {
var ss = SpreadsheetApp.openById("1CHvnejDrrb9W5txeXVMXxBoVjLpvWSi40ehZkGZYjaY");
var lastNames = ss.getSheetByName("Campbell").getRange(2, 2, 18).getValues();
var firstNames = ss.getSheetByName("Campbell").getRange(2, 3, 18).getValues();
//Logger.log(firstNames);
var fullNames = [];
for(var i = 0; i < firstNames.length; i++){
var nameConcat = firstNames[i] + " " + lastNames[i]
fullNames.push(nameConcat);
}
//Logger.log(fullNames);
var doc = DocumentApp.getActiveDocument().getBody();
doc.appendTable(fullNames);
}
A:
One simple way to fix your code is by replacing
fullNames.push(nameConcat);
by
fullNames.push([nameConcat]);
The problem with your script is that fullNames is an Array of strings but your should pass an Array of Arrays of strings (or objects that might be coerced to strings).
Basic demo
var data = [
['A','B','C'],
[1, 'Apple','Red'],
[2, 'Banana','Yellow']
];
function myFunction() {
const doc = DocumentApp.getActiveDocument();
const body = doc.getBody();
body.appendTable(data);
}
As mentioned on Tanaike's answer there are other "improvement opportunities"
Reduce the number of calls to the Google Apps Script Classes and Methods
Use better ways to manage Arrays and to concatenate strings.
|
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Eye movement responses to active, high-frequency pitch and yaw head rotations in subjects with unilateral vestibular loss or posterior semicircular canal occlusion.
This study assessed the eye movement responses to active head rotation in six subjects with complete unilateral vestibular loss (UVL), five subjects with posterior canal plugging (PCP) and age- and sex-matched normal subjects. Subjects performed head rotations in the pitch and yaw planes at frequencies ranging from 2 to 6 Hz, while looking at an earth-fixed target. Vertical eye movement gains obtained in UVL, PCP and normal subjects were not significantly different. Vertical phases decreased with increasing head movement frequencies in both UVL and PCP subjects. Although this decrease produced significantly different vertical phases between UVL and normal subjects for head movements above 3.9 Hz, vertical phases in some normal subjects were similar to those obtained in UVL subjects. We conclude that active head oscillations in the pitch plane are not clinically useful for the detection of vertical canal impairment limited to one ear. As expected, UVL subjects showed reduced horizontal gains, and eye velocity asymmetries during active head rotation in the yaw plane. Results in some PCP subjects suggested possible minor impairments of horizontal vestibulo-ocular reflexes.
|
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|
1. Introduction {#sec1-toxins-08-00223}
===============
TNF is a classical pro-inflammatory cytokine involved in the modulation of acute inflammatory responses and host defense mechanisms \[[@B1-toxins-08-00223]\]. However, increased levels of this cytokine are closely associated with degenerative diseases, such as sepsis, rheumatoid arthritis, and inflammatory bowel disease, among others \[[@B2-toxins-08-00223]\]. It is mainly produced by monocytes and secreted as a transmembrane protein (mTNF-26 kDa) and cleaved by the TNF-converting enzyme (TACE), a zinc metalloprotease, in its soluble form (sTNF-17 kDa). Both fragments are biologically active and bind as trimers to either TNF receptors, TNFR1 (also referred as TNFRSF1A, p55, or CD120a) or TNFR2 (also called TNFRSF1B, p65, or CD120b) \[[@B3-toxins-08-00223],[@B4-toxins-08-00223]\]. Currently, monoclonal antibodies against TNF are commercially available to treat TNF-mediated pathologies. These antibodies are most frequently applied for treatment of rheumatoid arthritis, and promising results have been obtained for treatment of other inflammatory disorders \[[@B5-toxins-08-00223]\].
Metalloproteases are enzymes characterized by presenting a catalytic zinc ion in its active site \[[@B6-toxins-08-00223]\]. Snake venom metalloproteases (SVMPs) represent at least 30% of the toxin composition of many viperid snake venoms and they are responsible for hemorrhage through disturbances in the blood coagulation cascade of prey and snakebite victims \[[@B6-toxins-08-00223]\]. However, certain SVMPs lack hemorrhagic activity (P-I class of SVMPs), but present other biological effects, such as inhibition of platelet aggregation, induction of apoptosis, and pro- or anti-inflammatory activities \[[@B7-toxins-08-00223],[@B8-toxins-08-00223],[@B9-toxins-08-00223]\]. SVMPs are phylogenetically most closely related to the mammalian ADAM (a disintegrin and metalloprotease) and ADAMTS (ADAM with thrombospondin type-1 motif) family of proteins and, together, they constitute the M12B clan of metalloendopeptidases \[[@B6-toxins-08-00223]\].
The SVMPs are divided into three main classes according to their domain organization: SVMPs of the class PI contain only the metalloprotease domain in the mature protein, including the canonical zinc-binding motif HEXXHXXGXXH followed by a Met-turn motif. The class PII is comprised of enzymes containing a disintegrin domain following the metalloprotease domain. Class PIII SVMPs contain the metalloprotease domain, the disintegrin-like (Dis-like) domain and a cysteine-rich domain (Cys-rich). Post-translational processing of precursors of some PIII metalloproteinases results in the release of the Dis-like and Cys-rich domains (DC fragment) \[[@B10-toxins-08-00223],[@B11-toxins-08-00223]\]. Additional heterogeneity of these enzymes arises from the occurrence of PII and PIII SVMP dimers, and there are PIII SVMPs that contain an additional subunit constituted by a C-type lectin-like protein, linked to the main proteinase chain by disulfide bonds \[[@B7-toxins-08-00223],[@B10-toxins-08-00223],[@B11-toxins-08-00223]\].
BmooMP-alpha-I isolated from *B. moojeni* snake venom is a fibrin(ogen)olytic and non-hemorrhagic zinc metalloprotease of the class PI SVMPs with a molecular mass of 24.5 kDa \[[@B12-toxins-08-00223],[@B13-toxins-08-00223]\]. This enzyme exerts its biological activity by cleaving first the A-alpha-chain of fibrinogen, followed by its B-beta-chain, but with no effects on the gamma-chain. Also, it lacks hemorrhagic and thrombin-like activities \[[@B12-toxins-08-00223]\].
Previous study of the crystal structure of BmooMP-alpha-I showed that the enzyme presents a catalytic zinc ion displaying an unusual octahedral coordination, which includes three canonical histidines \[[@B13-toxins-08-00223]\]. From this structural study, as well as from comparative sequence analysis, it was concluded that the motif comprising amino acid segments 153--164 and 167--176 adjacent to the methionine-turn is a relevant feature that differentiates non-hemorrhagic and hemorrhagic class P-I SVMPs, and could directly be involved in the development of the hemorrhagic activity \[[@B13-toxins-08-00223]\].
Studies of BmooMP-alpha-I to date have focused only on its fibrin(ogen)olytic and non-hemorrhagic activity. The major aim of the present study was to investigate whether this metalloprotease could modulate TNF inflammatory properties, considering that the precursor form of this cytokine is targeted by TACE, another metalloprotease from the same class (zinc-dependent metalloendopeptidases).
2. Results and Discussion {#sec2-toxins-08-00223}
=========================
Venoms secreted by snakes constitute a complex mixture of molecules with various biological activities directed to different targets \[[@B14-toxins-08-00223]\]. This is an evolutive adaptation and well-integrated system of proteins and organic constituents, used as a defense by the snakes, as it leads to the immobilization, death, and digestion of the preys \[[@B15-toxins-08-00223]\]. The most evident activity of venoms produced by *Bothrops* snakes is proteolysis, which is responsible for the main clinical manifestations of bothropic acidents \[[@B16-toxins-08-00223]\].
In the present study BmooMP-alpha-I was isolated from crude venom by using combined chromatographic protocols. Ion exchange chromatography on DEAE-Sephacel column resulted in the separation of five protein fractions, (peaks E1--E5) ([Figure 1](#toxins-08-00223-f001){ref-type="fig"}A). Fraction E2, which showed substantial proteolytic activity towards azocasein and fibrinogen \[[@B12-toxins-08-00223]\], was chosen for additional procedure, based on chromatography in a Sephadex G-75 column. These procedures resulted in three peaks named E2G1, E2G2, and E2G3 ([Figure 1](#toxins-08-00223-f001){ref-type="fig"}B). The peak E2G2 showed major protein concentration and proteolytic activity and was submitted for further fractionation based on a Benzamidine-Sepharose column, resulting in two new fractions, named B1--B2. The peak B1 corresponded to the metalloprotease BmooMP-alpha-I ([Figure 1](#toxins-08-00223-f001){ref-type="fig"}C). BmooMP-alpha-I represented a quantity of 8.71% of the whole crude venom of *B. moojeni*, a significant amount if compared with other fibrin(ogen)olytic enzymes isolated from similar preparations \[[@B12-toxins-08-00223],[@B15-toxins-08-00223],[@B16-toxins-08-00223],[@B17-toxins-08-00223]\].
Next, 1D and 2D electrophoretic analysis was carried out of the B1 fraction under non-reducing conditions. 1D SDS-PAGE confirmed BmooMP-alpha-I as a monomer, with apparent molecular mass of 23 kDa ([Figure 1](#toxins-08-00223-f001){ref-type="fig"}D). The BmooMP-alpha-I fraction was further analyzed by 2D SDS-PAGE and the apparent molecular mass was calculated as 22.36 kDa, with pI \~6.82 ([Figure 1](#toxins-08-00223-f001){ref-type="fig"}E).
The effect of BmooMP-alpha-I fraction was assessed for TNF production by BMDMs stimulated with known TLR ligands. Treatment of BMDMs with BmooMP-alpha-I reduced significantly the TNF detection in LPS-primed macrophages for all enzyme concentrations that were tested ([Figure 2](#toxins-08-00223-f002){ref-type="fig"}A). In contrast, no significant alteration was observed in the levels of IL-12 after treatment with the same concentrations of the metalloprotease ([Figure 2](#toxins-08-00223-f002){ref-type="fig"}B). The priming of BMDMs with TLR2/TLR6 agonist FSL-1 induced strong production of TNF, which could be inhibited by the BmooMP-alpha-I, when tested in concentrations of 12 and 6 µg/mL ([Figure 2](#toxins-08-00223-f002){ref-type="fig"}C). BmooMP-alpha-I was also not able to alter IL-12 production ([Figure 2](#toxins-08-00223-f002){ref-type="fig"}D). Additionally, we observed that this induced effect is independent of cell cytotoxicicity, as determined by MTT cell viability assay using macrophages treated with agonists and/or BmooMP-alpha-I ([Figure S1](#app1-toxins-08-00223){ref-type="app"}).
To further confirm the inhibitory effect of the BmooMP-alpha-I metalloproteasee on TNF, we examined the effect of this enzyme in a model of LPS-induced sepsis in mice, as it was already known that death caused by septic shock is crucially dependent on TNF production \[[@B18-toxins-08-00223]\]. It was found that the serum levels of TNF were reduced by nearly 50% in animals pre-treated with BmooMP-alpha-I, when compared with mice inoculated with PBS only ([Figure 3](#toxins-08-00223-f003){ref-type="fig"}). LPS is a major structural component of Gram-negative bacteria cell walls and it is able to induce the systemic inflammation observed in septic shock by interacting with TLR4. Upon activation of TLR4, a sequence of signal transduction events occurs, leading to the nuclear translocation of NF-kB transcription factor, which results in transcription of various inflammatory cytokines, such as TNF, IL-1-beta, and IL-12p70. It has been described that these cytokines are responsible for the systemic inflammatory response observed during septic shock \[[@B19-toxins-08-00223]\]. Thus, strategies to decrease the TNF levels could be beneficial to control several pro-inflammatory pathologies, as the blockage of this cytokine improves the prognosis of these diseases \[[@B20-toxins-08-00223]\].
In order to verify whether TNF was directly cleaved by BmooMP-alpha-I, additional experiments were performed. First, the effect of this metalloprotease was determined on degradation of TNF or IL-12 by ELISA. Levels of TNF were determined under different conditions, as TNF and IL-12 standard cytokines or antibodies against them (capture antibodies) were incubated with the following preparations: pure protein (BmooMP-alpha-I); BmooMP-alpha-I inactivated with NA~2~EDTA (BmooMP-alpha-I(i)) It was observed that the levels of TNF decreased by 53.4% after incubation with the pure metalloprotease. In addition, the level of TNF was restored by 80% in the presence of NA~2~EDTA ([Figure 4](#toxins-08-00223-f004){ref-type="fig"}A). In contrast, no significant alterations were observed in IL-12 levels submitted to the same experimental conditions ([Figure 4](#toxins-08-00223-f004){ref-type="fig"}B). As controls, ELISA plates pre-sensitized with capture antibodies were previously incubated with pure protein (BmooMP-alpha-I), or BmooMP-alpha-I inactivated with NA~2~EDTA (BmooMP-alpha-I(i)). As demonstrated in [Figure 4](#toxins-08-00223-f004){ref-type="fig"}C,D, no significant alteration on the levels of TNF was observed. As shown in [Figure 4](#toxins-08-00223-f004){ref-type="fig"}C, the capture antibodies protect TNF from degradation by possibly masking the proteolytic sites in TNF, corroborating with the direct effect of BmooMP-alpha on TNF. Additional evidence was observed on the fact that the amount of TNF was not reduced in the presence of NA~2~EDTA, a chelating agent used to remove bivalent ions, which completely eliminates the biological activity of SVMPs \[[@B21-toxins-08-00223]\]. Furthermore, the polyclonal antibody anti-BmooMP-alpha-I probably binds to different domains from the catalytic domain of the enzyme responsible fot catalyzing the proteolysis of TNF \[[@B22-toxins-08-00223],[@B23-toxins-08-00223]\].
To confirm the proteolysis of TNF by metalloprotease BmooMP-alpha-I and to assess whether this effect could present a dose-dependent fashion, additional 1D SDS-PAGE and Western blotting experiments were carried out. The 1D SDS-PAGE with silver stained gel showed that 12 μg/mL of BmooMP-alpha-I was active against TNF and caused a degradation of this substrate, which could be evidenced by the fading of its chains, as demonstrated by the electrophoretic profile of the reaction ([Figure 5](#toxins-08-00223-f005){ref-type="fig"}A). The concentrations of 6 µg/mL and 3 µg/mL of BmooMP-alpha-I impaired the proteolytic activity towards TNF in a dose-dependent fashion, although the effect was still present at the lower concentration ([Figure 5](#toxins-08-00223-f005){ref-type="fig"}A,B). These results obtained by Western blotting demonstrated that BmooMP-alpha-I is able to impair TNF levels to a point that was not recognized by its specific monoclonal antibody ([Figure 5](#toxins-08-00223-f005){ref-type="fig"}C), suggesting that the biological effect imposed by the metalloprotease induced the loss of the TNF tridimensional structure. These findings are in agreement with previous results in the literature concerning a recombinant fibrinogenase rF II, designed from a metalloprotease of *Agkistrodon acutus* snake, which showed a protective role in sepsis by promoting proteolysis of fibrin and TNF, accompanied by a decrease of the plasmatic concentration of this cytokine \[[@B24-toxins-08-00223],[@B25-toxins-08-00223]\]. The same recombinant fibrinogenase rF II showed a protective role in a model of acute severe pancreatitis induced by sodium taurocolate that was dependent of TNF proteolysis \[[@B26-toxins-08-00223]\].
To explore the mechanism of the protein-protein interaction, docking analyses of BmooMP-alpha-I protein (3GBO) and TNF (2TNF) were performed using the available protein structures (PDB), followed by structural alignment in the Swiss PDB Viewer. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment that presented LRMS = 1.05 Å and IRMS = 1.01 Å ([Figure S2](#app1-toxins-08-00223){ref-type="app"}). This result is compatible with a realistic complex, once the docking possesses high accuracy had been demonstrated, when (LRMS ≤ 1.0 Å or IRMS ≤ 1.0 Å), intermediate accuracy (LRMS ≤ 5.0 Å or IRMS ≤ 2.0 Å), tolerable accuracy (LRMS ≤ 10.0 Å or IRMS ≤ 4.0 Å), and unrealistic (LRMS \> 10.0 Å and IRMS \> 4.0 Å) \[[@B27-toxins-08-00223],[@B28-toxins-08-00223],[@B29-toxins-08-00223]\]. The ZDOCK benchmark 3 docking validation, which considers conformational changes occurring between unbound and bound state of the ligand, also presented similar classification to that utilized in the present study, defining the interaction as uncomplicated (C~α~--I_rmsd \< 1.5 Å), intermediate (1.5 Å \< C~α~--I \_rmsd ≤ 2.2 Å), and hard (C~α~--I \_rmsd \> 2.2 Å) \[[@B28-toxins-08-00223],[@B29-toxins-08-00223],[@B30-toxins-08-00223]\]. Next, we assessed the possible binding cavities and the hydrogen bonds using Swiss Pdb Viewer. It was found that the residues Arg28, His32, Glu33, Val35, Asn36, Ser37, Met38, Gly40, Arg43, Ala49, Asn131, Leu132, Gln133, Glu135, Val136, and Val171 from metalloprotease and Gln31, Arg32, Asn39, Asp42, Leu48, Asp53, Ser86, Tyr87, Glu89, Val91, and Glu 127 from TNF constitute the interactive site of the complex. Additionally, we observed that one of the possible binding cavities interacted with TNF ([Figure 6](#toxins-08-00223-f006){ref-type="fig"}).
In order to evaluate the stability of the potential interactions, an electrostatic analysis was carried out. The interaction between the BmooMP-alpha-I and TNF complex occurs among the following residues, respectively: Glu33-Arg32, Val171-Gln31; Ala49-Asn39; Arg28-Glu89, Arg43-Asp53; Arg43-Glu127; Arg43-Asp53; Arg43-Glu127; Val35-Asn39; Ala49-Asn39; Gln133-Gln31; Gly40-Asp42; His32-Tyr87; His32-Val91; Tyr42-Asn39; Ala49-Ser86; Val35-Tyr87 ([Figure 7](#toxins-08-00223-f007){ref-type="fig"}A,B, [Figure S3](#app1-toxins-08-00223){ref-type="app"}A--D and [Figure S4](#app1-toxins-08-00223){ref-type="app"}). This analysis also demonstrated several hydrogen bonds that are important for stabilization of the complex and in promoting the hydrophobic interactions, while being considered the main mechanism of action of metalloproteinases interaction, also indicating a consistent interaction between TNF and BmooMP-alpha-I \[[@B31-toxins-08-00223],[@B32-toxins-08-00223]\]. In addition, it was possible to identify that chains A and C of TNF interact with BmooMP-alpha-I ([Figure S2](#app1-toxins-08-00223){ref-type="app"}B), and this piece of information was further confirmed by the electrostatic potential analysis ([Figure S4](#app1-toxins-08-00223){ref-type="app"}).
The Ramachandran plot and alanine scanning analysis were used to validate the structure of complexes formed by protein interactions. The analysis of the complex in PDB sum generated a Ramachandran plot, where the majority of amino acids residues (*n* = 98%) were located in allowed regions ([Figure 8](#toxins-08-00223-f008){ref-type="fig"}A). Additionally, *G-factor* value (0.43) was determined, which is consistent with a favorable model of interaction (*G-factor* \> −0.5) ([Figure 8](#toxins-08-00223-f008){ref-type="fig"}B). Concerning the alanine scanning analyses, the following interacting residues were demonstrated: Arg28, Glu33, His32, Val35, Asn36, Arg43, Val136, Val171 in the metalloprotease and Gln31, Arg32, Asn39, Asp53, Ser86, Tyr87, Glu89, Val91, and Glu127 in TNF. As shown in [Figure S5](#app1-toxins-08-00223){ref-type="app"}, these residues were considered important for upholding the complex. Therefore, it was found that the following residues are determinant for maintenance of the complex interaction between BmooMP-alpha-I and TNF, respectively: Glu33-Arg32; Val171-Gln31; Arg28-Glu89; Arg43-Asp53; Arg43-Glu127; Arg43-Asp53; Arg43-Glu127; His32-Tyr87; His32-Val91; Ala49-Ser86; and Val35-Tyr87. Indeed, alanine scanning is a powerful method to detect important interactions in protein-protein interfaces, as this detection occurs mainly by the measurement of the effect in the amino acid side-chain change in the Cβ carbon atom on the complex affinity \[[@B33-toxins-08-00223],[@B34-toxins-08-00223]\]. Additionally, individual substitutions of several amino acids with alanine could generate a map that indicates which interactions are critical or not for maintenance of interactive complex. Moreover, alanine scanning is an important tool for identification of hotspot residues in protein-protein interfaces that is essential for complex maintenance \[[@B34-toxins-08-00223],[@B35-toxins-08-00223]\].
The platform CLUSPRO has been generally used for docking analysis, as in actin-actin interaction \[[@B36-toxins-08-00223]\]. This docking application was successfully used in the present study for assess the interaction prediction between BmooMP-alpha-I and TNF molecules. It was observed that the metalloprotease BmooMP-alpha-I interacts with the TNF through the amino acids Arg28, Glu33, His32, Val35, Asn36, Arg43, and Val171. Previous study demonstrated that this zinc metalloprotease (BmooMP-alpha-I) possesses an active site located in the upper domain (about 150 *N*-terminal residues) and lower domain (about 50 *C*-terminal residues), which is consistent with other metzincins, such as adamalysin-II \[[@B13-toxins-08-00223]\]. This active site allows the binding to a variety of residues for different sites located in this protein. In addition, the active site is divided into three major subsites (S2, S1, and S′1 subsites) that can confer certain specificity to BmooMP-alpha-I \[[@B36-toxins-08-00223]\]. In this context, the S1 subsite, which is composed by Ile106, Val136, His140, and Leu168, and the main-chain of residues forming the Met-turn, can interact with large, hydrophobic, neutral, side chains such as Leu, Qln, and Phe \[[@B37-toxins-08-00223]\]. It is important to note that Gln133 interacts with Val 136 which is part of the cleavage subsite S1 of metalloprotease ([Figure 7](#toxins-08-00223-f007){ref-type="fig"}E), corroborating with our hypothesis that TNF is cleaved by this metalloprotease.
Studies of homology among sequences cleaved by metalloproteases utilizing bioinformatics have been developed once the classes of proteases possess homology on their preferential cleavage sites. For instance, a study pointed out that A and PA-BJ metalloproteases from *Bothropos jararaca* possess propensity for the amino acid arginine in the position 1, although a difference exists in the residue preferred at position 6 and 6′, conferring certain specificity for the class of metalloproteases \[[@B38-toxins-08-00223]\]. The prediction of cleavage sites carried out by PROSPER in the present study demonstrates various points where cleavage can occur, as this metalloprotease owns proline next to the P1 of cleavage ([Figure 9](#toxins-08-00223-f009){ref-type="fig"}). It was observed that several sequences cleaved by this proteinase contain proline \[[@B37-toxins-08-00223]\], corroborating with our results. In addition, the predicted site of cleavage is probably near to the interacting residues, which also indicates the possible cleavage of TNF by this metalloprotease. Furthermore, it is possible to consider that there is recognition of the substrate after conformation change for catalyzing the substrate \[[@B39-toxins-08-00223]\]. In this context, such type of changes in metalloproteases from cavities distant from the active site have been described, indicating a long-range communication network \[[@B40-toxins-08-00223],[@B41-toxins-08-00223]\]. Another important fact is that, although the snake venom metalloproteases and those metalloproteases including Adam 17 (Tumor necrosis factor-α converting enzyme) possess a high conserved domain, located in the regions between the loop connecting H4 an H5 helices, it is necessary to take into account that there are variable regions among metalloproteases. These variabilities are import for substrate recognition, because this feature makes it possible to turn these regions in the substrate-binding pocket wall, as has already been described in the literature \[[@B41-toxins-08-00223],[@B42-toxins-08-00223],[@B43-toxins-08-00223]\]. It is also necessary to consider that the methionine-turns are as important as the zinc catalytic domain for the metalloproteinase activity \[[@B40-toxins-08-00223]\]. Thus, BmooMP-alpha-I may recognize Gln31, Arg32, Asn39, Asp53, Ser86, Tyr87, Glu89, Val91, and Glu127 in TNF and might cleave anteriorly and posteriorly the sequence QLVVPADG, considering that this sequence possesses a proline, which is an important residue recognized by the metalloprotease BmooMP-alpha-I.
It is important to emphasize that the metalloprotease BmooMP-alpha-I is a fibrin(ogen)olytic non-hemorrhagic SVMP that is naturally produced by *B. moojeni* which we found able to hydrolyze TNF. In the literature a high degree of homology among snake venom metalloproteases (SVMPs), metalloproteases from mammalian extracellular matrix (MMPs), and the metalloproteases from disintegrin family (ADAMs), have been described. These families of enzymes are able to degrade subtracts from different sources. In this context, MMPs can cleave cytokines and chemokines, even though the existence of components from the extracellular matrix \[[@B44-toxins-08-00223]\]. Concerning TNF, it is already known that TNF-converting enzyme (TACE) processes the precursor form of this cytokine in order to release its soluble form. Similar to the other members of the ADAM family, the structure of TACE is characterized by distinct domains that include a pro-domain, a metalloprotease, and a disintegrin domain, followed by a cysteine-rich domain containing an epidermal growth factor (EGF)-like repeat, a transmembrane domain, and a cytoplasm tail. Considering the strong evidence that TACE is the major TNF convertase, this enzyme has attracted considerable interest as a specific therapeutic target in several inflammatory disorders, known to benefit from anti-TNF treatment, such as rheumatoid arthritis, Crohn's disease, and perhaps ulcerative colitis. Consequently, TNF has emerged as an important target for the development of the therapeutic strategies for treatment of chronic autoimmune disorders, and its inhibitors have been approved for clinical use \[[@B45-toxins-08-00223]\]. These studies suggest that the regulation process of the proteolysis from metalloproteases is critical in providing appropriate "*start*" or "*stop*" signaling during an inflammatory response \[[@B45-toxins-08-00223]\]. Thus, an anti-inflammatory agent may be the result of TNF light structural changes, which may hamper its biological activities \[[@B46-toxins-08-00223]\].
In summary, the results described in the present study shed light for future investigations concerning the clinical applications of the zinc metalloprotease BmooMP-alpha-I, since it was demonstrated that this enzyme is able to promote significant proteolysis of TNF. The next step will be to confirm the TNF sequence that is cleaved by this metalloprotease. Therefore, future studies are necessary to determine whether this enzyme could induce protection in experimental models in vivo, particularly those involving TNF as a critical mediator of inflammatory diseases, in order to verify its potential protective role, as well as the existence of possible side effects from its therapeutic use.
3. Experimental Section {#sec3-toxins-08-00223}
=======================
3.1. Animals {#sec3dot1-toxins-08-00223}
------------
Male C57BL/6 mice (18--22 g) were housed in temperature-controlled rooms and received water and food ad libitum until enrolled in experimental conditions. These studies were approved by the Experimental Animals Committee of Universidade Federal de Uberlândia (CEUA-UFU---Protocol \# 089/012, approved on 26 September 2012) in accordance with the procedures established by the University Federation for Animal Welfare.
3.2. Crude Venom and Toxin {#sec3dot2-toxins-08-00223}
--------------------------
Desiccated *B. moojeni* venom was purchased from Bioagents Serpentarium (Batatais-SP, Brazil). BmooMP-alpha-I was isolated and its purity and biological activity assessed as previously published \[[@B12-toxins-08-00223],[@B13-toxins-08-00223]\], with modifications. Briefly, the purification steps included anion-exchange chromatography on DEAE-Sephacel (Sigma Chem. Co., Saint Louis, MO, USA), followed by size-exclusion chromatography on Sephadex-75 (GE Healthcare, Uppsala, Sweden) and affinity chromatography on Benzamidine-Sepharose (GE Healthcare). The purified toxin was diluted, dialyzed against 50 mM ammonium bicarbonate (pH 7.8), lyophilized, and stored at −20 °C until used. Protein concentration was determined by the Bradford method \[[@B47-toxins-08-00223]\].
3.3. Electrophoretic Analysis {#sec3dot3-toxins-08-00223}
-----------------------------
Samples of the BmooMP-alpha-I were boiled for 3 min in the presence of sample buffer and resolved in 1D SDS-PAGE at 12%, as previously described \[[@B12-toxins-08-00223]\]. The slab gels were stained with Coomassie Blue R-250, 0.2% (*w*/*v*) in acetic acid:methanol:water (1:5:5, *v*/*v*) solution. The relative molecular mass of the purified enzyme was estimated by Kodak 1D image analysis software (version 3.5, Eastman Kodak Company, Rochester, NY, USA, 2001). BmooMP-alpha-I was also submitted to 2D electrophoresis, by taking120 μg of samples solubilized in 125 μL of isoelectric focalization (IEF) solution (urea 8 M, bromofenol blue 0.002%, CHAPS 2%) and resolved into IEF capillary gel for 12 h, followed by 12% SDS-PAGE.
3.4. In Vitro Model for Assessment of TNF Production {#sec3dot4-toxins-08-00223}
----------------------------------------------------
To determine the effect of BmooMP-alpha-I in the TNF molecule, it was used an in vitro model based on bone marrow derived macrophages (BMDM) priming with known Toll-like receptor (TLR) agonists, as previously described \[[@B48-toxins-08-00223]\]. Suspensions of 2 × 10^5^ macrophages/well were maintained in 96-well plates in triplicates, for 24 h, in RPMI 1640 medium (ThermoFisher Scientific, Waltham, MA, USA), supplemented with 10% fetal calf serum (FCS; Cultilab, Campinas, SP, Brazil), at standard mammalian cell culture conditions (37 °C and 5% CO~2~). BMDMs were then primed with known TLR agonists (TLR4: LPS from *E. coli* K12, 1 μg/mL; TLR2/TLR6: FSL-1, 1 μg/mL; InvivoGen, San Diego, CA, USA) for 3 h. Next, BmooMP-alpha-I preparations were added at concentrations of 12 µg/mL, 6 µg/mL or 3 µg/mL and the plates were incubated for an additional 24 h. Supernatants were collected and stored at −80 °C until assayed for cytokine production. As negative controls, cells were incubated with medium only, while positive controls consisted of cells incubated with TLR agonists. Cell viability rates were determined by MTT assay, as previously described \[[@B49-toxins-08-00223]\].
3.5. In Vivo Model for Assessment of TNF Production {#sec3dot5-toxins-08-00223}
---------------------------------------------------
Lipopolysaccharide (LPS) from *Escherichia coli* (serotype O111:B4; Sigma, St. Louis, IL, USA) was injected intraperitoneally (i.p.) in mice to induce acute systemic TNF, following a model for induction of endotoxic shock, as published elsewhere \[[@B18-toxins-08-00223]\]. Briefly, C57BL/6 mice (*n* = 10/group) were pre-treated i.p. with PBS (control) or BmooMP-alpha-I (50 μg), 60 min prior to LPS stimulation (100 µg/mouse). Blood samples were collected from the retro-orbital plexus after 90 min of LPS challenge and serum samples were obtained by centrifugation (500 *g*, 10 min, 4 °C), and stored at −80 °C until assayed for cytokine measurement.
3.6. Cytokine Measurements {#sec3dot6-toxins-08-00223}
--------------------------
TNF levels were determined in supernatants from cell cultures and serum samples using a commercial ELISA kit, following the manufacturer's instructions (R & D Systems, Minneapolis, MN, USA). In addition, IL-12p40 production was also assessed in these samples, using an appropriate kit (BD, Franklin Lakes, NJ, USA). The cytokine concentrations in the samples were calculated by comparison with standard curves of the respective murine recombinant cytokine.
3.7. Inhibitory Effect of BmooMP-Alpha-I on TNF Detection {#sec3dot7-toxins-08-00223}
---------------------------------------------------------
To determine whether BmooMP-alpha-I was able to inhibit TNF detection, mouse recombinant protein (rTNF, 1000 pg/mL; R & D Systems) was pre-incubated with BmooMP-alpha-I (12 μg) or medium alone, as negative controls. Samples of BmooMP-alpha-I inactivated by 10 mM NA~2~EDTA or BmooMP-alpha-I incubated for 2 h at 37 °C with specific polyclonal antibodies (pAb) were included in each assay, as additional controls. In parallel, anti-TNF antibody samples were also submitted to the same conditions, to ensure assay specificity. After incubation, the samples were submitted for detection of TNF by sandwich ELISA (ELISA kit R & D Systems).
3.8. SDS-PAGE to Assess Proteolytic Effect of BmooMP-Alpha-I on TNF Protein {#sec3dot8-toxins-08-00223}
---------------------------------------------------------------------------
Different BmooMP-alpha-I masses (12 μg, 6 µg, and 3 µg) were mixed with rTNF (0.7 ng) in PBS pH 7.2 and incubated at 37 °C for 45 min. Negative controls consisted of metalloprotease masses incubated with sterile PBS only. After incubation, each sample was analyzed by 1D SDS-PAGE (18%), as previously described \[[@B50-toxins-08-00223]\]. Gels were stained by silver nitrate staining kit (ThermoFisher Scientific, Waltham, MA USA) and band intensities were estimated by a dedicated imaging and analysis system (GE Healthcare).
3.9. Western Blotting for TNF {#sec3dot9-toxins-08-00223}
-----------------------------
TNF proteolysis was further assessed by Western blotting. For this purpose, samples of rTNF (1.4 ng) were incubated with BmooMP-alpha-I (24 μg) or sterile PBS at 37 °C for 45 min. After incubation, the samples were electrotransferred to nitrocellulose membranes, as described \[[@B51-toxins-08-00223]\]. Blotted membranes were blocked with 5% non-fat skim milk in PBS containing 0.05% Tween 20 (PBS-T), for 2 h at room temperature. The membranes were washed with PBS-T and probed with a monoclonal antibody directed to TNF (BD Biosciences, San Jose, CA, USA), diluted 1:250 in 1% PBS-T plus 1% skim milk, for 18 h at 4 °C. Immunoreactive bands were visualized and analyzed after assay development with chemiluminescent buffer (Promega, Madison, WI, USA), through sequential images captured by a proper imaging system (Bio-Rad, Hercules, CA, USA).
3.10. Molecular Docking {#sec3dot10-toxins-08-00223}
-----------------------
The X-ray crystallography or nuclear magnetic resonance (NMR) of the primary sequence was searched in the RCSB Protein Data Bank \[[@B52-toxins-08-00223]\]. Both BmooMP-alpha-I protein (3GBO) and recombinant murine TNF (2TNF) were chosen to be analyzed. The crystals were refined using the platform ModRefiner freely available at \[[@B53-toxins-08-00223]\] This platform was assessed to generate algorithms that were used to build and enhance protein structures utilizing the traces of Cα established by two-step atomic-level of energy minimization. Next, molecular docking analyses were performed using the Cluspro program \[[@B54-toxins-08-00223]\] to verify protein interaction. The BmooMP-alpha-I was selected as receptor and TNF as ligand, without selecting a presumed area of interaction. This docking approach utilizes Fast Fourier Transform (FFT), and it is considered an extensive assessment of simplified energy functions of the protein mutual orientations in discretized 6D space. During the procedure, the center of receptor is at the origin of the coordinated system. Meanwhile, the ligand rotates freely, being evaluated through an assumed level of discretization. Several docked structures were created, and the shape complementarity was used as scoring function. The final scoring was given according to the energy function, which was composed of the summation of the shape complementarity, electrostatic, and desolvation contributions. Additionally, the top ten structures resulting from clustering were aligned using a structural alignment by the Swiss Pdb Viewer program and ranked according to LRMS and IRMS values. The best structure, defined after alignment, was further analyzed by Swiss Pdb Viewer for H bonds identification and Discovery Studio 3.5.0 to confirm previous interaction. The protein binding cavities were identified using MetaPocket 2.0 \[[@B55-toxins-08-00223]\]. The PDB sum platform \[[@B56-toxins-08-00223]\] was utilized to create the Ramachandram plot. The structure was considered reliable whether *G factor* \> −0.5. Drugscore PPI 2.2 \[[@B57-toxins-08-00223]\] was assessed for the alanine scanning. Finally, the platform Prosper \[[@B58-toxins-08-00223]\] was employed for prediction of possible cleavage sites. This platform utilized homology from other known sequences to be cleaved by proteases, as a parameter to identify points of cleavage in the sequences that had already been determined.
3.11. Statistical Analysis {#sec3dot11-toxins-08-00223}
--------------------------
Statistical analysis of data concerning cytokine concentrations was performed using dedicated software (version 6.0h, GraphPad, La Jolla, CA, USA, 2015), using One-way ANOVA or Two-way ANOVA, followed by post-test comparisons. Values of *p* \< 0.05 were considered significant and the results are representatives from at least three independent experiments.
This study was financially supported by Brazilian Research Agencies (FAPEMIG, Fundação de Amparo a Pesquisa no Estado de Minas Gerais; CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico; CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; and FINEP/MCT (Financiadora de Estudos e Projetos do Ministério de Ciência de Tecnologia) from Brazil.
The following are available online at [www.mdpi.com/2072-6651/8/7/223/s1](www.mdpi.com/2072-6651/8/7/223/s1), Figure\~S1: Cell viability determined by MTT assay of macrophages treated with PRR agonists and/or BmooMP-alpha-I. (A) Cells were cultured in 96-well plates for 24 h and treated with BmooMP-alpha-I (12 to 1.5 μmL) for additional incubation of 24 h; (B) Cells were cultured in 96-well plates for 24 h, activated for 3 h with agonist of Toll-like receptor (TLR): LPS (1 μmL); (C) Cells were cultured in 96-well plates for 24 h, activated for 3 h with agonist of TLR: FSL-1 (1 μmL). Cells were washed with RPMI, and treated with BmooMP-alpha-I (12 to 1.5 μmL) for additional incubation of 24 h; (D) Cells were cultured in 96-well plates for 24 h and incubated with RPMI medium only (absence of BmooMPalpha-I) or activated for 3 h with TLR agonists: LPS and FSL-1 for additional incubation with medium of 24 h. The negative control cells were incubated with RPMI medium only. The negative control cells were incubated with RPMI medium only. The results are expressed as mean ± SD of the percentage of viable cells compared to control and in (A--C) the results are plotted in a non-linear regression represented by a dose response curve with 95% confidence interval. Figure S2: The docking analysis and interacting residues. (A) Structure interaction resulted from CLUSPRO analysis in which BmooMP-alpha-I is represented in blue and magenta, and murine TNF in green and yellow; (B) BmooMP-alpha-I and murine TNF complex in 3D vision determined by PYMOL. Figure S3: Analysis of the BmooMP-alpha-I and TNF interaction by Discovery Studio 3.5.0. (A--D) Demonstration of interacting residues in zoom out view. BmooMP-alpha-I is represented in red, and murine TNF in green. Figure S5: Interaction between the residues of BmooMP-alpha-I and TNF. Interaction specifications between BmooMP-alpha-I and TNF were obtained by Discovery Studio 3.5.0. The letter in front of the residue indicates the chain of the molecules. Figure S4: Alanine scanning analysis. Representation of the amino acid residues according to their sidechain\'s contribution to the binding free energy, as given in the color scale. The chain representations of the TNF for each residue contributions are shown in white, whereas the correspondent chains of the BmooMP-alpha-I are shown in magenta. (A) BmooMP-alpha-I and TNF chain A; (B) BmooMP-alpha-I and TNF chain B; (C) BmooMP-alpha-I and TNF chain C; (D) The relevant residues for interaction between TNF and BmooMP-alpha-I in terms of ddGcalc (kcal/mol).
######
Click here for additional data file.
M.C.S., T.L.S., T.W.P.M. and J.R.M. conceived and design the experiments; M.C.S., T.L.S., M.V.S., C.M.M., F.M.S., K.C.F. performed the experiments; F.O. contributed reagents and analysis tools; M.C.S., T.L.S., M.V.S., F.O., T.W.P.M. and J.R.M. analyzed the results; M.C.S., T.L.S., J.R.M. wrote the paper.
The authors declare that there are no conflicts of interest.
The following abbreviations are used in this manuscript:
BmooMP-alpha-I: metalloprotease of class P-I from *B. moojeni* snake venom; rTNF: recombinat tumor necrosis factor; TACE: metalloprotease converser of TNF; TNF-RI, TNF-R1, TNFRSF1A, p55, p60 or CD120a: receptor I of TNF; TNF-RII TNF-R2, TNFRSF1B, p75, p80 or CD120b: receptor II of TNF; ADAM: A desintegrin and metalloproteinase; NA~2~EDTA: acid ethylene-diamino-tetraacetic disodium salt; SFB: fetal calf serum; MTT: thiazolyl blue; DMF: *N*,*N*-dimethyl formamide; EGF: epidermal growth factor.
{#toxins-08-00223-f001}
{#toxins-08-00223-f002}
{#toxins-08-00223-f003}
{#toxins-08-00223-f004}
######
Direct proteolytic effect of BmooMP-alpha-I on TNF cytokine. (**A**) Silver stained 18% SDS-PAGE. Lanes: 1-Molecular weight standard proteins; 2-Mouse recombinant TNF without incubation with BmooMP-alpha-I enzyme (control); 3-4-Mouse recombinant TNF incubated with 12; 6; or 3 μg/mL of BmooMP-alpha-I, respectively, for 45 min at 37 °C; (**B**) Percentage of TNF degradation by BmooMP-alpha-I (12; 6; and 3 μg/mL), determined by band intensity of the reaction products estimated by Kodak 1D image software in relation to negative control versus relative molecular mass of TNF; (**C**) Western blot of TNF protein treated with BmooMP-alpha-I. Immunoreactive bands were developed with ECL (Electron Chemiluminescent) Western substrate and visualized with an enhanced chemiluminescence system. Lanes: 1-Mouse recombinant TNF incubated with PBS (control); 2-Mouse recombinant TNF incubated with 24 µg/mL of BmooMP-alpha-I for 45 min at 37 °C.
{#toxins-08-00223-f006}
{#toxins-08-00223-f007}
{#toxins-08-00223-f008}
{#toxins-08-00223-f009}
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{
"pile_set_name": "PubMed Central"
}
|
By Sven Mikulec
Before Warner Bros. decided to take a chance and hire him to make The Wild Bunch, the classic revisionist western that would completely revitalize his career, Sam Peckinpah was laboring on television, an isolated Hollywood outcast paying the price for his pesky reputation of a highly skilled director who was often impossible to work with. With the tender fable of the dying West called The Ballad of Cable Hogue (1970), the controversially daring Straw Dogs (1971) and the action-packed crime thriller The Getaway (1972), Peckinpah enjoyed the most productive period of his brief but turbulent career. However, when his heavily-edited, studio-cut Pat Garrett and Billy the Kid hit the theaters in 1973, it turned out a box office disappointment (even though it more than compensated for the costs of its troubled production) and the critics were far from delighted. Disappointed, disillusioned and completely depleted by the unsuccessful struggle with the studio, with waning health, Peckinpah decided to make his next picture, a more than slightly bizarre combination of an action adventure, love story and a personal redemption journey, down in Mexico. One month into principal photography, Peckinpah stated: “For me, Hollywood no longer exists. It’s past history. I’ve decided to stay in Mexico because I believe I can make my pictures with greater freedom from here.” Given his record of constantly being challenged by supervisors, neverendingly fighting with his producers and, as it has since become common knowledge, intrinsically battling his overpowering alcoholic and drug-abuse demons, it comes as no surprise Peckinpah chose to shake off the chains and find a place where he could pursue his art in peace and with complete authority, with the goal of making a “pure” film unburdened with box office projections, marketing nuisance, and studio expectations.
Having gathered a film crew comprised mostly of Mexicans, the filmmaker shot Bring Me the Head of Alfredo Garcia in the five months period between August and December of 1973, taking a week-long break before jumping onto supervising the editing process. When the film premiered on August 14, 1974, it was thoroughly hacked to pieces by the critics’ circle, with a good deal of reviews exhibiting bile, hatred and utter disdain for the work of a man who had the nerve to make the outrageous claim he didn’t need Hollywood to make his movies. Even though there were a couple of people who championed the film back then, such as Roger Ebert, who immediately called it “some kind of bizarre masterpiece,” Bring Me the Head of Alfredo Garcia bombed in the financial sense. The most personal film Peckinpah had ever made was rejected by the American film community, labeled as chaos, instability and senseless violence just like its outcast author. “I did Alfredo Garcia and I did it exactly the way I wanted to,” confessed Peckinpah later, serenely and without regret. “Good or bad, like it or not, that was my film.” In the following decades, as it’s often the case with misunderstood masterpieces by great artists, Bring Me the Head of Alfredo Garcia found the love, dedication and praise it deserved in 1974, with a lot of film scholars and critics now highlighting it as one of the most important entries in Peckinpah’s career and quintessential movies of the seventies.
While Peckinpah was working on The Ballad of Cable Hogue, his friend and screenwriter Frank Kowalski approached him with the basic plot idea of Alfredo Garcia, and Peckinpah loved it. He started working on the script as early as during the production of Straw Dogs in England and hired Gordon Dawson, an associate producer from The Ballad of Cable Hogue and The Getaway who had previously done some uncredited screenwriting work on Cable Hogue, to help him with the script. Martin Baum, a talent agent turned producer who had recently formed his own production company Optimus Productions, was approached with the screenplay and agreed to produce it. After Peter Falk and James Coburn allegedly passed on the offer, the main role went to character actor Warren Oates, while the outside of Mexico virtually anonymous Isela Vega landed the main actress gig.
Shot by the Mexican cinematographer Alex Phillips, Jr., whom the director grew quite fond of, with the score by American jazz musician Jerry Fielding, written by Peckinpah and Dawson based on a story developed by Kowalski and Peckinpah, Bring Me the Head of Alfredo Garcia tells the story of a retired US army officer Bennie, who makes his living by managing a bar where he also plays the piano. When he learns there’s a huge bounty on the head of his current girlfriend’s former lover, he finds out the man’s been killed in a car accident, which means he only has to dig him up and cut off his head as proof to earn the money that, he believes, would change his life and enable him to settle and provide a new start for him and Elita, a maid and prostitute who loves him. The journey they decide to embark on is nothing but violent, bloody, messy and extremely dangerous; the chance of success is slim at best, but the elusive idea of a new beginning leads them through the amoral landscape of crime-ridden Mexico. Acquiring the head of this poor sucker and the consequential reward for this weird undertaking might be the prime motivation for the main character—pure greed, the pursuit of financial security, because as all our poor-but-greedy film heroes tell us, money equals a chance for a fresh start. The secondary goal of the sickening road trip is making sure his girlfriend’s love for her former lover becomes as extinguished as the lover himself. In time, however, money gives way to a weird mixture of duty, redemption, love, friendship and retribution. Bennie has to deliver the head, because at the end of the journey, he literally has nothing else to cling to.
As much as Bring Me the Head of Alfredo Garcia is an exhilarating action film with dozens of dead bodies littered about the dusty, desolate landscape, this is a strange but powerful love story, an examination of people, emotions, relationships, love and sex. Think of the (improvised!) scene in which Elita confronts Bennie with the issue of their marital prospects–pure, intense, touching and deeply authentic. Peckinpah made a film that deeply resonates with the theme of lost time, ungrasped opportunities and the subtlety and complexity of true love. “This is Peckinpah making movies flat out, giving us a desperate character he clearly loves, and asking us to somehow see past the horror and the blood to the sad poem he’s trying to write about the human condition,” wrote Ebert in his original review 43 years ago. It took some time for the public to understand this poem, but Peckinpah, unfortunately, didn’t live to experience this deserved re-evaluation, being on the downward spiral during the very making of it. Co-writer Gordon Dawson saw this on set and pledged never to work with him again. “He really lost it on Alfredo. It tore my heart out.” Garner Simmons, the author of Peckinpah: A Portrait in Montage (1983), recollected how the filmmaker “did not strike him as someone capable of the legendary mayhem and madness generally attributed to him,” calling Peckinpah “fragile.” Much like the antihero of Alfredo Garcia, Peckinpah was worn out, near the end of his road, almost beaten, but not quite. The most productive and acclaimed period of his career was crowned with a beautifully sad but triumphant picture which might have been forced to deal with a lot of negativity and misunderstanding but now stands as perhaps the filmmaker’s most intense, interesting and probably subconsciously autobiographical work of art.
A monumentally important screenplay. Screenwriter must-read: Sam Peckinpah & Gordon T. Dawson’s screenplay for Bring Me the Head of Alfredo Garcia [PDF]. (NOTE: For educational and research purposes only). The DVD/Blu-ray of the film is available at Arrow Films and other online retailers. Absolutely our highest recommendation.
Bring Me the Head of Alfredo Garcia went into production in late September 1973 and in an October issue of Variety magazine, Peckinpah was quoted as saying, “For me, Hollywood no longer exists. It’s past history. I’ve decided to stay in Mexico because I believe I can make my pictures with greater freedom from here.” This upset the Motion Picture and Television Unions and they openly censured the director for his statement at their National Conference in Detroit. They also threatened Alfredo Garcia with union boycotts upon its release, labeling it a “runaway” production. In his defense, Peckinpah claimed that he was misquoted. Before the film was to be released, the unions relented on their boycott threat. —Sam Peckinpah going to Mexico by Paul Schrader, Cinema Magazine, 1969
A glimpse into the mind—and heart—of wild western elegist Sam Peckinpah during the making of his still underestimated 1974 quasi-self-portait. The following is an excerpt from British Film Institute, written by Garner Simmons, ‘Just the films, ma’am: behind the scenes of Peckinpah’s Bring Me the Head of Alfredo Garcia.’
Later, after they had left and we were alone finishing off what was left of the brandy, Sam looked at me and said: “You understand…? Why I had to do it…? The film comes first. Nothing else matters.” And the next morning in his trailer, Katy Haber took charge of his day, making certain that Sam was in control of the one thing in his life that mattered most: the film he was making. — Just the films, ma’am: behind the scenes of Peckinpah’s Bring Me the Head of Alfredo Garcia
Between the laughter and Mexican brandy, Begonia picked her moment and suggested to Sam that she not return to Mexico City but stay there with him. They could even send for the baby. Be a family again. Clearly she wanted to rekindle their relationship. Listening to her, Sam became very quiet as Begonia continued to press her case. And then in an instant, Sam’s mood completely changed as he turned on her, his voice filled with a dark cryptic edge. In a heartbeat, she knew she had crossed a line as Sam summoned Juan Jose and ordered him to drive her back to town, and never bring her back.
Petite and radiant, Begonia was charmingly animated. And as the evening made its way towards midnight it became clear that she was attempting to invite both herself and their baby back into Sam’s life. As he had been with the actresses in the casting session, Sam was both courtly and flirtatious, telling stories of how they’d met while shooting Major Dundee, and how he’d married her and the time they’d spent in Europe as Sam was trying to resurrect his career after the short-lived debacle of The Cincinnati Kid.
Around six that evening, Peckinpah’s assistant Katy Haber came up to say that Sam would like Sheila and I to join him for dinner and drinks in his trailer. His ex-wife, Begonia Palacios, had arrived from Mexico City, brought out by her brother, Juan Jose, who also happened to be Peckinpah’s personal driver. Having prematurely given birth to their daughter and only child Lupita in October, Begonia had spent several weeks recuperating as Sam’s guest in the home he was renting in the Zona Rosa in Mexico City. But once the baby had been discharged from the hospital, Begonia had taken her and gone to live with her mother. Since Sheila and I were the only other couple on location, Sam’s invitation made sense. We obviously accepted.
By week’s end, Peckinpah had completed the scenes for what would be the opening of the film—the discovery of the girl’s pregnancy and her father’s command that they find Alfredo and bring him his head. Having been cast as one of El Jefe’s bodyguards, I was given the opportunity to observe Peckinpah at work firsthand. It was an invaluable experience. He had also cast my wife, Sheila, who had flown down from Chicago, as one of the ladies in waiting. Taking Sunday off, he began preparing for what is perhaps the film’s most complicated sequence: Bennie’s confrontation with El Jefe and the final shootout.
On Tuesday 11 December 1973, Peckinpah completed shooting the complicated sequence that takes place along the rural road where Sappensly and Quill brutally murder the Moreno family and in turn are dispatched by Bennie. The following day the company would travel to its final location, the Hacienda de San Juan north of Mexico City, not far from the pyramids of Teotihuacan. Since it would provide us an uninterrupted time to talk, Peckinpah suggested I join him in his trailer for the move. And so we spent that night drinking and discussing his life, his films and filmmaking in general as he candidly answered every question I posed. We arrived at the Hacienda a little before midnight. In the background of the audio tapes I made at the time, it is possible to hear the constant chanting of the pilgrims as they make their way to the nearby Basilica of the Virgin of Guadalupe. A strange eerie mix of pagan and Catholic rituals. As a sign of devotion, many make the journey literally on their knees in hope of a miracle. It was dawn by the time they finally stopped. And so did we.
An extended version of this documentary, featuring more than ten hours of additional interview footage, is featured on the second disc of the Bring Me the Head of Alfredo Garcia (1974) limited edition Blu-ray released in 2017 by Arrow Video.
A candid conversation with the screen’s “Picasso of violence,” Playboy interview, August 1972. “The director’s role was one accepted ambivalently by Sam Peckinpah, so much so that much of his work aimed to reconcile his positions as artist, employer and businessman, and entertainer. In his August, 1972, Playboy interview, he likened himself to a hired hand and a whore. It was just a job, directing, lucrative after some successes; on the other hand, writing was the most painstaking activity ever undertaken by a man. He seemed to denigrate his status and to knock his artistic capabilities; however, a look at The Wild Bunch, The Ballad of Cable Hogue, and Bring Me the Head of Alfredo Garcia reveals that whores, most of all, have a monopoly on humanity, nobility, and common sense among Sam’s characters. Furthermore, he who hired most of the film crew willfully opposed the demands and decisions of other bossmen: studio heads and the producers. Their interference left him with unequivocal feelings: ‘There are people all over the place, dozens of them, I’d like to kill, quite literally kill.’ Metaphorically, he got his chance to kill them.” —The Film Journal
Kael compares you to Norman Mailer and says you’re both in the same machismo bag, but the difference is that Mailer worries about it. For you, she thinks it’s the be-all and end-all.
I like Kael; she’s a feisty little gal and I enjoy drinking with her—which I’ve done on occasion—but here she’s cracking walnuts in her ass. Look, what if they’d given me War and Peace to do instead of Trencher’s Farm? I’m reasonably sure I’d have made a different picture.
But you picked The Siege of Trencher’s Farm yourself, didn’t you?
I didn’t pick anything. I’ve never picked any of my films. Except one, The Ballad of Cable Hogue. That’s the only movie I ever picked to do.
Tell us how it works, then. You’re offered a lot of projects—
I’m looking for a job. I’m a whore. I go where I’m kicked. But I’m a very good whore.
Whatever material you’re given to work on, you then proceed to make it your own picture. There’s certainly no mistaking the Peckinpah touch.
The Peckinpah touch! Jesus! Read the goddamn book. You’ll die gagging in your own vomit.
When you say you’re a whore, isn’t that a half-truth at best? If you weren’t as good as you are, no one would pay any attention to you; there are plenty of whores around.
Once I’m handed something to do, then I take the material and try to work something out of it and, not to sound too goddamn pompous about it, what I put into it is what I see, how I feel about how things are or the way they’re going. But I try to tell a story, above all, in terms of the material I’m given, and very seldom have I been given a decent piece of material.
What interested you most about what became Straw Dogs?
What really turned me on was the amount of money I was given to do it. You start with the money and after you get that into focus, you try to figure out what the hell you’re doing. In this case, David Goodman and I sat down and tried to make something of validity out of this rotten book. We did. The only thing we kept was the siege itself.
David Sumner, the character Dustin Hoffman plays in the movie, is an intellectual who’s running away from himself and refuses to take a stand on anything. You portray him as a kind of worm. When he does take a stand, it’s an excruciatingly violent one and you imply that he becomes a man through this resort to violence. And that he enjoys the mayhem.
Totally wrong. I don’t know what movie you saw. There’s a point in the middle of the siege when David almost throws up, he’s so sick, and he says, “Go ahead, pull the trigger.” He’s sick of it, sick of himself, sick of the violence that he recognizes in himself. I can’t believe anyone can miss this in the movie. He’s just used a poker to kill a man who’s just tried to kill him. He looks at what he’s done with despair and absolute horror and he doesn’t care at that moment whether he lives or dies.
What about the last shot in the movie, when Hoffman is driving away from the scene of that carnage? One critic saw a look of enjoyment on his face when he tells the half-wit he doesn’t know his way home anymore.
It’s not enjoyment at all. Neither Dustin nor I interpreted it that way. The line was written while driving to location on the last day of shooting. David Warner had cued it off at rehearsal by saying, “I don’t know my way home.” I turned to Dustin and said, “And you don’t either, and that’s the whole point of the picture.” “Yes,” he said, “and I’ll say it with a smile, because the irony is too much for him to say it straight.” Dustin wanted to do it that way and he was right. David Sumner had recognized in himself the enormous suppressed violence that he had been living with. And once it had come out, there was no going back. You see, he really set the whole thing up. He could have stopped it any one of a dozen times. He was testing his wife; he was testing himself. He was maneuvering himself into a situation where he’d be forced to let the violence in himself out, as a lot of so-called pacifists and supposedly passive people do. You remember reading about that kid who shot 45 people from the top of a tower on some campus? Boy, there was the honor student, the good guy, the boyscout leader who was kind to his mother and small animals. Whether he enjoyed shooting all those people isn’t the issue. The issue is that he did it. He had all that violence in him and he went up into the tower and let it out. Now, you hear all this talk about the violence in Straw Dogs and in some of my other pictures, as if that violence were contributing to the violence of our society. The point is that the violence in us, in all of us, has to be expressed constructively or it will sink us. I’m a great believer in catharsis. Do you think people watch the Super Bowl because they think football is a beautiful sport? Bullshit! They’re committing violence vicariously. Look, the old basis of catharsis was a purging of the emotions through pity and fear. People used to go and see the plays of Euripides and Sophocles and those other Greek cats. The players acted it out and the audience got in there and kind of lived it with them. What’s more violent than the plays of William Shakespeare? And how about grand opera? What’s bloodier than a romantic grand opera? Take a plot, any plot—brother kills brother to sleep with the wife, who then kills her father, and so on and so on. Want to have some fun? Read Grimm’s Fairy Tales. When you point things like this out to the New York cats, they tell you it was all art, which is crap. These plays and operas and stories were the popular entertainment of their day.
But they weren’t as concerned as you are with the physical details of violence. The violence in your pictures is executed lovingly, superrealistically and almost always in close-up.
You can’t make violence real to audiences today without rubbing their noses in it. We watch our wars and see men die, really die, every day on television, but it doesn’t seem real. We don’t believe those are real people dying on that screen. We’ve been anesthesized by the media. What I do is show people what it’s really like—not by showing it as it is so much as by heightening it, stylizing it. Most people don’t even know what a bullet hole in a human body looks like. I want them to see what it looks like. The only way I can do that is by not letting them gloss over the looks of it, as if it were the seven-o’clock news from the DMZ. When people complain about the way I handle violence, what they’re really saying is, “Please don’t show me; I don’t want to know; and get me another beer out of the icebox.”
Many people want to put a stop to whatever, on television or movie screens, could contribute to the public violence of our time. Are they wrong?
I think it’s wrong—and dangerous—to refuse to acknowledge the animal nature of man. That’s what Robert Ardrey is talking about in those three great books of his, African Genesis, The Territorial Imperative and The Social Contract. Ardrey’s the only prophet alive today. Some years ago, when I was working on The Wild Bunch, a friend of mine came to me with African Genesis and said I had to read it because Ardrey was writing about what I was dealing with, that we were both on the same track. So after I finished Wild Bunch I read him and I thought, wow, here’s somebody who knows a couple of nasty secrets about us. Straw Dogs is about a guy who finds out a few nasty secrets about himself—about his marriage, about where he is, about the world around him. Some people don’t like facing that sort of thing; it makes them itch. You see, David Sumner gets the blinkers pulled off. The man said you can’t go home again and David can’t either. He can go on—we all can—but he can’t go back to what he was. I don’t know what could be clearer.
What about his wife, Amy? What does she find out about herself?
Well, there are two kinds of women. There are women and then there’s pussy. A woman is a partner. If you can go a certain distance by yourself, a good woman will triple it. But Amy is the kind of girl—and we’ve all seen them by the millions—they marry, they have some quality, but they’re so goddamn immature, so ignorant as far as living goes, as to what is of value in life, in this case about marriage, that they destroy it. Amy is pussy, under the veneer of being a woman. Maybe because of what happens to her, she’ll eventually become a woman.
Are you implying that Amy couldn’t become a woman until David became a man?
No, David was always a man. It’s just that he didn’t see deeply enough into himself. He didn’t know who he was and what he was all about. We all intellectualize about why we should do things, but it’s our purely animal instincts that are driving us to do them all the time. David found out he had all those instincts and it made him sick, sick unto death, and at the same time he had guts enough and sense enough to stand up and do what he had to do.
But Amy was the instrument of his self-discovery, wasn’t she? Didn’t she push and prod him to “act like a man”?
She didn’t know what she wanted. She pushed him, as you say, but not in any constructive way. To start out with, she asked for the rape. But later she could barely bring herself to pull the trigger to save his life. I don’t know whether they’ll get back together again. At least they’ll have to deal with each other on a different plane. What I hope he does is keep going in that car at the end—not turn back. He obviously married the wrong dame. She is basically pussy. What I favor is marriages made in heaven, and that’s the only place marriages ought to be performed. And speaking of rape, I’d like to point out to Miss Kael and these other so-called critics that rear entry does not necessarily mean sodomy, as they said in their reviews. In the picture, Amy is taken by one guy she used to go with and then she’s taken from the rear by another guy she didn’t want any part of anywhere. The double rape is a little bit more than she bargained for. Anyway, I guess Miss Kael and her friends have anal complexes. Perfectly justified in this day and age.
If Amy is pussy, why did David marry her?
Come on, that’s beneath you. Most of us marry pussy at one time or another. A smart, unscrupulous cunt can always use her looks to get some poor slob to marry her. And in marriage, so often, especially if the man is lonely, he will clothe her in the vestments of his own needs—and if she’s very young, she’ll do the same thing to him. They don’t really look at what the other person is but at what they want that person to be. All of a sudden the illusion wears off and they really see each other and they say, “Hey, what’s all this about?” Now that David can see himself, too, he can begin to build his life. As for her, probably she’ll never change.
You sound like a man who’s had a lot of experience with pussy.
I wouldn’t have it any other way. One of the advantages of being a celebrity is that a lot of attractive pussy that wasn’t available to you before suddenly becomes available. Groupies and star-fuckers abound and you certainly don’t have to marry them, though a lot of poor fools do.
How do you account for the mutual attraction of stars and groupies?
It’s the same thing that attracts all men to women, and vice versa. Men are primarily turned on by physical beauty, magnetism, or maybe just the way a woman moves and the kind of atmosphere she surrounds herself with. But what attracts a woman to a man is entirely different. It has a lot more to do with where a man is with his life. I’m not talking about money; I’m talking about success. I’m talking, really, about territory. How much and where and how secure. It’s the most basic human urge. Watch the behavior of any herd. Who’s got the cows? The biggest, strongest bull. And every year he has to fight off all challengers until eventually someone does him in. But while he reigns, he has it all his own way. It’s the most basic and fascinating evolutionary process there is.
Ethologists might agree with you, but it’s doubtful that women’s lib would buy much of what you’re saying.
I ignore women’s lib. I’m for most of what they’re for, socially as well as politically and economically, but I can’t see why they have to make such assholes of themselves over the issue. Those bull dykes and the crazies in their tennis sneakers and burlap sacks—just try to explain a few facts of life to them. Like the fact that I have a penis that thrusts into a woman and she has a vagina to receive me. The basic male act, by its very nature, starts out as an act of physical aggression, no matter how much love it eventually expresses, and the woman’s begins as one of passivity, of submission. It’s a physical fact. Except to a bull dyke. Not that I’m knocking lesbianism. I consider myself one of the foremost male lesbians in the world. I don’t care what goes on in people’s heads; we are physically constructed in a certain way and we’ve been handed a set of instincts to go with the machinery. Tell that to any of these women’s lib freaks and they’ll swear you’re a male-chauvinist pig. What can happen when you deny your basic instincts and drives is what Straw Dogs is all about. I read somewhere recently that some cat was having trouble making it with women today because half the ones he took to bed began by making geographical demands. They lay out a whole sexual battle plan before they start. They want this, they want that. You’re expected to provide instant satisfaction by delivering like some kind of computerized acrobat. That’s logistics, not sex—and certainly not love. In sex, when you do it only for yourself or the other person, you’re masturbating either yourself or her. Any good whore knows more about sex than Betty Friedan.
Do you really like whores?
Of all the whores I’ve been with—American, Chinese, English, Mexican, any nationality—I’ve failed to end up in some kind of warm personal relationship with only about 10 percent. I’ve lived with some good whores. They’ve taken me home or I’ve taken them home. We’ve been human beings together. I never thought of these women as objects to be used. I put a lot of the relationships I’ve had with whores into the love story of Cable Hogue and his whore, Hildy. They had a relationship that was truer and more tender than that between most husbands and wives. The fact that she was a whore and went to bed with men for money didn’t change anything. Most married women fuck for the money that’s in it.
Regardless of your relationship with whores, doesn’t the fact that you relate so well to them signify some need on your part to remain either superior or emotionally uninvolved?
Possibly, but I believe it signifies mostly that I like an honest woman, a woman who’s honest with herself and the people she cares about. Not infrequently, in one way or another, she turns out to be a prostitute.
Come to think of it, most of the women in your movies have been prostitutes.
You find something good, you stay with it.
Like violence. You’ve always dealt with it, haven’t you?
One of my big themes. But if you want to find out something about violence in this country, you ought to talk to the people in our prisons, as I’ve been doing lately in connection with The Getaway. Those guys’ll wake you up. For them it’s a way of life, a life lived according to certain codes. There are some things you do and others you don’t do. The whole thing is built into the fabric of their lives, as it was for those cats in The Wild Bunch. They were people who lived not only by violence but for it. But the whole underside of our society has always been violent and still is. It’s a reflection of the society itself. Do you know, people came up and threw punches at me because they were incensed by the violence in The Wild Bunch? These pacifists came up and actually tried to hit me. They didn’t understand who they were. In George Bernard Shaw’s play The Devil’s Disciple, a preacher discovers his true nature, which is that of a man of action, a man of violence, and the man of action discovers he’s really a preacher. Doesn’t that suggest anything to you?
That maybe you’re a bit of a preacher yourself.
Right on. Something to do with my background, maybe.
Do you think pacifists are dishonest with themselves or out of touch with reality? Or just plain unmanly?
Of course not. True pacifism is manly. In fact, it’s the finest form of manliness. But if a man comes up to you and cuts your hand off, you don’t offer him the other one. Not if you want to go on playing the piano, you don’t. I’m not saying that violence is what makes a man a man. I’m saying that when violence comes, you can’t run from it. You have to recognize its true nature, in yourself as well as in others, and stand up to it. If you run, you’re dead, or you might as well be.
When you say that someone is a real man, what do you mean by it?
That he doesn’t have to prove anything. He’s himself. My dad put it another way. When the time comes, he used to say, you stand up and you’re counted. For the right thing. For something that matters. It’s the ultimate test. You either compromise to the point where it destroys you or you stand up and say, “Fuck off.” It’s amazing how few people will do that. So if I’m a fascist because I believe that men are not created equal, then all right, I’m a fascist. But I detest the term and I detest the kind of reasoning that labels that point of view fascistic. I’m not an anti-intellectual, but I’m against the pseudo intellectuals who roll like dogs in their own verbal diarrhea and call it purpose and identity. An intellectual who embodies his intellect in action, that’s a complete human being. But sitting back and quarterbacking from the stands is playing with yourself.
David Sumner in Straw Dogs is the first intellectual you’ve ever made the hero of a movie.
He’s not a hero. He’s a heavy. I’m crazy about heavies.
Is that how you felt about your characters in The Wild Bunch? You’ve been quoted as saying that you hated Pike Bishop, the Bill Holden part, and his buddies, that they were dangerous and had to go; but the way you handle them in the movie seems to contradict you. It expresses respect and even love for them and what they stand for.
Sure I loved them. I love outsiders. Look, unless you conform, give in completely, you’re going to be alone in this world. But by giving in, you lose your independence as a human being. So I go for the loners. I’m nothing if not a romantic and I’ve got this weakness for losers on the grand scale, as well as a kind of sneaky affection for all the misfits and drifters in the world.
Aren’t your losers and misfits conformists to outdated codes?
Outdated codes like courage, loyalty, friendship, grace under pressure, all the simple virtues that have become clichés, sure. They’re cats who ran out of territory and they know it, but they’re not going to bend, either; they refuse to be diminished by it. They play their string out to the end.
But isn’t the hard truth about the frontier that it had no real code—other than survival of the fittest?
Yep, but I don’t make documentaries. The facts about the siege of Troy, of the duel between Hector and Achilles and all the rest of it, are a hell of a lot less interesting to me than what Homer makes of it all. And the mere facts tend to obscure the truth, anyway. As I keep saying, I’m basically a storyteller. I’m not even sure anymore what I believe in. I once directed a Saroyan play in which one of the characters asked another if he would die for what he believed in. The guy answered, “No, I might be wrong.” That’s where I am. I’m not going to get between my audience and the story. I hate the feeling in a theater of being more aware of what the director’s doing than of what’s actually up there on the screen.
Is that why you like doing Westerns, because the West is almost the only mythology we have?
Hell, no. I came by it naturally. My earliest memory is of being strapped into a saddle when I was two for a ride up into the high country. We were always close to the mountains, always going back to them. When my grandfather was dying, almost his last words were about the mountains. We’d summer in them and some winters I ran trap lines in the snow. We loved that country, all of us. My granddad, Denver Church, had a 4100-acre cattle ranch in the foothills of the Sierras, about 25 miles east of Fresno, and the whole family, the Peckinpahs and the Churches, had been wandering in that country since moving out from the Midwest in the middle of the 19th Century. We even have a mountain named after us.
Have you used your family as characters in your pictures?
No, they got too respectable. They went into real estate, politics, the law. My mother, who’s still very much around, believes absolutely in two things: teetotalism and Christian Science. My father was a judge. He believed in the Bible as literature, and in the law. He was an authority, and we all grew up thinking he could never, ever be wrong about anything. The law and the Bible and Robert Ingersoll were our big dinner-table topics. When I was still a kid, Dad made me go to the trial, in his court, of a 17-year-old boy accused of statutory rape. He thought it would be a good lesson for me. It was, but not for the reasons he thought. In addition to being a judge, my dad was probably the worst cattleman in the business. He went broke 13 times. And in the mountains, he made his own laws. He believed that you didn’t hunt unless you ate what you killed. But he claimed that all the animals on his land were his to do what he liked with. I was 20 years old before I knew there was such a thing as a hunting season or a game warden, and I was 30 before I began paying any attention to it. The people, the places in that area! It’s mostly all gone now. Fresno’s like a little LA today, and the country around it is chopped up with new roads and resort facilities and overrun with all these shit-ass tourists and campers. My brother Denny and I were in on the last of it. A lot of the old-timers dated back to when the place had been the domain of hunters and trappers, Indians, gold miners—all the drifters and hustlers. All that’s left now are the names to remind you, and what names: towns like Coarsegold and Finegold, Shuteye Peak, Dead Man Mountain, Wild Horse Ridge, Slick Rock. And the old-timers had their stories to tell, too. Denny and I rode and fished and hunted all over that country. We thought we’d always be a part of it. The last few years I haven’t even been hunting anymore, but I’m thinking of taking it up again.
Do you agree with your father that it’s wrong to hunt unless you eat what you kill?
Yes, and you also shouldn’t kill more than you can eat. A deer tastes good, but it’s also beautiful animal. Anyone will kill, though, if he gets hungry enough—even those who refuse to hunt at all, for moral reasons. A gnawing in the belly is a great equalizer of principles. Of course, most men kill only out of principle, and then it’s usually his fellow man. Nice principle.
Do you think it’s possible, as one critic once said about you, that you’re really a 19th century man and that in your work you’re living vicariously the period you’d have preferred to live in?
When you’re doing a picture, first of all, the period matters less than what the thing is about. You become all the characters. I’ve been every character in my pictures. The actors do the same. They wear each other’s parts to try them on for size, to test them and themselves, sometimes against each other. But I did like that period in American life. And I liked the period I grew up in, the Thirties. It was a different America. We hadn’t run out of ground.
With your hard-nosed WASP background and your commitment to the outdoors, how did you make the leap into show business?
By chance. I was just out of the Marine Corps after World War II and I had nothing very specific in mind. Denny had gone into law. The only thing I was sure of was that I didn’t want to do that. I went back to school, to Fresno State, because I had nothing better to do. There I met my first wife, Marie, who wanted to be an actress. Fresno State had a small but active theater department and I tagged along after Marie one day into a directing class. It turned me on right away. I especially dug the plays of Tennessee Williams, and my big project at school was a one-hour version of The Glass Menagerie that I adapted and directed. I guess I’ve learned more from Williams than anyone. He’s easily America’s greatest playwright. I’ve always felt strongly moved by him. I’ve also directed Streetcar, as well as most of his one-acts. He’s a tremendous artist and I wish him the best of luck, always. I think I learned more about writing from having to cut Menagerie than anything I’ve done since.
Writing was what opened doors for you, wasn’t it?
Yeah, but it was hell, because I hate writing. I suffer the tortures of the damned. I can’t sleep and it feels like I’m going to die any minute. Eventually, I lock myself away somewhere, out of reach of a gun, and get it on in one big push. I’d always been around writers and had friends who were writers, but I’d never realized what a lot of goddamn anguish is involved. But it was a way to break in. I paid my dues in this business. I was a gofer, a stagehand. I swept out studios and I watched a few good people work. Then I started writing and finally selling TV scripts. And after a while I decided to try my hand at movies. I always had two or three projects going at a time. I’d put everything into them and I’d sell a few and then they’d disappear. I wrote two pretty good scripts in those days, and what happened to them was typical. One, Villa Rides, was produced with Yul Brynner in the lead. It was awful. I’ve put in a lot of time in Mexico and I know Mexican history. Brynner said I didn’t understand Mexico and Villa Rides is the result of the changes they made. It’s a phony. The other script became One-Eyed Jacks, directed by and starring Brando. I had adapted the thing from a novel by Charles Neider called The Authentic Death of Hendry Jones, based on the true story of Billy the Kid. It was the definitive work on the subject, but Marlon screwed it up. He’s a hell of an actor, but in those days he had to end up as a hero and that’s not the point of the story. Billy the Kid was no hero. He was a gunfighter, a real killer. But I don’t want to knock actors. Some of my best friends are actors. It was Brian Keith, who’d worked with me on The Westerner series, who got me my first movie-directing break. He’d been signed to star opposite Maureen O’Hara in The Deadly Companions and he persuaded the producer of the picture, who happened to be Miss O’Hara’s brother, to take me on. It wasn’t the best deal in the world: I wanted to make a picture and this guy wanted to push me around. The script needed lots of work, but I’d get told to go back in my corner. Brian knew we were in trouble, so between us we tried to give the thing some dramatic sense. The result was that all of his scenes worked, while all of hers were dead. I found out about producers, all right.
You’ve always had trouble with producers. Are there any you’ve ever enjoyed working with?
One, maybe two, and even then not much. I don’t work well under people. I think there has to be one person who’s making a picture and that person has to be the director. Producers are often only administrators and they’re too interested in defending their own prerogatives. I’ve got a temper and I can’t stand stupidity, so I’m always at war with these cats. I want control of everything, from the script to the cutting room. And if I don’t get what I want from people, I put them on the bus. The trouble with producers is you can’t do that to them. Everybody else comes and goes on a picture, but the producer and the director are with it from beginning to end. The best producer is a guy who’ll let you make your own movie. There aren’t many around.
What directors have that clout?
Kurosawa has it. Fellini. Bergman. But no American has it. Some, like Kubrick and Nichols, think they do, but they don’t. It’s not just a question of what happens to you during shooting and editing: it’s what they do to you once the film is entirely out of your hands. Huston once almost had total control, but he blew it on The Red Badge of Courage, when he walked away from the cutting of the picture. I’m a great admirer of his, anyway. Every picture of Huston’s has tried not only to tell a story but to make some kind of statement. The perfect films of this kind are The Maltese Falcon and The Treasure of the Sierra Madre. I wish I could make a film that good. Compared with John Huston, I’m still in seventh grade—but I’m moving up.
We’ve heard that Huston didn’t run out on Red Badge, that he had another commitment.
Well, even if he did run, I wouldn’t blame him at all. This isn’t a game. There’s too much at stake. And the woods are full of killers, all sizes, all colors. I didn’t know about all of this when I was just a writer. I couldn’t stand being so alone with myself, and it was very, very hard work; but writing has one very big advantage over directing: You only have to deal with yourself: you can escape into your fantasies and be a king. The outside world. as far as a writer’s work goes, is limited to dealing with an agent and maybe a couple of editors, some of whom can be pretty good people. But a director has to deal with a whole world absolutely teeming with mediocrities, jackals, hangers-on and just plain killers. The attrition is terrific. It can kill you. The saying is that they can kill you but not eat you. That’s nonsense. I’ve had them eating on me while I was still walking around. My basic job is dealing with talent in terms of a story and getting it on. I wish the rest of it were that simple. But there’s all the shit that comes before and after.
Now that the big studios don’t control the industry anymore, don’t you and a few other top directors have much more freedom to make the kind of movies you want to make? Isn’t that what the so-called New Hollywood is all about?
I’m not talking about Hollywood, new or old. What I’m talking about is money, doctor. That’s what it’s all about. Unlike a novelist, for instance. I’m dealing with a product that costs several million dollars. When you’re dealing in millions, you’re dealing with people at their meanest. Christ, a showdown in the old West is nothing compared with the infighting that goes on over money. To get my films made, especially at the beginning, I always had to lie and cheat and steal. It was the only way I could cope with all the muscle that stood behind the weight of the money. And even then I couldn’t win. MGM saw Ride the High Country as a low-budget quickie they could throw away in the second halves of summer double features, and if I’d tried to talk to them about the basic theme of that picture, which was salvation and loneliness, they’d have fired me on the spot. Even so, they hated what I’d done, and they threw me out before I could finish cutting, dubbing and scoring. Major Dundee, which had a good man in it, Chuck Heston, and could have been something, was butchered by the studio and the producer turned out to be a weasel whose real talent was for poisoning wells. Marty Ransohoff fired me from The Cincinnati Kid after only four days. He gave a story out to the trades that I was vulgarizing the picture by injecting a nude scene into it. There was a scene in a hotel room between Rip Torn and this girl who was playing a dreary little hooker. Well, we worked on it and the scene got sadder and sadder. It just happened that the girl turned out to be naked under her coat. It was only one element in a much bigger scene. But I learned one thing about Marty: He had a tremendous hatred of real talent. It was nearly four years before I worked again. I got by on moonlighting, borrowed money and an occasional script. I couldn’t get people on the phone or get through a studio gate. I was out. It wasn’t until Danny Melnick, who’d seen High Country and liked it, hired me to adapt and direct Katherine Anne Porter’s Noon Wine on television that I found myself back in business. And when word got out that I was being hired, Melnick got calls from people who not only had never worked with me but who didn’t even know me. They all tried to warn him off me.
Why?
A lot of cats in this business are overpaid and guilty about it. To them I’m a threat.
Or maybe you just haven’t gone out of your way to make friends in the movie business. In any case, after Noon Wine, you really established yourself. Didn’t this make things easier?
Not much. My next two pictures, Wild Bunch and Cable Hogue, got made but were practically wiped out. Warner Bros. cut Wild Bunch to pieces and you have to go to Europe to see the picture in anything like the version I made. Cable Hogue was thrown away in multiple release despite the fact that people had begun to pay some attention to my work and Wild Bunch made a lot of money for the studio. Before I started on Straw Dogs. I had five pictures in the can, not one of which was visible anywhere in this country either at all or in anything like the form I wanted it to be in. What I’d done had been butchered or thrown away. The worst that can happen to a novelist is that his book goes out of print, but it survives somewhere, in libraries, at least, in its original form. There are people all over the place, dozens of them. I’d like to kill, quite literally kill. You know, you put in your time and you pay your dues and these cats come in and destroy you. I’m not going to work for people who do that anymore.
So where are you going from here?
Logistically or spiritually?
Both.
Logistically, all I want out of my work now is health and happiness for my precious family, as Williams puts it in The Glass Menagerie. That means I’ll keep working. I have two scripts in hand at the moment, but they both need work. All scripts need work.
Why do you feel you always have to rewrite?
No matter how good a script is, you have to adapt it to the needs of the actors.
How about your own needs? All your scripts, whether originals or adapted from a book, have a distinctive style, a unique kind of language, that identifies them as yours.
The Peckinpah touch again? Well, some people think my pictures are pretty dreadful, including your movie reviewer, who I’d like to see cut a tin bill and go out and pick shit with the chickens.
We’ll give him the message. You seem to be pretty vulnerable to what people think of you.
I think the role of the critic is very important to films, and that’s why I get so goddamn angry when the critics don’t pick up on good films and go along with bullshit, as they did on Bogdanovich’s film, The Last Picture Show, which was a crashing bore, and ignore something like Two-Lane Black-top, which I thought was a potential work of art. The Last Picture Show was artsy-craftsy, jacksy-offsky and a real pain in the ass. I was supposed to have dinner one night with Ben Johnson, who was superb in it, but I knew Peter would be there and I’d have to hit him right in the fucking mouth, so I didn’t go. I really hated that film.
What films have you liked recently?
My own. I make marvelous films. I think Junior Bonner, which I shot in 40 days, may possibly be my best picture. I’m truly delighted with it. And I don’t think McQueen has ever been better, which is saying a lot. The picture’s about three days in the life of a bull rider, a loner on the rodeo circuit.
Are there any other films, besides your own, that you’d care to talk about?
I haven’t seen much. But I loved Dirty Harry, even though I was appalled by it. A terrible piece of trash that Don Siegel really made something out of. Brilliantly done. Hated what it was saying, but the day I saw it the audience was cheering.
What about The Godfather?
Haven’t seen it—but I hate Coppola, too.
Why?
Because I hear the film is great and the only movies I want to like are my movies. I don’t want any other son of a bitch making good movies.
So you hate the good directors as well as the bad ones.
I detest every filmmaker except the innocuous ones. I love Ross Hunter. Ross Hunter is my idol. I’d like to be Ross Hunter. He knows where it’s at, baby. But you asked me back there where I was going logistically and spiritually and I’ve only answered the first part of the question.
Well?
Spiritually, I need rest and refreshment, and that usually means Mexico. I’ve been working steadily now for a long time and I’m tired.
Why do you always go back to Mexico?
Mexico has always meant something special to me. My Mexican experience is never over. I first went there right after the war, because I’d been to China with the Marines and wanted to go back there and couldn’t after the Communists took over. Mexico was the nearest place to go, and it was a time of going. We were all on the road in those days, just as Kerouac wrote about it. I loved Mexico. I stayed three months that first trip and I’ve gone back ever since. I took Marie there first. My second wife was Mexican. And I married my current wife, Joie, in Juárez, when we got to El Paso with The Getaway. Everything important in my life has been linked to Mexico one way or another. The country has a special effect on me.
Can you define it?
You bet I can. In Mexico it’s all out front—the color, the life, the warmth. If a Mexican likes you, he’ll touch you. It’s direct. It’s real. Whatever it is, they don’t confuse it with anything else. Here in this country, everybody is worried about stopping the war and saving the forests and all that, but these same crusaders go out the door in the morning forgetting to kiss their wives and water the flowers. In Mexico they don’t worry so goddamn much about saving the human race or about the wheeling and dealing that’s poisoning us. In Mexico they don’t forget to kiss each other and water the flowers.
You don’t put much faith, we gather, in social or political solutions.
None. You know what this country’s all about, doctor? It’s advertising. It’s brainwashing. It’s bullshit. It’s hustling products and people, making no distinction between the two. We’re in the Dark Ages again. Look at who the people are voting for—Nixon, Wallace—killer apes right out of the caves, all dressed up in suits and talking and walking around with death in their eyes. And what’s the alternative to these cats? Humphrey and Muskie? Two guys with absolutely no souls of their own, no concept of where they stand, who they are, no fundamental morality.
And George McGovern?
I doubt whether he’s tough enough to cut it. If he turns out to be, they’d better throw a metal shield around the poor bastard and keep it there. The rifle shot that rang out in Dallas in 1963 was a very big and ugly noise. You know, I wouldn’t film any part of The Getaway in Dallas. We were set to go in there and shoot some railroad sequences. I was driving around and I stopped for a stop sign and I looked up and there was this plaque on a building and I realized I was at that crossing. I said, “Let’s get the hell out of here. We aren’t going to shoot any part of my picture in this town.” You want to go shopping at Neiman Marcus? Fine. Great store, the greatest in the world. But staying in Dallas to put some part of yourself on the line there? No. Anyway, to get back to politics, I guess I agree with something my brother said some time back. The time will come, he said when you’ll look back on Harry Truman as possibly the best President this country ever had. Even Eisenhower was better than these guys. At least he knew who he was. He wasn’t dead and the society wasn’t dead.
What about those who are fighting to change things? America seems to be full of good causes these days and good people actively committed to them. Don’t you think there are some grounds for optimism, for hope?
No. Boredom will kill them off. The country has no attention span. We’re television oriented now. We’d better all wake up to the fact that Big Brother is here. And now, with cable TV and video cassettes coming in, no one will ever have to get up off his ass, even to go to the corner for a movie. It’s awful. One of the great things about going to a movie or the theater is the act itself—the getting out, the buying of the tickets, the sharing of the experience with a lot of other people. Eighty percent of the people who watch television watch it in groups of three or less, and one of those three is half stoned. Most people come home at night after work, have a couple of knocks before dinner and settle down in their living-death rooms. The way our society is evolving, doctor, has been very carefully thought out. It’s not accidental. We’re all being programed, and I bitterly resent it.
What can we do about it?
We have to water the flowers—and screw a lot.
You think love is the answer?
What are you, some kind of nut? All I know about love is: Don’t fuck with it.
Well, at least you’re making money these days. What are you doing with all of it?
I’ve got four kids and a big load to carry. I don’t own much and I don’t want to. I still have an ocean-front lot I bought years ago in Malibu and a small cattle ranch outside Ely, Nevada, but I’m trying to unload both of them. I’m selling everything I can. I want to get rid of this creature-comfort thing.
What’s wrong with some of the more pleasant amenities success can bring you? Why not live a little?
I live plenty. I like good drink, good food, comfortable clothes and fancy women. But if I get sucked into this consumer-oriented society, then I can’t make the pictures about it that I want to make. I’m a goddamn nomad. I live out of suitcases and my home is wherever I’m making a picture.
If the money means so little to you and you don’t care about possessions, then what do you really want from your career? Is it just an ego trip?
Fuck you, buddy. OK, ego has a lot to do with it, sure. But it’s not what the game’s about, and you know it.
If it’s a game, then what’s the game about?
I’ll put it to you this way. I’ve come a ways and I’ve paid a price. It’s cost me plenty—maybe my sanity and at least a couple of marriages—and I’m not sure the game is worth it. Sometimes I want to say the hell with it and pack it in, but I can’t do that. I stick or I know I’m nothing. Then I look around and I notice I’m not entirely alone. There are maybe 17 of us left in the world. And we’re a family. That family is composed of the cats who want to do their number and get it on. It’s the only family there is. My father said it all one day. He gave me Steve Judd’s great line in Ride the High Country: “All I want is to enter my house justified.”
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Selina Thompson is an artist and performer based in Leeds. Her work is playful, participatory and intimate, focused on the politics of identity, and how this defines our bodies, lives and environments. She has made work for pubs, cafes, hairdressers, toilets, and sometimes even galleries and theatres, including Spill Festival of Performance, The National Theatre Studio, The Birmingham REP, East Street Arts and the West Yorkshire Playhouse.
Over the past couple of years she’s been developing a body of works called ‘Edible Women’, exploring the fat body, dieting, control around food, and how much of a mess she can get away with creating with an audience and a taste for excess. This group of works saw her make a theatre show, build a dress out of cake, and spend quite a lot of time listening to people confess their food sins, as well as sharing many of her own.
She is currently in the middle of developing two new projects: the first exploring black identity within the UK and further afield (for this one she built a giant ball of hair) and the second looking at unemployment and job centres (built a job centre for that one). It’s not as much fun as working with food, but it is less sticky.
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Thomas Wildman
Colonel Thomas Wildman (1787 – 1859) was a British Army officer during the Napoleonic Wars, a draftsman, and landowner.
Life
He was the eldest son of Thomas Wildman of Bacton Hall, Suffolk, by Sarah, daughter of Henry Hardinge, of Durham. A nephew of the political reformer John Horne Tooke and friend of Lord Byron at Harrow, Wildman purchased a cornetcy in the 7th Light Dragoons in 1808 and later the same year he was promoted lieutenant without purchase. At the Battle of Waterloo, he was an extra aide-de-camp to Lord Uxbridge. His letter after the battle described Uxbridge's wounding at the end of the battle (grapeshot to the knee) and the subsequent amputation. Wildman himself was slightly wounded in the battle. In 1816, he purchased a majority in the 2nd West India Regiment, and later transferred to the 9th Light Dragoons. In 1828, he became captain of the Mansfield Troop of the Nottinghamshire Yeomanry and a few months later became major-commandant of the Sherwood Rangers Yeomanry. He was promoted colonel in the Army in 1837. In 1840, he transferred to be lieutenant-colonel of the 5th Dragoon Guards.
He recorded his service during the Peninsular War in a diary, which was subsequently published.
The Wildman family had obtained Quebec Estate, a large sugar plantation in Jamaica, from William Beckford, who was having financial problems. The wealth generated from this plantation provided Wildman with the means to purchase Newstead Abbey in 1818 for £95,000 from a Mr. Clawton, who had bought it of Lord Byron for £14,000. The Abbey was owned by his friend and old schoolmate, Lord Byron who, like Beckford, was having financial difficulties. Byron had been trying to sell the Abbey since 1812. Of the sale, Byron's half-sister Augusta said Wildman had "soul enough to value the dear Abbey..."
Although Wildman's purchase ended almost four centuries of Byron family ownership of the Abbey, he was considered to be the man who saved Byron's home. He spent £100,000 restoring it, hiring the architect John Shaw to make improvements. He also amassed a large collection of Byron memorabilia there. He served as High Sheriff of Nottinghamshire for 1821-22.
The Wildmans entertained many guests who wished to visit the home of Lord Byron, including Franz Liszt and Washington Irving. The Duke of Sussex visited annually for a six-week holiday with his chaplain. After Wildman's death, Louisa sold the Abbey to William Frederick Webb.
Personal life
In 1816, he married a Swiss woman, Louisa Preisig. They had no children.
References
Category:1787 births
Category:1859 deaths
Category:People educated at Harrow School
Category:West Indies merchants
Category:7th Queen's Own Hussars officers
Category:West India Regiment officers
Category:9th Queen's Royal Lancers officers
Category:5th Dragoon Guards officers
Category:British Army personnel of the Napoleonic Wars
Category:Sherwood Rangers Yeomanry officers
Category:High Sheriffs of Nottinghamshire
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GAZA — Hundreds of women and children protested cutbacks in a United Nations food-assistance program on Wednesday, the latest in a growing backlash by Palestinian refugees and their offspring in this forlorn coastal strip against the agency that for decades has provided them with nutrition, education and health services.
“People are getting poorer, and the agency’s directors nurture bellies,” they chanted outside the locked gates of the United Nations Relief and Works Agency. “We are under siege!”
Adnan Abu Hasna, a spokesman for the agency, said that it was facing a $55 million budget shortfall this year. The cuts that led to the recent complaints and rallies by Gaza residents and politicians were part of a shifting of resources based on a re-evaluation of the population’s needs, he said.
About 9,500 families were removed from the food program, Mr. Hasna said, because their economic situations had improved, while 5,400 poorer families were added. An additional 4,000 had their benefits increased.
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Qiaodong District, Zhangjiakou
Qiaodong District () is a district and the seat of the city of Zhangjiakou, Hebei province, China.
Administrative divisions
Subdistricts:
Hongqilou Subdistrict (红旗楼街道), North Shengli Road Subdistrict (胜利北路街道), Wuyi Road Subdistrict (五一大街街道), Huayuan Avenue Subdistrict (花园街街道), Zuanshi Road Subdistrict (钻石路街道), Nanzhan Subdistrict (南站街道), Maludong Subdistrict (马路东街道)
Towns:
Laoyazhuang Town (老鸦庄镇), Yaojiazhuang Town (姚家庄镇), Dacanggai Town (大仓盖镇)
Townships:
Dongwangshan Township (东望山乡)
References
External links
Category:County-level divisions of Hebei
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Wednesday, April 20, 2016
Wonder and Humility
Last week, Patrick and I sat down to record a podcast on tasting beer. (Give it a listen!) The simple idea was that, in blind-tasting our way through a few beers, we could illustrate how much your eyes, noses, and tongue will tell you about the beer you're drinking. Beer's many flavor and aroma compounds can easily bewilder, and it takes years of sampling to find your way through their thicket. I've led tastings where we sample a beer and break it down, and for people new(ish) to beer, it can be revelatory. Being able to connect flavors to ingredient and process creates a map that drinkers can use with any beer--a rosetta stone that demystifies all that complexity.
Is Fred about to listen to his beer?
But in deciding to do the tasting blind, we revealed another truth to beer: so much of our "knowledge" comes from things that we don't learn through our eyes, noses, and tongues. I'd asked Sally to buy some beers for the experiment and prepare them for us. We didn't coordinate about anything--style, brewery, country. Stripping away all those cues left us with only our senses, and that's a surprisingly naked experience. You want to reach for the bottle to see what the brewery says about the beer. Our second bottle was a saison by Bend's Crux Fermentation Project. It had a lot of clovey phenolics and a touch of banana-y isoamyl acetate. I looked at the cloudy liquid in the glass and wondered whether it was a saison or a slightly offbeat Bavarian weizen. I had no crutch to lean on, though, so I just settled further into the experience. Not knowing let me get to know that beer on fresh terms.
Even more remarkable was the experience of bottle three, a beer we had already reviewed on the podcast. It was my favorite beer of the flight, and such a curious experience! The aromas were richly malty, with layers of cocoa, nuts, toffee, and chicory. The flavors were if anything more varied. There was a fragile layer of roastiness floating on top of the palate, and it gave way to a buffet of malty goodness underneath. There was a vanilla/butterscotch note so pronounced we were pretty sure it had been bourbon-aged. Amazingly, the beer was light and delicate, and as you swallowed, it disappeared with a satisfyingly crisp snap.
It turned out to be Black Boss, which we sampled for the porters and stouts podcast (one of my favorites). In that case, I condemned it because I found it wanting as a porter. And indeed, when we blind-tasted it, we agreed it wasn't a porter. The roast is far too subtle. It was a ruby color, very bright, with an ecru head and, poured into a Rodenbach glass, did a decent enough visual impersonation of Roselare's finest. But my impression of the beer as a bad Baltic porter clouded my judgment about the beer itself. What I "knew" about Black Boss prevented me from experiencing something much more obvious and accessible. Absolutely every time I do a blind tasting, I find myself re-learning the lessons of humility, and this was a prime example.
Recently, Bryan Roth wrote a great post about bringing ears into the equation and listening to your beer. Fred Eckhardt used to exhort drinkers to listen to their beers, too. Like Bryan, he meant it partly literally--you can hear a head collapse, he pointed out--but Eckhardt was a bit of a mystic. He meant it poetically, as well. We "know" so much about beer because of what the label tells us, what its reputation is, what our previous experience has been, and what style it was brewed to. But this isn't knowledge, not really. When Fred told us to listen to our beers, he was saying, "put everything else aside." Every beer will tell you about itself, if only you stop to listen to the story.
Real knowledge is naked experience, untroubled by extraneous details. We so often foreclose the possibility of discovery because we already have the answers, the knowledge. If we know a beer is a well-regarded dubbel from a famous brewery in Belgium, we mold our experience (subtly, unintentionally) to fit that knowledge. We lose the opportunity for wonder. We can't meet someone we already know.
Periodically I have an experience that reminds me of these truths. Afterward, in the few days when I can remember to recapture my wonder and humility, I marvel at the experience and pure pleasure of a pint of beer. This is one of those moments. I better have another beer soon.
|
{
"pile_set_name": "Pile-CC"
}
|
---
abstract: 'The top quark pair production and decay are considered in the framework of the smeared-mass unstable particles model. The results for total and differential cross sections in vicinity of $t\bar{t}$ threshold are in good agreement with the previous ones in the literature. The strategy of calculations of the higher order corrections in the framework of the model is discussed. Suggested approach significantly simplifies calculations compared to the standard perturbative one and can serve as a convenient tool for fast and precise preliminary analysis of processes involving intermediate time-like top quark exchanges in the near-threshold region.'
address:
- 'Institute of Physics, Southern Federal University, Rostov-on-Don 344090, Russia'
- |
Theoretical High Energy Physics, Department of Astronomy and Theoretical Physics,\
Lund University, SE 223-62 Lund, Sweden
- 'Institute of Physics, Southern Federal University, Rostov-on-Don 344090, Russia'
author:
- 'V. I. KUKSA[^1]'
- 'R. S. PASECHNIK[^2]'
- 'D. E. VLASENKO[^3]'
title: MASS SHELL SMEARING EFFECTS IN TOP PAIR PRODUCTION
---
Introduction
============
The top pair production and decay are the key processes for precision tests of the Standard Model (SM) (see e.g. Ref. \[\] and references therein). They were intensively studied in the framework of the Quantum Chromodynamics (QCD) and Electro-Weak (EW) perturbation theory during last two decades, and various methods and schemes were proposed. The major goal of these investigations is to define the basic physical parameters of the top quark, such as its mass, width and couplings with other SM particles. In the past, the top quark physics was one of the primary research objectives at Tevatron. Nowadays, the biggest attention is paid to the process of the top quark production at the LHC (see e.g. Refs. \[\]). However, the highest precision measurements of the top quark properties can best be reached at the future Linear Collider (LC) which supposedly operates in a clean experimental environment. The top quark physics is one of the most interesting and challenging targets for future $e^+e^-$ or $\mu^+\mu^-$ LC experiments \[\].
The top pair production is followed by a decay chain with intermediate gauge boson states, i.e. the full process under consideration is $e^+e^-\to t^*\bar{t^*}\to b\bar{b}W^+W^-\to
b\bar{b}4f$. The widths of both the top quark and the $W$-boson are large, and one necessarily needs to take into account corresponding Finite-Width Effects (FWE). In the framework of the standard perturbative approach, these effects are typically described by means of dressed propagators which are regularized by the total decay width. In order to analyze the full process of the top pair production relevant for phenomenological studies, we also have to take into account the background contribution coming from many other topologically different diagrams leading to the same six-fermion final states, which is a rather non-trivial task.
The Born-level cross-sections of the processes $e^+e^-\to
b\bar{b}u\bar{d}\mu^-\bar{\nu}_{\mu}$ and $e^+e^-\to b\bar{b}4q$ were calculated in Refs. \[\] and \[\], respectively. Other exclusive reactions with $b\bar{b}d\bar{u}\mu^+\nu_{\mu},\,b\bar{b}c\bar{s}d\bar{u}$ and $b\bar{b}\mu^+\nu_{\mu}\tau^-\bar{\nu}_{\tau}$ final states were considered in Ref. \[\]. In particular, it was shown that the contribution of the top-pair signal $e^+e^-\to t^*\bar{t}^*\to
b\bar{b}4f$ is dominant, but the background (caused by one-resonant or non-resonant diagrams) can be quite significant too. However, it can be drastically decreased by applying certain kinematical cuts on the appropriate invariant masses.
The QCD corrections for the reaction $e^+e^-\to t\bar{t}$ in the continuum above the threshold were previously obtained in Refs. \[\]. As well as the one-loop EW corrections were calculated in many papers (for corresponding references, see e.g. Introduction in Ref. \[\]). Concerning radiative corrections (RC) to reaction $e^+e^-\to b\bar{b}4f$ with six-fermion final states, the situation is more complicated and less clear \[\]. At the tree level, any of the reactions receives contributions from several hundreds of diagrams. The calculations of the full $O(\alpha)$ radiative corrections are very complicated, and different approximation schemes are typically applied. The most detailed analysis of the exclusive reactions $e^+e^-\to
b\bar{b}\mu^+\nu_{\mu}\mu^-\bar{\nu}_{\mu}$ and $e^+e^-\to
b\bar{b}d\bar{u}\mu^-\bar{\nu}_{\mu}$ was performed in Ref. \[\]. In this paper, the cross-sections were calculated taking into account the leading radiative corrections, such as the initial state radiation (ISR) and factorizable EW corrections to the on-shell top-pair production, to the decay of the top quark into $bW$ and to the subsequent decays of the $W$-bosons. Usually, such calculations are carried out automatically by Monte Carlo techniques (see Ref. \[\] and references therein).
In this work, we consider reactions like $e^+e^-\to t^*\bar{t}^*\to
b\bar{b}4f$ with any four-fermion final states $4f$. The analysis is performed in the framework of the smeared mass unstable particles model (below, SMUP model) \[\]. Due to exact factorization at intermediate $t,\bar{t}$ and $W^+,W^-$ states, the cross-section can be represented in a simple analytical form which is convenient for analytical and numerical analysis. So far, we have applied the SMUP approach only for unstable gauge boson production and decay (see e.g. Refs. \[\]). As a continuation of our earlier studies, in this work we test the SMUP approach for the case of unstable fermions, i.e., specifically, top quarks. In our calculations, we take into account NLO radiative EW and QCD factorizable corrections which dominate close to $t\bar{t}$ threshold. Also, we illustrate the influence of the mass smearing effects and various radiative corrections (RC’s) on the differential cross-sections. The results are compared with ones calculated by using the standard perturbative methods \[\], where cross-sections were represented for case of full $2\to 6$ process and, separately, for the top signal contribution alone. It was shown that in the Born approximation the results coincide with a rather high precision, and deviations of the higher-order corrected results from the standard ones are at the percentage level. So, the suggested approach can be applied in a fast preliminary analysis of various complicated processes involving intermediate top quark exchanges in the Standard Model and beyond.
Note, here we do not consider the near-threshold effects caused by the generation of the coupled $t\bar{t}$ state, which were considered in detail in many previous studies (see, for instance, Ref. \[\] and references therein). We postpone this issue for a forthcoming study.
The model cross-section of the top-pair production and decay at the tree level
==============================================================================
The process of top-pair production with subsequent decay $e^+e^-\to
t^*\bar{t^*}\to b\bar{b}W^+W^-\to b\bar{b}4f$ is schematically represented in Fig. \[fig1\]. The full process contains two steps with unstable intermediate time-like states, namely, $t,\bar{t}$ and $W^+,W^-$ states. In this case, as was shown in Ref. \[\], the double factorization takes place and can be described in the framework of the SMUP model \[\]. Due to this factorisation, the full process can be divided into three stages: $e^+e^-\to t^*\bar{t}^*$, $t^*\bar{t}^*\to b\bar{b}W^+W^-$ and $W^+W^-\to 4f$. Here, the top-quarks and $W$-bosons are treated as unstable particles, and finite-width effects should be taken into account.
![Feynman diagram of the top quark signal process $e^+e^-\to
t^*\bar{t^*}\to b\bar{b}W^+W^-\to b\bar{b}4f$.[]{data-label="fig1"}](tbart1.eps){width=".6\textwidth"}
The SMUP model cross-section of the first reaction $e^+e^-\to
t^*\bar{t}^*$ can be written as \[\] $$\label{2.1}
\sigma(e^+e^-\to
t^*\bar{t}^*)=\int_{m^2_0}^s\int_{m^2_0}^{(\sqrt{s}-m_1)^2}
\sigma(e^+e^-\to t(m_1)\bar{t}(m_2))\rho_t(m_1)\rho_t(m_2)dm^2_1
dm^2_2,$$ where $m_0\approx 2M_b$ ($M_b$ is the bottom quark mass) is the threshold value of the top mass variable, $\sigma(e^+e^-\to
t(m_1)\bar{t}(m_2))$ is the cross-section of top pair production with random masses $m_1$ and $m_2$ and $\rho_t(m)$ is the probability density which describes the mass smearing of top quarks. In our calculations we take it in the Lorentzian form as \[\] $$\label{2.2}
\rho_t(m)=\frac{1}{\pi}\frac{m\Gamma_t(m)}{(m^2-M^2_t)^2+m^2\Gamma^2_t(m)},$$ where $\Gamma_t(m)$ is the total decay width of the top quark with mass $m$. The decay mode $t\to bW$ has a very large branching ratio $\mathrm{Br}(t\to bW) \approx 0.999$, so formula (\[2.1\]) almost exactly describes the cascade process $e^+e^-\to t^*\bar{t}^*\to
b\bar{b}W^+W^-$ in the stable $W$-boson approximation. In order to take into account the instability of $W$-bosons we have to express the top quark width $\Gamma_t(m)\approx \Gamma(t\to bW)$ in Eq. (\[2.2\]) as a function of smeared $W$-boson mass $\Gamma(t\to
bW(M_W))$ with averaging over $M_W$. Thus, the model cross-section of the full inclusive process $e^+e^-\to t^*\bar{t}^*\to
b\bar{b}W^+W^- \to b\bar{b}\sum_f 4f$ depicted in Fig. \[fig1\] has the following convolution form: $$\begin{aligned}
\label{2.3}
\sigma(e^+e^-\to b\bar{b}\sum_f
4f)=&\int_{m^2_0}^s\int_{m^2_0}^{(\sqrt{s}-m_1)^2}
\sigma(e^+e^-\to t(m_1)\bar{t}(m_2))\times \notag\\
&\int_{(m_0-M_b)^2}^{(m_1-M_b)^2}\rho_t(m_1,m_{W^+})\rho_W(m_{W^+})dm^2_{W^+}\times\\
&\int_{(m_0-M_b)^2}^{(m_2-M_b)^2}\rho_t(m_2,m_{W^-})\rho_W(m_{W^-})dm^2_{W^-}dm^2_1
dm^2_2,\notag\end{aligned}$$ where $\rho_W(m)$ is defined by Eq. (\[2.2\]). In order to describe an exclusive reaction $e^+e^-\to t^*\bar{t}^*\to
b\bar{b}f_1f_2f_3f_4$ we have to replace the total decay widths of $W$-bosons, which enter the numerator in Eq. (\[2.2\]), by corresponding exclusive ones (see Section 4). The same result can be obtained exactly if one calculates the cross-section of this process explicitly in the framework of the SMUP model by using dressed propagators of unstable particles (UP’s). In Ref. \[\] it was shown that exact factorization of a decay chain process with UP’s in an intermediate state takes place when we exploit the model effective propagators for fermion and vector UP’s in the following form $$\label{2.4}
\hat{D}(q)=i\frac{\hat{q}+q}{P_F(q)},\qquad
D_{\mu\nu}(q)=-i\frac{g_{\mu\nu}-q_{\mu}q_{\nu}/q^2}{P_V(q)},$$ where $P_F(q)$ and $P_V(q)$ are the denominators of the fermion and vector boson dressed propagators, which contain corresponding total decay widths. The structure of numerators in Eq. (\[2.4\]) provides exact factorization and leads to a convolution-like expression (\[2.3\]) for the cross-section. So, there is a self-consistency between the model and UP effective theory description of the processes with UP in intermediate states. Thus, the process with a six-particles final state shown in Fig. \[fig1\] is described by a simple analytical expression (\[2.3\]) with four integrations over smeared unstable top and $W$-boson masses. Note, that the standard perturbative treatment of the six-particle final states in general case leads to $N=3\cdot
6-4=14$ independent parameters, from which 13 parameters have to be integrated over \[\]. Such a complicated problem can be solved by using involved Monte Carlo numerical simulations only.
The results of the SMUP model calculations are presented in Fig. \[fig2\]. Here, the dotted line represents the cross-section of the top-pair production in the stable particle approximation (SPA), i.e. without smearing of the top mass. The dashed line is the cross-section incorporating the top mass smearing or top finite-width effects (FWE) only, and the solid line gives the full mass smearing result, both top-quarks and $W$-bosons. Note, that the second case corresponds to the standard treatment of the process $e^+e^-\to t^*\bar{t}^*\to b\bar{b}W^+W^-$ in the stable $W$-boson approximation, and the third case – to the full process shown in Fig. \[fig1\].
![The cross-sections of the processes $e^+e^-\to t\bar{t}$, $e^+e^-\to b\bar{b}W^+W^-$ and $e^+e^-\to b\bar{b}\sum_f4f$.[]{data-label="fig2"}](SmearMass.eps){width=".6\textwidth"}
From Fig. \[fig2\], one can see that the contribution of the top quarks’ FWE’s is significant (up to a few percents in the near-threshold region), while the contribution of $W$-bosons’ FWEs is small. The comparison of our results with ones in the standard perturbative treatment shows that deviations are typically very small. For instance, it was obtained in Ref. \[\], that $\sigma(e^+e^-\to t^*\bar{t}^*\to b\bar{b}W^+W^-)$ for $\sqrt{s}=500\,\mbox{GeV}$ is equal to 629 fb for $M_t=150\,\mbox{GeV}$ and 553 fb for $M_t=180\,\mbox{GeV}$. For the same input data, we have obtained 630 fb and 554 fb, respectively, which are in a good agreement with the result mentioned above. This comparison proves the applicability of the SMUP model fermion propagator given by the first expression in Eq. (\[2.4\]). In Section 4, we make such a comparison for exclusive processes as well where both SMUP model fermion and boson propagators Eq. (\[2.4\]) are used.
It should be noticed also that we consider the FWE’s, which are significant in the near-threshold region, but we do not include near-threshold effects caused by possible intermediate $t\bar{t}$ bound states. Since the top mean lifetime is considerably shorter than the hadronisation time, the bound state effect has no sharp resonant nature. However, it can be comparable with FWE’s or mass-smearing effects under consideration, and this problem will be considered in more detail elsewhere.
Factorizable corrections to the cross-section
=============================================
As it was shown in previous papers \[\], the EW and QCD corrections give large contributions to the cross-section of the top-pair production at energy scales close to its threshold. In this Section, we describe the strategy of our model calculations and give the total cross-section including the principal part of NLO EW and QCD corrections. Note, that the strategy of calculations and the choice of input parameters are mainly caused and defined by the effective character of the model treatment. In the framework of the SMUP model, the instability (or finite width) of unstable particles is accounted for by the smearing of their masses, i.e. by the probability density function $\rho(m)$. In turn, this function contains momentum dependent parameters $M(q)$ and $\Gamma(q)$ in analogy with the standard perturbative treatment which uses dressed propagators. So, in that sense the corrections of self-energy type are already included at the “effective” tree level, and it is reasonable to use an effective couplings, such as running coupling, absorbing the major part of vertex-type corrections.
In our calculations we have used the following input data \[\]: $$\begin{aligned}
\label{3.1}
&\alpha(M_Z)=0.00781763,\,\,\,\alpha_s(M_Z)=0.118,\,\,\,\sin^2\theta_W(M_Z)=\hat{s}^2_Z=0.2313,\notag\\
&M_Z=91.1876\,\mbox{GeV},\,\,\,M_W=80.399\,\mbox{GeV},\,\,\,M_t=172.9\,\mbox{GeV}.\end{aligned}$$ The running coupling constants $\alpha_k(Q^2),\,k=1,2,3$ were used in the one-loop approximation: $$\label{3.2}
\alpha_k(Q^2)=\frac{\alpha_k(M_Z)}{1-(\beta_k/2\pi)
\ln(Q^2/M^2_Z)},\,\,\,\beta_k=(4.1,\,-19/6,\,-7).$$
The cross-sections are calculated including the following corrections:
- Vertex and self-energy type corrections for stable particles are mainly included into running couplings (\[3.2\]).\
- Self-energy corrections for unstable particles are included into the probability density function $\rho(m)$, which describes the smearing of UP’s masses.\
- Initial state radiation (ISR) is described by the photon radiation spectrum \[\], and the bremsstrahlung from the final $t$-quark states – by vertex $Q$-dependent factor \[\].\
- QCD corrections to the top production and decay are described by the vertex multiplicative factor \[\].\
- Contribution of the box diagrams to the total cross section was evaluated at energy scales close to the threshold by using numerical FormCalc v7.3 \[\] routines.
The higher order corrected cross-sections of the inclusive process $e^+e^-\to t^*\bar{t}^*\to b\bar{b}\sum_f4f$ are shown in Fig. \[fig3\]. There, the dotted line represents the Born model cross-section, the dashed line – the cross-section with ISR and the solid line – the cross-section with total factorisable corrections (without box diagrams contribution). From the figure, one can see that the main contribution is given by ISR correction, which significantly reduces the cross-section in the near-threshold energy range and increases it at energy scales above $\sim$0.6 TeV. At large energies ($\sqrt{s}>0.5\,\mbox{TeV}$) the contribution of EW and QCD corrections becomes significant and has to be properly taken into account.
![The higher order corrected cross-sections of the process $e^+e^-\to b\bar{b}\sum_f4f$.[]{data-label="fig3"}](Corrections.eps){width=".6\textwidth"}
In Fig. \[fig4\] we present the invariant mass distribution and illustrate the influence of various corrections on it. One can see that the corrections which we have taken into account according to the procedure above give noticeable contribution into this distribution in the peak area. We, also, illustrate such influence on the angular differential cross-section presented in Fig. \[fig5\]. Again, we notice that this influence is quite significant and should be taken into account.
The cross-sections of exclusive processes
=========================================
So far, we have considered the cross-section of inclusive process $e^+e^-\to t^*\bar{t}^*\to b\bar{b}\sum_f4f$ where the final state is summed up over all possible fermion flavors. As was noticed in the second Section, in order to get the cross-section of exclusive process $e^+e^-\to t^*\bar{t}^*\to b\bar{b}f_1f_2f_3f_4$ we can include the corresponding branching ratios $\mathrm{Br}(W\to
f_1f_2)$ and $\mathrm{Br}(W\to f_3f_4)$. Acting this way we obtain $$\label{4.1}
\sigma(e^+e^-\to b\bar{b}f_1f_2f_3f_4)=\sigma(e^+e^-\to
b\bar{b}\sum_f4f)\mathrm{Br}(W\to f_1f_2)\mathrm{Br}(W\to f_3f_4)\,.$$ where we omit intermediate virtual $t^*\bar{t}^*$ state for simplicity. This relation directly follows from the Eq. (\[2.3\]) when one substitutes a partial decay width of the $W$-boson into numerator of the probability distribution function $\rho_W(m)$ instead of the total width. It can be also derived by straightforward calculation of the $\sigma(e^+e^-\to
b\bar{b}f_1f_2f_3f_4)$ in the framework of the effective theory (see Ref. \[\]).
The expressions for the branchings ratios $\mathrm{Br}(W\to f_1f_2)$ were considered in detail in Ref. \[\]. Here, we use very simple but sufficiently precise formulae which incorporate QCD corrections: $$\label{4.2}
\mathrm{Br}(W\to
l\bar{\nu}_l)=\frac{1}{9(1+2\alpha_s(M_Z)/3\pi)},\,\,\,\mathrm{Br}(W\to
u_i\bar{d}_k)=\frac{|V_{ik}|^2(1+\alpha_s(M_Z)/\pi)}{3(1+2\alpha_s(M_Z)/3\pi)},$$ where $V_{ik}$ are elements of the Cabibbo-Kobayashi-Maskawa mixing matrix. We, also, employ the QCD corrected expression for the top quark width \[\]: $$\label{4.3}
\Gamma(t\to
bW)=\frac{1}{16}\alpha_2(M_t)|V_{tb}|^2\,\eta_{QCD}\,M_t\,
f(M_t,M_W,M_b),$$ where $$\begin{aligned}
\label{4.4}
&&f(M_t,M_W,M_b)=\lambda(M^2_b,M^2_W;M^2_t)\left(\frac{(M^2_t-M^2_b)^2}{M^2_t
M^2_W}
+\frac{M^2_t+M^2_b-2M^2_W}{M^2_t}\right);\\
&&\lambda(M^2_b,M^2_W;M^2_t)=\left(1-2\frac{M^2_b+M^2_W}{M^2_t}
+\frac{(M^2_W-M^2_b)^2}{M^4_t}\right)^{1/2};\nonumber \\
&&\eta_{QCD}=1-\frac{2\alpha_s(M_t)}{3\pi}\left(\frac{2\pi^2}{3}-\frac{5}{2}\right).
\nonumber\end{aligned}$$
Using Eqs. (\[4.1\])–(\[4.3\]) we can calculate the exclusive cross-section for an arbitrary six-fermion final state $(b\bar{b}f_1f_2f_3f_4)$. Such calculations taking into account the factorizable EW corrections were performed within the standard perturbative approach for the case of $(b\bar{b}\mu^+\nu_{\mu}\mu^-\bar{\nu}_{\mu})$ and $(b\bar{b}\mu^+\nu_{\mu}d\bar{u})$ final states in Ref. \[\]. In this work, the full set of topologically different Born diagrams leading to the same six-fermion final state was considered. It was shown, that certain cuts on invariant masses of the $Wb$ and $f_if_k$ pairs, which correspond to intermediate $t,\bar{t}$ and $W^+,W^-$ states for signal diagrams, significantly reduce the relative contribution of the background (see Table \[tab1\]).
In Tables \[tab1\] and \[tab2\] the cross-sections are given for two distinct reactions $$\label{4.5}
(1):\quad e^+e^-\to b\bar{b}\mu^+\nu_{\mu}\mu^-\bar{\nu}_{\mu},\qquad (2):\quad e^+e^-\to
b\bar{b}\mu^+\nu_{\mu}d\bar{u}.$$ for the energies $\sqrt{s}=430,\,500,\,1000,\,\mbox{GeV}$. In Table \[tab1\] the cross-sections are presented in the Born approximation for total set of diagrams ($\sigma_{Born}^{(k)}$(total)) and for the signal diagrams ($\sigma_{Born}^{(k)}(t^*\bar{t}^*)$), where $k=1,2$ denotes the first and second reactions in Eq. (\[4.5\]), respectively. These values (in fb) are taken from Table 1 in Ref. \[\] and are calculated with the kinematical cuts $\delta_i<0.1$, where $\delta_i$ is the deviation of the ratio $m_i^{inv}/M_i$ from unity and index $i$ is related to different $t,\bar{t},W^+,W^-$ states (for more details, see Ref. \[\]).
[@|c|c|c|c|c|@]{} $\sqrt{s}$, GeV &$\sigma_{Born}^{(1)}$(total)&$\sigma_{Born}^{(1)}(t^*\bar{t}^*)$& $\sigma_{Born}^{(2)}$(total)&$\sigma_{Born}^{(2)}(t^*\bar{t}^*)$\
430&5.9117&5.8642&17.727&17.592\
500&5.3094&5.2849&15.950&15.855\
1000&1.6387&1.6369&4.9134&4.9106\
\[tab1\]
In Table \[tab2\] the results for the total cross sections (in fb) of processes $(1)$ and $(2)$ from Eq. (\[4.5\]) in the Born approximation are shown in the second column. The cross-sections with separate ISR and factorizable EW (FEWC) corrections are presented in the third and forth columns, respectively, and the cross-section with both the FEWC and ISR corrections included – in the fifth column. All values are calculated with the kinematical cuts mentioned above.
[@|c||c|c|c|c|@]{} $\quad\sqrt{s},\,\rm{GeV}\quad$& $\quad\sigma^{t^*\bar{t}^*}_{\rm Born}\quad$ & $\quad\sigma_{\rm Born+ISR}\quad$ & $\quad\sigma_{\rm Born+FEWC}\quad$ & $\quad\sigma_{\rm Born+ISR+FEWC}\quad$\
\
430 & $5.8642(45)$ & $5.2919(91)$ & $5.6884(55)$ & $5.0978(53)$\
500 & $5.2849(43)$ & $5.0997(51)$ & $4.9909(49)$ & $4.8085(48)$\
1000 & $1.6369(15)$ & $1.8320(18)$ & $1.4243(14)$ & $1.6110(16)$\
\
430 & $5.86476$ & $5.27613$ & $5.77727$ & $5.19941$\
500 & $5.27352$ & $5.08651$ & $5.18407$ & $5.00291$\
1000 & $1.63061$ & $1.83508$ & $1.58925$ & $1.79079$\
\
430 & $17.592(13)$ & $15.857(20)$ & $17.052(16)$ & $15.283(16)$\
500 & $15.855(13)$ & $15.311(15)$ & $14.977(16)$ & $14.438(14)$\
1000 & $4.9106(46)$ & $5.4949(55)$ & $4.2697(40)$ & $4.8287(47)$\
\
430 & $17.8163$ & $16.0351$ & $17.5540$ & $15.8019$\
500 & $16.0203$ & $15.4517$ & $15.7516$ & $15.1979$\
1000 & $4.95397$ & $5.57465$ & $4.82889$ & $5.44011$\
\[tab2\]
From Table \[tab2\], it follows that the differences of the model and standard Born cross-sections are of an order of 0.1 percent and ISR correction increases it only slightly. In principle, these deviations can be further reduced. The situation becomes worse, when we take into account all major corrections. The deviations increase and become up to a few percents. This discrepancy is caused by the fact that in Ref. \[\] an additional contribution from the non-signal (background) diagrams was included while we consider the signal contribution only. Moreover, we do not include the contribution of the box diagrams which becomes very important at large energies far from the threshold. According to estimations in the framework of the standard perturbative treatment, the box diagrams contribution is of an order of a few percents in the near-threshold energy range. Rough estimations in the framework of the SMUP model give the box contribution equal to $1.5 - 2$ percents in the energy region under consideration, and these estimations decrease the deviations. However, in the framework of the SMUP model, as well as in the effective theory of UP, the higher order corrections have an effective character, and a consistent formulation of the perturbative treatment with this model is required. This problem leads to using the model propagators inside loop diagrams, but the validity of such a procedure has still to be justified theoretically. In particular, one should first analyze the asymptotic properties of the propagators. The analysis is not carried out yet, but it is in progress now. Note, that a good agreement of the SMUP model and standard Born-level results, illustrated in Table \[tab2\], provides a good basis for such an analysis.
Conclusion
==========
The production of the $t\bar{t}$ pair and its subsequent decay into six fermion final states in $e^+e^-$ annihilation has been previously analyzed within the standard perturbative treatment in a vast literature. In this work, we performed the corresponding analysis in the framework of SMUP model. So far, this approach was applied mainly to the gauge boson production, where the structure of the model boson propagators was successfully tested \[\]. In the present work, we have tested the structure of the model fermion propagator, and the top quark production mechanism has been chosen as an important example. It was shown that the results of Born-level calculations are in a good agreement with the standard perturbative ones, providing the applicability of the SMUP approach to the top-quark production and decay processes.
The SMUP model provides simple analytical expressions for the total cross-sections of inclusive and exclusive processes with top quark pair production and its subsequent decay. It is a convenient and simple instrument for description of complicated multi-step processes with unstable particles participation. The precision of this approach at the tree level is of an order of 0.1 percent or better. The method gives a possibility to include, in principle, all factorizable corrections. Our approach can be useful in a preliminary analysis of complicated processes with intermediate time-like top quark exchanges within the Standard Model and beyond.
[99]{}
D. Chakraborty, J. Konigsberg and D. L. Rainwater, [*Ann. Rev. Nucl. Part. Sci.*]{} [**53**]{}, 301 (2003).
T. Han, [*Int. J. Mod. Phys. A*]{}, [**23**]{}, 4107 (2008).
W. Bernreuther, [*J. Phys. G*]{} [**35**]{}, 083001 (2008).
T. Abe [*et al.*]{}, [*American Linear Collider Working Group Collaboration*]{}, [**SLAC-R-570**]{}, [*Resource book for Cnowmass 2001*]{}; arXiv:hep-ex/0106056.
K. Kolodziej, [*Eur. Phys. J. C*]{} [**23**]{}, 471 (2002).
F. Yuasa [*et al.*]{},[*Phys. Lett. B*]{} [**414**]{}, 178 (1997). E. Accomando [*et al.*]{}, [*Nucl. Phys. B*]{} [**512**]{}, 19 (1998). F. Gangemi [*et al.*]{}, [*Nucl. Phys. B*]{} [**559**]{}, 3 (1999). K. G. Chetyrkin [*et al.*]{}, [*Nucl. Phys. B*]{} [**482**]{}, 213 ((1996). R. Harlander, M. Steinhauser, [*Eur. Phys. J. C*]{} [**2**]{}, 151 (1998). K. Kolodziej [*et al.*]{}, [*Eur. Phys. J. C*]{} [**46**]{}, 357 (2006). V. I. Kuksa, [*Int. J. Mod. Phys. A*]{} [**24**]{}, 1185 (2009). V. I. Kuksa and N. I. Volchanskiy, [*Int. J. Mod. Phys. A*]{} [**25**]{}, 2049 (2010).
V. I. Kuksa, R. S. Pasechnik, [*Int. J. Mod. Phys. A*]{} [**23**]{}, 4125 (2008). V. I. Kuksa, R. S. Pasechnik, [*Int. J. Mod. Phys. A*]{} [**24**]{}, 5765 (2009). R. S. Pasechnik and V. I. Kuksa, [*Mod. Phys. Lett. A*]{} [**26**]{}, 1075 (2011). A. H . Hoang [*et al.*]{}, [*Eur. Phys. J. C*]{} [**3**]{}, 1 (2000). R. Kumar, [*Phys. Rev.*]{} [**185**]{}, 1865 (1969). A. Ballestrero [*et al.*]{}, [*Phys. Lett. B*]{} [**333**]{}, 434 (1994). K. Nakamura [*et al.*]{} ([*Particle Data Group*]{}), [*J. Phys. G*]{} [**37**]{}, 075021 (2010). J. Fleisher [*et al.*]{}, [*Phys. Rev. D*]{} [**47**]{}, 830 (1993). W. Beenakker [*et al.*]{}, in [*Physics at LEP2*]{}, eds.G. Altarelli, T. Sjöstrand and F. Zwirner (CERN 96-01, Geneva, 1996), Vol. 1, p. 79; arXiv:hep-ph/9602351. A. Denner, [*Fortschr. Phys.*]{} [**41**]{}, 307 (1993).
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[^1]: kuksa@list.ru
[^2]: roman.pasechnik@thep.lu.se
[^3]: vlasenko91@list.ru
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Yi Ho-woo
Yi Ho-woo (Hangul: 이호우) was a South Korean poet and journalist.
Life
Yi Ho-woo was born on March 1, 1912 in Cheongdo, Gyeongsangbuk-do, Korea. The name Lee Hou is the poet's pen name, and represented by Chinese characters different from those of his birth name. He graduated from Gyeongseong Je-il High School. Yi attended the Tokyo Arts University. He worked on the editorial and management boards of the Taegu Ilbo, going on to serve as the manatding editor and an editorial writer of the Daegue Maeil Shinmun. Yi debuted as a poet in 1940 when his work Moonlight NIght was published in Munjang Magazine.
Yi died on January 6, 1970.
Work
Yi was most famous for his emotional reserve and concern with reality as he wrote about the beauty of simple rural life. As a journalist, he was also aware of the inequities of his time, an awareness that fostered his work, particularly in the difficult times after national liberation and the Korean War.
The Korea Literature Translation Institute, summarizes Yi's work and life:
The life and poetry of Lee Hou is typified by the poet’s dogged determination to live, his burning passion, and his strong critical awareness of contemporary realities. Coupled with his modern poetical sensibility toward sijo and its free verse potential, the poet’s sijo possessed the power to communicate for and to the people.
In a sijo contest sponsored by the Dong-a Ilbo and judged by poet jurist Lee Byeonggi in 1939, Yi's poems Fallen Leaves” (Nagyeop) and "Azaleas” (Jindalle) were awarded prizes Yi's formal debut came a year later with the publication of the sijo "Moonlit Night" (Dalbam) in Composition (Munjang) magazine upon the recommendationof Lee Byeonggi. Yi belonged to the Bamboo Shoots (Juksun) and Naggang literary circles and published the sijo collections Collected Sijo Works of Lee Hou (Lee Hou sijojip, 1955) and Dormant Volcano (Hyuhwasan, 1968).
Works in Korean (Partial)
Poetry
Collected Sijo Works of Lee Hou (1955)
Dormant Volcano (1968)
Awards
Gyeongbuk Literary Prize (1955)
References
Category:1912 births
Category:1970 deaths
Category:Korean male poets
Category:20th-century Korean poets
Category:20th-century male writers
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Q:
How to update the values of one column's row where another column value matches specific value?
I have a dataframe with four columns id1, id2, config_type, call_frequency, however, the id1 and id2 don't matter much.
I need to replace the value of the call_frequency column with a specific string where a condition matches another column.
Input:
Output:
Basically I need to replace the values in the corresponding call_frequency column when config_types are matched.
{'type2':'string2', 'type3':'string3', 'type4':'string4'}
and the non-matching values should be left untouched.
I tried:
df[df.config_type == 'dict_key', 'column'] = 'dict_value'
But it's giving me error.
TypeError: 'Series' objects are mutable, thus they cannot be hashed
Any idea how to fix this?
A:
use loc.
d = {'type2':'string2', 'type3':'string3', 'type4':'string4'}
for k,v in d.items():
df.loc[df.config_type==k, 'call_frequency'] = v
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Off The Field
On The Field
News
All Blacks
Horwill to miss Hurricanes match
Sportal.co.nz 26 Feb 2013 Getty Images
Reds skipper James Horwill has ruled himself out of Friday's Investec Super Rugby clash with the Hurricanes after failing to shake an ankle injury.
Horwill, who missed the end of last season and the entire Wallabies campaign with a serious hamstring tear, injured his left ankle in a training mishap prior to his side's opening-round loss to the Brumbies.
The 27-year-old had originally planned to return in last Saturday's 25-17 triumph over the Waratahs but will have to wait at least one more week before making his long-awaited return.
"I won't be playing this week," Horwill, wearing a moonboot, said."It's been a little bit frustrating but [the moon boot is] hopefully coming off by Tuesday and then I can get back into it.
"We're hopeful I can get back in the next couple of weeks but we just need to see what the response is to running.
"I ran last week and pulled up a little bit sore so hence the reason I went back into the boot to try and de-load it a bit and take a bit of the pressure off while walking around."
The Wallabies captain is confident the injury is not worse than first thought and is confident his latest set-back will not threaten his dream of playing against the British and Irish Lions in June and July.
"I hope so, that's the plan," Horwill said when asked if he'll be fit and firing in time for the first Test in Brisbane on June 22.
"First, I just have to get on the field, it's been a long time off for me but there's still a lot of rugby to be played.
"We've only had two rounds of Super Rugby so there's plenty of footy to play and I'm hoping not to be out for too much longer but when I get back and make sure that I'm still playing to my ability that I know I can then we'll see where that goes from there."
Another man confident of returning in time for the 'once-in-a-career' series against the Lions is Reds and Wallabies half-back Will Genia.Genia tore his anterior cruciate ligament in Australia's Rugby Championship win over South Africa in September.
"At this stage hopefully round five or round six, the whole rehab process has gone really well and really smoothly," Genia said of his likely return date.
"I've also got to tick off a few boxes and start doing contact as of this afternoon so hopefully everything goes well."
But the 25-year-old is adamant he will not risk further injury by coming back too soon.
"I think it's really important [to be patient], not just for the Lions series but in terms of my well being as a player moving forward," he said.
"I spoke to James [Horwill] and spoken to a lot of guys who have done their knees previously and they said the worst thing you can do is try to rush back so I'll just go and if it feels right I'll play and if it doesn't I'll give it a few more weeks."
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Kilcommon (County Mayo civil parish)
Kilcommon () is a civil parish in Erris, north Mayo consisting of two large peninsulas; Dún Chaocháin and Dún Chiortáin. It consists of 37 townlands, some of which are so remote that they have no inhabitants. Habitation is concentrated mainly along both sides of Sruwaddacon Bay which flows into Broadhaven Bay, in villages including Glengad, Pollathomas, Rossport, Inver and Carrowteige, and in the Glenamoy area further inland.
History
Kilcommon parish takes its name from St. Comán who lived around the end of the sixth century AD. The saint is allegedly buried in the old church yard at Pollatomais, near to the entrance where the walls of the old Church can still be seen. In the Ordnance Survey Letters of 1838 (O'Donovan), the writers says "of the old church itself only a part of one gable remains from which little can be learned of its style or age".
Topography
Much of the Kilcommon landscape of elevated moorland, borders the Atlantic coast. It is a wild and rugged landscape with large tracts of blanket bog, tiny isolated villages, white sandy beaches and towering cliffs of Benwee Head which, for thousands of years has remained relatively unscathed by overdevelopment by successive generations of Kilcommon inhabitants. Farming is small scale non-intensive.
Situated at the mouth of Broadhaven Bay, on its 21st century surface, Kilcommon is characterised by its scenery, huge towering cliffs and rugged sea stacks interspersed with miles of white sandy beaches, tranquil islands and vast tracts of blanket bog with its rare and fragile biodiversity. Unlike the west of Ireland landscape further south in Galway and Clare, there are few huge rocks randomly scattered across this landscape.
The blanket bog dominates the landscape changing its hues and texture in accordance with the seasons – sometimes fresh and brightest green, sometimes purple and gold and covered with billowing white bog cotton, and, in November and December, the wonderful rustic tones of golden orange/red species light up the winter landscape. At all times the bog is a living habitat for many species of insects, spiders and plants for whom this is the perfect habitat not found anywhere else. Grey fronted geese fly across on their way to their breeding grounds further north and it is possible to spot the corncrake and the rare red-necked phalarope whose only breeding ground left in Ireland is in this remote corner of the country.
Geology
Kilcommon parish comprises a very ancient landscape of glittering schist and pale creamy psammite along with some two billion year old pre-Cambrian pink striped gneisses. Boulders of snow white quartz which intruded into the bedrock from geological turmoil below, some 450 million years ago (Silurian period) are to be found in the western part of the parish. The bedrock, exposed when the blanket bog is cut away to provide fuel for the rural community here, demonstrate that this land has seen geomorphological turmoil over the last two billion years – periods of intense heat, intense cold, pressure and tectonic shifts which have moulded and remoulded the landscape into what it is today.
There are two main peninsulas in the parish - Dún Chiortáin and Dún Chaocháin. They are named for two 'giant' brothers who live on in the folklore of the area. They each had a Dún or a promontory fort and folktales relate that they shared kitchen utensils which they used to throw across Sruwaddacon Bay (Sruth Fhada Chonn - Bay of the Long Hound) which divided their territories.
Sea cliffs run along much of the coast from the high Benwee Head and along the north coastline to Glinsk mountain. The rocky islands known as The Stags, pictured below are to be seen off the North Kilcommon coastline.
Archaeology
The fossilised remains of ancient Scots pine trees which were part of the ancient forests which covered most of inland Ireland after the retreat of the last Ice Age some 15,000 years ago are to be seen across the landscape, exposed by turf cutting in recent years. There are many archaeological remains throughout the parish also, mainly in the western portion as the land to the east was, and still remains to a great extent, inaccessible and uninhabited. The area has a very large number of megalithic tomb remains and most types of megalithic are represented although because there has been no money spent on archaeological investigation in this parish, the archaeological resource is little documented. In the eastern portion of the parish there is evidence of the presence of possible crannogs in lakes which point towards some habitation in the past. In recent times the growth of blanket bog, conifer forestry plantations and the absence of roads through the area, has made townlands such as Bunalty, Barrooskey, Baralty, Srahnaplaigh and Muingnabo difficult to access except by the most intrepid of explorers. In the western parts of the parish, archaeological remains stretching from the Mesolithic through Neolithic, Bronze Age, Iron Age, Early Christian, Plantations, to the current day are widely seen.
Cliff walks - way-marked walks
There are several way-marked walks along the remote cliffs of Benwee Head in the north of the parish. Maps have been published by Comhar Dún Chaocháin Teo, Ceathru Thaidhg as Dún Chaocháin Walks and Suiloídi Iorrais.
Gaeltacht
Much of Kilcommon (Cill Chomáin) parish is Gaelic speaking and Catholic Mass is celebrated in Irish in Ceathru Thaidhg in the far north of the parish. There is an Irish language summer school in Ceathru Thaidhg.
There are between 700-1,000 native Irish speakers in the parish.
Churches
There are five Roman Catholic Churches in the parish namely:
Christ the King Church, Aughoose,
St. Paul's Church, Glenamoy,
St. Patrick's Church, Inver,
Star of the Sea Church, Cornboy, and
Séipéal Muire gan Smál, Ceathru Thaidhg
During the 18th century, at a time known as the Penal Times, the imperial British government restricted the number and movement of Roman Catholic clergy. At that time the parish of Kilcommon comprised all of 'mainland' Erris (from Claggan, Ballycroy to Portacloy). That territorial name and boundary is still used for civil administration.
Civil parishes and townlands
Kilcommon used to refer to almost all of Erris but it was so large that in the early 19th century, it was further divided into three districts - Ballycroy, Kilcommon West and Kilcommon East. In 1873 it was again reorganised and divided into four civil-parishes - Kilmore, Ballycroy, Kiltane and Kilcommon which remain to this day. There are 37 townlands in the modern parish of Kilcommon.
Notable people
Brian Rua U'Cearbhain 17th century prophet from Inbhear.
Willie Corduff Winner of Goldman Environmental Prize 2007.
Patrick O'Boyle
N.Y.P.D. Heroism Award.
Erris Exile Person of The Year
Recipient Distinguished N.Y.P.D. Combat Medal.
Corrib Gas
Since around the turn of the 21st century, Kilcommon parish has been affected by Corrib gas project, under the ownership of Royal Dutch Shell. After many years and many changes of proposed route for a high pressure raw gas pipeline running through the area many aspects of the proposed project have been strongly disputed. A refinery has been built 10 kilometres inland by Royal Dutch Shell that has no access to the proposed landfall site. There have been several Oral Hearings held about this problem by An Bord Pleanála but Permission has now been granted. Works commenced in July 2011. There have been many protests
Natural resources
Kilcommon Erris has some of the best natural alternative energy resources in the world due to its location on the Atlantic Ocean which brings almost constant winds from the sea. The natural resources of ocean and wind available in Kilcommon are very valuable resources for sustainable alternative, renewable energy production for the future.
There are opportunities for the development of ocean wave power projects, one of the best wave energy resources in the world lies off the shores of North Mayo. Tidal power, hydroelectric schemes, and extensive wind farms are amongst many other clean, alternative energy generation opportunities for which the area has great potential for a beneficial sustainable future.
References
Lewis, Samuel, Topographic Dictionary
External links
http://www.vimeo.com/8668733
http://www.arasinisgluaire.ie/
http://shelltosea.com
http://www.mayowalks.ie
http://www.uisce.ie/
http://errisunitedfc.ie
http://bangorerrisangling.com
Category:History of County Mayo
Category:Civil parishes of County Mayo
Category:Archaeological sites in County Mayo
Category:Gaeltacht towns and villages
Category:Erris
Category:Gaeltacht places in County Mayo
Category:Tourist attractions in County Mayo
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Molecular weight determination of commercial heparin sodium USP and its sterile solutions.
A liquid chromatographic assay for the characterization of heparin sodium USP, and heparin sterile solutions was developed. The method employs size exclusion chromatography and computer-based data collection and manipulation. An examination of commercially available heparin showed only minor differences between the heparins extracted from beef lung and porcine intestinal mucosa. The molecular weight averages of the material and its sterile solutions were 9000-12,000 daltons. A correlation was observed between average molecular weight and anticoagulant activity for the heparin sodium samples examined.
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Finland in the Eurovision Song Contest 2014
Finland participated in the Eurovision Song Contest 2014 in Copenhagen, Denmark. Their entry was selected through the national competition Uuden Musiikin Kilpailu (UMK), organised by the Finnish broadcaster Yleisradio (Yle). Softengine represented Finland with the song "Something Better", which qualified from the second semi-final to compete in the final. Finland placed 11th in the final, scoring 72 points. This was Finland's best placing in the contest since Lordi's victory in the Eurovision Song Contest 2006.
Before Eurovision
Uuden Musiikin Kilpailu 2014
Uuden Musiikin Kilpailu, 2014, was the third edition of the Finnish national selection that selected Finland's entry for the Eurovision Song Contest 2014.
Format
Three introductory shows on 26 December 2013, 28 December 2013 and 4 January 2014 commenced the competition with the presentation of the jury selection process and the first live performances of the competing songs from the artists in front of the judges. Two heats with six competing songs in each took place on 11 and 18 January 2014 where the artist and song that placed first automatically advanced to the final, while the artist and song that placed last was eliminated from the competition. The remaining four songs in each heat that failed to advance to the final or be eliminated proceeded to the semi-final on 25 January 2014 where the top six songs qualified to the final. The final with the eight remaining finalists took place at the Barona Areena in Espoo on 1 February 2014. The entire competition series was hosted by Anne Lainto and Ile Uusivuori.
Yle enlisted four judges in order to assist the 12 competing artists with developing their song and performance. On 4 November 2013, Yle announced that the judges from the previous year would return, consisting of:
Tomi Saarinen, head of Yle youth radio channel YleX
Aija Puurtinen, singer and music professor
Toni Wirtanen, heavy metal singer and leader of the band Apulanta
Redrama, rapper
Competing entries
On 10 July 2013, Yle opened the submission period for interested artists and composers to submit their proposals to the broadcaster, which lasted until 16 September 2013. A total of 420 entries were received, of which 12 were ultimately be selected to compete by a special jury. Yle webcast a special introduction press event regarding the competition on 10 December 2013, where the twelve competing acts were revealed.
1. Selja is a proper noun in the context of the lyrics; otherwise it translates as Elder.
Shows
Introduction shows
Three introduction shows were aired on 26 December 2013, 28 December 2013 and 4 January 2014. On 26 December 2013, the top twelve entries that were selected for the competition were presented through commentary from the judges and interviews with the selected contestants. On 28 December 2013 and 4 January 2014, in each show six competitors performed the demo version of their respective entry live in front of the judges for the first time. On 28 December 2013, MadCraft, Clarissa featuring Josh Standing, Lauri Mikkola, Jasmin Michaela, Hanna Sky and MAKEA presented their entries. On 4 January 2014, Mikko Pohjola, Hukka ja Mama, Dennis Fagerström, Softengine, Lili Lambert and MIAU presented their entries. The live performances were filmed in November 2013 allowing the competitors to take feedback and suggestions provided from the judges and apply changes to their entries prior to the release of the final versions of their songs. The final versions of entries were presented on 1 January 2014 during a special radio broadcast on Yle Radio Suomi, hosted by Harri Hakanen and Anssi Autio.
Heat 1
The first live show took place on 11 January 2014, where the first half of the twelve competing artists presented their entries during a live performance at the Peacock Theatre in Helsinki. The combination of jury voting and televoting determined the one direct qualifier to the final, the four qualifiers to the semi-final and the artist and song that was eliminated from the competition. "Something Better" performed by Softengine qualified directly to the final, while "God/Drug" performed by MIAU, "My Little Honey Bee" performed by Dennis Fagerström, "Selja" performed by Hukka ja Mama and "Kertakäyttösydän" performed by Jasmin Michaela proceeded to the semi-final. "Let Me Take You There" performed by Lili Lambert was eliminated.
Heat 2
The second live show took place on 18 January 2014 where the second half of the twelve competing artists presented their entries during a live performance at the Peacock Theatre in Helsinki. The combination of jury voting and televoting determined the one direct qualifier to the final, the four qualifiers to the semi-final and the artist and song that was eliminated from the competition. "Hope" performed by Hanna Sky qualified directly to the final, while "Going Down" performed by Lauri Mikkola, "Top of the World" performed by Clarissa featuring Josh Standing, "Sängyn reunalla" performed by Mikko Pohjola and "Shining Bright" performed by MadCraft proceeded to the semi-final. "Painovoima" performed by MAKEA was eliminated.
Semi-final
The semi-final show took place on 25 January 2014 where four songs from each of the previous two heats had another opportunity to qualify to the final during a live performance at the Peacock Theatre in Helsinki. Public televoting solely decided which six songs qualified to the final and which two songs were eliminated from the competition. "Shining Bright" performed by MadCraft, "Selja" performed by Hukka ja Mama, "Going Down" performed by Lauri Mikkola, "God/Drug" performed by MIAU, "Sängyn reunalla" performed by Mikko Pohjola and "Top of the World" performed by Clarissa featuring Josh Standing qualified to the final while "Kertakäyttösydän" performed by Jasmin Michaela and "My Little Honey Bee" performed by Dennis Fagerström were eliminated.
Final
The final took place on 1 February 2014 at the Barona Areena in Espoo where the eight finalist songs were performed and the combination of votes from the jury and public televote selected a winner. In addition to the performances from the competing artists, the winner of UMK 2013, Krista Siegfrids, performed her single "Cinderella" during the interval. Softengine was the winner of the competition with the song "Something Better".
At Eurovision
During the semi-final allocation draw on 20 January 2014 at the Copenhagen City Hall, Finland was drawn to compete in the second half of the second semi-final on 8 May 2014. In the second semi-final, the producers of the show decided that Finland would perform 8th, following Lithuania and preceding Ireland. Finland qualified from the second semi-final, placing 3rd in a field of 15 songs with 97 points, and competed in the final on 10 May 2014. During the winner's press conference for the second semi-final qualifiers, Finland was allocated to compete in the second half of the final. In the final, the producers of the show decided that Finland would perform 18th, following Slovenia and preceding Spain. Finland placed 11th in the final, scoring 72 points, becoming the second best result of Finland since the introduction of semi-finals (after the victory of Lordi in 2006), and the best position for a non-winning song since 1989.
The Finnish performance featured the members of Softengine performing with a band setup that includes three guitars, a piano and drum kit. The stage atmosphere transitioned between red and white lighting and includes strobe light and spotlight effects.
In Finland, both the semi-finals and the final were broadcast on Yle TV2, with dual language commentary provided by Jorma Hietamäki and Sanna Pirkkalainen in Finnish, and Eva Frantz and Johan Lindroos in Swedish. In addition, all shows were also broadcast via radio on Yle Radio Suomi and Yle Radio Vega. The Finnish spokesperson revealing the result of the Finnish vote in the final was Redrama.
Points awarded to Finland
Points awarded by Finland
Semi-final 2
Points awarded in second semi-final:
Final
Points awarded in the final:
Split voting results
The following five members comprise the Finnish jury:
Kaija Kärkinen – Chairperson – artist, composer, represented Finland in the 1991 Contest
Saara Törmä – lyricist
Rauli Eskolin – producer
Jaako Hurme – radio DJ
Annette Lundell (Clarissa) – artist
Semi-final 2
The Finnish votes in the second semi-final were based on 50% jury voting and 50% televoting results.
Final
The Finnish votes in the grand final were based on 50% jury voting and 50% televoting results.
See also
Finland in the Eurovision Song Contest
Eurovision Song Contest 2014
References
External links
Official Uuden Musiikin Kilpailu 2014 website
Category:Countries in the Eurovision Song Contest 2014
Category:Finland in the Eurovision Song Contest
Eurovision
Category:Articles containing video clips
Category:2014 in Finnish television
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Q:
hibernate proxy object after system.out
I'm new to hibernate and i have this problem.
If i do this:
Session sesion = HibernateUtil.getSessionFactory().openSession();
Transaction tx = sesion.beginTransaction();
A obj = (A) session.load(A.class,id);
System.out.println(obj);
tx.commit();
session.close();
return obj;
There is no problem and the gui shows the object's data.
But if i do this:
Session sesion = HibernateUtil.getSessionFactory().openSession();
Transaction tx = sesion.beginTransaction();
A obj = (A) session.load(A.class,id);
// i don't use System.out.println(obj);
tx.commit();
session.close();
return obj;
The gui doesn't show anything and i got the following exception.
org.hibernate.LazyInitializationException: could not initialize proxy - no Session
I've been reading the api but it's a whole new world to me.
Does anyone knows what's going on?
A:
Instead of using session.load(..), you need to use session.get(..)
A obj = (A) session.get(A.class,id);
The session.load(..) lazy loads the object using a proxy, hence if the object is not accessed (in your example using System.out.println) the object stays uninitialised. When an uninitialised object is accessed outside the hibernate session (called a detached object), a LazyInitializationException is generated - as the proxy object has no way of retrieving the properties of the object from a hibernate session.
The session.get(..) doesn't lazy load the object, so it is still accessible outside the session. There are few other nuances of get vs load, thus, I highly recommend you visit the following post about their difference:
Understanding Get vs Load: http://razshahriar.com/2009/01/hibernate-load-vs-get-differences/
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Hero Info
All the Hero info you could want with counterpicks, general counters, lane synergy and more!
Here are a few of the most popular picks:
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A San Diego runner and cancer survivor says she was snubbed by a popular women's magazine that used a photo of her wearing a tutu to make fun of the fitness fashion trend.
Monika Allen says she was excited to receive an email from SELF magazine asking for permission to use a photo that showed her running the LA marathon dressed as Wonder Woman and wearing a tutu in an upcoming issue.
But when the April issue came out, Allen said she was “stunned and offended.”
The picture appears in a section of the magazine called “The BS Meter," with a caption that refers to a "tutu epidemic" and basically makes fun of the women's outfits, she said.
"A racing tutu epidemic has struck NYC's Central Park, and it's all because people think these froufrou skirts make you run faster," the caption reads. "Now, if you told us they made people run from you faster, maybe we would believe it."
Allen said the photo was "really offensive for a couple of reasons." The marathon came right in the middle of chemotherapy, and she says the outfit gave her motivation.
“The reason we were wearing those outfits is because this was my first marathon running with brain cancer,” Allen explained.
Another reason was that she made the tutu herself. Her company Glam Runners makes them and donates the money to Girls on the Run, a charity that sponsors exercise and confidence-building programs for young girls. She said she's raised about $5,600 for the nonprofit by making about 2,000 tutus over the past three years.
"I feel like we were misled in providing the picture. Had I known how the picture was going to be used, I wouldn't have wanted to send it,” she said.
Allen said she emailed SELF magazine Tuesday night. As of Wednesday afternoon, she had not received a response.
In a statement to NBC 7, SELF apologized "for the association of her picture in any way other than to support her efforts to be healthy."
"Of course if tutus make you run with a smile on your face or with a sense of purpose or community, then they are indeed worth wearing, for any race," the statement read.
This marathoner knows firsthand that a smile can go a long way.
“One little smile or an extra cheer from a stranger can really make things better," Allen said.
There are dozens of messages of support for Allen on the Glam Runner Facebook page. Allen says friends and customers have also sent letters to SELF.
Ed. Note: Since this article was published on March 26, SELF Magazine has apologized to Allen.
Even so, Allen told NBC 7 she was still hurt by the incident. San Diegans donned tutus for a run in support of Allen. And the magazine promises to change after the controversy.
|
{
"pile_set_name": "OpenWebText2"
}
|
Although advertisements on the web pages may degrade your experience, our business certainly depends on them and we can only keep providing you high-quality research based articles as long as we can display ads on our pages.
To view this article, you can disable your ad blocker and refresh this page or simply login.
In its latest 13F filing, Soros Fund Management, managed by George Soros, disclosed its equity positions as of the end of the second quarter of 2014. The portfolio has a market around $13.3 billion. In its filing with the SEC, Soros Fund Management reported a total of 363 positions mainly focused on finance, technology and energy stocks. Over the quarter, the fund acquired more than 180 new holdings. In this article, we will discuss Soros Fund Management’s top three new stocks for the second quarter.
The first one is CONSOL Energy Inc. (NYSE:CNX), in which Soros Fund Management reported holding a $234.4 million stake, which is contains 5.09 million shares. With a market cap of $9.2 billion, CONSOL Energy Inc. (NYSE:CNX) is an independent natural gas exploration, development and production company. Recently, the company closed an additional $250 million of its 5.875% senior notes due 2022. Other largest shareholders of CONSOL Energy Inc. (NYSE:CNX) include Geosphere Capital Management, run by Arvind Sanger, and Mason Hawkins’ Southeastern Asset Management, holding 115,782 shares and 22.71 million shares, respectively.
On the second spot is Google Inc. (NASDAQ:GOOG), in which the fund disclosed owning 194,489 shares, with a reported value of about $111.9 million. For the second quarter of 2014, Google Inc. (NASDAQ:GOOG) reported GAAP net income of $3.42 billion, compared to $3.23 billion in the same quarter of the last year. The company posted non-GAAP net income of $4.18 billion, compared to $3.36 billion last year, according to a press release. Aside from Soros Fund Management, Boykin Curry’s Eagle Capital Management owns 791,934 shares of the company. Ken Fisher’s Fisher Asset Management disclosed holding 638,736 Class C shares of the company, with a market value of $367.5 million.
In its latest 13F filing, Robert Millard’s Realm Partners, reported holding 239,200 shares of Level 3 Communications Inc. (NYSE:LVLT), which have a market value of more than $10 million. Southeastern Asset Management, led by Mason Hawkins, disclosed ownership of 47.11 million shares of the company.
|
{
"pile_set_name": "Pile-CC"
}
|
Gordon Hears a Hooter
Tags:
Gordon Smith
While most of the media attention on Capitol Hill last month focused on Medicare reform, Congress came closer than a pig's whisker to passing one of the most offensive bills to reach the Senate floor in recent memory. And there, standing cheek-to-jowl with the lobbyists who loaded it up with pork, was Oregon's junior senator, Gordon Smith.
President Bush's long-awaited energy bill was a toxic joke, dressed up as a Christmas tree, starting with the $1.5 billion tax break for the nuclear industry and the $2 billion bailout of oil companies that have polluted water supplies with the fuel additive MTBE.
But there were plenty of outrages to go around.
Two-thirds of the $23 billion in tax breaks were slated for fossil-fuel producers, three times what President Bush had asked for. It had only token incentives for conservation or renewable energy and did nothing to raise fuel-efficiency standards. There was even a clause giving a tax break to four shopping malls--one of which includes a Hooters restaurant, famed for its scantily clad buxom waitresses--in the districts of influential lawmakers.
That fact prompted Washington Democratic Sen. Maria Cantwell to deride the bill as a handout for "Hooters and polluters." Across the river, fellow Dem Ron Wyden blasted the bill as "a hodgepodge of subsidies for the politically well-connected."
Of course, it's no surprise that tree-loving Bush-whackers from the Left Coast were whining like a well-oiled weed-eater. But this bill also infuriated conservatives from sea to shining sea.
"This was an energy bill that busted the budget," said New Hampshire's Sen. John Sununu, a Republican whose dad worked for Bush No. 1 and whose state has been hit hard
by MTBE. "[It] distorts markets, distorts investments and tries to micromanage the American economy."
Sen. John McCain, of Arizona, dubbed the measure the "Leave No Lobbyist Behind Act."
Even in central Illinois, where farmers stood to benefit from a mandate to double ethanol production, the stench was too much. "If the bill passes you will know why, and it's not because it will make the nation less dependent on foreign oil," wrote the Peoria Journal Star. "It is because it oils the powerful."
And what about Smith? After the House passed the bill in mid-November, he applauded, saying it would help the Northwest's renewable power sources: wind, geothermal and hydro.
"There's lots of green stuff in these tax credits," he told The Oregonian. "This is a bill that incentivizes reliability and renewability of our energy sources."
He was among those senators who voted to keep the bill alive on Nov. 21, though his enthusiasm seemed to dim. His spokesman, Chris Matthews, told the Associated Press his boss, though troubled by some aspects of the bill, was hoping it could be fixed.
Kind of an odd position for a Republican who campaigned as a guy who could protect your pocketbook and the environment. A guy who supported his president's income-tax break but opposed his plans to drill in Alaska.
What came over him? Maybe it was the visions of short-shorts dancing in his head. Or maybe, when Smith heard the bill's backers propose a subsidy for Hooters, he thought they were talking about spotted owls.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
Struts2 : How to access session variable in JSP?
I have set a ArrayList in the Session object inside my Action class as shown
public class HelloWorld implements SessionAware
{
private Map session;
public HelloWorld() {
}
public String execute() {
List list = new ArrayList();
list.add("One");
list.add("One2");
list.add("One3");
list.add("One4");
list.add("One5");
list.add("One6");
list.add("One7");
session.put("MyList", list);
System.out.println("Hi inside ");
return "SUCCESS";
}
public void setSession(Map session) {
this.session = (Map) session;
}
public Map getSession() {
return (Map) session;
}
}
Please tell me how can i access this Session object "MyList" inside my JSP page
I have tried this way
<html>
<head>
<meta http-equiv="Content-Type" content="text/html; charset=UTF-8">
<title>Hello World</title>
</head>
<body>
<%
Map session = ContextAction.getContext().getSession();
%>
</body>
</html>
But i doesn't know whether using ContextAction is preferable or not ??
Please tell me how can i access this Session "MyList" inside my JSP
A:
I think you mean ActionContext, not ContextAction. Either way, that's not the way to do it. The following examples show how to iterate over the list using both OGNL (standard Struts2 way) and JSTL (standard JSP way). You can use either approach.
Using OGNL
<s:iterator value="%{#session.MyList}">
<s:property/>
</s:iterator>
Using JSTL
<c:forEach items="${sessionScope.MyList}" var="item">
<c:out value="${item}"/>
</c:forEach>
Here's some more information on the <s:iterator/> tag: http://struts.apache.org/2.2.3/docs/iterator.html
|
{
"pile_set_name": "StackExchange"
}
|
Pelvic exenteration.
Exenteration, or complete excision of the pelvic viscera, is an ultra-radical surgical procedure intended for curative treatment of the patient with advanced pelvic malignancy--primary or recurrent. At the time of introduction of this procedure, enthusiasm for its use was marred by the high incidence of serious surgical morbidity and mortality, which approached the five-year survival rate. With more careful physiological and psychological selection of patients, concentration of this kind of procedure in centres familiar with its use, improved urinary conduit techniques and careful attention to covering the pelvic floor with omentum and/or synthetic materials, the morbidity and mortality rate has been significantly reduced thus making exenteration a more acceptable treatment option to a wider spectrum of patients. More sophisticated haemodynamic monitoring, both intra- and postoperatively, intravenous hyperalimentation, prophylactic antibiotics and low-dose heparin are undoubtedly important adjuncts to the improvements in surgical technique and judgment. Psychosexual 'rehabilitation' in the broadest sense must be an integral part of patient care for those undergoing exenteration and in most instances necessitates involvement of the patient's partner. Exenteration has only a very limited role in palliation and all attempts should be made to avoid this procedure when cure is clearly not a possibility.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
A case of valproate intoxication with excessive brain edema.
A 29-year-old man, who had been treated with sodium valproate for 3 years because of generalized cerebral seizures, ingested a large amount of this drug in an attempt to suicide. The exact amount he had swallowed could not be determined. The patient arrived in the intensive care unit in a deep coma, was intubated, and artificially ventilated. He developed a massive cerebral edema, as proved by computerized tomography (CT). This was supported by electroencephalography (EEG). The measured value for the concentration of valproate in serum was markedly elevated on the day of admission (2300 mumol/l; therapeutic range 350-700 mumol/l). Treatment with sodium thiopental, glycerol, and glucocorticoids was initiated. A second CT scan performed 9 days after admission showed a complete normalization and the EEG yielded a markedly improved pattern. At this point the patient slowly regained consciousness. We conclude that in patients with an acute sodium-valproate intoxication, care should be taken with regard to the development of a severe cerebral edema, which in the reported case could be treated successfully.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Peripheral vascular smooth muscle responsiveness to tumour-promoting phorbol esters in pacing-induced heart failure.
Contractions of the dorsal pedal artery and saphenous vein to phorbol 12,13-dibutyrate (PDBu), 12-O-tetradecanoylphorbol 13-acetate (TPA), and 4 alpha-phorbol 12,13-didecanoate (4 alpha-phorbol) were measured from dogs with and without pacing-induced heart failure. The effects of polymyxin B (a relatively selective protein kinase C inhibitor), nifedipine (calcium channel blocker), and prazosin (alpha 1-adrenoceptor antagonist) were examined on the contractions developed to PDBu before heart failure, after 1 week of pacing, and at end-stage heart failure. PDBu and TPA, but not 4 alpha-phorbol, produced concentration-dependent increases in contractile force in both the artery and the vein. In the dorsal pedal artery, efficacy of and sensitivity to PDBu and TPA were enhanced after 1 week of pacing, but returned to control level at end-stage heart failure. In the saphenous vein, the concentration-effect curve to PDBu was displaced to the left after 1 week of pacing; EC50 values for PDBu were 3.2 x 10(-9) and 3.2 x 10(-8) M for 1 week paced and control, respectively. Polymyxin B significantly decreased the efficacy of PDBu in the dorsal pedal artery at all time points, but was less effective with advancing heart failure. In contrast, in the vein, there was a significant increase in inhibitory potential at end-stage heart failure. In all cases, nifedipine inhibited PDBu in a concentration-dependent manner. With the progression of heart failure, the contractions of the saphenous vein, developed to PDBu, became more sensitive to inhibition by nifedipine. Prazosin failed to inhibit vascular effects of PDBu. These results are discussed in terms of protein kinase C involvement in vascular contractions and its role in the pathogenesis of heart failure.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Just as inflation can destroy a nation's currency, so too inflation of another kind can destroy a nation's citizenry.
I'm talking about the Democrat plot to vastly expand the voter base by first importing illegal aliens and then making it as easy as possible for them to vote — sometimes up to and including giving them legal access to state and local elections.
This, coupled with the Democrat effort to diminish trust in our elections by constantly inventing ever-more ludicrous claims of voter suppression, has resulted in a deadly attack on our national sovereignty. If people no longer believe they can trust our elections, then they will feel justified in rejecting the legitimacy of the government itself.
Sound familiar? That's the faux justification of the resistance in rejecting loyalty to the duly elected president. Remember, according to the Democratic left, President Trump is only in office as a result of foreign interference and voter suppression. Reality doesn't matter. In the eyes of the far left, Stacey Abrams is the governor of Georgia even though she lost the election by 50,000 votes.
Now, Democrats rarely talk about allowing illegal immigrants to vote in elections, but that is not always the case. Following the Cass Sunstein strategy of effecting transformational change in society through small incremental “nudges,” some Democrats currently call for allowing illegal aliens to vote in school and other local elections on the theory that all residents have a stake in the operation of schools and city services. Sure they do, and all illegal immigrants also have a stake in federal immigration policy, which will eventually be the argument why they should be allowed to vote in federal elections as well.
Nor can we discount the possibility of non-eligible voters participating in federal elections as long as voter ID is not mandatory. Progressives typically label as “voter suppression” any policy that requires voters to present a legal ID before voting. The claim is that Democrat voters are less likely to be able to obtain such an ID, though there is never any realistic explanation of why that is the case. Nor can they explain why they think cashing a check at a grocery store should have a higher bar than exercising your sacred trust of participating as a sovereign voice in the government of the United States.
Since many illegal immigrants now have access to a driver’s license in “sanctuary states” such as California, it is difficult if not impossible to tell a legal citizen from an interloper. The only thing that prevents illegal immigrants from voting is an unwillingness to break the law, and they have already proven that they think the law doesn’t apply to them.
Mark Hemingway wrote exhaustively at RealClearInvestigations earlier this month that it’s not only illegal aliens who present a threat to the sanctity of our elections. According to his report, Los Angeles by itself has 1.6 million more people registered to vote than eligible voters. But it’s not just Los Angeles or California that present a risk. According to Hemingway:
“Eight states, as well as the District of Columbia, have total voter registration tallies exceeding 100%, and in total, 38 states have counties where voter registration rates exceed 100%. Another state that stands out is Kentucky, where the voter registration rate in 48 of its 120 counties exceeded 100% last year. About 15% of America’s counties where there is reliable voter data – that is, over 400 counties out of 2,800 – have voter registration rates over 100%.”
If you think it is absurd that Democrats might want to take advantage of the large illegal immigration population to increase their vote totals, consider this: When passing their first piece of legislation in the Nancy Pelosi-led House of Representatives in 2019, Democrats rejected a GOP amendment stating that “allowing illegal immigrants the right to vote devalues the franchise and diminishes the voting power of United States citizens.”
There’s that idea of inflation again, which brings us back to the question of the value of citizenship. This is no longer a merely academic exercise, as we learned in the first round of Democratic presidential debates. Many of the candidates confirmed they want to decriminalize illegal immigration and even offer government benefits to those who are in the country without permission. Moreover, we’ve been told by the Supreme Court that we can’t ask about citizenship on the census unless our “motive” is politically correct. This raises the question of whether citizenship even matters in the world that Marx built.
What, for instance, makes an American an American? If citizenship rights are fungible — if, for instance, you can exchange your Guatemalan citizenship for quasi U.S. citizenship merely by stepping across a border — then what obligations does government have to its own citizens? Don’t we at some point surrender our own rights to the claims of sovereignty if borders are not barriers but merely props for a social-justice docudrama? At least in the realm of rhetoric, citizenship should no longer be considered a once-and-for-all privilege. Easy come, easy go.
I wonder if that’s what President Trump had in mind when he made the supposedly outrageous comments about “the Squad” of four socialist Democrats who want to demolish our borders. He has been attacked for asking, “Why don’t they go back and help fix the totally broken and crime infested places from which they came.” Three of the four congresswomen were born in the United States, so Trump was technically wrong to say the “‘Progressive’ Democrat Congresswomen … originally came from countries whose governments are a complete and total catastrophe,” but under the new rules of fluid citizenship, he may have been even closer to the target than even he knew.
If citizenship no longer protects us, if we are obligated to shelter anyone who crosses our borders, then the value of that citizenship has been deflated just as the voter rolls have been inflated. Will the Squad really be “sent back” to some ancestral homeland? No, obviously not, but their advocacy of a country without borders makes them an apt target for those who want to defend our sovereignty.
President Trump, as usual, is ahead of the curve. He has pushed the open-borders argument to its natural conclusion. Citizenship and the responsibilities of citizenship either mean something specific or they don’t. Since Democrats in Congress refuse to acknowledge that U.S. citizenship has a real and permanent and impermeable meaning in law, then they need to live with the consequences of their globalist agenda. Sure, they are citizens of our great country, but if they are right in their defense of illegal immigrants, then that citizenship has no lasting value and offers no guarantees to those who possess it. In the brave new world without borders, the four congresswomen — and the rest of us — will have no certainty where we belong nor whether our citizenship rights can be taken away from us as easily as our protections.
|
{
"pile_set_name": "OpenWebText2"
}
|
Comparative Study of Different Polar Groups of EPA-Enriched Phospholipids on Ameliorating Memory Loss and Cognitive Deficiency in Aged SAMP8 Mice.
Recent studies have shown that omega-3 PUFAs enriched phospholipids (n-3 PUFA-PLs) have beneficial effects on memory and cognition. However, most reports only attribute the benefit to docosahexaenoic acid (DHA) and pay little attention to eicosapentaenoic acid (EPA). We investigate the effect of EPA-enriched phospholipids on cognitive deficiency in senescence-accelerated prone 8 (SAMP8) mouse. Ten-month-old SAMP8 mice are fed with 2% (w/w) EPA-enriched phosphatidylcholine/phosphatidyl ethanolamine (EPA-PC/PE; EPA:DHA = 46.8:3.01) or 2% EPA-enriched phosphatidylserine (EPA-PS; biosynthesized from EPA-PC/PE) for 8 weeks; we then test the behavioral performances in the Barnes maze test and Morris maze test; the changes of oxidative stress, apoptosis, neurotrophic factors, tau phosphorylation, and Aβ pathology are also measured. The results of behavior tests indicate that both EPA-PC/PE and EPA-PS significantly improve memory and cognitive deficiency. It is found that remarkable amelioration of oxidative stress and apoptosis occurs in both EPA-PC/PE and EPA-PS groups. EPA-PS shows more ameliorative effects than EPA-PC/PE on neurotrophic activity by decreasing hyper-phosphorylation of tau and depressing the generation and accumulation of β-amyloid peptide (Aβ). These data suggest that EPA-PS exhibits better effects than EPA-PC/PE on ameliorating memory and cognitive function, which might be attributed to the phospholipid polar groups.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Q:
Why doesn't my clojure.contrib.sql/update-values query work?
I thought the query is correct and I printed out every parameter before the call I used to make sure it is in fact a string i'm looking for.
http://clojuredocs.org/clojure_contrib/clojure.contrib.sql/update-values
(clojure.contrib.sql/with-connection db (
(clojure.contrib.sql/update-values "tableName" ["column1=?" (nth contentVals 0) "column2=?" (nth contentVals 1) "column3=?" (nth contentVals 2)] {"column1" (nth submittedRow 0) "column2" (nth submittedRow 1) "column3" (nth submittedRow 2)}))
What's wrong?
A:
Figure it out.
The following is correct.
(sql/update-values "tableName" ["column1=? AND column2=? AND column3=?" (nth contentVals 0) (nth contentVals 1) (nth contentVals 2) {:column1 (nth submittedRow 0) :column2 (nth submittedRow 1) :column3 (nth submittedRow 2)})
|
{
"pile_set_name": "StackExchange"
}
|
Health Information
von Willebrand Disease
Everyone has to deal with bruises and bloody noses from time to time. But for people with a condition called von Willebrand disease, these things can sometimes be a problem.
Some people with von Willebrand disease never even know they have it because the symptoms are so mild. People with more severe forms of the disease are less likely to have problems if they get the proper diagnosis and treatment.
What Is von Willebrand Disease?
When people have von Willebrand disease (vWD for short) their blood doesn't clot properly. That means cuts and wounds can't scab over as well, so they bleed longer than normal.
Bleeding is usually a sign that a blood vessel has been cut or torn. Normally, when someone bleeds, small cells in the blood called platelets plug the hole. With the help of calcium, vitamin K, and a protein called fibrinogen, the platelets create a mesh to hold the plug in place and close the wound. As this mesh dries, it hardens into a scab.
A substance in the blood called von Willebrand factor helps platelets stick to damaged blood vessels. Special proteins known as clotting factors are also needed to help blood clot — von Willebrand factor includes one of these clotting factors, called factor VIII.
People with vWD have bleeding problems because the levels of von Willebrand factor or factor VIII in their blood are abnormal. In some cases, the factors don't work the way they're supposed to.
The disease is named after Erik von Willebrand, the doctor who first identified it. It's similar to another bleeding condition called hemophilia. Both conditions are rare. Unlike hemophilia, which usually affects only guys, both girls and guys can have vWD.
The Types of von Willebrand Disease
There are different kinds of vWD:
In type 1, a person has less von Willebrand factor in the blood than normal. This is the most common and mildest form of the disease. In fact, it might be so mild that the person never knows he or she has vWD. People with type 1 vWD sometimes have mild bruising or nosebleeds, and they can bleed a lot with injuries, surgery, or when they have a tooth pulled.
In type 2, the level of von Willebrand factor in the blood is normal, but it doesn't work properly. This can lead to moderate bleeding problems.
People with type 3 vWD have severe bleeding problems. They have no measurable von Willebrand factor in the blood and very low factor VIII levels.
In pseudo or platelet-type vWD, the person's platelets are abnormal, making them stick to von Willebrand factor too well. This causes clotting problems due to low numbers of platelets and levels of von Willebrand factor.
What Causes It?
A genetic disorder, von Willebrand disease is passed down from parent to child. If a parent has vWD, a child has a 50% chance of getting the gene for the condition.
When a child has type 1 or type 2, it usually means he or she inherited the gene from one parent. With type 3, the child usually inherits genes for the disease from both parents.
Signs and Symptoms
Signs of von Willebrand disease can include:
bruising easily
unusually heavy periods or other abnormal menstrual bleeding in girls
bleeding from the gums, nose, and lining of the intestines
prolonged oozing of blood from cuts
bleeding too much or for too long after a tooth is pulled or tonsils are removed
Mild cases of von Willebrand disease can be hard to diagnose. If a doctor thinks you have vWD, he or she will examine you and ask about your medical history. Your medical history includes things like your past health, your family's health, and any medicines you're taking. The doctor also may send a blood sample to a lab for tests.
What to Do
Having von Willebrand disease doesn't usually mean big life changes. People with more severe vWD should avoid contact sports like football and hockey, but other sports and activities are usually OK.
If someone with vWD starts bleeding, it's usually enough to put pressure on the area and wait for the bleeding to eventually stop. For nosebleeds, pinch the soft part of the nose to help stop the bleeding.
Girls with vWD who have started their periods might want to carry extra pads or even a change of clothes in case of accidents. Sometimes, a girl's doctor may prescribe birth control pills to help control heavy menstrual bleeding.
If you have vWD, talk with your doctor before taking medicine for pain or fever. Don't take aspirin and ibuprofen because they interfere with platelet function and can increase the risk of bleeding. It's usually OK to take acetaminophen for pain or fever, since it has no effect on platelet function.
Medicines for vWD
Some people with more serious vWD may need to take medicines. The most common medicine for type 1 von Willebrand disease is called desmopressin. It causes a temporary increase in the von Willebrand factor level in the blood. It can be given in two ways: by injection or by being sniffed into the nose. Desmopressin may also help some people with type 2 von Willebrand disease.
People with type 3 (and some with type 2) disease need a medicine called Humate-P. It contains both factor VIII and von Willebrand factor. Humate-P is injected into a vein. Patients with type 1 also might need a shot of Humate-P in certain situations, like after major surgery or a serious accident.
Other medicines, like Amicar, control bleeding by keeping blood clots from breaking down too quickly.
Most of the time, people with von Willebrand disease can do everything their friends do. Speaking of friends, if you have vWD, it doesn't hurt to let the people in your life (like friends, teammates, or coaches) know that you have it. Von Willebrand disease isn't contagious — you can't give it to anyone — and it can help to know someone has your back.
|
{
"pile_set_name": "Pile-CC"
}
|
I would just like to introduce our website we created to get everyone access to the lowest prices hurricane shutters you will find for sale. We deal direct with the manufacturer which allows us to sell them up to 50% cheaper than anyone else. We also have every size shutter in stock and wont charge you for custom sizes.
As you all know hurricanes should be taken very seriously and we don't like the idea of someone putting themselves or their property in jeopardy solely because they cant afford hurricane shutters.
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|
{
"pile_set_name": "Pile-CC"
}
|
package com.alipay.api.response;
import java.util.List;
import com.alipay.api.internal.mapping.ApiField;
import com.alipay.api.internal.mapping.ApiListField;
import com.alipay.api.domain.StandardCategoryInfo;
import com.alipay.api.AlipayResponse;
/**
* ALIPAY API: koubei.item.category.children.batchquery response.
*
* @author auto create
* @since 1.0, 2019-01-07 20:51:15
*/
public class KoubeiItemCategoryChildrenBatchqueryResponse extends AlipayResponse {
private static final long serialVersionUID = 8128293622517435852L;
/**
* 口碑标准后台类目信息列表
*/
@ApiListField("category_list")
@ApiField("standard_category_info")
private List<StandardCategoryInfo> categoryList;
public void setCategoryList(List<StandardCategoryInfo> categoryList) {
this.categoryList = categoryList;
}
public List<StandardCategoryInfo> getCategoryList( ) {
return this.categoryList;
}
}
|
{
"pile_set_name": "Github"
}
|
Underwater Mortgages Rise as Home Prices Fall ?
The number of Americans who owe more on their mortgages than their homes are worth rose at the end of last year, preventing many people from selling their homes in an already weak housing market.
CoreLogic said Tuesday that about 11.1 million households, or 23.1 percent of all mortgaged homes, were underwater in the October-December quarter. That’s up from 22.5 percent, or 10.8 million households, in the July-September quarter.
The number of underwater mortgages had fallen in the previous three quarters. But that was mostly because more homes had fallen into foreclosure.
Underwater mortgages typically rise when home prices fall. Home prices in December hit their lowest point since the housing bust in 11 of 20 major U.S. metro areas. In a healthy housing market, about 5 percent of homeowners are underwater.
About 2.4 million people have only 5 percent equity or less in their homes, putting them near the tipping point if prices in their area fall.
Roughly two-thirds of homeowners in Nevada with a mortgage had negative home equity, the worst in the country. Arizona, Florida, Michigan and California were next, with nearly 50 percent of homeowners with mortgages in those states underwater.
Oklahoma had the smallest percentage of underwater homeowners in the October-December quarter, at 5.8 percent. Only nine states recorded percentages less than 10 percent.
When a mortgage is underwater, the homeowner often can’t qualify for mortgage refinancing and has little recourse but to continue making payments in hopes the property eventually regains its value.
The slide in home prices began stabilizing last year. But prices are expected to continue falling in many markets due to still-high levels of foreclosure and unemployment.
That means homes purchased at the height of the real estate boom are unlikely to recover lost value for years.
Underwater mortgages also dampen home sales. Homeowners who might otherwise sell their home refuse to take a loss or can’t get the bank to agree to a short sale ? when a lender lets a borrower sell their property for less than the amount owed on the mortgage.
Home sales have been weaker in areas where there are a large number of homeowners with negative equity.
The total amount of negative equity increased to $751 billion nationwide, up from $744 billion in the previous quarter.
|
{
"pile_set_name": "Pile-CC"
}
|
---
author:
- 'David Harvey, Brendan Hassett, and Yuri Tschinkel'
bibliography:
- 'hodgehilb.bib'
title: Characterizing projective spaces on deformations of Hilbert schemes of K3 surfaces
---
Introduction {#sect:intro}
============
Let $X$ be an irreducible holomorphic symplectic manifold, i.e., a compact Kähler simply-connected manifold admitting a unique nondegenerate holomorphic two-form. Let $\left(,\right)$ denote the Beauville–Bogomolov form on the cohomology group ${\mathrm{H}}^2(X,{{\mathbb Z}})$, normalized so that it is integral and primitive. When $X$ is a K3 surface this coincides with the intersection form. In higher dimensions, the form induces an inclusion $$\label{eqn:incl}
{\mathrm{H}}^2(X,{{\mathbb Z}}) \subset {\mathrm{H}}_2(X,{{\mathbb Z}}),$$ which allows us to extend $\left(,\right)$ to a ${{\mathbb Q}}$-valued quadratic form.
Lagrangian projective spaces play a fundamental rôle in the birational geometry of these classes of manifolds. If $X$ contains a holomorphically embedded projective space ${{\mathbb P}}^{\dim(X)/2}$ we can consider the [*Mukai flop*]{} of $X$, obtained by blowing up the projective space and blowing down the exceptional divisor $$E\simeq {{\mathbb P}}(\Omega^1_{{{\mathbb P}}^{\dim(X)/2}})$$ along the opposite ruling. Our goal is to characterize possible homology classes of such submanifolds, modulo the monodromy representation on the cohomology of $X$.
Assuming $X$ contains a Lagrangian projective space ${{\mathbb P}}^{\dim(X)/2}$, let $\ell\in {\mathrm{H}}_2(X,{{\mathbb Z}})$ denote the class of a line in ${{\mathbb P}}^{\dim(X)/2}$, and $\lambda=N\ell\in {\mathrm{H}}^2(X,{{\mathbb Z}})$ a positive integer multiple. We can take $N$ to be the index of ${\mathrm{H}}^2(X,{{\mathbb Z}}) \subset {\mathrm{H}}_2(X,{{\mathbb Z}})$. Hodge theory [@Ran; @Voisin] shows that the deformations of $X$ containing a deformation of the Lagrangian space coincide with the deformations of $X$ for which $\lambda \in {\mathrm{H}}^2(X,{{\mathbb Z}})$ remains of type $(1,1)$. Infinitesimal Torelli implies this is a divisor in the deformation space, i.e., $$\lambda^{\perp} \subset {\mathrm{H}}^1(X,\Omega^1_X) \simeq {\mathrm{H}}^1(X,{{\mathcal T}}_X).$$
We seek to establish intersection theoretic properties of $\ell$ for various deformation-equivalence classes of holomorphic symplectic manifolds. Previous results in this direction include
1. If $X$ is a K3 surface then $\left(\ell,\ell\right)=-2$.
2. If $X$ is deformation equivalent to the Hilbert scheme of length-two subschemes of a K3 surface then $\left(\ell,\ell\right)=-5/2$. [@HTGAFA08]
3. If $X$ is deformation equivalent to a generalized Kummer fourfold then $\left(\ell,\ell\right)=-3/2$. [@HT10]
Here we prove
\[theo:main\] Let $X$ be a six-dimensional Kähler manifold, deformation equivalent to the Hilbert scheme of length-three subschemes of a K3 surface. Let ${{\mathbb P}}^3 \subset X$ be a smooth subvariety and $\ell \subset {{\mathbb P}}^3$ a line. Then $\left(\ell,\ell\right)=-3$ and $\rho=2\ell \in {\mathrm{H}}^2(X,{{\mathbb Z}})$. Furthermore, we have $$\left[ {{\mathbb P}}^3 \right]=\frac{1}{48}\left( \rho^3 + \rho^2c_2(X)\right).$$
This uniquely characterizes the class of the Lagrangian plane, modulo the monodromy action, which acts transitively on the $\rho \in {\mathrm{H}}^2(X,{{\mathbb Z}})$ with $\left(\rho,\rho\right)=-12$ and $\left(\rho,{\mathrm{H}}^2(X,{{\mathbb Z}})\right)=2{{\mathbb Z}}$ [@GHS §3].
In general, we conjectured in [@HT09] that if $X$ is of dimension $2n$ then $\left(\ell,\ell\right)= -(n+3)/2$, if $X$ is deformation equivalent to a Hilbert scheme of a K3 surface. Our main motivation for making these conjectures is to achieve a classification of extremal rational curves on irreducible holomorphic symplectic varieties (i.e., generators of extremal rays of birational contractions) in terms of intersection properties under the Beauville-Bogomolov form.
The structure of this paper is as follows: Section \[sect:cohomology\] reviews the cohomology groups of Hilbert schemes of K3 surfaces; Section \[sect:ring\] focuses on the ring structure. We employ representation theory to get results on the Hodge classes in Section \[sect:representation\]. The Hilbert scheme of length-three subschemes is studied in detail in Section \[sect:lengththree\]. We extract the distinguished absolute Hodge class in the middle cohomology in Section \[sect:indecomp\]; here ‘absolute Hodge classes’ are those that remain Hodge under arbitrary deformations of complex structure. The computation of the class of the Lagrangian three planes is worked out in Section \[sect:LTP\], modulo a number theoretic result. This is proved in Section \[sect:DA\].
[**Acknowledgments:**]{} We are grateful to Noam Elkies, Lothar Göttsche, Manfred Lehn, Eyal Markman, and Christoph Sorger for useful conversations. The second author was supported by National Science Foundation Grant 0554491 and 0901645; the third author was supported by National Science Foundation Grants 0554280 and 0602333. We appreciate the hospitality of the American Institute of Mathematics, where some of this work was done.
Cohomology of Hilbert schemes {#sect:cohomology}
=============================
Let $X$ be deformation equivalent to the punctual Hilbert scheme $S^{[n]}$, where $S$ is a K3 surface. For $n>1$ the Beauville-Bogomolov form can be written [@beauville §8] $${\mathrm{H}}^2(X,{{\mathbb Z}}) \simeq {\mathrm{H}}^2(S,{{\mathbb Z}})_{\left(,\right)} \oplus_{\perp} {{\mathbb Z}}\delta, \quad
\left(\delta,\delta\right)=-2(n-1)$$ where $2\delta$ is the class of the ‘diagonal’ divisor $\Delta^{[n]} \subset S^{[n]}$ parameterizing nonreduced subschemes. For each homology class $f\in {\mathrm{H}}^2(S,{{\mathbb Z}})$, let $f \in {\mathrm{H}}^2(X,{{\mathbb Z}})$ denote the class parameterizing subschemes with some support along $f$. This is compatible with the lattice embedding above. Duality gives a ${{\mathbb Q}}$-valued form on homology $${\mathrm{H}}_2(X,{{\mathbb Z}}) \simeq {\mathrm{H}}_2(S,{{\mathbb Z}})_{\left(,\right)} \oplus_{\perp} {{\mathbb Z}}\delta^{\vee}, \quad
\left(\delta^{\vee},\delta^{\vee}\right)=-\frac{1}{2(n-1)},$$ where $\delta^{\vee}$ is characterized as the homology class orthogonal to ${\mathrm{H}}^2(S,{{\mathbb Z}})$ and satisfying $\delta^{\vee}\cdot \delta =1$.
[@Gott90] Let $S$ be a K3 surface and $S^{[n]}$ its Hilbert scheme. Consider the Poincaré polynomial $$p(S^{[n]},z)=\sum_{j=0}^{4n} \beta_j(S^{[n]})z^j.$$ Then $$\sum_{n=0}^{\infty} p(S^{[n]},z)t^n= \prod_{m=1}^{\infty}
(1-z^{2m-2}t^m)^{-1}(1-z^{2m}t^m)^{-22}(1-z^{2m+2}t^m)^{-1}.$$
To save space, we write $$q(S^{[n]},z)=\sum_{j=0}^{n} \beta_{2j} z^j,$$ which determines the Poincaré polynomial by Poincaré duality. We have $$\begin{array}{rcl}
q(S,z)&=& 1+ 22z \\
q(S^{[2]},z) &=& 1 + 23 z + 276 z^2 \\
q(S^{[3]},z) &=& 1 + 23 z + 299 z^2 + 2554 z^3.
\end{array}$$
A theorem of Verbitsky [@Verb Theorem 1.5] asserts that the homomorphism arising from the cup product $$\mu_{k,n}:\mathrm{Sym}^k {\mathrm{H}}^2(S^{[n]},{{\mathbb Q}}) {\rightarrow}{\mathrm{H}}^{2k}(S^{[n]},{{\mathbb Q}})$$ is injective for $k \le n$. Thus its image has dimension $$\binom{22+k}{k}.$$ In light of the computations above, $\mu_{2,2}$ is an isomorphism, $\mu_{2,3}$ has cokernel of dimension $23$, and $\mu_{3,3}$ has cokernel of dimension $$2554-\binom{25}{3}=254=\binom{23}{2}+1.$$ The cup product also induces a homomorphism $$\mathrm{coker}(\mu_{2,3}) \otimes {\mathrm{H}}^2(S^{[3]},{{\mathbb Q}}) {\rightarrow}\mathrm{coker}(\mu_{3,3}).$$ This homomorphism has been observed by Markman [@MarkCrelle p. 80]. More generally, he analyzes what classes are needed to generate the cohomology ring ${\mathrm{H}}^*(S^{[n]},{{\mathbb Q}})$, beyond those coming ${\mathrm{H}}^2(S^{[2]},{{\mathbb Q}})$. Markman uses Chern classes of universal sheaves over the product $S^{[n]} \times S$; a detailed discussion of the $n=3$ case is given in [@MarkCrelle Ex. 14].
The ring structure on cohomology {#sect:ring}
================================
Lehn-Sorger [@LS] and Nakajima [@Nakajima] described ${\mathrm{H}}^*(S^{[n]},{{\mathbb Q}})$ in terms of ${\mathrm{H}}^*(S,{{\mathbb Q}})$. We review the Lehn-Sorger formalism for the cup product on the cohomology ring.
Let $S$ be a K3 surface and $A={\mathrm{H}}^*(S,{{\mathbb Q}})(1)$, the cohomology ring shifted so that it has weights $-2,0$, and $2$; this is written as ${\mathrm{H}}^*(S,{{\mathbb Q}})[2]$ in their paper. Shifting the weights changes the sign of the intersection form, which is denoted by $\left<,\right>$; this has signature $(20,4)$. Let $T:A {\rightarrow}{{\mathbb Q}}$ denote the linear form $$\gamma \mapsto -\int_S \gamma$$ and $\left<,\right>$ the induced bilinear form $$\left<\gamma_1,\gamma_2\right>=T(\gamma_1\gamma_2)=-\int_S \gamma_1 \gamma_2.$$
For each $n \in {{\mathbb N}}$, we endow $A^{\otimes n}$ with an analogous structure. We shall use the fact that $A$ has only graded pieces of [*even*]{} degrees to simplify the description in [@LS]. In this situation, graded commutative multiplication rules are in fact commutative, given by the rule $$(a_1 \otimes \cdots \otimes a_n)\cdot (b_1 \otimes \cdots \otimes b_n)=
(a_1b_1)\otimes \cdots \otimes (a_nb_n).$$ The linear form $$T:A^{\otimes n} {\rightarrow}{{\mathbb Q}}$$ is defined by $$T(a_1\otimes \cdots \otimes a_n) =T(a_1)\cdots T(a_n).$$ Let $\left<,\right>$ denote the associated bilinear form $$\left<a,b\right>=T(a\cdot b).$$
The symmetric group ${{\mathfrak S}}_n$ acts on $A^{\otimes n}$ by the rule $$\pi(a_1 \otimes \cdots \otimes a_n)=
a_{\pi^{-1}(1)} \otimes \cdots \otimes a_{\pi^{-1}(n)}.$$
Given a partition $n=n_1+\ldots+n_k$ with $n_1,\ldots,n_k \in {{\mathbb N}}$, we have a generalized multiplication map $$\begin{array}{rcl}
A^{\otimes n} & {\rightarrow}& A^{\otimes k}\\
a_1\otimes \cdots \otimes a_n & \mapsto & (a_1\cdots a_{n_1})
\otimes \cdots \otimes
(a_{n_1+\cdots+n_{k-1}+1}\cdots a_{n_1+\cdots+n_k}).
\end{array}$$
Given a finite set $I\subset \{1,\ldots,n\}$, let $A^{\otimes I}$ denote the tensor power with factors indexed by elements of $I$. Given a surjection $\phi:I {\rightarrow}J$, there is an induced multiplication $$\phi^* \colon A^{\otimes I} {\rightarrow}A^{\otimes J}$$ defined as above. Let $$\phi_*: A^{\otimes J} {\rightarrow}A^{\otimes I}$$ denote the [*adjoint*]{} of $\phi^*$, i.e., $$\left< \phi^*a,b \right>=\left<a,\phi_* b\right>$$ for $a \in A^{\otimes I}$ and $b\in A^{\otimes J}$.
We have the composite $$A \stackrel{\Delta_*}{{\rightarrow}} A\otimes A {\rightarrow}A,$$ where the first map is adjoint comultiplication and the second is multiplication. Let $e:=e(A)$ denote the image of $1$ under the composed map.
We evaluate the signs of $\Delta_*1$ and $e(A)$. Let $\Delta_S$ denote the fundamental class of the diagonal in ${\mathrm{H}}^*(S\times S,{{\mathbb Z}})={\mathrm{H}}^*(S,{{\mathbb Z}}) \otimes {\mathrm{H}}^*(S,{{\mathbb Z}})$. Using the adjoint property, we have $$\begin{array}{rcl}
\left<\Delta_*1, \alpha \otimes \beta \right> &=& \left< 1, \alpha\beta \right> \\
&=& T(\alpha\beta) \\
&=& -\int_S \alpha \beta
\end{array}$$ whereas $$\begin{array}{rcl}
\left<\Delta_S, \alpha \otimes \beta \right> &=& \left< \sum_j e_j \otimes e_j^{\vee}, \alpha\otimes \beta \right> \\
&=& \sum_j T(e_j \alpha) T(e_j^{\vee}\beta)\\
&=& \int_S \alpha \beta,
\end{array}$$ where $\{e_j\}$ is a homogeneous basis for ${\mathrm{H}}^*(S,{{\mathbb Q}})$ with Poincaré-dual basis $e_j^{\vee}$. Therefore, we find $$\Delta_*1=-[\Delta_S]. \label{eqnsignswitch}$$ Furthermore, we have $$\int_S e(A)=-T(e(A))=-\left<e(A),1\right>=-\left<\Delta_*1,\Delta_*1\right>=-\chi(S)=-24,$$ so $e(A)$ is a [*negative*]{} multiple of the point class. Nevertheless, we still have (cf. [@LS §2.2]) $$e(A)=\chi(S) \mathrm{vol}, \quad \text{ where } \quad T(\mathrm{vol})=1,$$ but $\mathrm{vol}$ differs from the standard volume form by sign.
Let $\left<\pi\right> \backslash [n]$ denote the set of orbits of $[n]=\{1,2,\ldots,n\}$ under the action of $\pi$. Set $$A\{{{\mathfrak S}}_n\}=\oplus_{\pi\in {{\mathfrak S}}_n} A^{\otimes \left<\pi\right> \backslash [n]} \cdot \pi$$ which admits an action of ${{\mathfrak S}}_n$. First, note that $\sigma \in {{\mathfrak S}}_n$ induces a bijection $$\begin{array}{rcl}
\sigma:\left<\pi\right> \backslash [n] & {\rightarrow}& \left<\sigma \pi \sigma^{-1}\right>
\backslash [n] \\
x & \mapsto & \sigma x.
\end{array}$$ Thus we obtain an isomorphism $$\begin{array}{rcl}
\tilde{\sigma}: A\{S_n\} & {\rightarrow}& A\{S_n\} \\
a \pi & \mapsto & \sigma^* \sigma\pi \sigma^{-1}.
\end{array}$$
[@LS 2.9, 2.17] We have $A\{{{\mathfrak S}}_2\}=A^{\otimes 2}\mathrm{id} \oplus A (12)$ and $$A\{{{\mathfrak S}}_3\}=A^{\otimes 3}\mathrm{id}\oplus A^{\otimes 2}(12) \oplus
A^{\otimes 2}(13)\oplus A^{\otimes 2}(23)
\oplus A(123) \oplus A(132).$$
Let $A^{[n]}\subset A\{{{\mathfrak S}}_n\}$ denote the invariants under this action. Then we have [@LS §2] $$A^{[n]}=\sum_{\| \alpha \|=n} \bigotimes_{i}{\mathrm{Sym }}^{\alpha_i}A,$$ where $\alpha$ corresponds to a partition $$\underbrace{1+\cdots+1}_{\alpha_1 \text{ times}}+
\underbrace{2+\cdots+2}_{\alpha_2 \text{ times}}+\cdots$$ and $$n=\|\alpha \|=\alpha_1+2\alpha_2+\cdots+n\alpha_n.$$ Note that this is compatible with Hodge structures; in particular, $A^{[n]}$ is a representation of the Hodge group of $S$ and the special orthogonal group $G_S$ associated with the intersection form on ${\mathrm{H}}^2(S,{{\mathbb R}})$. We interpret this as acting on $A$, trivially on the summands ${\mathrm{H}}^0(S,{{\mathbb R}})$ and ${\mathrm{H}}^4(S,{{\mathbb R}})$.
[@LS Theorem 3.2] Let $S$ be a K3 surface. Then there is a canonical isomorphism of graded rings $$({\mathrm{H}}^*(S,{{\mathbb Q}})[2])^{[n]} \stackrel{\sim}{{\rightarrow}}{\mathrm{H}}^*(S^{[n]},{{\mathbb Q}})[2n].$$
In the cohomology of the Hilbert scheme, the subring generated by ${\mathrm{H}}^2(S^{[n]})$ plays a special role. We have an isomorphism $${\mathrm{H}}^2(S^{[n]},{{\mathbb Z}}) = {\mathrm{H}}^2(S,{{\mathbb Z}}) \oplus {{\mathbb Z}}\delta,$$ where $2\delta$ parameterizes the non-reduced schemes of $S$. We express this in terms of our presentation. Given $D \in {\mathrm{H}}^2(S,{{\mathbb Z}})$, the class $$\sum_{i=1}^n 1_{\{1\}} \otimes \cdots \otimes 1_{\{i-1\}} \otimes D_{\{i\}}
\otimes 1_{\{i+1\}}\otimes \cdots \otimes 1_{\{n\}} (\mathrm{id})$$ is the corresponding class in ${\mathrm{H}}^2(S^{[n]},{{\mathbb Q}})[2n]$. Using the explicit form of the isomorphism in [@LS 2.7] and Nakajima’s isomorphism ([@LS Thm. 3.6]), we find that $$\delta=\sum_{1 \le i<j \le n} 1_{\{1\}} \otimes \ldots \otimes 1_{\{i-1\}} \otimes 1_{\{i,j\}}
\otimes 1_{\{i+1\}} \otimes \cdots \otimes 1_{\{j-1\}} \otimes 1_{\{j+1 \}} \otimes \cdots \otimes 1_{\{n\}}(ij).$$ Here is the essence of the computation: the interpretation of the nonreduced subschemes via the correspondence $$Z_2=\{(\xi,x,\xi'):|\xi'|-|\xi|=2x \} \subset S^{[n-2]} \times S \times S^{[n]}$$ allows us to express $\delta$ in terms of Nakajima’s creation and annihilation operators, and thus in $${\mathrm{H}}^*(S^{[n]},{{\mathbb Q}})[2n].$$
We describe the general rule for evaluating the fundamental class in $A^{[n]}$. Let $$[\mathrm{pt}]\in {\mathrm{H}}^4(S,{{\mathbb Z}})[2] \subset A$$ be the point class, which is of degree $-2$. Let $$[\mathrm{pt}]_{\{1\}} \otimes \cdots \otimes [\mathrm{pt}]_{\{n\}} (\mathrm{id})
\in A^{[n]}$$ denote the unique class of degree $-2n$ up to scalar. Then the class of a point in $S^{[n]}$ is equal to [@LS 2.10] $$\label{eqn:pointclass}
[\mathrm{pt}_{S^{[n]}}]=\frac{1}{n!}
[\mathrm{pt}]_{\{1\}} \otimes \cdots \otimes [\mathrm{pt}]_{\{n\}} (\mathrm{id})
.$$
Decomposition of the cohomology representation {#sect:representation}
==============================================
We summarize general results from representation theory. For an orthogonal group of odd dimension $2r+1$, the highest weights $\lambda=(\lambda_1,\ldots,\lambda_r)$ of irreducible representations $V(\lambda)$ are vectors consisting entirely of integers (or half integers) in the fundamental chamber $$\{\lambda_1 \ge \lambda_2 \ge \ldots \ge \lambda_{r-1} \ge \lambda_r \ge 0 \}.$$ Since we only consider even-weight representations, we ignore cases where the $\lambda_j$ are half-integers. For orthogonal groups of even dimension $2r$, the fundamental chamber is $$\{\lambda_1 \ge \lambda_2 \ge \ldots \ge \lambda_{r-1} \ge |\lambda_r| \ge 0 \}.$$ Recall that
- [$V(1,0,\ldots)$ is the standard representation $V$.]{}
- [We have $$V(\underbrace{1,\cdots,1}_{k \text{ times}},0,\cdots)=\bigwedge^k V,$$ provided $k < r$ (in the even case) or $k\le r$ (in the odd case); see, for instance, [@FulHar Thms. 19.2 and 19.14].]{}
- [$V(k,0,\ldots)={\mathrm{Sym }}^k(V)/{\mathrm{Sym }}^{k-2}(V)$, embedded via the dual to the quadratic form on $V$.]{}
- [For the odd orthogonal group, we have $$\dim V(\lambda)=\prod_{i<j} \frac{\ell_i-\ell_j}{j-i} \prod_{i \le j}\frac{\ell_i+\ell_j}{2n+1-i-j}$$ where $\ell_i=\lambda_i+n-i+\frac{1}{2}$ [@FulHar p. 408].]{}
- [For the even orthogonal group, we have $$\dim V(\lambda)=\prod_{i<j} \frac{\ell^2_i-\ell^2_j}{(j-i)(2n-i-j)}$$ where $\ell_i=\lambda_i+n-i$ [@FulHar p. 410].]{}
- [Let $V_X(\lambda)$ denote an irreducible representation of an orthogonal group $G_X$ of dimension $2r+1$, $G_S \subset G_X$ the orthogonal subgroup $G_S\subset G_X$ of dimension $2r$ fixing a non-isotropic vector with negative self-intersection, and $V_S(\overline{\lambda})$ the representation of $G_S$ with highest weight $\overline{\lambda}$. Then we have the branching rule [@FulHar p. 426] $$\mathrm{Res}^{G_X}_{G_S}V_X(\lambda)= \oplus_{{\overline \lambda}} V_S(\overline \lambda),$$ where the sum ranges over all $\overline{\lambda}$ with $$\lambda_1 \ge {\overline \lambda_1} \ge \lambda_2 \ge {\overline \lambda_2} \ge \cdots
\lambda_r \ge |{\overline \lambda_r}|.$$]{}
Let $X$ be a generic deformation of $S^{[n]}$. Our goal is to decompose ${\mathrm{H}}^*(X,{{\mathbb Q}})$ into irreducible representations for the action of the identity component $G_X$ of the special orthogonal group associated with the Beauville-Bogomolov form on ${\mathrm{H}}^2(X,{{\mathbb Q}})$. Let $G_S$ denote the identity component of the special orthogonal group associated with the intersection form on ${\mathrm{H}}^2(S,{{\mathbb Q}})$. The decomposition $${\mathrm{H}}^2(S^{[2]},{{\mathbb Z}})={\mathrm{H}}^2(S,{{\mathbb Z}}) \oplus_{\perp} {{\mathbb Z}}\delta$$ induces an inclusion $G_S \subset G_X$.
Let $X$ be deformation equivalent to $S^{[n]}$ for some $n$. Then $G_X$ admits a representation on the cohomology ring of $X$.
Let $\mathrm{Mon}\subset \mathrm{Aut}({\mathrm{H}}^*(X,{{\mathbb Z}}))$ denote the monodromy group, i.e., the group generated by the monodromy representations of all connected families containing $X$. Let $\mathrm{Mon}^2\subset \mathrm{Aut}({\mathrm{H}}^2(X,{{\mathbb Z}}))$ denote its image under projection to the second cohomology group, so we have an exact sequence $$1 {\rightarrow}K {\rightarrow}\mathrm{Mon} {\rightarrow}\mathrm{Mon}^2 {\rightarrow}1.$$ Markman has shown [@Mark1 §4.3] that $K$ is finite.
Note that $G_X$ is a connected component of the Zariski closure of $\mathrm{Mon}^2$ (see, for example [@Mark1 §1.8]). Since $\mathrm{Mon}$ and $\mathrm{Mon}^2$ differ only by finite subgroups, it follows that the universal cover $\widetilde{G_X}{\rightarrow}G_X$ acts on the cohomology ring of $X$. Since the cohomology of $X$ is nonzero only in even degrees, this representation passes to $G_X$.
In principle, we can decompose ${\mathrm{H}}^*(X,{{\mathbb R}})$ explicitly into isotypic components as follows:
1. [Fix an embedding $G_S \subset G_X$, e.g., using the isomorphism $${\mathrm{H}}^2(X,{{\mathbb Z}})\simeq {\mathrm{H}}^2(S,{{\mathbb Z}}) \oplus_{\perp} {{\mathbb Z}}\delta,$$ and compatible maximal tori (both of which have rank $11$).]{}
2. [Identify the highest-weight irreducible $G_S$-representation $V_{S}(\lambda) \subset {\mathrm{H}}^*(S^{[n]},{{\mathbb R}})$, which is a summand of the restriction of an irreducible $V_{X}(\lambda) \subset {\mathrm{H}}^*(X,{{\mathbb R}})$. Decompose $V_X(\lambda)$ into irreducible $G_S$-representations.]{}
3. [Repeat step two for ${\mathrm{H}}^*(X,{{\mathbb R}})/V_{X}(\lambda)$ and subsequent quotients.]{}
First consider $X=S^{[2]}$. We have decompositions $${\mathrm{H}}^*(S^{[2]})=A \oplus {\mathrm{Sym }}^2(A)$$ inducing $$\begin{array}{rcl}
{\mathrm{H}}^2(S^{[2]})&=& {\mathrm{H}}^0(S) \oplus ({\mathrm{H}}^0(S)\otimes {\mathrm{H}}^2(S))={\bf 1}_S \oplus V_S(1,0,\ldots) \\
{\mathrm{H}}^4(S^{[2]})&=& {\mathrm{H}}^2(S) \oplus ({\mathrm{H}}^0(S)\otimes {\mathrm{H}}^4(S)) \oplus {\mathrm{Sym }}^2({\mathrm{H}}^2(S)) \\
&=& V_S(1,0,\ldots) \oplus {\bf 1}_S^{\oplus 2} \oplus V_S(2,0,\ldots)
\end{array}$$ Let $V_{X}(2,0,\ldots,0)$ denote the highest-weight representation associated to ${\mathrm{Sym }}^2({\mathrm{H}}^2(X))$ so that $${\mathrm{Sym }}^2({\mathrm{H}}^2(X))=V_{X}(2,0,\ldots) \oplus {\bf 1}_X.$$ The branching rule gives $$V_{X}(1,0,\ldots)= V_S(1,0,\ldots) \oplus {\bf 1}_S$$ and $$V_{X}(2,0,\ldots)= V_S(2,0,\ldots) \oplus V_S(1,0,\ldots) \oplus
{\bf 1}_S.$$ Therefore we obtain $$\begin{array}{rcl}
{\mathrm{H}}^2(X) &=& V_X(1,0,\ldots) \\
{\mathrm{H}}^4(X) &=& V_X(2,0,\ldots)\oplus {\bf 1}_X.
\end{array}$$
Now consider $X=S^{[3]}$. We have $${\mathrm{H}}^*(S^{[3]})= A \oplus (A\otimes A) \oplus {\mathrm{Sym }}^3(A)$$ inducing following decompositions (as described in [@LS Example 2.9]): $$\begin{array}{rcl}
{\mathrm{H}}^2(S^{[3]}) &=& ({\mathrm{H}}^0(S)^{\otimes 2}) \oplus ({\mathrm{H}}^2(S)\otimes {\mathrm{H}}^0(S)^{\otimes 2}) \\
&=& {\bf 1}_S \oplus V_S(1,0\ldots) \\
{\mathrm{H}}^4(S^{[3]}) &=& {\mathrm{H}}^0(S) \oplus ({\mathrm{H}}^0(S)\otimes {\mathrm{H}}^2(S))^{\oplus 2} \\
& &\oplus ({\mathrm{Sym }}^2({\mathrm{H}}^2(S))\otimes {\mathrm{H}}^0(S)) \oplus ({\mathrm{H}}^4(S)\otimes {\mathrm{H}}^0(S)^{\otimes 2}) \\
&=& {\bf 1}_S^{\oplus 3} \oplus V_S(1,0,\ldots)^{\oplus 2} \oplus V_S(2,0,\ldots) \\
{\mathrm{H}}^6(S^{[3]}) &=& {\mathrm{H}}^2(S) \oplus ({\mathrm{H}}^2(S)\otimes {\mathrm{H}}^2(S))
\oplus
({\mathrm{H}}^0(S) \otimes {\mathrm{H}}^4(S))^{\oplus 2} \\
& &\oplus {\mathrm{Sym }}^3({\mathrm{H}}^2(S)) \oplus ({\mathrm{H}}^4(S) \otimes {\mathrm{H}}^2(S) \otimes {\mathrm{H}}^0(S)) \\
&=& {\bf 1}_S^{\oplus 3} \oplus V_S(1,0,\ldots)^{\oplus 3} \oplus V_S(1,1,0,\ldots)\\
& & \oplus V_S(2,0,\ldots) \oplus V_S(3,0,\ldots).
\end{array}$$ Let $V_{X}(1,1,0,\ldots)=\bigwedge^2 V_X(1,0,\ldots)$ and $V_X(3,0,\ldots)$ denote the highest weight representation in ${\mathrm{Sym }}^3(V_X(1,0,\ldots))$ so that $${\mathrm{Sym }}^3(V_X(1,0,\ldots))=V_X(3,0,\ldots) \oplus V_X(1,0,\ldots).$$ Therefore we obtain $$\begin{array}{rcl}
{\mathrm{H}}^2(X) &=& V_X(1,0,\ldots) \\
{\mathrm{H}}^4(X) &=& V_X(2,0,\ldots) \oplus V_X(1,0,\ldots) \oplus {\bf 1}_X \\
{\mathrm{H}}^6(X) &=& V_X(3,0,\ldots) \oplus V_X(1,1,0\ldots)\oplus V_X(1,0,\ldots) \oplus
{\bf 1}_X.
\end{array}$$ The trivial factor in ${\mathrm{H}}^4(X)$ corresponds to the Chern class $c_2(X)$; our main task is to analyze the trivial factor in ${\mathrm{H}}^6(X)$.
Cohomology computations for length-three subschemes {#sect:lengththree}
===================================================
The general rule for multiplication in $A\{{{\mathfrak S}}_n\}$ is fairly complicated, so we will only give a formula in the case ($n=3$) we need. The fact that $A$ only has terms of even degree simplifies the expressions of [@LS 2.17]:
$$\begin{array}{rcl}
(\alpha_{\{1,2\}}\otimes \beta_{\{3\}})(12) \cdot
(\gamma_{\{1,3\}} \otimes \delta_{\{2\}})(13) &=&
\alpha \beta \gamma \delta (132) \\
(\alpha_{\{1,2\}} \otimes \beta_{\{3\}})(12) \cdot
(\gamma_{\{1,2\}} \otimes \delta_{\{3\}})(12) &=&
\Delta_*(\alpha \gamma) \otimes (\beta \delta) (\mathrm{id}) \\
\alpha_{\{1,2,3\}} (123) \cdot \beta_{\{1,2,3\}}(123) &=&
(\alpha \beta e)(132) \\
\alpha_{\{1,2,3\}}(123) \cdot \beta_{\{1,2,3\}}(132) &=&
(\Delta_*(\alpha \beta))_{\{1,2,3\}} (\mathrm{id}),
\end{array}$$ where $\Delta_*$ is the adjoint of the threefold multiplication $A\otimes A \otimes A {\rightarrow}A$.
The remaining products can be deduced as formal consequences using the associativity of the multiplication, e.g., $$\begin{array}{l}
(\alpha_{\{1,2\}} \otimes \beta_{\{3\}})(12) \cdot \gamma_{\{1,2,3\}}(132) \\
\quad = (\alpha_{\{1,2\}} \otimes \beta_{\{3\}})(12) \cdot (\gamma_{\{1,2\}} \otimes
1_{\{3\}})(12)\cdot (13) \\
\quad = (\Delta_*(\alpha \gamma)_{\{1,2\}} \otimes \beta_{\{3\}})(\mathrm{id}) \cdot
(1_{\{1,3\}} \otimes 1_{\{2\}})(13) \\
\quad = \alpha \beta \gamma (\Delta_*(1))_{\{1,3\}, \{2\}} (13),
\end{array}$$ where $\alpha,\beta,$ and $\gamma$ act on the diagonal via either the first or second variable. Thus in particular $$(12)\cdot (132)=(\Delta_*(1))_{\{1,3\},\{2\}}(13).$$
We compute intersections among the absolute Hodge classes for $S^{[3]}$, i.e., classes that are Hodge for general K3 surfaces $S$. From now on, to condense notation we omit factors of the form $1_{\{i\}},1_{\{i,j\}}$, etc. from our expressions.
Based on the representation-theoretic analysis in Section \[sect:representation\], we expect one independent classes in codimension one, three in codimension two, and three in codimension three. We have the unique divisor $$\delta = (12)+(13)+(23).$$ In codimension two, we have $$\begin{array}{rcl}
P &=& [\mathrm{pt}]_{\{1\}}+ [\mathrm{pt}]_{\{2\}} + [\mathrm{pt}]_{\{3\}} \\
Q &=& \sum_{j=1}^{22}
{e_j}_{\{1\}} \otimes {e^{\vee}_j}_{\{2\}} +
{e_j}_{\{1\}} \otimes {e^{\vee}_j}_{\{3\}} +
{e_j}_{\{2\}} \otimes {e^{\vee}_j}_{\{3\}} \\
R &=& (132)+(123).
\end{array}$$ In codimension three, we have $$\begin{array}{rcl}
U &=& [\mathrm{pt}]_{\{1,2\}} (12) +
[\mathrm{pt}]_{\{1,3\}} (13) +
[\mathrm{pt}]_{\{2,3\}} (23) \\
V &=& [\mathrm{pt}]_{\{3\}} (12) +
[\mathrm{pt}]_{\{2\}} (13) +
[\mathrm{pt}]_{\{1\}} (23) \\
W &=& \sum_{j=1}^{22} {e_j}_{\{1,2\}} \otimes {e_j^{\vee}}_{\{3\}} (12) +
{e_j}_{\{1,3\}} \otimes {e_j^{\vee}}_{\{2\}} (13) +
{e_j}_{\{2,3\}} \otimes {e_j^{\vee}}_{\{1\}} (23).
\end{array}$$ Thus we have $$\begin{array}{rcl}
\delta^2&=& (\Delta_*1)_{\{1,2\}}(12)+ (\Delta_*1)_{\{1,3\}}(13)+(\Delta_*1)_{\{2,3\}}(23)
\\
& & \mathbin{+} \,\, 3((132)+(123)) \\
&=&-2P-Q+3R.
\end{array}$$ Furthermore, we have $$\begin{array}{rcl}
\delta \cdot P &=& ((12)+(13)+(23))\cdot
([\mathrm{pt}]_{\{1\}} + [\mathrm{pt}]_{\{2\}} + [\mathrm{pt}]_{\{3\}}) \\
&=& 2U+V \\
\delta \cdot Q &=& ((12)+(13)+(23))\cdot (\sum_{j=1}^{22}
{e_j}_{\{1\}} \otimes {e^{\vee}_j}_{\{2\}} +
{e_j}_{\{1\}} \otimes {e^{\vee}_j}_{\{3\}} \\
& & \quad \quad +\,\, {e_j}_{\{2\}} \otimes {e^{\vee}_j}_{\{3\}} ) \\
&=& 22([\mathrm{pt}]_{\{1,2\}}(12) +[\mathrm{pt}]_{\{1,3\}}(13) + [\mathrm{pt}]_{\{2,3\}}(23)) \\
& & +2 ( \sum_{j=1}^{22} {e_j}_{\{1,2\}} \otimes {e_j^{\vee}}_{\{3\}} +
{e_j}_{\{1,3\}} \otimes {e_j^{\vee}}_{\{2\}} +
{e_j}_{\{2,3\}} \otimes {e_j^{\vee}}_{\{1\}}) \\
&=& 22U + 2W \\
\delta \cdot R &=&((12)+(13)+(23))((132)+(123))\\
&=&2({\Delta_*1}_{\{1,2\},\{3\}}(12)+{\Delta_*1}_{\{1,3\},\{2\}}+{\Delta_*1}_{\{2,3\},\{1\}})\\
&=& -2(U+V+W).
\end{array}$$ We deduce then that $$\delta^3=\delta(-2P-Q+3R)=-32U-8V-8W.$$
Finally, we compute the intersection pairing on the subspace of the middle cohomology spanned by $U,V,$ and $W$. Dimensional considerations give vanishing $$U^2=V^2=U\cdot W=V\cdot W=0.$$ For the remaining numbers, we get $$\begin{array}{rcl}
U\cdot V &=&
([\mathrm{pt}]_{\{1,2\}} (12) +
[\mathrm{pt}]_{\{1,3\}} (13) +
[\mathrm{pt}]_{\{2,3\}} (23) ) \\
& & \quad \quad \cdot ([\mathrm{pt}]_{\{3\}} (12) +
[\mathrm{pt}]_{\{2\}} (13) +
[\mathrm{pt}]_{\{1\}} (23)) \\
&=&-3 [\mathrm{pt}]_{\{1\}} \otimes [\mathrm{pt}]_{\{2\}} \otimes [\mathrm{pt}]_{\{3\}} \mathrm{id}
\end{array}$$ and $$\begin{array}{rcl}
W^2 &=&
(\sum_{j=1}^{22} {e_j}_{\{1,2\}} \otimes {e_j^{\vee}}_{\{3\}} (12) +
{e_j}_{\{1,3\}} \otimes {e_j^{\vee}}_{\{2\}} (13) +
{e_j}_{\{2,3\}} \otimes {e_j^{\vee}}_{\{1\}} (23))^2 \\
&=& -3\cdot 22 \cdot
[\mathrm{pt}]_{\{1\}} \otimes [\mathrm{pt}]_{\{2\}} \otimes [\mathrm{pt}]_{\{3\}} \mathrm{id}.
\end{array}$$
As a consistency check, we evaluate $$\begin{array}{rcl}
\delta^6&=&(-32U-8V-8W)^2=2^6 (8UV+W^2)\\
&=&2^6 (-24-66)
[\mathrm{pt}]_{\{1\}} \otimes [\mathrm{pt}]_{\{2\}} \otimes [\mathrm{pt}]_{\{3\}} \mathrm{id}.
\end{array}$$ Using the formula for the point class (Equation \[eqn:pointclass\]), we obtain $$\delta^6=-\frac{2^7 \cdot 3^2 \cdot 5}{2\cdot 3}=-2^6 \cdot 3 \cdot 5.$$ This is compatible with the Fujiki-type identity $$D^6=15\left(D,D\right)^3, \quad D\in H^2(S^{[3]},{{\mathbb Q}}),$$ as $\left(\delta,\delta\right)=-4$.
Evaluation of the distinguished absolute Hodge class {#sect:indecomp}
====================================================
Let $S$ be a general K3 surface and $X$ a general deformation of $S^{[3]}$. The computations above show that the middle cohomology of $X$ admits one Hodge class $${\mathrm{H}}^6(X,{{\mathbb Q}})\cap {\mathrm{H}}^{3,3}(X)={{\mathbb Q}}\eta$$ and the middle cohomology of $S^{[3]}$ admits three Hodge classes $${\mathrm{H}}^6(S^{[3]},{{\mathbb Q}}) \cap {\mathrm{H}}^{3,3}(S^{[3]})= {{\mathbb Q}}\eta \oplus {{\mathbb Q}}\delta^3 \oplus {{\mathbb Q}}c_2(X)\delta.$$ Our goal is to compute the self-intersection of $\eta$, at least up to the square of a rational number. Note that $\eta$ is orthogonal to $\delta^3$ and $\delta c_2(X)$ under the intersection form, by the analysis in Section \[sect:representation\]. The analysis here gives the one structure constant left open in [@MarkCrelle Ex. 14].
\[prop:eta\] Let $X$ be deformation equivalent to $S^{[3]}$, for $S$ a K3 surface. Let $\eta\in {\mathrm{H}}^6(X,{{\mathbb Q}})$ denote the unique (up to scalar) absolute Hodge class. Then $\eta^2=-3\cdot 443$.
The argument relies heavily on the analysis in Section \[sect:lengththree\]. We extract the decomposable classes in codimension three. We have $\delta^3$ already and $$\delta \cdot P=2U+V.$$ Hence the subspace $\mathrm{span}\{2U+V,V-W \}$ is spanned by decomposable classes and has orthogonal complement spanned by $2U-V+11W$. Thus we have $$\eta=2U-V+11W$$ and $$\begin{array}{rcl}
\eta^2&=&-4UV+121W^2 \\
&=&(12-121 \times 66)([\mathrm{pt}] \otimes [\mathrm{pt}] \otimes
[\mathrm{pt}] )\mathrm{id} \\
&=&-3 \cdot 443.
\end{array}$$
Proof of the main theorem {#sect:LTP}
=========================
We compute the cohomology class of a Lagrangian subspace ${{\mathbb P}}^3 \subset X$, where $X$ is deformation equivalent to the Hilbert scheme of length three subschemes. As we shall see, the formula for $[{{\mathbb P}}^3]$ involves only decomposable classes, and not the absolute Hodge class $\eta$:
Let ${{\mathbb P}}^n \subset X$ be embedded in a general irreducible holomorphic symplectic variety of dimension $2n$. Then we have $$c_{2j}({{\mathcal T}}_X|{{\mathbb P}}^n)=(-1)^jh^{2j}\binom{n+1}{j},$$ where $h$ is the hyperplane class.
This is proved using the exact sequence $$0 {\rightarrow}{{\mathcal T}}_{{{\mathbb P}}^n} {\rightarrow}{{\mathcal T}}_X|{{\mathbb P}}^n {\rightarrow}{{\mathcal N}}_{{{\mathbb P}}^n/X} {\rightarrow}0$$ and $${{\mathcal N}}_{{{\mathbb P}}^n/X}\simeq {{\mathcal T}}_{{{\mathbb P}}^n}^{\vee},$$ reflecting the fact that ${{\mathbb P}}^n$ is a Lagrangian subvariety of $X$.
Regarding $${\mathrm{H}}^2(X,{{\mathbb Z}}) \subset {\mathrm{H}}_2(X,{{\mathbb Z}})$$ as a subgroup of index four, we can express $\ell=\lambda/4$ for some divisor class $\lambda \in {\mathrm{H}}^2(X,{{\mathbb Z}})$. (This might not be primitive.)
Given a deformation of $X$ such that $\lambda$ remains algebraic, the subvariety ${{\mathbb P}}^3$ deforms as well [@HTGAFA99]. Without loss of generality, we can deform $X$ to a variety containing a ${{\mathbb P}}^3$, but otherwise having a general Hodge structure. In particular, we have a injection $${\mathrm{Sym }}({\mathrm{H}}^2(X,{{\mathbb Q}})) \hookrightarrow {\mathrm{H}}^*(X,{{\mathbb Q}}).$$ We expect to be able to write $$\left[ {{\mathbb P}}^3 \right]=a\lambda c_2(X) + b \lambda^3 + d \eta$$ for some $a,b,d \in {{\mathbb Q}}$.
Furthermore, the Fujiki relations [@Fujiki] imply that for each $f\in {\mathrm{H}}^2(X,{{\mathbb Z}})$, $$f^6= e_0 \left(f,f\right)^3, \quad
c_2(X)f^4= e_2 \left(f,f\right)^2, \quad
c_4(X)f^2 = e_4 \left(f,f\right)$$ for suitable rational constants $e_0,e_2,e_4$. Precisely, we have [@EGL] $$c_2^2(X)f^2=\frac{5}{2}c_4(X)f^2.$$
The Riemann-Roch formula gives $$\chi({{\mathcal O}}_X(f))=\frac{f^6}{6!}+ \frac{c_2(X)f^4}{12 \cdot 4!}+
\frac{f^2(3c_2^2-c_4)}{720 \cdot 2!}+4.$$ On the other hand, we know that $$\chi({{\mathcal O}}_X(f))=\frac{1}{3!2^3}(\left(f,f\right)+8)(\left(f,f\right)+6)
(\left(f,f\right)+4).$$ Perhaps the quickest way to check this formula is to observe that if $X=S^{[3]}$ and $f$ is a very ample divisor on $S$ with no higher cohomology then the induced sheaf ${{\mathcal O}}_X(f)$ has no higher cohomology and $$\dim \Gamma({{\mathcal O}}_X(f))=\dim {\mathrm{Sym }}^3(\Gamma({{\mathcal O}}_S(f)))=
\binom{\chi({{\mathcal O}}_S(f))+2}{3}.$$ Equating coefficients, we find $$\begin{array}{rcl}
f^6 &=& 15 \left(f,f\right)^3 \\
f^4c_2 &=& 108 \left(f,f\right)^2 \\
f^2c_4 &=& 480 \left(f,f\right) \\
f^2c_2^2 &=& 1200 \left(f,f\right)
\end{array}$$
We generate Diophantine equations for $a,b,\left(\lambda,\lambda\right)$ and eventually, $d$. First, observe that $$\left(\lambda,\ell \right)=\lambda\cdot \ell =\deg \lambda|{{\mathbb P}}^3$$ so that $\lambda|{{\mathbb P}}^3$ is $\left(\lambda,\lambda \right)/4$ times the hyperplane class. Thus we have $$\left[{{\mathbb P}}^3 \right]\lambda^3 = (\left(\lambda,\lambda \right)/4)^3$$ and $$\left[{{\mathbb P}}^3 \right]\lambda^3 = a\lambda^4c_2(X)+b\lambda^6.$$ Equating these expressions and evaluating the terms, we find $$\left(\lambda,\lambda\right) (15 b -1/64)+108a=0.$$ We have divided out by $\left(\lambda,\lambda \right)$; the solution $\left(\lambda,\lambda\right)=0$ is not possible for geometric reasons, and we shall exclude it algebraically below.
Second, the Lemma on restrictions of Chern classes implies $$\left[{{\mathbb P}}^3 \right] \lambda c_2(X)=-\left(\lambda,\lambda\right)$$ whereas the formula for the class of ${{\mathbb P}}^3$ yields $$\left[{{\mathbb P}}^3 \right]\lambda c_2(X)=a\lambda^2c_2(X)^2 + b \lambda^4 c_2(X).$$ Thus we obtain $$108 b \left(\lambda,\lambda \right) + (1200 a + 1)=0.$$
The cup product of ${\mathrm{H}}^*(X)$ is compatible with the $G_X$-action, so the subring generated by Chern classes and elements of ${\mathrm{H}}^2(X)$ is orthogonal to $\eta$. Thus even if the decomposition of $[{{\mathbb P}}^3]$ were to involve $\eta$, the computations up to this point would not reflect this.
Finally, the fact that $$\left[{{\mathbb P}}^3 \right]^2=c_3({{\mathcal N}}_{{{\mathbb P}}^3/X})=c_3({{\mathcal T}}_{{{\mathbb P}}^3}^{\vee})=-4$$ yields the [*cubic*]{} equation $$15b^2 \left(\lambda,\lambda\right)^3 + 216 ab \left(\lambda,\lambda\right)^2
+ 1200 \left(\lambda,\lambda \right)a^2 + d^2 \eta \cdot \eta =-4.$$ Proposition \[prop:eta\] implies that $\eta \cdot \eta = -11\cdot 443$. In particular, $\left(\lambda,\lambda\right)=0$ is excluded.
Eliminating $a$ and $b$ from these equations and setting $L=\left(\lambda,\lambda\right)$, we obtain $$\label{eqn:elliptic}
2^{14}\cdot 3^2\cdot 11\cdot 443 d^2 = 5^2 L^3 + 2^5\cdot 3^2 L^2 + 2^8\cdot 5 L + 2^{16}\cdot 3\cdot 11.$$ We know, [*a priori*]{}, that $L \in {{\mathbb Z}}$ and $d\in {{\mathbb Q}}$.
The only solution to (\[eqn:elliptic\]) with $L \in {{\mathbb Z}}$ and $d\in {{\mathbb Q}}$ is $d=0$ and $L=-48$.
We assume this for the moment; its proof can be found in Section \[sect:DA\].
Back-substitution yields $$a=1/96, \quad b=1/384, \quad \left(\ell,\ell\right)=-3.$$ We claim that $\lambda/2 \in {\mathrm{H}}^2(X,{{\mathbb Z}})$, i.e., $\lambda$ is not primitive. Using the isomorphism $${\mathrm{H}}_2(X,{{\mathbb Z}})={\mathrm{H}}_2(S,{{\mathbb Z}}) \oplus_{\perp} {{\mathbb Z}}\delta^{\vee}, \quad
\left(\delta^{\vee},\delta^{\vee}\right)=-1/4$$ we can express $$\ell=D+m\delta^{\vee}, \quad D \in {\mathrm{H}}_2(S,{{\mathbb Z}}),m \in {{\mathbb Z}}.$$ If $\lambda$ were primitive then $m$ would have to be odd and $$-3=\left(\ell,\ell\right)=\left(D,D\right) - m^2 /4.$$ Since $\left(D,D\right) \in 2{{\mathbb Z}}$, we have a contradiction.
Diophantine analysis {#sect:DA}
====================
The only solution to $$2^{14}{\mathord{\cdot}}3^2{\mathord{\cdot}}11{\mathord{\cdot}}443 d^2 = 5^2 L^3 + 2^5{\mathord{\cdot}}3^2 L^2 + 2^8{\mathord{\cdot}}5 L + 2^{16}{\mathord{\cdot}}3{\mathord{\cdot}}11$$ with $L \in {{\mathbb Z}}$ and $d \in {{\mathbb Q}}$ is $L = -48$, $d = 0$.
Put $x = 2^{-4}{\mathord{\cdot}}5^2{\mathord{\cdot}}11{\mathord{\cdot}}443 (L + 48)$ and $y = 2{\mathord{\cdot}}3{\mathord{\cdot}}5^2{\mathord{\cdot}}11^2{\mathord{\cdot}}443^2d$. The equation then takes the form $$\label{eq:weierstrass}
E: y^2 = x^3 + ax^2 + bx$$ where $$a = -3^2{\mathord{\cdot}}11{\mathord{\cdot}}23{\mathord{\cdot}}443, \qquad b = 2^2{\mathord{\cdot}}5^2{\mathord{\cdot}}11^3{\mathord{\cdot}}13{\mathord{\cdot}}443^2.$$ It suffices to prove the stronger statement that there are no solutions to with $x, y \in {{\mathbb Z}}[\frac12]$, apart from $x = y = 0$.
The proof is given in two steps. Proposition \[prop:MW\] below determines explicitly the structure of the Mordell–Weil group $E({{\mathbb Q}})$. Proposition \[prop:integral\] then identifies the integral points.
Algorithms for both of these steps are implemented in computer algebra systems such as [Sage]{} [@sage-4.4.1] and [Magma]{} [@magma], and the theorem may be verified this way. To avoid depending on the correctness of these systems, we give alternative proofs that use as little machine assistance as possible. The only step that is perhaps unreasonable to verify by hand is that a certain point $P$ with large coordinates (about $30$ digits) lies in $E({{\mathbb Q}})$.
We first set notation and briefly recall some facts about point multiplication on elliptic curves. Let $O$ denote the zero element of $E({{\mathbb Q}})$ (the point at infinity). For nonzero $R \in E({{\mathbb Q}})$ we write $$R = (x(R), y(R)) = \left( \frac{\alpha(R)}{e(R)^2}, \frac{\beta(R)}{e(R)^3} \right),$$ where $\alpha, \beta, e \in {{\mathbb Z}}$, $e \geq 1$ and $(\alpha, e) = (\beta, e) = 1$.
Let $R \in E({{\mathbb Q}})$, $R \neq O$. If $p$ is a prime, then $p {\mathbin{|}}e(R)$ if and only if $R$ reduces to the identity in $E({{\mathbb F}}_p)$. If $m \geq 1$ and $mR \neq O$, then $e(R) {\mathbin{|}}e(mR)$. For $m = 2$ we have the following formula: $$\label{eq:double}
x(2R) = \frac{\alpha(2R)}{e(2R)^2} = \frac{(\alpha(R)^2 - b {\mathord{\cdot}}e(R)^4)^2}{4e(R)^2\big(\alpha(R)^3 + a {\mathord{\cdot}}\alpha(R)^2 e(R)^2 + b {\mathord{\cdot}}\alpha(R) e(R)^4\big)}.$$ Moreover, if $R$ reduces to a nonsingular point in $E({{\mathbb F}}_p)$, then $p$ cannot divide both the numerator and denominator of the fraction on the right side of . In other words, there is no cancellation locally at $p$. One proof of this is given in [@Wut-thesis Prop. IV.2]; as pointed out in that paper, it can also be proved from properties of real-valued non-archimedean local heights.
The discriminant of the Weierstrass equation is given by $$\Delta = 16b^2(a^2 - 4b) = -2^8 {\mathord{\cdot}}5^4 {\mathord{\cdot}}11^8 {\mathord{\cdot}}13^2 {\mathord{\cdot}}113 {\mathord{\cdot}}127 {\mathord{\cdot}}443^6,$$ so the model is minimal, and the primes of bad reduction are $2$, $5$, $11$, $13$, $113$, $127$ and $443$. For $p = 2, 5, 11, 13, 443$, we have that $p {\mathbin{|}}\alpha(R)$ if and only if $R$ reduces to a singular point of $E({{\mathbb F}}_p)$, i.e. the only singular point of $E({{\mathbb F}}_p)$ is $(0:0:1)$ for these primes. The point $Q = (0, 0)$ has order two, and addition with $Q$ is given by the formula $$\label{eq:add-Q}
R + Q = \left(\frac{b}{x(R)}, \frac{-b {\mathord{\cdot}}y(R)}{x(R)^2}\right).$$
\[prop:MW\] We have $E({{\mathbb Q}}) \cong {{\mathbb Z}}\times ({{\mathbb Z}}/2{{\mathbb Z}})$, where the free part is generated by the point $P$ with coordinates $$\left(\frac{2 {\mathord{\cdot}}3^2 {\mathord{\cdot}}11^2 {\mathord{\cdot}}83^2 {\mathord{\cdot}}443^2 {\mathord{\cdot}}6481^2}{7^4 {\mathord{\cdot}}41^2 {\mathord{\cdot}}71^2 {\mathord{\cdot}}193^2}, \frac{2 {\mathord{\cdot}}3 {\mathord{\cdot}}11^3 {\mathord{\cdot}}31 {\mathord{\cdot}}83 {\mathord{\cdot}}163 {\mathord{\cdot}}443^2 {\mathord{\cdot}}6481 {\mathord{\cdot}}240623 {\mathord{\cdot}}3691717}{7^6 {\mathord{\cdot}}41^3 {\mathord{\cdot}}71^3 {\mathord{\cdot}}193^3} \right)$$ and the torsion part by $Q = (0, 0)$.
We first check that the torsion subgroup is as described. We have $E({{\mathbb F}}_3) = {{\mathbb Z}}/2{{\mathbb Z}}\times {{\mathbb Z}}/2{{\mathbb Z}}$ and $E({{\mathbb F}}_{19}) = {{\mathbb Z}}/2{{\mathbb Z}}\times {{\mathbb Z}}/7{{\mathbb Z}}$. For $\ell$ prime, by [@Sil-AEC Prop. VII.3.1] we see that $E({{\mathbb Q}})[\ell]$ injects into $E({{\mathbb F}}_3)$ for $\ell \neq 3$ and that $E({{\mathbb Q}})[\ell]$ injects into $E({{\mathbb F}}_{19})$ for $\ell \neq 19$. These facts force $E({{\mathbb Q}})[2] = {{\mathbb Z}}/2{{\mathbb Z}}$, $E({{\mathbb Q}})[3] = 0$, and $E({{\mathbb Q}})[\ell] = 0$ for $\ell \neq 2, 3$. Hence $E_{{\text{tors}}}({{\mathbb Q}}) = \langle Q \rangle$.
Now we consider the free part. The point $P$ was found using Cremona’s mwrank library [@Cre-mwrank] included in [Sage]{} [@sage-4.4.1]. We may check that $P \in E({{\mathbb Q}})$ using a computer; this shows that ${\mathrm{rank}}\, E \geq 1$. (The point $P$ is reasonably difficult to find from scratch; indeed the standard functions for computing $E({{\mathbb Q}})$ in both [Magma]{} and [Sage]{} fail to find $P$.)
To show that ${\mathrm{rank}}E \leq 1$ we use a standard $2$-descent strategy (see for example [@ST-ratpoints Ch. III]). Consider the auxiliary curve $$E' : y^2 = x^3 - 2ax^2 + (a^2 - 4b)x.$$ There are isogenies $\phi : E \to E'$ and $\hat\phi : E' \to E$ of degree $2$, and injections $$\begin{gathered}
E({{\mathbb Q}})/\hat\phi(E'({{\mathbb Q}})) \overset{\psi}{{\hookrightarrow}} S \subset {{\mathbb Q}}^*/({{\mathbb Q}}^*)^2, \\
E'({{\mathbb Q}})/\phi(E({{\mathbb Q}})) \overset{\psi'}{{\hookrightarrow}} S' \subset {{\mathbb Q}}^*/({{\mathbb Q}}^*)^2,\end{gathered}$$ where $S$ consists of the cosets $\delta({{\mathbb Q}}^*)^2$ for $\delta {\mathbin{|}}2 {\mathord{\cdot}}5 {\mathord{\cdot}}11 {\mathord{\cdot}}13 {\mathord{\cdot}}443$, and $S'$ of the cosets for $\delta {\mathbin{|}}11 {\mathord{\cdot}}113 {\mathord{\cdot}}127 {\mathord{\cdot}}443$ (these are the primes dividing $b$ and $a^2 - 4b$ respectively). We must determine which elements of $S$ and $S'$ arise from points in $E({{\mathbb Q}})$ and $E'({{\mathbb Q}})$. This is achieved by testing for the existence of rational points on the two families of quartic curves $$\begin{gathered}
\notag
C_\delta : \delta w^2 = \delta^2 z^4 + \delta a z^2 + b, \qquad \delta \in S, \\
\label{eq:Cprime}
C'_\delta : \delta w^2 = \delta^2 z^4 - 2\delta a z^2 + (a^2 - 4b), \qquad \delta \in S'.\end{gathered}$$
We first consider the $C'_\delta$. If $443 {\mathbin{|}}\delta$ then has no solution in ${{\mathbb Q}}_{443}$; if $(\delta/5) = -1$ then it has no solution in ${{\mathbb Q}}_5$; and if $\delta \neq 1 \pmod 8$ then it has no solution in ${{\mathbb Q}}_2$. These conditions rule out all but $\delta = 1$ and $\delta = -113{\mathord{\cdot}}127$. These correspond to the classes in $E'({{\mathbb Q}})/\phi(E({{\mathbb Q}}))$ of $O$ and the unique two-torsion point of $E'({{\mathbb Q}})$; both have trivial image in $\hat\phi(E'({{\mathbb Q}}))/2E({{\mathbb Q}})$.
Now we examine the $C_\delta$. For $\delta = 11{\mathord{\cdot}}13$ there is the trivial rational point $z = 0$, $w = 2{\mathord{\cdot}}5{\mathord{\cdot}}11{\mathord{\cdot}}443$, corresponding to the class of $Q$ in $E({{\mathbb Q}})/\hat\phi(E'({{\mathbb Q}}))$. For $\delta = 2$ there is a (highly nontrivial) rational point corresponding to $P$, namely $z = (\frac 12x(P))^{1/2}$, $w = y(P) (2x(P))^{1/2}$. Rational points are automatic for $\delta = 1$ and $\delta = 2{\mathord{\cdot}}11{\mathord{\cdot}}13$ since the image of $\psi$ is a subgroup of $S$. We will show that $C_\delta({{\mathbb Q}}) = \emptyset$ for all other $\delta$.
Rewriting the equation for $C_\delta$ as $4\delta w^2 = (2\delta z^2 + a)^2 - (a^2 - 4b)$, we see immediately that $\delta > 0$ since $a^2 - 4b < 0$. Next, note that $(p/113) = 1$ for $p = 2, 11, 13, 443$, but $(5/113) = -1$. Thus if $5 {\mathbin{|}}\delta$ we have $(\delta/113) = -1$; this is impossible as $v_{113}(a^2 - 4b) = 1$. Therefore $5 {\nmid}\delta$.
To finish the argument for the $C_\delta$ it suffices to show that $C_\delta({{\mathbb Q}}) = \emptyset$ for $\delta = 11$, $443$ and $11{\mathord{\cdot}}443$; the statement for the remaining $\delta$ will then follow automatically from the subgroup property.
Let $\delta = 11$, $443$, or $11{\mathord{\cdot}}443$. Let $u = z^2$ and let $(u, w) = (u_0/t, w_0/t)$ be a rational point on the conic $\delta w^2 = \delta^2 u^2 + \delta a u + b$, where $u_0, w_0, t \in {{\mathbb Z}}$. Intersecting the conic with a line of slope $X/Y$ through $(u_0/t, w_0/t)$, we obtain the parameterization $z^2 = f(X,Y)/g(X,Y)$ where $$\begin{aligned}
f(X, Y) & = u_0 X^2 - 2w_0 XY + (ta + \delta u_0)Y^2, \\
g(X, Y) & = t(X^2 - \delta Y^2),\end{aligned}$$ and where we may assume that $X, Y \in {{\mathbb Z}}$ and $(X, Y) = 1$. Taking resultants, we find that any prime $p$ dividing $f(X, Y)$ and $g(X, Y)$ must divide $t$ or $a^2 - 4b = -11^2{\mathord{\cdot}}113{\mathord{\cdot}}127{\mathord{\cdot}}443^2$. Thus $$\begin{aligned}
\label{eq:eps-1}
f(X, Y) & = {\varepsilon}Z^2, \\
\label{eq:eps-2}
g(X, Y) & = {\varepsilon}W^2\end{aligned}$$ for some ${\varepsilon}{\mathbin{|}}11{\mathord{\cdot}}113{\mathord{\cdot}}127{\mathord{\cdot}}443 t$, and some $W, Z \in {{\mathbb Z}}$. We now consider each $\delta$ in turn, summarizing the local obstructions encountered for each possible ${\varepsilon}$.
Let $\delta = 11$. We take $u_0 = 3 {\mathord{\cdot}}5^2 {\mathord{\cdot}}443$, $w_0 = 2^2 {\mathord{\cdot}}5 {\mathord{\cdot}}11 {\mathord{\cdot}}443$, $t = 1$. Then ${\varepsilon}{\mathbin{|}}11{\mathord{\cdot}}113{\mathord{\cdot}}127{\mathord{\cdot}}443$. If $443 {\mathbin{|}}{\varepsilon}$ then has no solution in ${{\mathbb Q}}_{443}$. If $11 {\mathbin{|}}{\varepsilon}$ then has no solution in ${{\mathbb Q}}_{11}$. If $({\varepsilon}/11) = -1$ then has no solution in ${{\mathbb Q}}_{11}$. This leaves ${\varepsilon}\in \{1, 113, -127, -113{\mathord{\cdot}}127\}$. For these ${\varepsilon}$ we have $({\varepsilon}/443) = 1$. Equation implies that $X = 14Y$ or $X = 110Y \pmod{443}$; both options contradict .
Now consider $\delta = 443$. We take $u_0 = -3 {\mathord{\cdot}}11 {\mathord{\cdot}}13$, $w_0 = 11 {\mathord{\cdot}}13 {\mathord{\cdot}}443$, $t = 2$. Then ${\varepsilon}{\mathbin{|}}2{\mathord{\cdot}}11{\mathord{\cdot}}113{\mathord{\cdot}}127{\mathord{\cdot}}443$. Suppose that $443 {\nmid}{\varepsilon}$. If $({\varepsilon}/443) = 1$ then has no solution in ${{\mathbb Q}}_{443}$, and if $({\varepsilon}/443) = -1$ then has no solution in ${{\mathbb Q}}_{443}$. Now let ${\varepsilon}= 443{\varepsilon}'$. If $({\varepsilon}'/443) = -1$ then has no solution in ${{\mathbb Q}}_{443}$. Now assume that $({\varepsilon}'/443) = 1$. Observe that $(p/443) = (p/11)$ for $p \in \{-1, 2, 113, 127\}$, but $(11/443) = -1$. This implies that either $11 {\nmid}{\varepsilon}'$ and $({\varepsilon}'/11) = 1$, or $11 {\mathbin{|}}{\varepsilon}'$ and $(\frac{{\varepsilon}'}{11}/11) = -1$. In both cases, forces $Y = 10X \pmod{11}$, and this contradicts .
Finally let $\delta = 11{\mathord{\cdot}}443$. We take $u_0 = 5^3 {\mathord{\cdot}}11$, $w_0 = 2 {\mathord{\cdot}}5 {\mathord{\cdot}}11 {\mathord{\cdot}}443$, $t = 3^2$. Then ${\varepsilon}{\mathbin{|}}3{\mathord{\cdot}}11{\mathord{\cdot}}113{\mathord{\cdot}}127{\mathord{\cdot}}443$. If $11 {\nmid}{\varepsilon}$ then there are no solutions to in ${{\mathbb Q}}_{11}$. Suppose that $11 {\mathbin{|}}{\varepsilon}$. Then since $(p/13) = 1$ for $p \in \{-1, 3, 113, 127, 443\}$ and $(11/13) = -1$, we have $({\varepsilon}/13) = -1$; then has no solution in ${{\mathbb Q}}_{13}$.
This completes the $2$-descent. In particular, we have found that $$|E({{\mathbb Q}})/2E({{\mathbb Q}})| = |E({{\mathbb Q}})/\hat\phi(E'({{\mathbb Q}}))| \cdot |\hat\phi(E'({{\mathbb Q}}))/2E({{\mathbb Q}})| = 4 \cdot 1 = 4,$$ and that $E({{\mathbb Q}})/2E({{\mathbb Q}})$ is generated by $P$ and $Q$. Moreover, for $R \neq O, Q$ the image of $x(R)$ in ${{\mathbb Q}}^*/({{\mathbb Q}}^*)^2$ is one of $\{1, 2, 11{\mathord{\cdot}}13, 2{\mathord{\cdot}}11{\mathord{\cdot}}13\}$.
At this stage we know that $\langle P, Q \rangle$ is of finite index in $E({{\mathbb Q}})$; we must still check that it exhausts $E({{\mathbb Q}})$. Suppose not; then for some prime $\ell$ and some $R \in E({{\mathbb Q}})$ we have $\ell R = P$ or $\ell R = P + Q$. We cannot have $2R = P$ as $P$ is not divisible by $2$ in $E({{\mathbb F}}_3$); similarly $2R = P + Q$ is excluded by considering $E({{\mathbb F}}_7)$. Thus we may assume that $\ell$ is odd. If $\ell R = P + Q$ we replace $R$ by $R + Q$, so now may assume that $\ell R = P$ and $\ell (R+Q) = P + Q$.
In this case $e(R) {\mathbin{|}}e(P) = 7^2 {\mathord{\cdot}}41 {\mathord{\cdot}}71 {\mathord{\cdot}}193$. From we have $$x(P + Q) = \frac{2 {\mathord{\cdot}}5^2 {\mathord{\cdot}}7^4 {\mathord{\cdot}}11 {\mathord{\cdot}}13 {\mathord{\cdot}}41^2 {\mathord{\cdot}}71^2 {\mathord{\cdot}}193^2}{3^2 {\mathord{\cdot}}83^2 {\mathord{\cdot}}6481^2},$$ so similarly $e(R + Q) {\mathbin{|}}3 {\mathord{\cdot}}83 {\mathord{\cdot}}6481$. Moreover by we have $$\alpha(R) \alpha(R+Q) = b {\mathord{\cdot}}e(R)^2 e(R+Q)^2.$$ Since $(\alpha(R), e(R)) = (\alpha(R+Q), e(R+Q)) = 1$ this implies that $\alpha(R) = b_1 e(R+Q)^2$ and $\alpha(R+Q) = (b/b_1) e(R)^2$ for some $b_1 {\mathbin{|}}b$. Since $P$ has singular reduction at $p = 2, 11, 443$, so does $R$, so $2{\mathord{\cdot}}11{\mathord{\cdot}}443 {\mathbin{|}}b_1$. Similarly we find that $2{\mathord{\cdot}}5{\mathord{\cdot}}11{\mathord{\cdot}}13 {\mathbin{|}}(b/b_1)$. Comparing with the classes of ${{\mathbb Q}}^*/({{\mathbb Q}}^*)^2$ found by the $2$-descent shows that we must have $b_1 = 2{\mathord{\cdot}}11^2{\mathord{\cdot}}443^2$ and $b/b_1 = 2{\mathord{\cdot}}5^2{\mathord{\cdot}}11{\mathord{\cdot}}13$.
At this point we have reduced to $24$ possibilities for $e(R)$ and $8$ possibilities for $\alpha(R)$, and it is straightforward to check using a computer that the only pair defining a point on $E({{\mathbb Q}})$ is $R = P$. Alternatively one may finish the argument using congruences. We sketch one quick way to do it: first prove that $3 {\mathbin{|}}\alpha(R)$ by considering images in $E({{\mathbb F}}_3)$. Then for only 10 remaining values of $x(R)$ is $x^3 + ax^2 + bx$ a square in ${{\mathbb Q}}_{11}$, and for only one of these is it a square in ${{\mathbb Q}}_{31}$.
\[prop:integral\] The only solution to with $x, y \in {{\mathbb Z}}[\frac12]$ is $x = y = 0$.
Let $n \in {{\mathbb Z}}$, $k \in \{0, 1\}$. We must prove that $x(nP + kQ) \notin {{\mathbb Z}}[\frac12]$ for $n \neq 0$. We consider several cases.
First suppose that $k = 0$ and $n \neq 0$. Since $7 {\mathbin{|}}e(P)$, also $7 {\mathbin{|}}e(nP)$, so $x(nP) \notin {{\mathbb Z}}[\frac12]$.
Next suppose that $k = 1$ and that $n$ is odd. Since $3 {\mathbin{|}}e(P + Q)$, we have $3 {\mathbin{|}}e(n(P + Q)) = e(nP + Q)$, so $x(nP + Q) \notin {{\mathbb Z}}[\frac12]$.
Now suppose that $k = 1$ and $n = 2r$ where $r$ is odd. Since $79 {\mathbin{|}}e(2P + Q)$, we have $79 {\mathbin{|}}e(r(2P + Q)) = e(nP + Q)$, so $x(nP + Q) \notin {{\mathbb Z}}[\frac12]$.
The last case is $k = 1$, $n = 0 \pmod 4$, $n \neq 0$. Write $n = 2^i r$ for some $i \geq 2$ and odd $r$. To continue the pattern we must find a prime $q$ playing the same role as $79$ from the previous case. For this, we first establish that $$\label{eq:mod7}
\alpha(2^j P) = \pm 4 \pmod 7 \qquad \text{for $j \geq 2$.}$$ Indeed, one checks that $4P$ has nonsingular reduction for all $p$. The doubling formula and the comments regarding cancellation immediately following it then imply that $\alpha(2^{j+1}P) = \pm (\alpha(2^j P)^2 - b e(2^j P)^4)^2$ for all $j \geq 2$. Since $7 {\mathbin{|}}e(2^j P)$ and $\alpha(4P) = \pm 4 \pmod 7$, identity follows by induction.
In particular $\alpha(2^i P) = \pm 4 \pmod 7$, so there must exist some prime $q$, not congruent to $1$ modulo $7$, dividing $\alpha(2^i P)$. We cannot have $q = 113$ or $q = 127$, as both of these are $1 \pmod 7$. Also, $q \notin \{2, 5, 11, 13, 443\}$, since for all of these primes the point $(0:0:1)$ is singular in $E({{\mathbb F}}_p)$, whereas $2^i P$ has nonsingular reduction for all $p$. Therefore $q$ is not a prime of bad reduction. From we obtain $q {\mathbin{|}}e(2^i P + Q)$. Finally, since $nP + Q = r(2^i P + Q)$, we have also $q {\mathbin{|}}e(nP + Q)$, so that $x(nP + Q) \notin {{\mathbb Z}}[\frac12]$.
In several places in the above proof we use certain facts about $2P$ and $4P$. It is not necessary to compute their full coordinates, which are quite large (for example $\alpha(4P)$ has 256 digits). In every case it is possible to work $p$-adically to low precision. For example, to check that $4P$ has nonsingular reduction at $2$, it suffices to apply the doubling formula twice, using as input $a = 1 \pmod{2^3}$, $b = 28 \pmod{2^5}$ and $x(P) = 2 \pmod{2^4}$, to find that $x(2P) = 4 \pmod{2^5}$ and $x(4P) = 2^{-4} \pmod{2^{-3}}$.
|
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"pile_set_name": "ArXiv"
}
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Half A Day In Kyoto
Given its deserved reputation as the centre of traditional culture in Japan, it’s almost redundant to say that Kyoto has more than its fair share of sightseeing spots and landmarks for any tourist, whether local or international, to enjoy. However, as anyone who has ever cracked open a guidebook to the area will surely testify, the sheer amount of temples, shrines and castles in Kyoto city and its surrounding area can initially feel quite daunting, especially if you’re only stopping off as part of a larger tour of the country or simply on a whirlwind weekend visit.
However, the volume of places to visit also means that certain parts have a high density of spots that you’ll surely want to see, so, with careful planning, anyone can easily check off two or three of Kyoto’s highlights in as little as half a day with relatively little fuss. In this article, you’ll find how you can visit Kinkakuji, Ryoan-ji and Ninna-ji, three of the seventeen locations listed as part of the Historic Monuments of Ancient Kyoto on UNESCO’s World Heritage Sites list, in half a day.
Kinkaku-ji (The Temple of the Golden Pavillion)
Arguably the most famous of Kyoto’s zen temples, and home to one of the most popular buildings in Japan, Kinkaku-ji is swarmed by tourists from all over the world all year round and is one of the first places people think of when they think of Kyoto. It’s most famous and iconic structure, the Golden Pavillion, was rebuilt in the 1950s after it was the victim of an arson attack by a monk, an event fictionalized by Yukio Mishima in The Temple of the Golden Pavillion and its subsequent film adaptation by Kon Ishikawa. Despite its relative youth, the pavilion is still a sight to behold and an absolute must for anyone stepping foot in Japan, never mind Kyoto.
Open from 9am, and located in Northern Kyoto, Kinkaku-ji is isolated from the city’s limited subway system but can easily be reached by bus; the quickest way to get there is to use the subway Karasuma line to go north up to Kitaoji Station (15 minutes and Y260 from Kyoto Station) before switching to the 101, 102, 204 or 205 numbered buses (10 minutes and Y230). Getting off at Kinkakujimae bus stop will place you directly across from the entrance into the temple grounds, with entry costing just Y400. Luckily for tourists, an informative brochure, that will help you appreciate Kinkaku-ji’s numerous features a little more, is included in the ticket price. Once through the gate, you’ll find yourself almost immediately facing the beautiful gold-plated pavilion itself, each floor representing a different style of architecture, as it presides over the beautiful kyoko-chi, or mirror pond, so called because it provides a beguiling reflection of the central structure.
Even though the main attraction of the temple is the first thing you see, that’s not to say the remainder of the site is an anti-climax. Laid out as a strolling garden, you can slowly ease your way around and past the pavilion towards the other, less extravagant sights on show, such as the hojo (the former priest’s living quarters), An-min-taku pond, and a small group of statues which people throw coins at as it is believed to bring good luck. This leads into a brief uphill walk, at the peak of which you can enjoy the sight of the pavillion’s roof poking above the tops of the trees, and then the Sekkatei Tea House. The house was built in honour of an imperial visit in the 17th century and has a purposefully plain appearance in order for those drinking there to focus on the tea itself, rather than their surroundings; a common feature of traditional Japanese tea culture.
Across from Sekkai Teahouse you will find a small souvenir shop, mainly selling charms and other mementos, before you exit the paid grounds. If you like, from here you can partake in refreshments at the small tea garden or from the ubiquitous vending machines, check out another, larger, souvenir shop, or take a brief stop at Fudo Hall, a small Buddhist temple, and perhaps light one of the numerous charm candles for sale on the left side of the hall. As soon as you are ready to leave, it’s time to move onto Ryoan-ji and its renowned rock garden.
Ryoan-ji (The Temple of the Dragon at Peace)
After leaving Kinkaku-ji, walk back to the road where you got off the bus and turn right to start heading towards Ryoan-ji; it’s a pleasant 20-minute walk westward which allows you to get a feel for the more relaxed atmosphere of northern Kyoto. Eventually you’ll reach San-Mon, the main gate into the temple grounds, and, upon entry, you will be greeted by Kyoyo-chi pond and it’s surrounding strolling garden. Kyoyo-chi’s three small, accessible islands, and the fact that the grounds are a little more spacious and a little less busy than Kinkaku-ji allows for more room for a relaxed stroll that you can enjoy at your pace. Additionally, if you find yourself wanting to something to eat it’s possible to try Yudofu, a Kyoto speciality, at a small tatami-matted restaurant.
After you’ve finished soaking up the atmosphere, it’s time to move on to the main reason for coming. Heading north through Chokushi-Mon, pay the Y500 fee and you will enter into the Kuri, the temple’s main building. Although a number of places of interest are unfortunately, closed off to the public, you can still see the abbot’s chamber before heading straight to the famed Kare-sansui Zen Rock Garden.
Built to be viewed from a seated position on the hojo veranda, Kare-sansui has gained its reputation partly thanks to its ambiguity. A history muddied by uncertainty as to when exactly it was built and by whom, plus the fact it was reconstructed after a fire in the late 18th century, has resulted in the intention and the meaning behind the garden’s idiosyncratic layout being lost to the ages. The garden is made up of fifteen stones (some sources place the garden as originally containing nine stones, so it is unknown when, and where, the additional six were placed), only fourteen of which can be seen at anyone time, denying any viewer a perfect view of the garden. This has led to a great amount of discussion as to what the implicit meaning of purposefully obscuring at least one stone at any given angle (save from above, of course) is, though perhaps the simplest answer is the traditional adage that one can not see the complete garden until full enlightenment is achieved. Regardless, as with any piece of art, the true meaning of Kare-sansui is down to the individual and there are a lot of interesting theories, from academic to spiritual, that are out there to be found if such things grab your interest.
Ninna-ji
Assuming you started your half-day journey through Northen Kyoto at 9am, the time will probably now be around 11:00am, giving you just enough time to check out one more place before you have lunch. By exiting Ryoan-ji the same way you came in and carrying on down the same road as before, you’ll soon come across Ninna-Ji, a temple located to the south-west, less than 10 minutes away; it’s hard to miss thanks to the huge wooden gate standing at its entrance.
Entrance into Ninna-ji’s grounds is free (except for during Cherry Blossom season, when a Y500 fee is charged). Upon walking through the Nio-mon gate, you have a choice to make. If you look to your left you will see the entrance to the Goton Palace and it’s associated gardens. This is one of two parts of Ninna-ji that you will have to pay to see, (the other being Reiho-kan Hall which you will see ahead to your right) though the Y500 fee is more than worth it as the Goton Palace Gardens are, rightly, considered the highlight of what Ninna-ji has to offer. If, however, you don't want to pay any money then Ninna-ji still has a significant amount of sights to see, including the Kon-do, a Japanese national treasure, and a five-storied pagoda; the first pagoda of the three temples you will have visited on your sojourn through Northern Kyoto’s world heritage sites.
Near to Kon-do you will always also see the temple’s famous grove of Omura Zakura cherry trees, which were planted in the 17th century, when a significant proportion of the temple had to be rebuilt following it being destroyed during the Onin War 150 years previously. With a varied selection of sights to see and an interesting and varied history, Ninna-ji is a worthy, if relatively unheralded, place to visit and acts as a nice cap to your half-day in Kyoto’s northern sector.
So, with the morning trek completed you’re surely in the mood for something to eat and drink. From here, it’s probably most efficient to catch the JR Bus back to Kyoto station, which costs just Y230 and takes thirty minutes. However, if you want to continue exploring outside of central Kyoto, you can catch a train to beautiful Arashiyama by using the nearby Kiefuku Kitano line. The choice, as they say is yours.
|
{
"pile_set_name": "Pile-CC"
}
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/* -*- Mode: C++; tab-width: 4; indent-tabs-mode: nil; c-basic-offset: 4 -*- */
/*
* This file is part of the LibreOffice project.
*
* This Source Code Form is subject to the terms of the Mozilla Public
* License, v. 2.0. If a copy of the MPL was not distributed with this
* file, You can obtain one at http://mozilla.org/MPL/2.0/.
*
* This file incorporates work covered by the following license notice:
*
* Licensed to the Apache Software Foundation (ASF) under one or more
* contributor license agreements. See the NOTICE file distributed
* with this work for additional information regarding copyright
* ownership. The ASF licenses this file to you 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 .
*/
#ifndef INCLUDED_SAL_OSL_UNX_BACKTRACE_H
#define INCLUDED_SAL_OSL_UNX_BACKTRACE_H
#if defined (LINUX)
#include <execinfo.h>
#else
#ifdef __cplusplus
extern "C" {
#endif
/* backtrace function with same behaviour as defined in GNU libc */
int backtrace( void **buffer, int max_frames );
char ** backtrace_symbols(void * const * buffer, int size);
void backtrace_symbols_fd( void **buffer, int size, int fd );
/* no frame.h on FreeBSD */
#if defined (FREEBSD) || defined (NETBSD) || defined (OPENBSD) || \
defined (DRAGONFLY)
struct frame {
struct frame *fr_savfp;
long fr_savpc;
};
#endif
#ifdef __cplusplus
} /* extern "C" */
#endif
#endif
#endif
/* vim:set shiftwidth=4 softtabstop=4 expandtab: */
|
{
"pile_set_name": "Github"
}
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Young and old porn
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{
"pile_set_name": "Pile-CC"
}
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/*!
* 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.
*/
@mixin columns($arg: auto) {
// <column-count> || <column-width>
@include prefixer(columns, $arg, webkit moz spec);
}
@mixin column-count($int: auto) {
// auto || integer
@include prefixer(column-count, $int, webkit moz spec);
}
@mixin column-gap($length: normal) {
// normal || length
@include prefixer(column-gap, $length, webkit moz spec);
}
@mixin column-fill($arg: auto) {
// auto || length
@include prefixer(column-fill, $arg, webkit moz spec);
}
@mixin column-rule($arg) {
// <border-width> || <border-style> || <color>
@include prefixer(column-rule, $arg, webkit moz spec);
}
@mixin column-rule-color($color) {
@include prefixer(column-rule-color, $color, webkit moz spec);
}
@mixin column-rule-style($style: none) {
// none | hidden | dashed | dotted | double | groove | inset | inset | outset | ridge | solid
@include prefixer(column-rule-style, $style, webkit moz spec);
}
@mixin column-rule-width ($width: none) {
@include prefixer(column-rule-width, $width, webkit moz spec);
}
@mixin column-span($arg: none) {
// none || all
@include prefixer(column-span, $arg, webkit moz spec);
}
@mixin column-width($length: auto) {
// auto || length
@include prefixer(column-width, $length, webkit moz spec);
}
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{
"pile_set_name": "Github"
}
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Hymod Board Database
(C) Copyright 2001
Murray Jensen <Murray.Jensen@csiro.au>
CSIRO Manufacturing Science and Technology, Preston Lab
25-Jun-01
This stuff is a set of PHP/MySQL scripts to implement a custom board
database. It will need *extensive* hacking to modify it to keep the
information about your custom boards that you want, however it is a good
starting point.
How it is used:
1. a board has gone through all the hardware testing etc and is
ready to have the flash programmed for the first time - first you
go to a web page and fill in information about the board in a form
to register it in a database
2. the web stuff allocates a (unique) serial number and (optionally)
a (locally administered) ethernet address and stores the information
in a database using the serial number as the key (can do whole
batches of boards in one go and/or use a previously registered board
as defaults for the new board(s))
3. it then creates a file in the tftp area of a server somewhere
containing the board information in a simple text format (one
per serial number)
4. all hymod boards have an i2c eeprom, and when U-Boot sees that
the eeprom is unitialised, it prompts for a serial number and
ethernet address (if not set), then transfers the file created
in step 3 from the server and initialises the eeprom from its
contents
What this means is you can't boot the board until you have allocated a serial
number, but you don't have to type it all twice - you do it once on the web
and the board then finds the info it needs to initialise its eeprom. The
other side of the coin is the reading of the eeprom and how it gets passed
to Linux (or another O/S).
To see how this is all done for the hymod boards look at the code in the
"board/hymod" directory and in the file "include/asm/hymod.h". Hymod boards
can have a mezzanine card which also have an eeprom that needs allocating,
the same process is used for these as well - just a different i2c address.
Other forms provide the following functions:
- browsing the board database
- editing board information (one at a time)
- maintaining/browsing a (simple) per board event log
You will need: MySQL (I use version 3.23.7-alpha), PHP4 (with MySQL
support enabled) and a web server (I use Apache 1.3.x).
I originally started by using phpMyBuilder (http://kyber.dk/phpMyBuilder)
but it soon got far more complicated than that could handle (but I left
the copyright messages in there anyway). Most of the code resides in the
common defs.php file, which shouldn't need much alteration - all the work
will be in shaping the front-end php files to your liking.
Here's a quick summary of what needs doing to use it for your boards:
1. get phpMyAdmin (http://phpwizard.net/projects/phpMyAdmin/) - it's an
invaluable tool for this sort of stuff (this step is optional of course)
2. edit "bddb.css" to your taste, if you could be bothered - I have no
idea what is in there or what it does - I copied it from somewhere else
("user.css" from the phpMyEdit (http://phpmyedit.sourcerforge.net) package,
I think) - I figure one day I'll see what sort of things I can change
in there.
3. create a mysql database - call it whatever you like
4. edit "create_tables.sql" and modify the "boards" table schema to
reflect the information you want to keep about your boards. It may or
may not be easier to do this and the next step in phpMyAdmin. Check out
the MySQL documentation at http://www.mysql.com/doc/ in particular the
column types at http://www.mysql.com/doc/C/o/Column_types.html - Note
there is only support for a few data types:
int - presented as an html text input
char/text - presented as an html text input
date - presented as an html text input
enum - presented as an html radio input
I also have what I call "enum_multi" which is a set of enums with the
same name, but suffixed with a number e.g. fred0, fred1, fred2. These
are presented as a number of html select's with a single label "fred"
this is useful for board characteristics that have multiple items of
the same type e.g. multiple banks of sdram.
5. use the "create_tables.sql" file to create the "boards" table in the
database e.g. mysql dbname < create_tables.sql
6. create a user and password for the web server to log into the MySQL
database with; give this user select, insert and update privileges
to the database created in 3 (and delete, if you want the "delete"
functions in the edit forms to work- I have this turned off). phpMyAdmin
helps in this step.
7. edit "config.php" and set the variables: $mysql_user, $mysql_pw, $mysql_db,
$bddb_cfgdir and $bddb_label - keep the contents of this file secret - it
contains the web servers username and password (the three $mysql_* vars
are set from the previous step)
8. edit "defs.php" and a. adjust the various enum value arrays and b. edit
the function "pg_foot()" to remove my email address :-)
9. do major hacking on the following files: browse.php, doedit.php, donew.php,
edit.php and new.php to reflect your database schema - fortunately the
hacking is fairly straight-forward, but it is boring and time-consuming.
These notes were written rather hastily - if you find any obvious problems
please let me know.
|
{
"pile_set_name": "Github"
}
|
Failure analysis of explanted sternal wires.
To classify and understand the mechanisms of surface damages and fracture mechanisms of sternal wires, explanted stainless steel sternal wires were collected from patients with sternal dehiscence following open-heart surgery. Surface alterations and fractured ends of sternal wires were examined and analyzed. Eighty fractured wires extracted from 25 patients from January 1999 to December 2003, with mean implantation interval of 55+/-149 days (range 5-729 days) after cardiac surgery, were studied by various techniques. The extracted wires were cleaned and the fibrotic tissues were removed. Irregularities and fractured ends were assayed by a scanning electron microscopy. After stereomicroscopy and documentation, the explants were cleaned with 1% sodium hypochlorite to remove the blood and tissues and was followed by cleaned with deionized water and alcohol. The explants were examined by stereomicroscopy, and irregularities on surface and fracture surfaces of sternal wires were assayed by scanning electron microscopy, energy dispersive X-ray analysis (EDAX) and X-ray mapping. The explants with surrounding fibrotic tissue were stained and examined with stereomicroscopy and transmission electronic microscopy. Corrosion pits were found on the surface of explanted sternal wires. EDAX and X-ray mapping examinations revealed diminution of nickel concentration in the severely corroded pits on sternal wires. A feature of transgranular cracking was observed for stress corrosion cracking and striation character for typical corrosion fatigue was also identified. TEM examination of tissue showed the metallic particles in phagolysosomes of macrophages inside the surrounding sternal tissue. The synergic effect of hostile environment and the stress could be the precursors of failures for sternal wires.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
An Idiot's Guide to Beating Your Wife
Warning: I’m NG Hatfield and I’m a jokester. Not only that, I’m a kidder. I’m also a trickster, a clown, a con artist, a swindler, a cheat, a charlatan, a slippery customer, and an avid fan of Microsoft Word’s shift+F7 feature. Go ahead, try it on.
That said, I should warn you that I’ve been dubbed not only a douchebag, but a funny douchebag. Which makes sense to me. I laugh at all sorts of shit, and I make light of the worst in people. At the same time, though, I say things out of place and generally with a strange timing; so, sometimes, listeners and readers actually take me seriously.
For instance, today, I looked at a news report of a baby being fried in a microwave by her mother. Then, I looked for the humor (mind you, I didn’t have to look very far). I began writing this article and then thought of the phrase: “Mother Sues Microwave Company Because Popcorn Option Doesn’t Fully Pop Baby.” And that’s funny. I just thought of it. And now that I’m bragging about it, you can see that the “huge douchebag” argument against me holds a substantial amount of water.
“A bag of oranges leaves no bruises. So what’s the fun in that?”
Regardless, this week, I decided to do a little something different. Something that is funny, but also embraces the douchebaggery that engulfs me, to the deepest parts of my soul.
You’ll like it, or I’m not a douchebag.
An Idiot’s Guide to Beating Your Wife
Picture this: It’s 5 o’clock and the whistle blows. Time to go home. You get in your middle-income SUV that your wife insisted you buy instead of that black Mazda RX8 with the sound system and wearily head home. You pull up your driveway, and the garage isn’t spotless. You see oil stains and smell discarded tampons baking in the trashcan beside the heater. Inside, your wife frowns, throws a plate of cold, burnt pork chops and begins bitching at you for leaving your underwear on the floor.
When you were dating, she waited on you hand and foot. You got a blowjob every night, and when you fucked, it was great because she stayed in shape for you. Now, you’re used to flabby, pale thighs and boobs that droop to disgustingly low depths. You’re used to biting your tongue when her sister says something so fucking retarded that your head might explode. You’re her whipping boy, bitch. You’re the modern, real-life version of Kunta Kinte.
You have two choices now. One: sit there and take like it Whitney Houston. Or two: give her an excellent reason to shut the fuck up, clean up the garage, put the kibosh to her goddamned menstrual cycle and give you that pussy like it’s your bowl of Lucky Charms. If you, like myself, have any sort of testosterone in your bloodstream, you realize what needs done. The bitch needs hit.
Sure, some may say that spousal abuse is horrible. That men who “resort to it” are cowards and should be punished to the full extent of the law.
I disagree.
I think that beating your wife should be not only legal, but embraced. I think, also, that it should be lawful to beat other men’s wives, girlfriends, daughters and concubines, when warranted. I also think that nothing proves manliness quite like thrashing things that are weaker than you. Small children, for instance.
So, in this piece I hope I’ll be able to give you a few great techniques of getting the most out of your wife, and even promote the idea that domestic violence is cool.
Let’s get started, shall we?
First, in order to properly thump your wife, you must successfully remove any doubt that what you’re doing is morally wrong. After all, we don’t want you holding back.
Consider these facts…
-Women caused the fall of humanity.
-Women are fickle.
-Women get abortions.
-Women like salad more than meat.
-Hillary Clinton.
And if you need more convincing than that, think about this: For the last 60 plus years, women have been shrieking like banshees for “equal rights.” Yet, they still aren’t eligible for the draft. They still get the majority of sympathy in a courtroom. They still have cleaner, more welcoming public bathrooms than we do (bathrooms including cappuccino machines and full living room sets, provided by Ethan Allen). They have all of the benefits and none of the responsibilities of equal rights.
And it’s not us men who say shit about it; it’s women who vilify spousal abuse. Think about it… who is dubbed “The Most Powerful Woman in America?” Oprah. That’s right. Oprah fucking Winfrey. And if you’d take two seconds to turn on her shitty program, you’d see that all she bitches is about is the “pain” and “anguish” caused by “abusive men.” She actually demonizes guys like you or me. She makes it not okay to beat your wife. I say FUCK YOU, OPRAH.
I mean really guys, do you want to start listening to her, now? Do you want to have to start respecting black women? Do you want, once a month, to read some horrible, hackneyed book about finding your vagina empowering? Do you want to trash all those high-res pictures of a 13-year-old Jennifer Love Hewitt rubbing her beautiful pink pussy? I’m not willing to make that sort of sacrifice. I have a feeling you agree.
If you don’t agree, I’ve got one more piece of straw that might break the camel’s back (ironically allowing you to break your wife’s back with great vehemence). That is, on a more personal level, you may notice these simple facts: Your wife paints her face like a whore. She’s getting fat and her ass looks like an unfortunately-shaped balloon. Hell, the bitch has always been about as intelligent as the majority of Tucker Max’s fans.
Face it buddy, your wife is an inflatable clown dummy. She has no worth to you other than maybe receiving a few kicks to the kidneys every now and then; and yet, the bitch still thinks that you owe her the “respect” of not cleaning out her clock. Well guess what? It’s time to set things straight: you’re the man and she’s the woman. “Wo-” means “lesser than” and I’ll be goddamned if I know a single man out there who does not abide by the basic fundamentals of mathematics.
If she thinks it’s her responsibility to do anything other than cook, clean and conceive your children… if she does anything at all that you feel is unwomanly… then, my good man, it’s time to beat your wife.
First, begin by punching that cunt right in that big, ugly, red nose, and let her fall on her back. Then, casually wait for her to rise. Proceed with the pounding until she’s deflated, emotionally and physically. If she doesn’t rise, kick her in the ribs. Be careful with her ovaries, though. You don’t want your future son to come out looking like Gilbert Gottfried. After all, when you’re too old to beat your whore, you’ll need somebody there so that you may vicariously beat other women. It’s the Circle of Life, and it moves us all.
If your wife has the balls to hit you first, or even try to swing at you, then you should consider her a proverbial buffet for worms. There will be other, less “independent” women out there who will let you fatten their lips with a clean jab to the teeth. There will be other women out there who will let you smack your dick off their eyelids. There will be other women out there who will suck your balls while frying up some chicken. I promise you. Women might think they’re tough, but once you break their spirit, it’s easier than parallel-parking the new Lexus. Or what I like to call “curb-stomping fish in a barrel.”
A few other tips for a fun, flawless beating:
1. Include a list of acceptable excuses for the bruises on the visible parts of her body. Such excuses include, but are not limited to:
“My husband and I have a wild sex life. He hits me and I enjoy it…sexually.”
“I have low iron in my blood… these are from smelling the daisies my husband bought me. I love him and obey everything he says.”
“I incorrectly put the mayo on the ham in his sandwich, and my husband set me straight.”
2. Limit her ability to watch The View, Dateline, Oprah, and other television shows by not subscribing to cable. If you want to watch the game, go to the bar. If your wife bitches, you know what to do.
3. Let her be conscious for awhile. This way, you can say neat things like, “Welcome to the jungle, bitch!” and have her hear it. It may ruin Guns N’ Roses for her, but really, women shouldn’t be listening to Rock n’ Roll music anyways.
6. Be arbitrary in what pisses you off. Think of it like this: if you hook an electrode up to one wire on a gerbil’s cage, the little bastard will eventually learn not to touch it. Your wife is similar. If you want to keep beating her, you can’t keep getting pissed off about things like, say, her perfume choice or the fact that a diet product exists in your household. You’ve got to make up new and exciting triggers. Think: old boyfriends or past mistakes. Goldmines.
Or hell, if you don’t need to get pissed off, don’t worry about it. Just smack her around a little.
|
{
"pile_set_name": "Pile-CC"
}
|
Q:
How can I perform a GET request without downloading the content?
I am working on a link checker, in general I can perform HEAD requests, however some sites seem to disable this verb, so on failure I need to also perform a GET request (to double check the link is really dead)
I use the following code as my link tester:
public class ValidateResult
{
public HttpStatusCode? StatusCode { get; set; }
public Uri RedirectResult { get; set; }
public WebExceptionStatus? WebExceptionStatus { get; set; }
}
public ValidateResult Validate(Uri uri, bool useHeadMethod = true,
bool enableKeepAlive = false, int timeoutSeconds = 30)
{
ValidateResult result = new ValidateResult();
HttpWebRequest request = WebRequest.Create(uri) as HttpWebRequest;
if (useHeadMethod)
{
request.Method = "HEAD";
}
else
{
request.Method = "GET";
}
// always compress, if you get back a 404 from a HEAD it can be quite big.
request.AutomaticDecompression = DecompressionMethods.GZip;
request.AllowAutoRedirect = false;
request.UserAgent = UserAgentString;
request.Timeout = timeoutSeconds * 1000;
request.KeepAlive = enableKeepAlive;
HttpWebResponse response = null;
try
{
response = request.GetResponse() as HttpWebResponse;
result.StatusCode = response.StatusCode;
if (response.StatusCode == HttpStatusCode.Redirect ||
response.StatusCode == HttpStatusCode.MovedPermanently ||
response.StatusCode == HttpStatusCode.SeeOther)
{
try
{
Uri targetUri = new Uri(Uri, response.Headers["Location"]);
var scheme = targetUri.Scheme.ToLower();
if (scheme == "http" || scheme == "https")
{
result.RedirectResult = targetUri;
}
else
{
// this little gem was born out of http://tinyurl.com/18r
// redirecting to about:blank
result.StatusCode = HttpStatusCode.SwitchingProtocols;
result.WebExceptionStatus = null;
}
}
catch (UriFormatException)
{
// another gem... people sometimes redirect to http://nonsense:port/yay
result.StatusCode = HttpStatusCode.SwitchingProtocols;
result.WebExceptionStatus = WebExceptionStatus.NameResolutionFailure;
}
}
}
catch (WebException ex)
{
result.WebExceptionStatus = ex.Status;
response = ex.Response as HttpWebResponse;
if (response != null)
{
result.StatusCode = response.StatusCode;
}
}
finally
{
if (response != null)
{
response.Close();
}
}
return result;
}
This all works fine and dandy. Except that when I perform a GET request, the entire payload gets downloaded (I watched this in wireshark).
Is there any way to configure the underlying ServicePoint or the HttpWebRequest not to buffer or eager load the response body at all?
(If I were hand coding this I would set the TCP receive window really low, and then only grab enough packets to get the Headers, stop acking TCP packets as soon as I have enough info.)
for those wondering what this is meant to achieve, I do not want to download a 40k 404 when I get a 404, doing this a few hundred thousand times is expensive on the network
A:
When you do a GET, the server will start sending data from the start of the file to the end. Unless you interrupt it. Granted, at 10 Mb/sec, that's going to be a megabyte per second so if the file is small you'll get the whole thing. You can minimize the amount you actually download in a couple of ways.
First, you can call request.Abort after getting the response and before calling response.close. That will ensure that the underlying code doesn't try to download the whole thing before closing the response. Whether this helps on small files, I don't know. I do know that it will prevent your application from hanging when it's trying to download a multi-gigabyte file.
The other thing you can do is request a range, rather than the entire file. See the AddRange method and its overloads. You could, for example, write request.AddRange(512), which would download only the first 512 bytes of the file. This depends, of course, on the server supporting range queries. Most do. But then, most support HEAD requests, too.
You'll probably end up having to write a method that tries things in sequence:
try to do a HEAD request. If that works (i.e. doesn't return a 500), then you're done
try GET with a range query. If that doesn't return a 500, then you're done.
do a regular GET, with a request.Abort after GetResponse returns.
|
{
"pile_set_name": "StackExchange"
}
|
Inhibition of Nerve Growth Factor Signaling Alleviates Repeated Dural Stimulation-induced Hyperalgesia in Rats.
Our previous study showed that acid-sensing ion channel 3 (ASIC3) in the trigeminal nucleus caudalis (TNC) is involved in the pathogenesis of recurrent migraine. ASIC3 is regulated by nerve growth factor (NGF), which induces hyperalgesia in various pain disorders. Neutralization of NGF is considered an effective treatment method. However, the contribution of NGF to repeated migraine-like attacks in chronic migraine (CM) remains unclear. Therefore, this study investigated the effect of NGF on ASIC3 expression in the TNC and the role of NGF signaling in chemical dural stimulation-induced hyperalgesia. A rat model was established by repeated dural infusions of inflammatory soup (IS) for seven days to simulate CM attacks. After repeated IS infusions, cutaneous hyperalgesia appeared in the rats' periorbital region and hind paws, which showed significantly lower pain thresholds. IS infusions upregulated the mRNA and protein of NGF in the TNC, and NGF was mainly expressed in the cytoplasm of TNC neurons. An intracerebroventricular injection of an anti-NGF-neutralizing antibody relieved the cutaneous hyperalgesia of CM rats and decreased protein kinase C (PKC), ASIC3, calcitonin gene-related peptide (CGRP) and c-Fos expression in the TNC. Moreover, intracerebroventricular injection with the PKC blocker chelerythrine chloride alleviated IS infusion-induced hyperalgesia and reduced ASIC3, CGRP and c-Fos levels in the TNC. These results indicate that NGF might regulate ASIC3 expression via PKC activity in the TNC following repeated IS dural stimulation, and this signaling pathway might participate in IS-induced hyperalgesia.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
Migraine is a paroxysmal headache that lasts 4 to 72 hours, accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, or the like [The Merck Manual, Seventeenth Edition, Chapter 168; Therapeutic Guideline of The Japanese Society of Neurology; International Classification of Headache Disorders-II: ICHD-II, 2004]. Vasodilation in the extra- and/or intra-cranial vessels including the superficial temporal artery has been proposed as one of the pathophysiology of migraine and its pathogenesis [Arch. Neurol. Psychiatr., Vol. 39, p. 737-763 (1938); Cephalagia, Vol. 1, p. 143-147 (1981); Internal medicine, Vol. 81, p. 601-609 (1998); Internal Medicine, Vol. 81, p. 639 (1998)]. It has also been known that ergot alkaloid and sumatriptan, hydrophilic agonists of serotonin receptor 5-HT1 (5-hydroxytryptamine 1), that do not cross the blood-brain barrier are effective for the treatment of migraine, because these agonists act on the serotonin receptor 5-HT1 in the cerebral vascular smooth muscle to constrict the dilated blood vessels [Ann. N.Y. Acad. Sci., Vol. 600, p. 587-600 (1990); Neurology, Vol. 43, p. S43-S47 (1993)].
It is thus believed that migraine can be treated by suppressing vasodilation in the extra- and/or intra-cranial vessels. Concerning the cause of migraine onset, there have also been reports presenting theories based on neurogenic inflammation around the trigeminal nerve and cerebral blood vessel, or around the dura mater blood vessel, or based on activation of the central nerve such as in cortical spreading depression [Lancet, Vol. 363, p. 381-391 (2004)].
There are further reports concerning migraine (see Non-Patent Documents 1 to 3).
Some of the examples of therapeutic agents for migraine currently in use in the clinic include non-steroidal antiphlogistic analgetics such as triptans (for example, sumatriptan), and ibuprophens. As for the preventive agents, for example, antiepileptic agents such as topiramate, and calcium antagonist agents such as flunarizine are currently used in the clinic.
It is known that the adenosine concentration in the blood plasma of migraine patients an hour after a migraine attack increases by an average of 68% from that during the normal period, and that the activation of the adenosine A2 receptor by adenosine suppresses the serotonin uptake by platelets in a manner that depends on adenosine concentration, and causes vasodilation as a result of a rapid serotonin release [Can. J, Neurol. Sci., Vol. 2, p. 55-58 (1998)]. Further, intravenous administration of an adenosine enhancer to a migraine patient is known to induce a migraine attack [Med. J. Aust., Vol. 162, p. 389-390 (1995)]. It is also known that adenosine possesses a strong vasodilating action, and that the adenosine A2A receptor and the adenosine A2B receptor are involved in vasodilation during migraine and in adenosine-induced vasodilation [Am. J. Physiol. Heart Circ. Physiol., Vol. 280, p. 2329-2335 (2001)]. It is thus believed that migraine can be treated by suppressing adenosine-induced vasodilation.
Caffeine, which has a non-selective adenosine antagonistic activity, is known to relieve migraine; however, caffeine has side-effects, namely, psychiatrical dependence, and causes caffeine withdrawal headache [see Pain, 1991, Vol. 44, p. 151-155; Drugs, 1995, Vol. 49, p. 37-50]. Further, xanthine derivatives are known to be useful as therapeutic drugs for migraine (see Patent Document 1).
It is known that adenosine is distributed abundantly in the whole body, and exhibits a variety of physiological activities on the central nervous system, the cardiac muscle, the kidneys, the smooth muscle, and the like through its receptors (see Non-Patent Document 4).
For example, adenosine A1 antagonists are known to facilitate defecation (Jpn. J. Pharmacol., 1995, Vol. 68, p. 119). Further, involvement of the adenosine A2A receptor, particularly in the central nervous system is known. The antagonists of the adenosine A2A receptor are known to be useful as, for example, therapeutic drugs for Parkinson's disease (see Non-Patent Document 5), or therapeutic drugs for sleep disorder (see Nature Neuroscience, 2005, p. 1; Patent Document 2).
There are some reports concerning the relationship between adenosine receptors and migraine (see Non-Patent Documents 6 to 13).
For example, compounds represented by the following formulae (I), (II), (III), (IV), (V), (VI), and (VII) are known as compounds having a selective adenosine A2A receptor antagonistic activity (see Patent Documents 3 to 9, and Non-Patent Documents 14 and 15).
(wherein R1 represents methyl, ethyl, propyl, butyl, or 3-methylbutyl, or any of these groups substituted with hydroxy; R2 represents phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl, or tetrahydropyranyloxy, or any of these groups substituted with 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy, and ethoxy; R3 represents pyridyl or tetrahydropyranyl; R4 and R5 may be the same or different, and each represent a hydrogen atom, a fluorine atom, or 2-methoxyethoxy; and R6 represents methyl, ethyl, propyl, or butyl)
|
{
"pile_set_name": "USPTO Backgrounds"
}
|
Q:
How to force textbox to take only numbers in WPF?
I want user to enter only numeric values in TextBox.
I got this code:
private void txtType1_KeyPress(object sender, KeyPressEventArgs e)
{
int isNumber = 0;
e.Handled = !int.TryParse(e.KeyChar.ToString(), out isNumber);
}
But I am not getting textbox_KeyPress event and e.KeyChar while using WPF.
Whats the solution in WPF?
Edit:
I made a Solution!
private void txtName_PreviewTextInput(object sender, TextCompositionEventArgs e)
{
CheckIsNumeric(e);
}
private void CheckIsNumeric(TextCompositionEventArgs e)
{
int result;
if(!(int.TryParse(e.Text, out result) || e.Text == "."))
{
e.Handled = true;
}
}
A:
protected override void OnPreviewTextInput(TextCompositionEventArgs e)
{
char c = Convert.ToChar(e.Text);
if (Char.IsNumber(c))
e.Handled = false;
else
e.Handled = true;
base.OnPreviewTextInput(e);
}
A:
You can use a validation rule...
http://www.codeproject.com/KB/WPF/wpfvalidation.aspx
Or make your own Maskable textbox
http://rubenhak.com/?p=8
|
{
"pile_set_name": "StackExchange"
}
|
Abbreviations used: GEF, guanine exchange factor; GPCR, G protein--coupled receptor; HUVEC, human umbilical vein endothelial cell; LAD, leukocyte adhesion deficiency; NMD, nonsense-mediated decay; PAF, platelet-activating factor; PLC, phospholipase C; SNP, single-nucleotide polymorphism.
R. Pasvolsky, S.W. Feigelson, and S.S. Kilic contributed equally to this paper.
Leukocyte arrest at target endothelial sites is nearly exclusively mediated by integrin receptors ([@bib1]). As circulating leukocytes maintain their integrins in a generally nonadhesive state, a key checkpoint in leukocyte arrest is the rapid modulation of integrin affinity and avidity to endothelial ligands ([@bib2]) by various agonists, predominantly chemoattractants or chemokines, presented on the endothelium ([@bib3], [@bib4]). Likewise, platelets maintain their major fibrinogen receptor, the integrin α~IIb~β~3~, in an inactive conformation, which is converted by multiple agonists, predominately ligands to G protein--coupled receptors (GPCRs), into an activated receptor with high affinity to multiple ligands ([@bib5]). The small GTPase Rap-1 has been implicated in the activation of leukocyte, platelet, and megakaryocyte integrins by multiple receptors, including GPCRs, the TCR, receptors to various inflammatory cytokines, and shear stress signals ([@bib6]--[@bib13]).
We recently described a human genetic deficiency of leukocyte adhesion to endothelium leukocyte adhesion deficiency (LAD) III that is distinct from LAD-I. Whereas LAD-I is a genetic defect in β~2~ integrin expression or function ([@bib14]), LAD-III leukocytes express intact integrins with an impaired ability to generate high avidity to their endothelial ligands at vascular endothelial contacts in response to rapid endothelial chemoattractant signals ([@bib15], [@bib16]). Patient leukocytes, however, express functionally intact GPCRs. A role for Rap-1 malfunction in the LAD-III syndrome was inferred by our finding that LAD-III lymphoblasts express normal levels of Rap-1, which fails to undergo activation in response to the prototypic chemokine CXCL12. Although Rap-1 is also implicated in the survival and function of many nonhematopoietic tissues ([@bib17]--[@bib19]), no severe developmental disorders or abnormalities in nonhematopoietic tissues were reported in the LAD-III patients ([@bib14]). Thus, we suggested that LAD-III and related integrin activation defects in hematopoietic systems are the result of a loss in a key Rap-1 guanine exchange factor (GEF) that is essential for the transduction of leukocyte and platelet GPCR signals into Rap-1 and integrin activation.
In this study, we report two similar LAD-III cases in which neutrophil and lymphocyte integrins cannot acquire adhesiveness upon rapid activation by GPCR agonists under shear flow conditions. Chemokine-induced activation of two LFA-1 conformations associated with integrin extension and high affinity states is also largely impaired in LAD-III T lymphocytes. In addition, platelets derived from the two patients fail to aggregate in response to prototypic inside-out signals, and their key integrin, α~IIb~β~3~, does not acquire a high affinity state essential for ligand binding and aggregation. These LAD cases share a homozygous mutation in the acceptor splice junction at the beginning of exon 16 of the Rap-1 GEF, CalDAG-GEFI (RasGRP2). Furthermore, LAD-derived total blood levels of CalDAG-GEFI mRNA and the protein expression in LAD platelets, neutrophils, and lymphocytes are diminished. These results are the first example of a human inherited disease caused by a Rap GEF deficiency that is linked to profound defects in both leukocyte and platelet integrin activation and adhesive functions in the vasculature.
RESULTS
=======
Patients
--------
The two patients, a 1-yr-old male (patient K) and a 2-yr-old female (patient A) of Turkish origin were each born to consanguineous parents. The two families, although not related, originally lived in the close villages in the eastern region of Turkey, suggesting a common ancestor. Both sets of parents are asymptomatic. Both patients shared a similar clinical presentation consisting of petechia from birth caused by a severe bleeding tendency and requiring repeated blood transfusions. They suffered recurrent and severe bacterial infections associated with marked leukocytosis (25--70,000/mm^3^, 60% neutrophils and 30% lymphocytes), but normal platelet counts. More than 95% of patient neutrophils expressed CD18, CD11a, and CD11b integrins, ruling out a LAD-I syndrome. Lymphocyte subsets and immunoglobulin levels were within normal range. Patient A suffered from recurrent severe pneumonias, necessitating constant antibiotic treatment. Patient K suffered from recurrent severe pneumonias and sepsis. He had surgery to correct a bowel intususception when he was 14 mo old, resulting in a large, nonhealing wound after the operation. Blood culture yielded B-hemolytic *Pseudomonas aeruginosa*. Patient K died at 2 yr of age from sepsis and pulmonary bleeding. Laboratory data showed hemoglobin around 8 gr%. Failure to thrive was consistent in both patients from early life, and both children were below the fifth percentile for both height and weight. Patient A\'s sister died at age 15 mo from pneumonia and sepsis and had suffered from anemia and bleeding tendency from early life. Patient A has only one healthy brother aged 6 yr. Patient K does not have siblings. Neither of the patients displayed overt neurological disorders.
Platelets derived from LAD patients fail to aggregate because of the inability of agonists to trigger high affinity α~IIb~β~3~
------------------------------------------------------------------------------------------------------------------------------
As both patients displayed major bleeding disorders in addition to their severe leukocytosis, we first analyzed their agonist-stimulated platelet aggregation. Platelet aggregation triggered by all GPCR agonists tested, i.e., ADP, epinephrine, arachidonic acid, and thrombin, was completely absent in patient-derived platelets ([Fig. 1 A](#fig1){ref-type="fig"} and not depicted), despite only moderate reduction in surface α~IIb~β~3~ (GpIIbβ3) expression ([Fig. 1 B](#fig1){ref-type="fig"}, inset). As this integrin is the main fibrinogen receptor on platelets ([@bib5]), these results suggested a major defect in GPCR-mediated inside-out activation of patient α~IIb~β~3~ ([Fig. 1 A](#fig1){ref-type="fig"}). An alternative GPCR-independent inside-out activation pathway that stimulates α~IIb~β~3~-mediated platelet aggregation involves the binding of collagen to platelet receptors such as GPVI and the α~2~β~1~ integrin ([@bib20]). Patient-derived platelets were also unable to aggregate in response to collagen signals ([Fig. 1 A](#fig1){ref-type="fig"}). However, these multiple defects were not caused by a global platelet aggregation defect because when GPCR signaling to α~IIb~β~3~ was bypassed with the vWF agonist ristocetin, patient platelets underwent robust aggregation, although at a twofold lower magnitude ([Fig. 1 A](#fig1){ref-type="fig"}). Defective platelet aggregation could result from a failure of α~IIb~β~3~ to undergo activation or from cytoskeletal defects that impair postligand occupancy of this integrin ([@bib5]). Direct activation by agonists of the α~IIb~β~3~ integrin, from an inactive state to a fully active integrin with high affinity to ligands, can be probed by binding of the ligand mimetic activation reporter antibody, PAC-1 ([@bib21]). PAC-1--specific staining of activated platelets derived from the LAD patients was slightly reduced in response to platelet GPCR agonists, whereas PAC-1 staining on control platelets was dramatically increased ([Fig. 1 B](#fig1){ref-type="fig"}). In contrast, P- selectin was normally activated by the same agonists in LAD-derived platelets (unpublished data). These results collectively indicate that affinity up-regulation of α~IIb~β~3~ by inside-out signals is severely impaired in patient platelets.
{#fig1}
Absence of CalDAG-GEFI transcripts and protein in LAD patient-derived platelets and neutrophils
-----------------------------------------------------------------------------------------------
The Rap-1 GEF CalDAG-GEFI has been implicated as a key regulator of agonist-induced α~IIb~β~3~ activation and platelet aggregation ([@bib22]). Therefore, we analyzed the level of CalDAG-GEFI by RT-PCR in total blood. Strikingly, several CalDAG-GEFI transcripts tested were nearly completely absent from blood obtained from both patients ([Fig. 2 A](#fig2){ref-type="fig"} and not depicted), whereas normal levels of this transcript were found in all four parents ([Fig. 2 A](#fig2){ref-type="fig"}). In contrast, levels of a second Rap-1 GEF, CalDAG-GEFIII, were completely normal in both patients compared with parents and age-matched control ([Fig. 2 A](#fig2){ref-type="fig"}). Quantitative PCR analysis revealed that CalDAG-GEFI was expressed at \>30-fold lower levels in LAD patient A compared with healthy age-matched control, whereas the expression level of CalDAG-GEFIII was comparable ([Fig. 2 B](#fig2){ref-type="fig"}). In agreement with the loss of CalDAG-GEFI in LAD patients, Western blot analysis with two mAbs against CalDAG-GEFI revealed a complete loss of the protein in lysates derived from platelets and neutrophils purified from patient A ([Fig. 2 C](#fig2){ref-type="fig"} and not depicted). Consistent with the RT-PCR results, both of patient A\'s parents expressed normal levels of the CalDAG-GEFI protein in both neutrophil and platelet lysates (unpublished data).
{#fig2}
Both LAD patients share an identical homozygous mutation in an intronic acceptor splice junction in CalDAG-GEFI
---------------------------------------------------------------------------------------------------------------
We next assessed whether the two patients were homozygous at the CalDAG-GEFI chromosomal locus 11q13.1. We identified a single microsatellite marker, located at chr11:64,428,757-64,429,006 (National Center for Biotechnology Information build 36), which is 159,253 bp away from the gene (chr11:64,250,960-64,269,504), and thus the closest published polymorphic marker to CalDAG-GEFI. We initially used this marker to analyze DNA of the two patients, their parents, and the healthy sibling of patient A ([Fig. 3 A](#fig3){ref-type="fig"}). In family A, two alleles, 252 and 260 bp long, were detected in the samples derived from the parents. Patient A was homozygous for the 260-bp allele, whereas his healthy sibling was homozygous for the 252-bp allele. In family K, DNA from both parents contained two alleles that were 248 and 260 bp in lengths, whereas patient K was homozygous for the 260 bp allele. These results indicated that the two patients are each homozygous for the same affected allele, which suggested that this allele may carry a mutation for CalDAG-GEFI.
{#fig3}
We next sequenced the genomic region of CalDAG-GEFI from 2,000 bp upstream to 500 bp downstream of the cDNA sequence (Fig. S1, available at <http://www.jem.org/cgi/content/full/jem.20070058/DC1>). 20 deviations from the reference genome were found, comprising 17 known single-nucleotide polymorphisms (SNPs) and 3 novel SNPs (Fig. S2). The PCR products containing novel SNPs were generated and sequenced in LAD patient A\'s healthy brother. Only one novel SNP, IVS15nt718c\>a, was unique in LAD patient A ([Fig. 3 B](#fig3){ref-type="fig"} and Fig. S3). The same mutation was found in LAD patient K ([Fig. 3 B](#fig3){ref-type="fig"} and Fig. S3). Importantly, this mutation was absent in all 116 control chromosomes tested from Turkish donors (unpublished data). The mutation occurs 3 bp upstream of the beginning of exon 16, disrupting the splice junction present at that location. An automated splice site analysis program based on information theory ([@bib23]) was used to predict the possible effects of this mutation on splicing. The program predicts that this mutation creates a putatively active cryptic splice site located 1 bp before the actual site, which is concomitantly weakened (Fig. S4). If this cryptic site is preferred by the transcription machinery, the products of such a splice would have a shifted reading frame and a premature stop codon, resulting in nonsense-mediated decay (NMD) ([@bib24]). Collectively, the LAD patients share a homozygous mutation in a critical acceptor splice region of CalDAG-GEFI that predicts the loss of message, which was indeed observed ([Fig. 2, A and B](#fig2){ref-type="fig"}).
CalDAG-GEFI--null neutrophils fail to arrest on inflamed endothelial cells and on ICAM-1 in spite of normal selectin-mediated capture and rolling
-------------------------------------------------------------------------------------------------------------------------------------------------
Neutrophils from the initial LAD-III patient characterized by us ([@bib15]) expressed normal levels of the two major β~2~ integrins implicated in neutrophil arrest on vascular endothelium, LFA-1 and Mac-1. Neutrophils derived from the two new LAD cases also expressed normal levels of LFA-1 and Mac-1 ([Fig. 4 A](#fig4){ref-type="fig"} and not depicted). The LAD-derived CalDAG-GEFI--null neutrophils were next perfused over a monolayer of TNF-stimulated human umbilical vein endothelial cells (HUVECs) under physiological shear flow; these cells express high levels of E-selectin and multiple β~2~ integrin ligands ([@bib25], [@bib26]). Patient and control neutrophils were captured by the cytokine-activated HUVEC at comparable rates and initiated normal rolling on the endothelial monolayer ([Fig. 4 B](#fig4){ref-type="fig"}). Shortly after capture on the endothelial surface, normal neutrophils spontaneously arrest on the activated endothelium, in a β~2~ integrin--dependent manner ([@bib26]) (unpublished data), whereas CalDAG- GEFI--null neutrophils failed to arrest and continued to roll over the cytokine-activated EC monolayer ([Fig. 4 B](#fig4){ref-type="fig"}), as was previously observed for LAD-III neutrophils ([@bib15]). Inhibition of phospholipase C (PLC) in control neutrophils completely eliminated their ability to arrest in a β~2~ integrin--dependent manner on the activated HUVECs (unpublished data), which is consistent with a role for PLC, an upstream regulator of CalDAG-GEFI ([@bib22]) in CalDAG-GEFI--mediated β~2~ integrin activation in normal neutrophils. Furthermore, whereas both normal and LAD neutrophils were efficiently captured by E-selectin coimmobilized with ICAM-1 ([Fig. 4 C](#fig4){ref-type="fig"}), nearly all normal neutrophils either immediately arrested on the E-selectin/ICAM-1 surface or rolled for several seconds before arrest, but none of the LAD neutrophils were able to arrest ([Fig. 4 C](#fig4){ref-type="fig"}). Exclusion of Mg^2+^ from the binding medium resulted in integrin inactivation and loss of arrest on the E-selectin/ICAM-1 surface only in control neutrophils ([Fig. 4 C](#fig4){ref-type="fig"}). As expected, this integrin inactivation did not affect the capture and rolling adhesions initiated by either control or LAD neutrophils. These results collectively indicate intact rolling capacity, but loss of adhesiveness of both LFA-1 and Mac-1 integrins in LAD neutrophils interacting with inflamed endothelial cells, as well as with purified ICAM-1 under shear flow conditions.
{#fig4}
Impaired spontaneous β~2~ integrin adhesiveness to ICAM-1 in CalDAG-GEFI--null neutrophils is associated with reduced levels of high affinity integrin conformations
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The inability of both LFA-1 and Mac-1 expressed by LAD neutrophils to develop firm adhesions could result from improper inside-out activation through E-selectin ([@bib27], [@bib28]). We therefore next compared β~2~-mediated attachments of normal and LAD neutrophils to isolated ICAM-1 coated at high density in the absence of E-selectin. Control blood-derived neutrophils retained moderate levels of spontaneous β~2~ integrin adhesiveness to high density ICAM-1, manifested by the ability of these leukocytes to generate both transient and firm tethers on the ligand under low shear flow ([Fig. 5 A](#fig5){ref-type="fig"}). Notably, β~2~ integrins on LAD-derived CalDAG-GEFI--null neutrophils failed to interact with ICAM-1 even under these permissive flow conditions ([Fig. 5 A](#fig5){ref-type="fig"}). Furthermore, prolonged association with ICAM-1 under static conditions allowed β~2~ integrins on normal, but not on LAD, neutrophils to generate high shear--resistant adhesions ([Fig. 5 B](#fig5){ref-type="fig"}). Thus, a considerable fraction of normal neutrophils settled on ICAM-1 for 1 min developed resistance to detachment by high shear stress, whereas only a negligible fraction of LAD neutrophils developed shear resistance on ICAM-1 after prolonged association with the ligand under static conditions ([Fig. 5 B](#fig5){ref-type="fig"}). These results suggested that LAD β~2~ integrins are inherently defective in their acquisition of the intermediate and/or high affinity states necessary for rapid ligand recognition and contact-dependent adhesion strengthening on ligands ([@bib29], [@bib30]). Comparing the levels of these β~2~ conformational states probed by specific reporter mAbs, we found, however, identical levels of the β~2~ integrin extension reporter KIM127 on both normal and LAD neutrophils ([Fig. 5 C](#fig5){ref-type="fig"}, top). Nevertheless, the appearance of the high affinity 327C β~2~ I domain epitope on LAD β~2~ integrins was reduced by fivefold ([Fig. 5 C](#fig5){ref-type="fig"}, bottom), which is consistent with defective acquisition of high affinity states by LAD β~2~ integrins.
{#fig5}
Mac-1 in CalDAG-GEFI--null leukocytes fails to undergo subsecond activation of adhesiveness by chemoattractants
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In a previous study on LAD-III neutrophils, we found that the neutrophil Mac-1 could undergo normal conformational activation by chemoattractants, but failed to respond to in situ inside-out stimulation by the same surface-bound chemoattractants under shear flow ([@bib15]). To directly assess in the present LAD syndrome the ability of Mac-1 to undergo inside-out activation by prototypic chemoattractants, we next assessed whether platelet-activating factor (PAF) can alter the integrin activation state in patient neutrophils. CBRM1/5 is a ligand mimetic mAb that detects high affinity Mac-1 subsets ([@bib31]). In contrast to platelets, PAF, as well as IL-8, effectively triggered the CBRM1/5 Mac-1 neoepitope in patient CalDAG-GEFI--null neutrophils, which is consistent with normal PAF and IL-8 signaling in these cells ([Fig. 6 A](#fig6){ref-type="fig"} and not depicted). Nevertheless CalDAG-GEFI--null neutrophils failed to mount any PAF- or IL-8--dependent in situ activation of their Mac-1 when perfused over fibrinogen coimmobilized with these chemokines ([Fig. 6 B](#fig6){ref-type="fig"}). The ability of IL-8 to trigger LAD neutrophil attachments to ICAM-1, which is a shared ligand of Mac-1 and LFA-1 ([@bib32]), was also abrogated ([Fig. 6 C](#fig6){ref-type="fig"}). Notably, neutrophils from the patient\'s mother, although confirmed to be a heterozygote carrier of the mutated gene ([Fig. 3](#fig3){ref-type="fig"} and Fig. S3), expressed normal levels of CalDAG-GEFI protein (not depicted) and underwent comparable in situ activation of Mac-1 by IL-8 ([Fig. 6 B](#fig6){ref-type="fig"}). This suggests that one normal allele is sufficient for full protein expression and function. As expected, neutrophils from the healthy sibling, who was a confirmed homozygote for the two normal CalDAG-GEFI alleles ([Fig. 3](#fig3){ref-type="fig"} and Fig. S3), were indistinguishable from healthy neutrophils in all adhesion assays tested (not depicted). Collectively, these results suggest that β~2~ integrins in LAD-derived, CalDAG-GEFI--null neutrophils are completely defective in their ability to undergo rapid, chemoattractant-triggered activation under shear stress conditions, despite retained chemoattractant-triggered conformational activation of their Mac-1 β~2~ integrin.
{ref-type="fig"} and [5](#fig5){ref-type="fig"}. The experiment shown is representative of three. Similar results were obtained in LAD patient K.](jem2041571f06){#fig6}
Abolished chemokine activation of LFA-1 and of VLA-4--mediated arrest in CalDAG-GEFI--deficient LAD lymphocytes
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Murine splenocytes express negligible levels of CalDAG-GEFI ([Fig. 7 A](#fig7){ref-type="fig"}) ([@bib22]). Strikingly, high levels of the GEF were found in primary freshly isolated T lymphocytes from healthy donors ([Fig. 7 A](#fig7){ref-type="fig"}). As CalDAG-GEFI was completely lost in primary LAD T lymphocytes ([Fig. 7 A](#fig7){ref-type="fig"}), we next assessed how the GEF deficiency affects the function of the two major lymphocyte integrins, the β~2~ integrin LFA-1 and the β~1~ integrin VLA-4. LAD lymphocytes expressed both integrins, as well as CXCR4, which is the main receptor for the prototypic lymphocyte chemokine CXCL12 (SDF-1α) at normal levels ([Fig. 7 B](#fig7){ref-type="fig"}). Nevertheless, CXCL12-mediated activation of LFA-1, assessed by the induction of the integrin extension epitope KIM127, as well as the high affinity integrin conformation, probed by the 327C mAb ([@bib33]), was greatly reduced in LAD-derived, CalDAG-GEFI--deficient T lymphocytes ([Fig. 7 C](#fig7){ref-type="fig"}). In agreement with defective chemokine-induced inside-out activation of LFA-1 in CalDAG-GEFI--deficient lymphocytes, CXCL12 failed to trigger any LFA-1 adhesions to ICAM-1 under shear flow ([Fig. 7 D](#fig7){ref-type="fig"}). Thus, CalDAG-GEFI is critical for CXCL12-mediated inside-out activation of LFA-1 in primary human T cells. We next assessed the role of CalDAG-GEFI in chemokine-mediated activation of VLA-4 in T cells interacting with VCAM-1 and coimmobilized CXCL12 under shear flow. In healthy T lymphocytes, this prototypic chemokine triggers robust VLA-4--dependent lymphocyte tethering, rolling, and arrest on VCAM-1 under shear flow ([@bib25]). Notably, VLA-4 of patient CalDAG-GEFI--null T lymphocytes could still undergo in situ activation by CXCL12 ([Fig. 7 E](#fig7){ref-type="fig"}), but CXCL12-triggered VLA-4 failed to arrest patient CalDAG-GEFI--null T lymphocytes on VCAM-1. These data suggest that CalDAG-GEFI is only partially required for inside-out activation of VLA-4. As VLA-4 activation epitopes are not induced in T lymphocytes by soluble CXCL12 ([@bib25]), and there are no available VLA-4 ligand mimetic mAbs, we could not confirm an inside-out defect in chemokine-triggered VLA-4 conformation or affinity state based on activation epitope analysis, as we could for LFA-1 ([Fig. 7 C](#fig7){ref-type="fig"}). We could rule out a defect in outside-in activation of VLA-4 by VCAM-1 because CalDAG-GEFI--null T lymphocytes arrested normally on high density VCAM-1 (unpublished data). Our data collectively suggest a defect in chemokine stimulation of high avidity VLA-4 bonds critical for immediate adhesion strengthening and lymphocyte arrest on VCAM-1 under shear stress conditions.
{#fig7}
DISCUSSION
==========
Integration of calcium and DAG signals triggered by PLC is a common theme shared by many biological targets, including immunoreceptors and integrins ([@bib34]). Although these two second messengers can promote integrin adhesiveness via their cooperative activation of classical protein kinase C family members ([@bib35]), chemokine activation of leukocyte integrins takes place independently of this kinase family ([@bib7], [@bib25], [@bib30]). Alternative effectors triggered by DAG and calcium are members of the CalDAG-GEF/RasGRP family, but the importance of these GEFs in leukocyte integrin activation just begins to unfold ([@bib36]). In mice, a Rap-1/2 and R-Ras--specific GEF, CalDAG-GEFI, was recently implicated in integrin activation underlying platelet aggregation, fibrinogen binding, and thrombus formation ([@bib22]). Genetic ablation of CalDAG-GEFI results in severely compromised integrin- dependent platelet aggregation and bleeding disorders ([@bib22]), but the role of this or other Rap-1 GEFs in leukocyte integrin activation has been vague.
We now report the first human genetic adhesion disorder that is associated with an aberrant expression of this GEF in lymphocytes, neutrophils, and platelets. In agreement with data on murine platelets derived from CalDAG-GEFI knockout mice ([@bib22]), patient-derived platelets that lack CalDAG-GEFI exhibit major defects in both GPCR- and collagen-induced platelet aggregation, as well as in GPCR-triggered α~IIb~β~3~ activation. We also provide the first indication for a key role of CalDAG-GEFI in neutrophil and lymphocyte integrin activation by various chemoattractant signals under shear stress conditions relevant for leukocyte interactions with blood vessels. Our genetic analysis has identified a homozygous mutation in the acceptor splice junction at the beginning of exon 16 of the CalDAG-GEFI gene in both LAD patients. Familial segregation analysis also indicates that the patients\' parents are heterozygous for this mutation, yet they are healthy and their leukocytes express normal levels of the GEF. Thus, we establish for the first time an autosomal recessive mutation in a LAD-III syndrome. Furthermore, this is a first implication of a single Rap-1 GEF as a critical inside-out regulator of integrin activation in two major types of human leukocytes and platelets.
The role of CalDAG-GEFI in lymphocyte integrin activation has been obscure because this GEF was not detected in the white pulp of the murine spleen or in the thymus ([@bib22]). We confirmed these results, but found considerable expression of the protein in healthy human peripheral blood T cells. Because primary LAD T cells lacked this GEF, we were prompted to dissect the contribution of CalDAG-GEFI to rapid chemokine-induced integrin activation in T lymphocytes. Chemokine activation of lymphocyte integrins involves simultaneous bidirectional activation by both inside-out and outside-in rearrangements in integrin headpieces and tails ([@bib37], [@bib38]). Choosing CXCL12 as a prototypic chemokine for lymphocyte integrin activation ([@bib39]), we assessed the ability of both LFA-1 and VLA-4 in CalDAG-GEFI--null LAD T lymphocytes to undergo in situ stimulation of adhesiveness under physiological conditions of shear flow. Because integrin tethers form within leukocyte contacts with integrin ligands in the range of 0.04--0.1 s ([@bib25], [@bib30]), any immediate adhesive tethers in situ stimulated by the surface-bound chemokine involves the contact of the integrin and the GPCR with their cognate ligands in this short time frame. Our results therefore indicate an indispensable role for CalDAG-GEFI in the earliest stages (i.e., subsecond-lived contacts) of chemokine-induced LFA-1 firm adhesiveness. Correspondingly, we also find this GEF to be essential for the triggering in T cells of two conformational states of LFA-1 associated with integrin extension and high affinity to ligand ([@bib30]). Furthermore, VLA-4 in CalDAG-GEFI--null T cells also fails to develop high avidity binding to its major endothelial ligand VCAM-1 in response to in situ activation signals from CXCL12, although a significant fraction of VLA-4 on CalDAG-GEFI--null lymphocytes could still undergo normal in situ activation by CXCL12 at subsecond contacts. Importantly, α~4~ integrin conformations can be regulated by shear forces without noticeable changes in integrin affinity to ligand under shear-free conditions ([@bib40], [@bib41]). Interestingly, the subset of firm arrest-mediating VLA-4--VCAM-1 tethers developed by healthy, but not by GEF-deficient, T cells is sensitive to inhibition by low levels of soluble VLA-4 ligands known to selectively block high affinity VLA-4 ([@bib25]). Although VLA-4--mediated adhesions require proper integrin anchorage to the cytoskeleton, we have ruled out a VLA-4 anchorage defect in LAD T cells because these cells normally tethered and arrested on high density VCAM-1 (unpublished data). Nevertheless, we cannot exclude the possibility that defective VLA-4--mediated T cell arrest in LAD T cells is caused by a failure of chemokine-activated VLA-4 to anchor to the cytoskeleton and develop optimal shear resistance in CalDAG-GEFI--deficient T cells. The GEF is dispensable, however, for chemokine-triggered VLA-4--mediated transient and rolling adhesions, which are generally mediated by low or intermediate affinity VLA-4 subsets ([@bib64]). We thus conclude that T cells lacking CalDAG-GEFI undergo incomplete chemokine-triggered activation of VLA-4, suggesting that unlike LFA-1, VLA-4 regulation by chemokines involves additional and redundant CalDAG-GEFI--independent signaling pathways.
A final step in integrin activation is the binding of the cytoskeletal adaptor talin to integrin tails ([@bib42]). A novel integrin activation pathway, which links inside-out signals to α~IIb~β~3~ affinity modulation via a Rap-1--RIAM--talin signaling complex was recently identified ([@bib43]). It is likely that CalDAG-GEFI acts upstream of this complex not only in platelets ([@bib20], [@bib22]) but also in neutrophils and lymphocytes. Neutrophil Rap-1 is strongly activated by cytosolic calcium and by phorbolester DAG analogues ([@bib44]), implicating these two secondary messengers and their key regulatory enzyme, PLC, in Rap-1 activation of neutrophil integrins. Indeed, β~2~-mediated neutrophil arrest on inflamed endothelium is highly sensitive to inhibition of PLC (unpublished data). Rap-1 is found in multiple membranal pools in various cell types ([@bib45]), but its activation by GPCRs occurs mainly in the plasma membrane ([@bib46], [@bib47]). Because these signals are transmitted within a fraction of a second at leukocyte--endothelial contacts ([@bib48]), at least on circulating cells, CalDAG-GEFI and its immediate targets are expected to preexist near the plasma membrane in proximity to their target integrins. CalDAG-GEFI may also activate integrins by triggering the small GTPase R-Ras, which was previously implicated in affinity modulation of the β~1~ integrin VLA-5 ([@bib49]). It is noteworthy that, apart from the loss of CalDAG-GEFI, we did not find any expression defect in either Rap-1 or talin in patient platelets and leukocytes (unpublished data). The involvement of CalDAG-GEFI in platelet, neutrophil, and lymphocyte integrin activation suggests that some of the previously published clinical studies of integrin activation defects in leukocytes and platelets ([@bib50]--[@bib53]) may involve deficiency in this key GEF. With the exception of RAPL, none of the aforementioned Rap-1 effectors are specific to hematopoietic cells; thus, a genetic defect in any of these effectors would not be restricted to the hematopoietic lineage, in contrast to the LAD-III defect described here. Indeed, the loss of CalDAG-GEFI in LAD patient blood did not appear to impair any Rap-1--related functions in nonhematopoietic cellular environments; although the two patients exhibited dense bone in x-ray scans, this is apparently caused by impaired migration of bone remodeling precursors into their skull tissues ([@bib54]). Similar to the phenotype of our patients, CalDAG-GEFI--null mice do not display any severe nonhematopoietic-associated disorder ([@bib22]).
It is quite surprising that the loss of CalDAG-GEFI in platelets and leukocytes could not be compensated by any other Rap-1 activating GEF. Leukocytes and platelets express multiple Rap-1 GEFs in addition to CalDAG-GEFI, including CalDAG-GEFIII, the receptor tyrosine kinase--stimulated GEF C3G, and the cAMP-triggered GEF EPAC ([@bib17], [@bib55]). EPAC is expressed at very low levels in neutrophils ([@bib53]), and thus cannot serve as a major Rap1 GEF in these cells. Importantly, we detected comparable levels of the two other Rap1 GEFs, CalDAG-GEFIII and C3G ([Fig. 2 B](#fig2){ref-type="fig"} and not depicted), in LAD neutrophils and lymphocytes, which suggest that these Rap-1 GEFs cannot functionally compensate for a loss of CalDAG-GEFI. Future studies will be required to address this point. Another open question is whether deficiency in CalDAG-GEFI in murine neutrophils results in a similarly dramatic loss of integrin inside-out activation under the experimental conditions studied in the present work. Lastly, although this Rap-1 GEF is missing in murine lymphocytes, Rap-1 activation is considered as important in murine integrin regulation as it is in human integrin regulation ([@bib56]). If so, one should expect to find in murine lymphocytes an alternative Rap-1 GEF that is critical for lymphocyte integrin activation.
In addition to regulating inside-out integrin activation in platelets, neutrophils, and lymphocytes, Rap-1 and CalDAG-GEFI may also control critical outside-in activation steps, imposed by ligand-induced rearrangements ([@bib2], [@bib57]). Indeed, in the present work, as well as in a study on neutrophils from a previous LAD-III patient ([@bib15]), the Mac-1 integrin could undergo normal inside-out activation in the presence of the prototypic chemoattractant PAF, but still failed to generate adhesiveness in response to rapid PAF signals under shear stress conditions, suggesting a defect in outside-in integrin activation of this integrin. Recent studies suggest that without proper anchorage to the cytoskeleton and a series of rearrangements of the β~2~ integrin LFA-1 by its ligand during subsecond contacts, this integrin, and possibly other integrins operating at leukocyte--endothelial contacts, may fail to generate shear-resistant adhesiveness ([@bib30]). Rearrangement of integrins by their ligands transduces specific cytoplasmic changes in integrin tails ([@bib58]), which may be stabilized by in situ GPCR-mediated Rap-1 activation ([@bib16]). Indeed, inhibition of Rap-1 by overexpression of its GAP, SPA-1, can interfere with integrin adhesiveness, even when the integrin ectodomain is artificially stabilized at a high affinity state by Mn^2+^ or by activating mAbs ([@bib59]), which is consistent with a major role of Rap-1, and potentially of CalDAG-GEFI, in outside-in integrin activation. Rap-1 is also implicated in diverse signaling pathways that link shear stress signals to integrin activation in various cell types ([@bib12], [@bib60]). Future studies will need to address these multiple potential roles of CalDAG-GEFI as an integrator of both inside-out and outside-in integrin activation events in different neutrophil and lymphocyte subsets.
MATERIALS AND METHODS
=====================
Reagents and mAbs.
------------------
Recombinant ICAM-1-IgG1 and E-selectin-IgG1 fusion protein, as well as human SDF-1α (CXCL12) and CXCL8 (IL-8), were purchased from R&D Systems. Recombinant soluble seven-domain human VCAM-1, sVCAM-1 ([@bib61]), was a gift from R. Lobb (Biogen, Cambridge, MA). BSA (fraction V), Ca^2+^, and Mg^2+^-free HBSS, EGTA, Hepes, fibrinogen, and Ficoll-Hypaque 1077 were obtained from Sigma-Aldrich. Human serum albumin (fraction V) was purchased from Calbiochem. The anti--β~2~ integrin subunit mAb TS1.18, the anti--LFA-1 TS2.4, and the anti--Mac-1 integrin mAbs CBRM1/2 and CBRM1/5 ([@bib62]) were gifts from T. Springer (Harvard University, Boston, MA). The Alexa Fluor 488--conjugated anti--β~2~ integrin neoepitope 327C mAb ([@bib33]) was a gift from D. Staunton (ICOS Corporation, Bothell, WA). The KIM127 mAb ([@bib68]) was a gift from M.K. Robinson (UCB Celltech, Slough, UK). The FITC-labeled antiactivated α~IIb~β~3~ mAb PAC-1 was purchased from Becton Dickinson. Anti--P-selectin mAb and the anti-α~IIb~β~3~ mAb were both purchased from Immunotech Coulter. Polyclonal goat anti-actin antibody (sc-1616) was purchased from Santa Cruz Biotechnology.
Platelet isolation and aggregation studies.
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Informed consent was obtained from each individual studied. This study was approved by the Institutional Review Board of the Rambam Medical Center, which is consistent with the provisions of the Declaration of Helsinki. Citrated blood was centrifuged at 150 *g* for 10 min at RT, and platelet-rich plasma was isolated ([@bib63]). Platelets were adjusted to a concentration of 3 × 10^8^/ml with 1/10 volume of 3.2% buffered sodium citrate. Aggregation was initiated by adding 5 μM ADP, 10 μM epinephrine, 10 μg/ml arachidonic acid, 2 μg/ml collagen, or 1.25 mg/ml ristocetin. Aggregation was monitored by light transmission using a two-channel aggregometer (Chrono-Log Corp.).
Isolation and culture of leukocytes.
------------------------------------
Human peripheral blood neutrophils and T lymphocytes were isolated from citrate-anticoagulated whole blood, as previously described ([@bib25], [@bib64]). Murine T lymphocytes were purified from C57BL/6 splenocytes, as previously described ([@bib65]). Murine platelets were isolated and purified from wild-type and CalDAG-GEFI knockout mice, as previously described ([@bib22]). Leukocytes were stored in cation-free HBSS containing 10 mM Hepes, pH 7.4, and 2 mg/ml BSA at room temperature for up to 2 h before experimentation.
RT-PCR analysis.
----------------
RNA prepared from EDTA-anticoagulated peripheral blood was extracted using the RNeasy mini kit (QIAGEN). cDNA was synthesized using random hexamer primers (Promega) with Superscript II RNase H-negative reverse transcriptase (Invitrogen). cDNA was amplified by PCR using specific primers, which are listed in Fig. S1. QRT-PCR was performed as previously described ([@bib66]), using a LightCycler (Roche) according to the manufacturer\'s instructions. PCR reactions were performed in duplicate. PCR amplification consisted of 35--50 cycles of denaturation, annealing, and extension. Denaturation was performed for 15 s at 95°C, annealing was performed at 60°C, and the extension was performed at 72°C for 20 s, with fluorescence detection at 72°C after each cycle. After the final cycle, melting point analyses of all samples were performed within the range of 62--99°C. Expression levels of GusB and of HPRT1 were used for sample normalization. A standard curve was obtained with serial dilutions of a reference cDNA sample amplified concomitantly with the tested samples. CalDAG-GEFI and CalDAG-GEFIII mRNA levels were determined by comparing experimental levels to the standard curves and are expressed as arbitrary units. The primers used are listed in Fig. S1.
Microsatellite analysis.
------------------------
Blood was drawn and DNA was isolated by standard methods. PCR amplification of one microsatellite marker with a maximal length of 260 bp, which contained 11.75 TATC perfect repeats and was located 159,253 bp upstream of CALDAG-GEFI on the minus strand on chromosome 11q13.1, was performed in single plex reaction by touchdown PCR (MJ Research). Two primers, flanking the microsatellite marker, were used in the reaction, one of which was fluorescently labeled: forward PCR primer, Fam-CGCCGAGACATATAAACACCC; reverse PCR primer, ACTTGAATCTGGGAGGCG. PCR products were separated on a 16-capillary automated genetic analyzer (AB 3100; Applied Biosystems). Results were analyzed using the GeneScan analysis software (AB 3100).
DNA sequencing.
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The full CalDAG-GEFI gene, including the 2,000-bp region upstream of the first exon and the 500-bp region downstream of the last exon (chr11:64,250,405-64,271,447), were PCR amplified, and 90% of these segments were successfully sequenced in LAD patient A as previously described ([@bib67]). The primers used for each segment are listed in Fig. S1. Primers of fragment 32 (Fig. S1) were used to amplify the region containing the IVS15nt718c\>a mutation, and thus were subsequently used to screen the genomic DNA of LAD patient K, the healthy brother of LAD patient A, the 4 parents of both patients, and 58 Turkish control donors. Sequence analysis was performed using Sequencher Version 4.7 (Gene Codes Corporation).
Flow cytometry.
---------------
Leukocyte surface staining was performed and analyzed by FACScan, as previously described ([@bib64]). For analysis of neutrophil expression of the Mac-1 activation neoepitope CBRM1/5, washed neutrophils were either left intact or stimulated with agonists for 10 min at 37°C, in the presence of the appropriate reporter mAb. Cells were washed at 4°C, stained with PE-conjugated secondary Ab (Jackson ImmunoResearch Laboratories), and FACScan analysis was performed as previously described ([@bib15]). Spontaneous β~2~ integrin activation was assayed by incubating the intact leukocytes with the reporter mAbs 327C ([@bib33]) or KIM127 ([@bib68]) for 10 min at 37°C, followed by secondary staining. CXCL12-induced activation of these epitopes was assayed in T lymphocytes as previously described ([@bib29]). Activation of α~IIb~β~3~ was measured on washed platelets incubated with 1.0 μg/ml ADP and 1.0 μg/ml epinephrine or control buffer in the presence of 10 μg/ml of FITC-labeled PAC-1 mAb ([@bib21]).
Western blot analysis.
----------------------
For Western blot analysis, platelet, neutrophil, human lymphocyte, or murine lymphocyte lysates were first centrifuged at 13,000 rpm for 20 min at 4°C before their protein concentrations were determined. Lysates were applied to a 7.5% SDS-PAGE under reducing conditions and then transferred to a nitrocellulose membrane. Cell lysis, gel electrophoresis, and transfer to membranes were performed as previously described ([@bib41]). The membrane was blocked and reacted overnight at 4°C with either monoclonal anti--CalDAG-GEFI antibody 18B11 ([@bib69]), polyclonal rabbit anti--CalDAG-GEFI antibody 3753 ([@bib22]), or polyclonal goat anti-actin control antibodies (Santa Cruz Biotechnology). After several washes, the membrane was probed with appropriate secondary IgG conjugated to horseradish peroxidase (Jackson ImmunoResearch Laboratories), and developed by ECL reaction.
Preparation of adhesive substrates and HUVEC monolayers.
--------------------------------------------------------
Preparation of substrates for the laminar flow adhesion assays were performed as previously described ([@bib64], [@bib70]). In brief, ICAM-1-Fc--coated substrates were prepared by plating polystyrene dishes with 1 μg/ml protein A, followed by coimmobilization of either heat-inactivated (−) or intact (+) chemokines and human serum albumin, each at 2 μg/ml. The protein A-chemokine substrates were overlaid overnight at 4°C with the indicated concentrations of ICAM-1-Fc. sVCAM-1 was coimmobilized with CXCL12 (both at 2 μg/ml), as previously described ([@bib25]). E-selectin/ICAM-1 substrates were prepared by coating 0.2 μg/ml E-selectin-Fc on high density protein A, followed by ICAM-1-Fc coating (5 ng/ml). Neutrophil arrests on this substrate were totally blocked by pretreatment with the β~2~ integrin--blocking mAb TS1.18. Fibrinogen was coated directly at 0.5 μg/ml and washed, and PAF (Sigma-Aldrich) was overlaid at 100 nM for an additional hour. PAF was verified to potently activate neutrophil integrins via their PAF receptors ([@bib26]). For adhesion experiments on resting or TNFα-activated endothelial cells, primary HUVECs (passage 2 or 3) were left intact or stimulated for 18 h with heparin-free culture media supplemented with TNFα (2 ng/ml, 100 U/ml; R&D Systems) ([@bib70]).
Analysis of leukocyte attachments and resistance to detachment developed during short, static contacts.
-------------------------------------------------------------------------------------------------------
All shear flow experiments were performed at 37°C. Neutrophils and T lymphocytes were suspended in binding medium (cation-free HBSS, containing 10 mM Hepes, pH 7.4, and 2 mg/ml BSA supplemented with Ca^2+^ and Mg^2+^ at 1 mM each) and immediately perfused through the chamber at controlled flow rates, as previously described ([@bib25]). All cellular interactions with the adhesive substrates were determined by a MatLab-based computerized tracking of individual cell motion within at least two fields of view (each 0.17 mm^2^ in area). "Transient" tethers were defined as cells attached briefly (\<2 s) to the substrate; "rolling tethers" were attached cells that persistently rolled for at least 2 s over the substrate; "rolling then arrested" were cells that stopped for at least 3 s after a rolling period; "arrest (firm) tethers" were defined as tethered cells that immediately stopped for at least 3 s ([@bib30]). For analysis of integrin-mediated adhesion strengthening at short stationary contacts, leukocytes were perfused into the flow chamber and allowed to settle onto the substrate for 1 min. Flow was then initiated and increased step-wise every 5 s through a programmed set of flow rates. At the end of each 5-s interval, the number of cells that remained bound was expressed relative to the number of cells originally settled on the substrate.
Online supplemental material.
-----------------------------
Fig. S1 shows the primers used for PCR amplification and sequencing of CalDAG-GEFI. Fig. S2 shows the polymorphisms found in the genomic sequencing. Note that all alleles refer to the minus strand. Fig. S3 depicts the sequence of the genomic DNA surrounding the putative mutation. The genomic DNA was amplified using primer set 32 (Fig. S1), and analyzed as described in Fig. 3. The base of the mutation is highlighted. Shown are the base alignment (left) and the trace alignment (right). Fig. S4 shows splice site analysis using information theory (23). The online version of this article is available at <http://www.jem.org/cgi/content/full/jem.20070058/DC1>.
Supplemental Material
=====================
###### \[Supplemental Material Index\]
We deeply thank Dr. E. Ben-Asher for helpful consultation and discussions. We also thank Dr. S. Schwarzbaum for editorial assistance and Drs. T. Feferman and G. Tarcic for technical assistance.
R. Alon is the incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research. R. Alon\'s research is supported by the Israel Science Foundation, the Minerva Foundation of Germany, and by MAIN, the EU6 Program for Migration and Inflammation. This work was also supported by National Institutes of Health HD28341 (A.M. Graybiel). A. Etzioni is the incumbent of the Marcus Family Chair for Life Sciences, and his research is supported by the Office of the Chief Scientist. G. Rechavi holds the Djerasi Chair for Oncology (Sackler School of Medicine, Tel-Aviv University).
The authors have no conflicting financial interests.
**Note added in proof.** A paper that describes multiple integrin activation in neutrophils derived from CalDAG-GEF1^−/−^ mice associated with loss of firm adherence to inflamed vessels was published online on May 10, 2007 in the *Journal of Clinical Investigation* (Bergmeier, W., T. George, H.-W. Wang, J.R. Crittendon, A.C.W. Baldwin, S.M. Cifuni, D.E. Housman, A.M. Graybiel, and D.D. Wagner. *J. Clin. Invest*. 117:1699--1797).
[^1]: CORRESPONDENCE Ronen Alon: <ronen.alon@weizmann.ac.il> OR Amos Etzioni: <etzioni@rambam.health.gov.il>
|
{
"pile_set_name": "PubMed Central"
}
|
4370560*r**3 - 4
Differentiate 157468*a*n + 2083*a + 252*n + 2156963 wrt a.
157468*n + 2083
What is the third derivative of 13961610*c**4 - 2*c**3 - 430*c**2 - 25*c - 2133?
335078640*c - 12
Find the second derivative of -23*h**3*s + 101777*h**2*s - 3*h*s + 263335*h - s + 2 wrt h.
-138*h*s + 203554*s
Find the third derivative of 2014443*c**4*z**2 - 2*c**3*z**2 - 3*c**2*z**2 - 3*c**2*z - 4339*c*z**2 - 13*z wrt c.
48346632*c*z**2 - 12*z**2
What is the second derivative of 15111*c**2*k*p + 397*c**2*k - 99*c*k*p + 13*c*k - 2*c + 2*k - 1 wrt c?
30222*k*p + 794*k
What is the second derivative of 64955*h*o**2 - 600*h + 465*o**2 - 89817*o wrt o?
129910*h + 930
Differentiate 5826989*j**4 - 89324869 wrt j.
23307956*j**3
Find the second derivative of -32*o**3*r**2 - 18*o**3*r - o**3 + 6*o**2*r**3 - o**2 - 76*o*r + o + 227483*r**2 + 5939 wrt r.
-64*o**3 + 36*o**2*r + 454966
What is the second derivative of 2*r**5 + 9544702*r**2 - 22415468*r?
40*r**3 + 19089404
What is the second derivative of 6793*j**3 - 2*j**2 - 2*j - 12061103 wrt j?
40758*j - 4
What is the third derivative of -37*d**3*j**2 - 344517*d**3*j + 8*d**3 - 1033*d**2*j - 5*d*j**2 - 996*j**2 - 2 wrt d?
-222*j**2 - 2067102*j + 48
Find the second derivative of -77242053*f**3 - 24003017*f wrt f.
-463452318*f
What is the second derivative of 769776972*z**2 + 329285214*z wrt z?
1539553944
What is the first derivative of 3*p**2*t**2 + 231626330*p**2 - 18283081*p*t**4 wrt t?
6*p**2*t - 73132324*p*t**3
Find the third derivative of -g**5 - 23*g**4 - 782872*g**3 + 14515831*g**2 + 3*g - 1 wrt g.
-60*g**2 - 552*g - 4697232
Find the first derivative of 22006*a*t**3 - 1134*a*t - 55835442*t**3 wrt a.
22006*t**3 - 1134*t
Find the third derivative of 825803202*n**4 + 12258*n**2 + 6*n - 211 wrt n.
19819276848*n
What is the third derivative of 466449389*n**3 - 117511449*n**2 - 3 wrt n?
2798696334
What is the first derivative of -172529777*l*n**2 + 31642873*n**2 wrt l?
-172529777*n**2
What is the second derivative of h**2*p + 8618920*h**2 - 8351*h*p - 2*h - 14*p - 7 wrt h?
2*p + 17237840
Find the second derivative of -19*j**4 - 10289*j**3 - 6*j**2 - 698050*j + 1 wrt j.
-228*j**2 - 61734*j - 12
Find the third derivative of 48448*r**6 + 2*r**4 - 27*r**3 + 18708748*r**2 wrt r.
5813760*r**3 + 48*r - 162
Differentiate 282870*c**4 - 24*c**3*w**3 - 29*w**3 - 2*w**2 - 2*w + 15777 wrt c.
1131480*c**3 - 72*c**2*w**3
Differentiate 2844753*v**3 - 13*v*y - 86764920*y with respect to v.
8534259*v**2 - 13*y
Find the third derivative of -918548059*a**3 + 457109264*a**2 + a - 2.
-5511288354
What is the third derivative of w**6 - 47615279*w**4 + 8272690*w**2?
120*w**3 - 1142766696*w
What is the first derivative of -53307*v**2 + 576*v + 1155862127 wrt v?
-106614*v + 576
What is the second derivative of -159*h**2*j**3 - h**2*j + 72*h**2 + h*j**3 - 2*h*j - 2180*j**3 - 155*j**2 - 2 wrt h?
-318*j**3 - 2*j + 144
Find the first derivative of -46339131*z + 60948872.
-46339131
Differentiate -s*u**2 + 566655*s*u*v - 3*u**2*v - 996044*u**2 - u*v wrt s.
-u**2 + 566655*u*v
Find the second derivative of -2*i**3 - 105253*i**2 + 3462*i - 645.
-12*i - 210506
What is the third derivative of -16*l**4 + 1185850*l**3 - 148*l**2 + 9*l + 689 wrt l?
-384*l + 7115100
What is the derivative of -4914278*z - 101324530?
-4914278
Differentiate 55838295*u - 105467842.
55838295
Find the first derivative of 1479*n**4 + 2*n**2 + 4571*n - 137009630.
5916*n**3 + 4*n + 4571
Find the third derivative of 598042461*h**6 + 2*h**5 - 47102554*h**2 - 3*h + 1.
71765095320*h**3 + 120*h**2
Differentiate 18057*b**3 - 40*b**2 + 12831970 wrt b.
54171*b**2 - 80*b
What is the derivative of 4172884*t - 3585387 wrt t?
4172884
Find the third derivative of -23*k*q**4 - 36378*k*q**3 + 1120*k*q**2 + 3*k - q**4 - 11*q - 11 wrt q.
-552*k*q - 218268*k - 24*q
What is the second derivative of 8024*n**5 - 1273*n**4 - n**3 - 211950099*n wrt n?
160480*n**3 - 15276*n**2 - 6*n
Differentiate y**2 + 6825537*y - 41398953 wrt y.
2*y + 6825537
What is the first derivative of -64692593*a**2 - 78596640?
-129385186*a
Differentiate 133503245*m - 91816689 wrt m.
133503245
What is the second derivative of -47160235*o**2 - o + 5927485?
-94320470
Find the third derivative of -10096256*w**4 - 54149520*w**2.
-242310144*w
What is the third derivative of 30275256*a**3 - 19117881*a**2?
181651536
Differentiate 113*o*s**2 - 2512*o*s + 310*o + 686609371*s**2 + 2 wrt o.
113*s**2 - 2512*s + 310
Find the second derivative of -2*q**2*v*x**2 - 6*q**2*x**2 - 6339*q**2*x + q*v*x**2 + q*v*x + 62*q*v + 2*q*x**2 - q*x + 8*v*x**2 + 32*v*x wrt q.
-4*v*x**2 - 12*x**2 - 12678*x
What is the second derivative of -10369185*q**2 + 12394555*q wrt q?
-20738370
Differentiate m**4 - 114*m**3 + 418*m + 5139821 with respect to m.
4*m**3 - 342*m**2 + 418
What is the derivative of 135*j*l**2 + 112433*j + 5308*l**3 - 2*l**2 - 16 wrt l?
270*j*l + 15924*l**2 - 4*l
Find the second derivative of -514074604*l**2 + 15552*l - 3321 wrt l.
-1028149208
Differentiate -10920586*f*g + 5576092*f wrt g.
-10920586*f
Find the third derivative of -340311*b**6 + 3*b**4 + b**2 + 3926*b + 271 wrt b.
-40837320*b**3 + 72*b
What is the second derivative of -158*j**2*l**3 + 1036*j**2*l**2 + 29*j**2 + 6*j*l**3 + 56*j*l**2 - 2*l**3 + 2*l**2 - 72*l - 3 wrt j?
-316*l**3 + 2072*l**2 + 58
Find the second derivative of -170*s**3*w**2 - 71630282*s**3*w - 4*s**3 + 671864*s**2*w**2 wrt w.
-340*s**3 + 1343728*s**2
What is the third derivative of 50320629*f**3*z**3 - 2*f**3 + 4447*f**2*z**2 - 22*f wrt z?
301923774*f**3
Find the third derivative of 407204*i**5 + 51*i**4 - 149*i**2 + 352*i + 1 wrt i.
24432240*i**2 + 1224*i
What is the second derivative of d**3*j*w**3 - 405421*d**2*j**2*w**3 + 9386*d*j**2*w**2 + j**2*w**2 + 68*w**3 wrt d?
6*d*j*w**3 - 810842*j**2*w**3
Find the second derivative of 3*y**4 + 4*y**3 + 5278*y**2 + 2585*y + 2083.
36*y**2 + 24*y + 10556
Find the third derivative of 132299*w**5 - 2*w**4 - 41*w**3 - 9952298*w**2.
7937940*w**2 - 48*w - 246
What is the first derivative of -4523752*t + 23986215 wrt t?
-4523752
Find the first derivative of 35980*h**2 - 1509*h + 119428183.
71960*h - 1509
Differentiate -f**3*p**3 - 202*f**3*p*x - 9*f**2*p**2 + 206*f*p**3 - 32*f*p**2 + 16396*p**3*x + 21*p**3 - 3*p with respect to x.
-202*f**3*p + 16396*p**3
Find the third derivative of 58*t**3*v**3 + 18407*t**3 - 115*t**2*v**3 - 9*t**2*v + 3*t*v**3 - 7*t*v**2 - 5*v**3 wrt t.
348*v**3 + 110442
What is the third derivative of 69968701*y**3 + 2384130*y**2 + 2 wrt y?
419812206
What is the third derivative of 2629358*v**3 + 35*v**2 - 475*v + 16?
15776148
What is the third derivative of -29*a*j*z**3 - 1540*a*z**3 - 58*a*z**2 + 2*j*z**3 + 2*j*z + 2*j + 2*z**3 + 1362 wrt z?
-174*a*j - 9240*a + 12*j + 12
What is the derivative of 84*m**2*n*v**2 + m**2*v**2 + 3*m**2 - 6*m + 138567*n*v**3 - 1261*v**3 + 29*v**2 wrt n?
84*m**2*v**2 + 138567*v**3
Differentiate 4881*t**2 - 2891*t - 43129205 with respect to t.
9762*t - 2891
Differentiate 271*q**2*w*z - 10125*q*w**3*z - 7*q + 15904*w**3*z - 52*w**3 - 25*w**2*z - 2*w**2 + 2*z + 2 wrt q.
542*q*w*z - 10125*w**3*z - 7
What is the second derivative of 12470526*l**2 + 13182311*l wrt l?
24941052
What is the second derivative of 845*f**4 - 711*f**3 - 15*f**2 + 300873*f - 2 wrt f?
10140*f**2 - 4266*f - 30
Find the first derivative of 5*a**2*d**3 - 230054*a*d**3 - 1821315*d**3 wrt a.
10*a*d**3 - 230054*d**3
What is the third derivative of 463660*o**5 + 38*o**3 + 540*o**2 + 4*o + 38887 wrt o?
27819600*o**2 + 228
Differentiate 10*b**4*f**2 - 6601818*b*f**2 + 270*f**2 - 227666*f wrt b.
40*b**3*f**2 - 6601818*f**2
Find the second derivative of 41101*g**5 + 6*g**4 - 694*g**3 + 38*g + 322624 wrt g.
822020*g**3 + 72*g**2 - 4164*g
Differentiate -14938558*b**3*k - 1154580*b**3 - b + 2 with respect to k.
-14938558*b**3
What is the third derivative of -88*c**4 + 116354*c**3 + 3*c**2 - 202616*c + 152?
-2112*c + 698124
Find the first derivative of 5*s**3 - 9364*s**2 - 64*s + 12007487.
15*s**2 - 18728*s - 64
Find the first derivative of -60*f*l**2 + 2*f*l - 2826*f - 1461569*l**2 wrt f.
-60*l**2 + 2*l - 2826
Find the second derivative of 8078019*x**2 + 66789954*x wrt x.
16156038
What is the second derivative of -17489*i**5 - 114*i**3 - 5*i + 2869478 wrt i?
-349780*i**3 -
|
{
"pile_set_name": "DM Mathematics"
}
|
Soret motion of a charged spherical colloid.
The thermophoretic motion of a charged spherical colloidal particle and its accompanying cloud of counterions and coions in a temperature gradient is studied theoretically. Using the Debye-Hückel approximation, the Soret drift velocity of a weakly charged colloid is calculated analytically. For highly charged colloids, the nonlinear system of electrokinetic equations is solved numerically, and the effects of high surface potential, dielectrophoresis, and convection are examined. Our results are in good agreement with some of the recent experiments on highly charged colloids without using adjustable parameters.
|
{
"pile_set_name": "PubMed Abstracts"
}
|
We've probably all theorized about fictional situations and how we'd deal with them. The zombie apocalypse, any end-of-the-world narrative, or maybe even less far-reaching scenarios like exploring and colonizing new planets in space. Well, just last week I got to put my hypothetical space adventure decisions to the test in the next chapter of Civilization.
I didn't get to spend more than about 30-45 minutes with it, but I started from the opening of the game and got a good understanding of its beginnings.
All the usual aspects of a Civilization game are here. You start off with a handful of people at your command at a solitary base that you can choose to grow in a way you see fit. So I did what any new player would do: I set out to explore.
The land of Mandira that you're trying to colonize is full of miasma—a gaseous toxin that's a new environmental hazard for the series.. So exploring is a little more risky than usual. Land on an area of the map that's infected by this toxin and your soldiers' health with slowly deplete each turn you leave them there.
Soon enough, though, larger threats surfaced. I stumbled upon an alien nest—filled with bug-like creatures that are fairly aggressive and will seek out any nearby invaders. I killed them off leaving my troops fairly unscathed, and set my explorer out a few more paces. Eventually I found a resource pod which set off a new mission quest: find three more resource pods. Easy enough! Except for the fact that the stretch of land I could see out in front of me was also infested with miasma and other alien nests. While I made my way to what looked like other resource pods across the map, simultaneously researching areas of biology and genetics for my civilization, a few things happened.
I met a few leaders of other civilizations. The first sighting was exciting—it was good to know fellow humans were surviving out in space, not that that was unexpected. Other leader introductions quickly followed the first one, and soon I was learning all about what Firaxis had explained in a presentation just before we went hands on: that different communities had different approaches to humanity's future, ideals that were replicated not only in their decisions, strengths and weaknesses as civilizations but even in their fashion choices.
I met Samatar Jama Barre of the People's African Union, for instance, whose strengths were in diplomacy, growth and health and weaknesses in production and religion. There was Suzanne Marjorie Fielding of the American Reclamation Corporation, too, whose nation has a focus in science, infrastructure and production while lacking in cultures religion.
Each civilization can specialize in what's called an "affinity," which represents one of three possible choices in steering humankind's future on this alien planet. They are: supremacy, purity, and harmony. Researching technologies, Firaxis said during their presentation, is the most common way of gaining points in your affinity. Eventually disagreements in how humans should be treating this planet and their life there could lead you towards war with nations whose ideals don't align with yours. Unfortunately my newfound relationships were just that—too new to start rashly declaring any allies or enemies.
In between exploring and meeting new civilizations, I had to make decisions about what station charters to support. Do I go for the Banu Musa science think tank? Or the Shackleton geological mapping enterprise? I would have to decide between Scyon group labs or to support the McDonough biomechanical research. At one point, I had to make a (very topical) choice on health care for the clinic workers I had just invested in.
Towards the end of my 40 turns with a pre-alpha build of Civilization: Beyond Earth, I was mostly on the defense. Giant alien worms known as siege worms were within scary distances of my city, and I quickly enlisted more soldiers to help stave off the attacks. Killing just the first worm was a feat of its own—it takes down soldiers like they're flies, one swipe and they'll die instantly.
Between my city's main missile attacks and my soldiers distracting the worms, I managed to get it down. Not only that, but I took down the other two attacking worms that surfaced while I battled the first one. With two simultaneous worms, I couldn't do much else besides swap between groups of soldiers to allow one to rest and heal up while the other group kept the worms' attentions. It was a rough back-and-forth battle, but I somehow killed all three before my time was up.
I didn't manage to get too in depth with the city I could build, research I could invest in or relationships I could explore, but it's clear that Mandira and the space civilization we embarked on is a dangerous one.
Civilization: Beyond Earth releases in the fall for PC, Mac and Linux.
|
{
"pile_set_name": "OpenWebText2"
}
|
#' Programme for International Student Assessment (PISA) 2012 Data for Australia
#'
#' About PISA
#'
#' The Programme for International Student Assessment (PISA) is a triennial international survey which aims to evaluate education systems worldwide by testing the skills and knowledge of 15-year-old students. To date, students representing more than 70 economies have participated in the assessment.
#'
#' While 65 economies took part in the 2012 study, this data set only contains information from the country of Australia.
#'
#' @details \itemize{
#' \item gender : Factor w/ 2 levels "female","male": 1 1 2 2 2 1 1 1 2 1 ...
#' \item age : Factor w/ 4 levels "4","5","6","7": 2 2 2 4 3 1 2 2 2 2 ...
#' \item homework : num 5 5 9 3 2 3 4 3 5 1 ...
#' \item desk : num 1 0 1 1 1 1 1 1 1 1 ...
#' \item room : num 1 1 1 1 1 1 1 1 1 1 ...
#' \item study : num 1 1 1 1 1 1 1 1 1 1 ...
#' \item computer : num 1 1 1 1 1 1 1 1 1 1 ...
#' \item software : num 1 1 1 1 1 1 1 1 1 1 ...
#' \item internet : num 1 1 1 1 1 1 1 1 1 1 ...
#' \item literature : num 0 0 1 0 1 1 1 1 1 0 ...
#' \item poetry : num 0 0 1 0 1 1 0 1 1 1 ...
#' \item art : num 1 0 1 0 1 1 0 1 1 1 ...
#' \item textbook : num 1 1 1 1 1 0 1 1 1 1 ...
#' \item dictionary : num 1 1 1 1 1 1 1 1 1 1 ...
#' \item dishwasher : num 1 1 1 1 0 1 1 1 1 1 ...
#' \item PV1MATH : num 562 565 602 520 613 ...
#' \item PV2MATH : num 569 557 594 507 567 ...
#' \item PV3MATH : num 555 553 552 501 585 ...
#' \item PV4MATH : num 579 538 526 521 596 ...
#' \item PV5MATH : num 548 573 619 547 603 ...
#' \item PV1READ : num 582 617 650 554 605 ...
#' \item PV2READ : num 571 572 608 560 557 ...
#' \item PV3READ : num 602 560 594 517 627 ...
#' \item PV4READ : num 572 564 575 564 597 ...
#' \item PV5READ : num 585 565 620 572 598 ...
#' \item PV1SCIE : num 583 627 668 574 639 ...
#' \item PV2SCIE : num 579 600 665 612 635 ...
#' \item PV3SCIE : num 593 574 620 571 666 ...
#' \item PV4SCIE : num 567 582 592 598 700 ...
#' \item PV5SCIE : num 587 625 656 662 670 ...
#' \item SENWGT_STU : num 0.133 0.133 0.141 0.141 0.141 ...
#' \item possessions: num 10 8 12 9 11 11 10 12 12 11 ...
#' }
#'
#' @docType data
#' @keywords datasets
#' @name australia_PISA2012
#' @usage data(australia_PISA2012)
#' @format A data frame with 8247 rows and 32 variables
#' @source \url{http://www.oecd.org/pisa/pisaproducts/database-cbapisa2012.htm}
NULL
|
{
"pile_set_name": "Github"
}
|
Ayub Ali
Ayub Ali (1887 – 1995) was a Bangladeshi educationist. He was awarded Ekushey Padak in 1976 by the Government of Bangladesh.
Early life and education
Ali was born in Pirojpur District to Maulavi Abdul Wahed and Abida Khatun. He earned BA Honors and MA degrees in Islamic Studies from University of Dhaka in 1943 and 1944 respectively. He obtained a second MA degree in Persian from the same University in 1950. He achieved Alamiah Diploma in 1953 and Ph.D. in 1955 from the Al-Azhar University in Cairo.
Career
Ali joined Dhaka College as a lecturer in 1944. He was Principal of Rajshahi Madrasa during 1958-1969.
References
Category:1887 births
Category:1995 deaths
Category:University of Dhaka alumni
Category:Al-Azhar University alumni
Category:Recipients of the Ekushey Padak
Category:Dhaka College faculty
|
{
"pile_set_name": "Wikipedia (en)"
}
|
Q:
How can I implement server-side rate limiting for a Perl web service?
I have a Perl-based CGI/Fast CGI web service and want to rate-limit clients by IP address to stop aggressive clients causing too much work.
I have looked around for some code and found Algorithm::TokenBucket in CPAN but that is for client requests; it has no persistence and has no per-user config so is not really useful for server-side rate limiting.
I am looking for suggestions for something that already exists, otherwise I'll need to roll my own based on some simple persistence such as tie to DB_File per-IP address and some batch job that does the token management.
A:
I've used Cache::FastMmap for rate-limiting by tracking hits per IP address. It's a cache so data will expire over time, but if you set the size and expire time right, this shouldn't be an issue.
The IP address is the hash key and the hash value is an array of timestamps. I have a second data structure (also backed by Cache::FastMMap) which is a hash of banned IP addresses, updated according to the data from the first structure.
A:
I know it's not what you asked, but have you considered handling this elsewhere in the stack where it's already been done for you? Clearly I don't know your deployment stack, but if it's apache you could use mod_evasive. Alternately if you're on Linux you could let iptables do its job using something like:
#Allow only 12 connections per IP
/sbin/iptables -A INPUT -p tcp --dport 80 -m conn-limit --connlimit-above 12 -j REJECT --reject-with tcp-reset
certainly more complicated rules are possible.
|
{
"pile_set_name": "StackExchange"
}
|
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