text
stringlengths 8
5.74M
| label
stringclasses 3
values | educational_prob
sequencelengths 3
3
|
|---|---|---|
Gene expression profiling using laser capture microdissection. Human disease is governed by a complex array of cellular populations and sub-population. Gene expression profiling is proving an important means of understanding and classifying pathophysiologic processes by identifying genes, gene pathways and pathway networks not previously known to be associated with particular diseases. However, disease-associated gene expression can be obscured by surrounding 'normal' tissue. Laser capture microdissection allows gene expression analysis of pooled single cells, cell subpopulations and cell populations. Analysis of laser capture microdissection-procured cells will allow a better understanding of the cellular components of disease. | High | [
0.710691823899371,
28.25,
11.5
] |
Pixel Pixel comes from "pix" (for "picture") and el (for "element"). A pixel is the smallest piece of information on an image. This is a unit for measuring image resolution, and the more pixels a picture consists of, the more detailed it is. | Mid | [
0.6528735632183901,
35.5,
18.875
] |
Q: What are Advantages to Content Repositories (not talking about CMS's) Given that a lot of people use content repositories. There must be a good reason. I'm building out a new web application that will need to store content. Can someone help me understanding this? What are the advantages to using a content repository like Apache Jackrabbit as opposed to writing your own code/API to store images or text pages? Writing your own requires time etc. but so too does implementing and learning a new framework like the content repository API. A benefit to rolling your own seems to me that you know your code and have immediate expertise if you need to enhance or fix it. Using another framework you need to learn its foibles, and it is always easier to modify code you know that don't know... i.e. you don't know that underlying framework code as well as your own. As I said a lot of people use them. There must be a reason. I can't see it as being just another "everyone is using them so, so should we." At least I hope it isn't that. :) A: A JCR repository allows you to store all your content (from structured database-type data to large multimedia files) in a single place and with a single API, which is extremely convenient and makes your code simpler, avoiding the impedance mismatch between files and data that you usually have in content-based systems. JCR also provides a lot of infrastructure functionality that you won't have to build or assemble yourself: search (including full-text), observation (callbacks when something changes) versioning, data types including multi-value, ordered nodes, etc... If you allow a shameless plug, my "JCR - best of both worlds" article at http://java.dzone.com/articles/java-content-repository-best describes this in more detail and also provides a reading list for the JCR spec, that should allow you go get a good overview without reading the whole thing. The article uses Apache Sling for its examples, which combined with a JCR repository provides a very nice (IMO, but as a Sling committer I'm biased ;-) platform for content-based applications. A: My most recent projects have involved both choices: a custom-built data store (MySQL and image files) wtih a multi-level caching mechanism, and a JCR-based commercial repository. A few thoughts: In the short run, a DIY solution offers reduced complexity: you only have to build and learn what you need. And there is at least the opportunity to optimize the data store for your particular application's needs -- more than likely speed of retrieval, but possibly storage footprint, security, or reliability concerns are foremost for you. However, in the long run, you're looking at a significant increment of work to extend the home-grown system to a new content type (video, e.g.) or to provide new functionality (maybe, versioning). Also, it's difficult to separate the choice of a data store approach from the choice of tools that content providers will use to populate and maintain the data store. You'll have to give your authors something more than an HTML form with a textarea and a submit button. | Mid | [
0.6403940886699501,
32.5,
18.25
] |
Greencastle woman dies in SUV crash April 13, 2012|By HEATHER KEELS | [email protected] WAYNESBORO, Pa. — A 35-year-old Greencastle, Pa. woman died Friday morning when the SUV she was driving rolled over on Five Forks Road northwest of Waynesboro, Pennsylvania State Police Trooper Shaun Maher said. Rebecca Jo Horst was pronounced dead at the scene at 6:48 a.m. by the Franklin County Coroner’s Office, according to a state police news release. The cause of death was listed as multiple blunt force trauma. The single-vehicle crash happened at 5:55 a.m. near 10355 Five Forks Road, about a mile south of the intersection with Pa. 316, Maher said. Horst was driving north on Five Forks Road in a 2002 Jeep Liberty SUV when she lost control of the vehicle and ran off the right side of the road, according to the release. The SUV rolled over twice and came to rest in a field facing south. Horst was thrown from the vehicle. Horst was the only person in the vehicle and no other vehicles were involved, Maher said. | Low | [
0.342783505154639,
16.625,
31.875
] |
The effectiveness of live lactobacilli in combination with low dose oestriol (Gynoflor) to restore the vaginal flora after treatment of vaginal infections. To evaluate the effectiveness of live lactobacilli in combination with low dose oestriol for restoration of the vaginal flora after anti-infective treatment. The study was designed as a single centre, randomised, placebo-controlled, double-blind clinical trial. University Hospital. Three hundred and sixty women out of 1750 were randomised. Three hundred and sixty women with the complaints of vaginal infections (bacterial vaginosis, candidiasis, trichomoniasis or fluor vaginalis) were randomly assigned two to seven days after the end of the anti-infective therapy, to therapy with live lactobacilli in combination with low dose oestriol (study group, n= 240) or placebo (n= 120). The follow up visits occurred three to seven days and four to six weeks after the end of the restoration therapy. The Normal Flora Index (NFI), which consists of numbers of lactobacilli, pathogenic microorganisms, leucocytes and vaginal pH, was used as the primary outcome of the study. Secondary outcomes included the total symptoms score, the degree of purity of the vaginal flora and the global assessment of the treatment by the investigator and the women. During restoration therapy, the NFI increased significantly more in the study group than in the control group in both first and second control visits (P= 0.002 and P= 0.006, respectively). The degree of purity of the vaginal flora also increased significantly more in the study group compared with the control group (P < 0.0001 and P= 0.001, respectively). No serious adverse event was reported during restoration therapy. Restoration of the vaginal flora can be significantly enhanced by the administration of live lactobacilli in combination with low dose oestriol. | High | [
0.6972010178117041,
34.25,
14.875
] |
Los Angeles, May 1 – in letter to Audrey Collins [1] - Chief Judge of the US District Court, Central District of California, Dr Joseph Zernik, Los Angeles County resident, repeated allegations of perversion of justice in litigations involving civil rights, where judges of the Superior Court of California and Countrywide Financial Corporation or Bank of America and their senior managers were named defendants. Furthermore, regarding a February 19, 2010 letter by Court Counsel Lydia Yurtchuk, [2] purporting to notice investigation into such allegations, Dr Zernik stated, “a reasonable person would be hard pressed to find the February 19, 2010 letter by US District Court Counsel, Lydia Yurtchuk as a notice of an honest valid, and effectual investigation.” Dr Zernik therefore repeated his request for initiation of corrective actions in the cases by the Chief Judge, as required by law. The cases, which were the specific subject of the letter to Chief Judge Collins, were Fine v Sheriff (2:09-cv-01914) and Zernik v Connor et al (2:08-cv-01550). The former was the habeas corpus petition of the 70 year old former US prosecutor Richard Fine, [3] [4] held for over a year in solitary confinement in Los Angeles, with no warrant ever issued for his arrest, and no judgment, conviction, or sentencing ever entered in his case. Less than two weeks prior to his arrest the California Governor signed “retroactive immunities” (pardons) for all Los Angeles Superior Court judges, who had taken “not permitted” payments, which had been exposed and protested by Mr Fine. The latter case named a dozen judges of the Superior Court, Countrywide Financial Corporation, Bank of America Corporation, and their senior management as parties to conduct at the Superior Court, typically associated with racketeering. [5] Beyond the specific allegations related to the two specific cases, the letter alleged that perversion of justice was enabled through fraud inherent in the design and the mode of operations of the Court’s online public access system – PACER - and the Court’s case management system – CM/ECF. Chief Judge Audrey Collins was asked to respond within ten days. Copies were forwarded to relevant US Senate and House Committee Chairs, and to the Basel Committee on International Banking and UN High Commissioner on Human Rights. On April 19, 2010, Dr Zernik filed report with the UN on behalf of Human Rights Alert, a Los Angeles based NGO, alleging large-scale violations of Human Rights by the US Government, and a central role for fraud in online public access and case management systems of the courts and correctional institutions in such alleged abuse. [6] The complaint file with the UN called for correction of such conditions through publicly accountable validation (certified functional logic verification) of such systems in the courts and in correctional institutions. LINKS [1] May 1, 2010 Letter to Audrey Collins – Chief Judge of the US District Court, Los Angeles. On the evening of Saturday, April 24, 2010, a group of armed, badge-wearing agents appeared at my residence in an attempt to apprehend me. I was not home. My neighbor told me on Sunday morning, and asked that I surrender, out of concern that others (including him and his family) may otherwise get hurt. It is not clear to me which agency it was, although I suspect it was US Marshals, and it is not clear to me what it was about their conduct that made the neighbor conclude that they were trigger eager. Regardless, I left the place, and am not available by phone right now. I would be grateful if you could let me know if the agents who appeared on Saturday night were indeed USMS, and what the legal basis for their action was. 11-12-10 Where should Occupy go next? Civil Disobedience in the footsteps of Thoreau and Gandhi!http:// www.scribd.com/doc/75348301/12-06-08 Courts and Judges as racketeering enterprises under RICO (the Racketeer Influenced and Corrupt Organizations Act) - key element in the current financial crisishttp://www.scribd.com/doc/96504009/Secede! The US in its current form is simply unmanageable... What did the experts say? * דוח סייג לזכויות האדם נכלל בדוח התקופתי של האו"ם לגבי זכויות האדם בישראל (2013), בלוויית ההערה: "חוסר יושרה בכתבים האלקטרוניים של בית המשפט העליון, בתי המשפט המחוזיים, ובתי הדין למוחזקי משמורת בישראל".* The Human Rights Alert (NGO) submission to the Human Rights Council of the United Nations was incorporated into the 2010 Periodic Review Report regarding Humnan Rights in the United States, with the note: "corruption of the courts and the legal profession and discrimination by law enforcement in California".* The Human Rights Alert (NGO) submission to the Human Rights Council of the United Nations was incorporated into the 2013 Periodic Review Report regarding Humnan Rights in Israel, with the note: "lack of integrity of the electronic records of the Supreme Court, the district courts and the detainees courts in Israel." The United States * "...it's difficult to find a fraud of this size on the U.S. court system in U.S. history... where you have literally tens of thousands of fraudulent documents filed in tens of thousands of cases." Raymond Brescia, a visiting professor at Yale Law School * Los Angeles County is"the epicenter of the epidemic of real estate and mortgage fraud."FBI (2004) * “…judges tried and sentenced a staggering number of people for crimes they did not commit."Prof David Burcham, Loyola Law School, LA (2000) * “This is conduct associated with the most repressive dictators and police states… and judges must share responsibility when innocent people are convicted.”Prof Erwin Chemerinksy, Irvine Law School (2000) http://www.scribd.com/doc/239647129/The HRA submission was incorporated into the 2015 HRC Professional Staff Report on the United States with the note: :“HRA NGO recommended restoring the integrity of the IT systems of the courts, under accountability to the Congress, with the goal of making such systems as transparent as possible to the public at large.” [2] Human Rights Alert (NGO) submission for the 2013 UPR of the State of Israel was incorporated into the UN Human Rights Council Professional Staff Report with the note: "Lack of integrity in the electronic record systems of the Supreme Court, the district courts and the detainees' courts in Israel". 2012-06-04 Human Right Alert's Submission; 2013 UPR of the State of Israel: Integrity, or lack thereof, of the [3] Human Rights Alert (NGO) submission for the 2010 UPR of the United States was incorporated into the UN Human Rights Council Professional Staff Report with the note: "Corruption of the courts and the legal profession and discrimination by law enforcement in California." 2010-04-19 Human Rights Alert (NGO) submission to the United Nations Human Rights Council for the 2010 Review (UPR) of Human Rights in the United States as incorporated into the UPR staff report: [1] 10-10-01 United Nations Human Rights Council Records for 2010 Review (UPR) of Human Rights in the United States, where Human Rights Alert (NGO) submission was incorporated with a note referring to "corruption of the courts and the legal profession and discrimination by law enforcement in California."http://www.scribd.com/doc/38566837/http://www.scribd.com/doc/108663259/ | Mid | [
0.641791044776119,
32.25,
18
] |
Letter: Reeves-Ellington a breath of fresh air I have known Richard Reeves-Ellington as a friend and neighbor for a number of years and was delighted when he decided to become a candidate for Town Supervisor. He is a breath of fresh air in politics – a person who has a keen interest in the pressing issues of our day, has thoughtful, insightful, and well informed views, and most of all is a person of integrity who knows what he believes in and can defend his positions which being influenced by the shifting winds of political expediency. I particularly appreciate Richard’s views on our healthcare crisis. Few disagree that we, in fact, have a crisis even though there is no apparent consensus on a solution. Richard has studied the issue and agrees that access to quality affordable healthcare is a basic human right and that a single payer Medicare for All system is the only appropriate approach to resolving the basic inequities of our current system. While many view this as a national issue, Richard knows that this is a local issue as well. The high cost of healthcare has a significant impact on our municipal and school budgets – and therefore on our local property tax rates. The exorbitant and ever increasing cost of paying for our current healthcare system impacts, as well, on the stability and quality of life of our friends, our neighbors, our local businesses, and ultimately our community. It’s unconscionable that people are forced into bankruptcy because they cannot pay for needed medical care. This is not hype; it is happening. How many people do you know who are running the risk of being uninsured because they cannot afford to pay health insurance premiums? How many young people entering the job market cannot find a job with benefits? Why do so many businesses only hire part-time employees, and avoid the cost of medical insurance premiums, when people, and our economy, need full time jobs? These are only some examples of the damage inflicted by our current healthcare system - and clearly we need a different approach. Richard Reeves-Ellington is ready, willing, and courageous enough to address the issues facing our community. I am supporting him for Town Supervisor and I urge you to do the same. | High | [
0.68235294117647,
36.25,
16.875
] |
Introduction {#s1} ============ T-LAK cell-originated protein kinase (TOPK) is a serine-threonine kinase, which is a member of MAPKK family. TOPK is also related with the mitotic spindle to the centromere. The studies showed that over-expression of TOPK leads to characteristic of cancerous cell, creating aneuploidy cells in transformed cells JB6 C141 cells ([@B26]). TOPK was highly expressed in several malignancies and promoted tumorigenesis and progression ([@B7]; [@B24]). Therefore, TOPK might be an excellent drug target for cancer chemotherapy. It is necessary to find TOPK inhibitors with low toxicity to overcome the side-effect of current TOPK inhibitors ([@B16]; [@B9]). There were several small molecule compounds from Chinese herbal medicine reported to be an inhibitor of TOPK to reduce the proliferation of tumor cells ([@B4]; [@B22]). However, the study of inhibiting TOPK in esophageal cancer has not been reported, although TOPK was highly expressed in esophageal cancer. In our study, we found that eupafolin can block TOPK and inhibit TOPK kinase activity. Materials and Methods {#s2} ===================== Reagents and Antibodies {#s2_1} ----------------------- Eupafolin or 6-methoxyluteolin was extracted from Ay Tsao (*Artemisia vulgaris* L.). The plant material was purchased from Anyang Jiutou Xian Ai Co. Ltd. (Anyang, China). Air-dried plant material (3.0 kg) of Ay Tsao was extracted with 95% ethanol under reflux three times, for 2 h for each time. The extract was concentrated in rotary vacuum evaporator to give a residue (23.5 g). The residue was dissolved in H~2~O and then extracted successfully with petroleum ether (2 L), EtOAC (2 L), and n-BuOH (each 2 L). The active EtOAC fraction (15.7 g) was subjected in to silica column chromatography to (200--300 mesh) and eluted with petroleum ether/EtOAc (90:10, 80:20, 50:50, 25:75) and followed by CHCl3/MeOH in a stepwise gradient (90:10, 80:20, 70:30, 60:40, 0:100) to obtain eight fractions (fr.1−8) on the basis of TLC profiles. Fraction 3 (1.785 g) was further chromatographed on Sephadex LH-20 eluted with (CHCl3/MeOH 1:1) to furnish four sub-fractions, designated as fr.3--1 to 3--4. Fr.3--2 (265.2 mg) was further purified by preparatory TLC to obtained pure compound 6-methoxyluteolin (14.8 mg). HI-TOPK-032 was purchased from National Institutes of Health (NIH). Recombinant active TOPK and inactive TOPK were purchased from Millipore (Billerica, MA). The CNBr-Sepharose 4B was purchased from GE Healthcare (Pittsburgh, PA). Antibodies to detect β-actin, p-histone H3, histone H3, and cleaved caspase-3 were from Cell Signaling Technology (Danvers, MA). Cell Culture and Cytotoxicity Assay {#s2_2} ----------------------------------- The cells were purchased from American Type Culture Collection. They were cultured at 37°C in a 5% CO2 incubator using DMEM medium containing 10% fetal calf serum. Cells were planted in 96 well plant and treated with different doses of eupafolin. The cytotoxicity of eupafolin was measured using 3-(4,5-Dimethylthiazol2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazdium (MTS) Assay Kit (Promega, Madison, WI) according to the manufacturer's instructions. Soft Agar Assay {#s2_3} --------------- The cell lines (8 × 10^3^/well) were suspended in a six-well plate were exposed or not exposed to EGF (20 ng/ml) and cultured in 1 ml of 0.3% Basal Medium Eagle Agar Medium (Sigma--Aldrich Corp.) containing 10% FBS over 3 ml of 0.5% BME agar containing 10% FBS. The cells were maintained about 5--10 days in a 37°C and 5% CO2 incubator, and then, their colonies were counted by microscopy. Molecular Docking Model {#s2_4} ----------------------- To estimate the interaction mode of TOPK and eupafolin, a TOPK structure was modeled and subsequent induced-fit docking was applied. Three-dimensional protein model of TOPK (5j0a) was downloaded from the Protein Data Bank (PDB). Among those with the highest sequence identity (30%) with TOPK, structures of 4L52, 2EVA, and 4GS6 (PDB entries) were protein-ligand complex, thus suitable for the modeling of the TOPK and eupafolin complex. The sequence of TOPK and the four templates, 4L52, 2EVA, 4GS6 and 2F4J, were aligned using SYBYL-X 2.0 server with the default parameters. Microscale Thermophoresis (MST) {#s2_5} ------------------------------- Inactive TOPK protein was labeled with the Monolith NT^™^ Protein Labeling Kit RED (Cat\#L001) according to the supplied labeling protocol. The TOPK proteins were diluted in a 20 mM HEPES (pH 7.4) and 0.05 (v/v) % Tween-20 to 50 nM. The eupafolin stock was dissolved in ddH~2~O in a concentration of 5 mM. We used 5 mM eupafolin as the highest concentration for the serial dilution. After 10 min incubation at room temperature, the samples were loaded into Monolith^™^ standard-treated capillaries, and the thermophoresis was measured at 25°C after 30 min incubation on a Monolith NT.115 instrument (NanoTemper Technologies, München, Germany). Laser power was set to 20% or 40% using 30 s on time. The LED power was set to 100%. The dissociation constant Kd values were fitted by using the NTAnalysis Software (NanoTemper Technologies, München, Germany) ([@B23]). *In Vitro* Beads Binding Assay {#s2_6} ------------------------------ KYSE450 cell lysates (1 mg) were incubated with eupafolin-Sepharose 4B beads in the reaction buffer \[5 mM ethylenediaminetet acid, 150 mM NaCl, 50 mM Tris (pH 7.5), 1 mM dithiothreitol, 2 µg/ml bovine serum albumin, 0.01% Nonidet P-40, 1 µg/ml protease inhibitor mixture, and 0.02 mM phenylmethylsulfonyl fluoride\]. After incubation with gentle rocking overnight at 4°C, the beads were washed five times, and proteins bound to the beads were detected by western blotting. Protein Expression and Purification of the GST-Histone H3 {#s2_7} --------------------------------------------------------- The human GST-histone H3 fusion protein was expressed in *Escherichia coli* BL21 bacteria. The bacteria were grown at 37°C to an absorbance of 0.8--0.9 at 600 nm, induced with 0.5 mM isopropyl-β-D-thiogalactopyranoside (IPTG) 2--3 h at 37°C, and then harvested by centrifugation. The cell pellets were suspended in phosphate buffered saline (PBS). After sonication and centrifugation, the supernatant fraction was incubated with Glutathione-Sepharose beads (GE, USA) overnight at 4°C. The beads were washed with PBS and then eluted with 50 mM glutathione. After protein quantitation, the samples were separated by a 10% SDS-PAGE and visualized by Coomassie brilliant blue staining. *In Vitro* Kinase Assay {#s2_8} ----------------------- The TOPK active kinase (0.2 μg) and inactive GST- histone H3 substrate (2 μg) were incubated at 32°C for 40 min in 1×kinase buffer (25 mM Tris-HCl pH 7.5, 5 mM beta- glycerophosphate, 2 mM dithiothreitol, 0.1 mM Na3VO4, 10 mM MgCl2, and 5 mM MnCl~2~) containing 100 μM ATP. The samples were added with 5×SDS buffer and detected by western blot. Western Blot {#s2_9} ------------ The cells were harvested with 300 μl of RIPA buffer and sonicated 15 s for three times and centrifuged at 13,000 rpm for 10 min. Then the quantity of protein was determined by the BCA method. The samples (30 μg) with 5×SDS loading buffer were heated at 95°C for 10 min and then separated on a 10%-15% SDS-PAGE and subsequently transferred onto a PVDF membrane, then the membrane was blocked with 5% milk for 1 h and added into special primary antibody at 4°C overnight. Then, the membrane was washed 5 min for three times, and added secondary antibody was labeled with HRP. The membrane was detected by chemiluminescence. Patient-Derived Xenograft (PDX) Mouse Model {#s2_10} ------------------------------------------- Esophageal cancer (Anyang Tumor Hospital) fragments (2--3 mm) were implanted into the immune deficient (SCID) mice. Mice were divided into three groups: control group and two eupafolin-treated (20 or 50 mg/kg) groups. Five days after tumor implantation, mice were treated with control (0.9% saline) or eupafolin by i.p. injection three times a week for 35 days. Body weight and tumor volume were measured once a week, tumor volume was calculated using the formula, tumor volume = length×width×height×0.5. Tumor tissues and peritumoral tissues were embedded in a paraffin block and stained by immunohistochemistry. This study was approved under a protocol approved by the Anyang Institute of Technology (Anyang, Henan, China). Immunohistochemistry Staining {#s2_11} ----------------------------- Then, the sections were incubated at 4°C overnight with an antibody against histone H3 and cleaved caspase-3 (diluted 1:200). Then, sections were washed in phosphate-buffered saline (PBS) and incubated with the secondary antibody (biotinylated goat anti-rabbit, 1:200; Vector Laboratories, Burlingame, CA) for 30 min. The sections were counterstained with hematoxylin after diaminobenzidine staining. Photomicrographs were taken with a digital camera. The positively stained cells within each photomicrograph were counted. Caspase-3 Activity Assay {#s2_12} ------------------------ Caspase-3 activity in the tumor and peritumoral tissues was determined by a Caspase-3 Activity Assay Kit (BioVision K106; BioVision, Milpitas, CA, USA) according to the manufacturer's instructions. Tissues were ground and then incubated with cold lysis buffer on ice for 15 min. The lysed tissues were centrifuged for 10 min at 16,000 g at 4°C; then, the supernatants were collected, and the protein concentrations were calculated. The supernatants were transferred to a 96-well plate containing detection buffer, and Ac-DEVD-pNA was added. After incubation at 37°C for 2 h, absorbance was measured at 405 nm with a microplate reader (Thermo Fisher Scientific). The caspase-3 activity of each sample was calculated according to the standard curve and normalized to the protein concentration. Statistical Analysis {#s2_13} -------------------- All quantitative data are expressed as mean values ± standard deviation, and significant differences were determined by Student's t test or by one-way ANOVA. P \< 0.05 was used as the criterion for statistical significance. Ethics Statement {#s2_14} ---------------- Primary tumor samples of ESCC were obtained from 10 consecutive patients with ESCC who had undergone curative esophagostomy at the Division of Digestive Surgery, Department of Surgery, Anyang Tumor Hospital (Anyang, China), between 2017 and 2019. Written consent was always obtained in the formal style and after approval by the local Ethics Committee. None of these patients had undergone endoscopic mucosal resection, palliative resection, preoperative chemotherapy, or radiotherapy, and none of them had synchronous or metachronous multiple cancer in other organs. The animal study was reviewed and approved by Henan Joint International Research Laboratory of Veterinary Biologics Research and Application, Anyang Institute of Technology. Results {#s3} ======= Eupafolin Binds With TOPK and Inhibits TOPK Activity {#s3_1} ---------------------------------------------------- To estimate whether eupafolin binds to TOPK, the homology modeling and subsequent molecular docking method were applied. The binding model generated by docking simulation indicated that the compound eupafolin was positioned at the hydrophobic pocket of TOPK, surrounded by the residues Tyr-271, Lys-65, Glu-210, Thr-209, and Gly-208, forming a stable hydrophobic binding ([**Figure 1A**](#f1){ref-type="fig"}). To further evaluate this binding model, the MST method can quantify protein and small molecule interactions with high sensitivity and low sample cost by detecting fluorescent changes of molecules during thermophoresis. We detected the binding affinity between several nature compounds and TOPK using this technology. The results showed that the eupafolin had the lowest equilibrium dissociation constant (Kd) of 21.3 ± 2.1 µM ([**Figure 1B**](#f1){ref-type="fig"}, [**Table 1**](#T1){ref-type="table"}), which meant the strongest binding between the eupafolin and TOPK. {#f1} ###### Binding affinity and inhibitory activities of screening hits. Compound ICM docking mf score[^a^](#fnT1_1){ref-type="table-fn"} Dissociation constant with TOPK Inhibitory activities against KYSE 450 cells ------------ --------------------------------------------------------- --------------------------------- ---------------------------------------------- Jaceosidin −87.11 674 ± 12.2 n.i[^c^](#fnT1_3){ref-type="table-fn"} Bergenin −146 438 ± 9.5 n.i[^c^](#fnT1_3){ref-type="table-fn"} Eupafolin −125 21.3 ± 2.1 145.2 Apigenin −89.27 384 ± 47.6 n.i[^c^](#fnT1_3){ref-type="table-fn"} Docking score/interaction potential of compounds with TOPK (kcal/mol). The Kd value is automatic calculated by the curve fitting, and presents as means ± SD. n.i. is no inhibition detected in the experiments. To validate the veracity of the MST method, we employed the *in vitro* beads binding assay to analyze the binding between eupafolin and TOPK in esophageal adenocarcinoma KYSE450 cell lysates which has high expression of TOPK. No obvious band representing TOPK was observed in the beads without eupafolin group, whereas a strong band was seen in eupafolin-conjugated beads group ([**Figure 1C**](#f1){ref-type="fig"}). The above results implied that eupafolin might inhibit the TOPK activity. To confirm this hypothesis, we performed an *in vitro* kinase assay with inactive GST-histone H3 as the substrate with active TOPK in the presence of 25, 50, and 100 µM of eupafolin and 10 nM ATP. The results showed that phosphorylation of histone H3 (Ser10) was substantially attenuated in a dose-dependent manner after treatment with eupafolin ([**Figure 1D**](#f1){ref-type="fig"}). HI-TOPK-032, a TOPK inhibitor, was used as a positive control ([@B11]). Eupafolin Inhibits EGF-Induced Neoplastic Transformation and Signal Transduction in JB6 Cl41Cells {#s3_2} ------------------------------------------------------------------------------------------------- The molecular structure of eupafolin was shown in [**Figure 2A**](#f2){ref-type="fig"}. In the present study, we first examined the cytotoxicity of eupafolin in JB6 Cl41 cells by MTS assay. The results indicated that eupafolin did not decrease the viability of JB6 Cl41 cells up to 100 µM at 24 h ([**Figure 2B**](#f2){ref-type="fig"}). Furthermore, we detected the effect of eupafolin on EGF-induced neoplastic transformation of JB6 Cl41 cells. Anchorage-independent growth ability is an *ex vivo* indicator and a key characteristic of the transformed cell phenotype ([@B5]). Treatment of JB6 Cl41 cells with eupafolin significantly inhibited EGF induced neoplastic transformation in a dose-dependent manner ([**Figure 2C**](#f2){ref-type="fig"}). Eupafolin at 20, 50, or 100 µM decreased 42, 57, or 81% compared to the control group, respectively. These results suggested that eupafolin can reduce the malignant potential of JB6 Cl41 cells induced by EGF. {#f2} In the above study, we have found that TOPK is a potential target of eupafolin, and we further detected the downstream signal pathway of TOPK in JB6C141 cells. Western blot results showed that eupafolin suppressed the phosphorylation of histone H3 in a dose- and time-dependent manner, and 2 µM TOPK inhibitor HI-TOPK-032 has the similar effect to 50 or 100 µM eupafolin ([**Figures 2D, E**](#f2){ref-type="fig"}). Eupafolin Inhibits Anchorage-Independent Growth of Esophagus Cancer Cells {#s3_3} ------------------------------------------------------------------------- Previous studies revealed that TOPK is highly expressed in human esophagus cancer ([@B17]). We attempted to determine whether eupafolin could affect anchorage-independent growth of esophagus cancer cells. We detected the TOPK expression in several esophagus cancer cell lines. We found that TOPK expression was high, medium, and low in three kinds of esophageal carcinoma cells KYSE450, KYSE510, and KYSE70, respectively. At the same time, the trend of p-histone H3 expression was consistent with that of TOPK ([**Figure 3A**](#f3){ref-type="fig"}). Besides, we determine the cytotoxicity of eupafolin by MTS assay. Different concentrations of the drug were used to treat esophagus cancer cell lines KYSE450, KYSE510, and KYSE70 for 48 h, respectively. The results indicated that eupafolin had different cytotoxicity toward different esophagus cancer cells. KYSE450 cells with high TOPK expression were more sensitive to eupafolin ([**Figure 3B**](#f3){ref-type="fig"}). What's more, neoplastic transformation results showed that eupafolin at 20, 50, and 100 µM inhibited colony formation of KYSE450 cells on 21, 63, and 82%; KYSE510 cells on 12, 35, and 52%; and KYSE70 on 8, 12, and 10% compared with the non-treated cells, respectively ([**Figures 3C--E**](#f3){ref-type="fig"}). Overall, our results suggested that inhibitory effect of eupafolin on colony formation was significant in KYSE450 cells with a high expression level of TOPK. {#f3} Knocking Down TOPK in KYSE450 Cells Decreased the Sensitivity of Eupafolin {#s3_4} -------------------------------------------------------------------------- We then examined whether knocking down TOPK expression influences the sensitivity of KYSE450 cancer cells to eupafolin. Firstly, we determined the efficiency of TOPK shRNA. The results showed that the expression of TOPK obviously decreased after shRNA transfection; the efficient of shTOPK1\# was better than shTOPK2\# ([**Figure 4A**](#f4){ref-type="fig"}). Then, the growth of cells on anchorage-independent growth assay also decreased over 30% after transfection shTOPK1\# compared with the mock group ([**Figure 4B**](#f4){ref-type="fig"}). Moreover, KYSE450 cells transfected with TOPK shRNA1\# or mock control were treated with eupafolin or vehicle and subjected to anchorage-independent growth assay. The results showed that eupafolin (20 µM) inhibited colon number of KYSE450 cells transfected with mock shRNA by about 65%. In contrast, the inhibition was only about 17% in KYSE450 cells transfected with shTOPK1\#, indicating that KYSE450 cells transfected with shTOPK1\# were more resistant to eupafolin treatment ([**Figure 4B**](#f4){ref-type="fig"}). These results suggested that TOPK plays an important role in the sensitivity of KYSE450 cells to the antiproliferative effects of eupafolin. We then investigated the effect of eupafolin on downstream targets of TOPK, the phosphorylation of histone H3 in KYSE450 cells which was relatively more sensitive to eupafolin. Western blot results showed that the phosphorylation level of histone H3 (Ser10) was significantly decreased with eupafolin treatment in a time dependent manner ([**Figure 4C**](#f4){ref-type="fig"}). The above results showed that TOPK is a direct target for eupafolin to suppress esophagus cancer cells growth. {#f4} Eupafolin Suppresses Esophageal Tumor Growth in a PDX Mouse Model {#s3_5} ----------------------------------------------------------------- Furthermore, to explore the anti-tumor effectiveness of eupafolin in patient-derived xenograft (PDX) with tumor tissues collected from esophageal cancer patients with high expression of TOPK to further investigate the effectiveness of eupafolin. The results showed that eupafolin (20 or 50 mg/kg) effectively inhibited PDX tumor growth compared with the vehicle-treated group ([**Figure 5A**](#f5){ref-type="fig"}) with no significant loss in body weight ([**Figure 5B**](#f5){ref-type="fig"}), suggesting minimal toxicity. Additionally, treatment with eupafolin suppressed phosphorylation of histone H3 expression downregulated the expression of Ki-67 and increased cleaved caspase 3 levels in tumor tissues. While, there were no significant different of cleaved caspase 3 expression in peritumoral tissues ([**Figure 5C**](#f5){ref-type="fig"}). The positive expression of [**Figure 5C**](#f5){ref-type="fig"} was statistically shown in [**Figure 5D**](#f5){ref-type="fig"}. Furthermore, we detected the activity of caspase 3 using Caspase 3 Activity Assay Kit in tumor and peritumoral tissues. The results showed that eupafolin inhibited the activity of caspase 3 significantly in a dose dependent manner in tumor tissues, but it had no effect on the peritumoral tissues ([**Figure 5E**](#f5){ref-type="fig"}). Overall, these results illustrated that eupafolin has potential as chemotherapeutic agent against esophageal cancer. {#f5} Discussion {#s4} ========== Esophageal cancer is a kind of malignancies, which is increasing gradually year by year with a higher incidence and mortality. The 5-year survival rate of esophageal cancer is only 10% ([@B20]). Esophageal squamous cell carcinoma and esophageal adenocarcinoma are two kinds of esophageal cancer. Esophageal squamous cell carcinoma accounts for 90% of all cases of esophageal cancer ([@B19]) and approximately 70% of esophageal cancer cases occur in China, especially in Anyang city of Henan province ([@B13]; [@B6]). Chemotherapy is a common method for treating esophageal cancer including 5-fluorouracil (FU), cisplatin, paclitaxel, and mitomycin which are commonly used to treat esophageal cancer as a single treatment or in combination ([@B3]; [@B12]). However, these agents are prone to hematological toxicity ([@B15]). Over the past few decades, most of targeted therapies against esophageal cancer has not been progressing as smoothly as hoped, and new targets and inhibitors need to be identified for the treatment of esophageal cancer. TOPK (also known as protein PBK) is a serine-/threonine-specific protein kinase and has been known to audience since 2000 ([@B1]). Whereafter, a series of discoveries of TOPK function were reported in many kinds of cancers and is involved in various biological processes, including cell proliferation, apoptosis, transcription, migration, and invasion ([@B8]). It's reported that TOPK is highly expressed in esophageal cancer and plays an important role in esophageal cancer metastasis ([@B17]). Therefore, TOPK inhibitor could be a promising therapeutic agent for application in esophageal cancer. Due to the natural compound have higher efficacy and lower toxicity, natural anticancer products have been studied for many years. Eupafolin also is called methoxyluteolin, a flavonoid compound from the Ay Tsao (*Artemisia*). It has shown anti-inflammation ([@B2]; [@B25]), anti-viral ([@B21]), anti-autism ([@B18]), anti-angiogenic, and anti-tumor ([@B14]; [@B10]) bioactivities. Eupafolin could be a superior drug for cancer treatment. In our study, we found that eupafolin effectively suppressed anchorage-independent cell growth of esophageal cancer cells with highly expressed TOPK and inhibited growth of patient derived xenograft tumor by suppressing TOPK activities *in vivo*. In conclusion, eupafolin is a promising therapeutic agent in esophageal cancer chemotherapy by directly targeting TOPK. Data Availability Statement {#s5} =========================== The datasets generated for this study are available on request to the corresponding author. Ethics Statement {#s6} ================ The animal study was reviewed and approved by Henan Joint International Research Laboratory of Veterinary Biologics Research and Application, Anyang Institute of Technology. Author Contributions {#s7} ==================== XF designed research, performed research and wrote the paper; JT analyzed the data; MF extracted Eupafolin from Ay Tsao; JW expressed Histone H3 protein; XC, ZJ performed animal research and analyzed data; SL, KZ designed research and analyzed data. Conflict of Interest {#s8} ==================== The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This work was supported by grants from PhD start-up fund of Anyang Institute of Technology \[40075815\]. This work was also supported by grants from National Natural Science Foundation of China \[81360128\]. Scientific and Technological Development Project of Yunnan Province \[2018FE001-162,2017FE467\]. Education Department Fund of Yunnan Province \[2017YJS076\]. [^1]: Edited by: Wei-Dong Zhang, Second Military Medical University, China [^2]: Reviewed by: Qiang Wang, Nanjing Drum Tower Hospital, China; Gunjan Arora, National Institutes of Health (NIH), United States [^3]: This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology | High | [
0.677731673582296,
30.625,
14.5625
] |
Blockchain & The Law Roundup: 2 November 2017 Another week, another case of too much blockchain is barely enough! If you are following the market, you’d better not blink over the upcoming holidays. Barely a day goes by without a major development, a new ICO or this week a new set of blockchain type technologies. This week we learnt about new technology / company Hashgraph out of the UK. At the moment we can’t tell you much, but, we are speaking with them tomorrow to try and understand what they are developing. We also want to see if their tech will be applicable to the business of law. We’ll leave you with their meme, if it is a meme, to start the process off. Superior Distributed Ledger Technology. Hashgraph is a superior consensus mechanism / data structure alternative to blockchain. A decentralized platform without servers built on Hashgraph technology will enable blockchain use cases to run: Extract: Donald Trump’s reported nominee for Federal Reserve chairman has previously spoken about the topic of distributed ledger technology, signaling a hesitancy to embrace the idea of a Fed-issued digital currency and appearing cautiously optimistic about other DLT use cases in the financial sector. Jerome H. Powell, a governor of the Federal Reserve who the New York Times reports is President Donald Trump’s nominee to be the next Fed chairman, discussed distributed ledger technology (DLT) at some length during a March 3, 2017, speech at the Yale Law School Center for the Study of Corporate Law. Powell, who has occupied his current Fed post since 2012, said at the event (called “Blockchain, The Future of Finance and Capital Markets?”) that central banks weighing the possibility of issuing digital currencies “should have serious reservations” about their abilities to combat “cyber attacks, cyber counterfeiting, and cyber theft.” Such acts of malfeasance, he warned, could be committed by actors the world over and could “significantly exceed historical experience with paper currency.” He also argued that a central bank-backed digital currency could have serious implications regarding its users’ privacy: “In today’s environment, commercial banks maintain extensive records for individual debit and credit card transactions and increasingly monitor patterns of behavior for fraud. Such records in the hands of a central bank or government entity, however, could raise serious privacy concerns.” Additionally, he claimed, as cryptographic security measures are enhanced to prevent fraud, digital currencies become more effective tools for hiding “illegal activity,” including money laundering. Extract:In his recent book entitled “Owned: Property, Privacy, and the New Digital Serfdom” by Cambridge University Press, Joshua A. T. Fairfield an internationally recognized law and technology scholar, specializing in digital property, electronic contract, big data privacy, and virtual communities offers some fresh perspectives on the intersection between digital property rights and the blockchain. Fairfield believes that the advent of new digital technologies is leading to confusion in terms of the application of traditional property rights laws within the digital sphere. He therefore is advocating for a more simplified model of property ownership that protects the integrity of products and services used by consumers. In an interview with BTCManager, Fairfield offers some fascinating insights on the changing crypto landscape and how it collides with prevailing property laws that are out of alignment with today’s rapidly growing digital landscape. Title: Deloitte publishes new principles for blockchain in financial services Extract: Deloitte has published a report today (31 October) that outlines how blockchain can have a positive effect on the financial sector while ensuring long-standing principles and working practices are protected with minimal disruption. In the Blockchain Control Principles in Financial Services report, Deloitte has considered what it deems to be crucial for the successful implementation of blockchain within the financial services space. Lory Kehoe, EMEA Blockchain Lab lead at Deloitte, explained that the technology has “attracted significant attention from the financial services industry in EMEA and around the globe, with many organisations exploring different structures and governance models as they move from exploration to implementation”. Extract: Templum has announced that it has closed a seed funding round totaling $2.7 million led Raptor Group, Galaxy Investment Partners, Blockchain Capital and firstminute.capital. The funding follows Templum’s recent agreement with broker dealer Liquid M Capital, LLC, to launch a regulatory compliant turn-key solution, known as Templum, for the initial issuance and secondary trading of Initial Coin Offerings (“ICOs”) as securities. Templum will use the seed capital for operational expansion, product development and talent acquisition | Low | [
0.529661016949152,
31.25,
27.75
] |
Phrenic nerve and diaphragm function following open heart surgery: a prospective study with and without topical hypothermia. In a prospective study, 100 patients undergoing open heart surgery were randomly allocated to receive ice/slush topical hypothermia for myocardial protection (Group I, n = 56) or not (Group II, n = 44). Chest radiographs, diaphragm screening, lung function and phrenic nerve conduction time were assessed pre-operatively and at 1 week and 1 month post-operatively in all patients and subsequently at 3 months, 6 months, 1 year and 2 years in all patients with radiological evidence of diaphragm paralysis. The two groups were similar in terms of age, sex, diabetes and smoking habits. Cardiopulmonary bypass and aortic cross-clamp times were similar in the two groups. Radiological evidence of partial left lower lobe collapse was more frequent in Group I (79 per cent vs. 36 per cent, p < 0.01). Twenty (36 per cent) Group I patients developed unilateral diaphragm paralysis (19 left-sided) compared with none in Group II. Diaphragm paralysis was still present in 19 patients (34 per cent) at 1 month, in five patients (9 per cent) at 1 year and in one patient (2 per cent) at 2 years post-operatively. Phrenic nerve conduction time was recorded in 98 per cent of patients pre-operatively, but was unrecordable on the appropriate side in all 20 patients with diaphragm paralysis 1 week post-operatively. Prolonged phrenic nerve conduction time on the left side was found in a further seven Group I patients 1 week post-operatively. There were no significant differences between the two groups in terms of post-operative arrhythmias, myocardial infarction or mortality.(ABSTRACT TRUNCATED AT 250 WORDS) | High | [
0.680306905370844,
33.25,
15.625
] |
Q: make variable available in all method of controller when passed in one method Here i send the user.id as params dd <h3><%= link_to("Lend Asset", {:controller => 'empassets', :action=> 'index', :dd => user.id})%></h3> In controller empassets i fetch it by def index @id = params[:dd] @empassets = Empasset.where(:ad => @id) respond_to do |format| format.html # index.html.erb format.json { render json: @empassets } end end def show @id = params[:dd] @empasset = Empasset.find(params[:id]) respond_to do |format| format.html # show.html.erb format.json { render json: @empasset } end end def new @id = params[:dd] @empasset = Empasset.new respond_to do |format| format.html # new.html.erb format.json { render json: @empasset } end end def edit @id = params[:dd] @empasset = Empasset.find(params[:id]) end I need this @id in all new show edit method. But it takes in index only as i mention it in index. How can i make such that if Lend asset is click then @id= params[:id] have value in all methods. How can it is possible to make it available for another @id = params[:id] is not send in that controller? A: Maybe will be better if you store the current user in session and after that, capture the user model with a filter in the controller, like this: # controllers/application_controller.rb class ApplicationController < ActionController::Base before_filter :set_current_user_in_model private def current_user @current_user ||= User.find(params[:dd]) || User.new end # This method save the current user in the user model, this is useful to have access to the current user from a model and not from the controller only def set_current_user_in_model User.current_user current_user if not current_user.nil? end end # models/user.rb class User < ActiveRecord::Base #... # This is useful to get the current user inside a model def self.current_user(user = nil) @@current_user = (user || @@current_user) end #... end Basically, my idea is store that information inside a model with a filter, you can use session if you wanth to get the information (user id). def index session[:user_id] = params[:dd] @empassets = Empasset.where(:ad => session[:user_id]) respond_to do |format| format.html # index.html.erb format.json { render json: @empassets } end end def show @empasset = Empasset.find(session[:user_id] || params[:dd]) respond_to do |format| format.html # show.html.erb format.json { render json: @empasset } end end Note I used session[:user_id] || params[:dd] because maybe, the session information was not stablished and you give it :dd parameter. But if you want to stablish the @id variable, you can use a filter like before. But I don't know what is the main problem. Edit # controllers/application_controller.rb class ApplicationController < ActionController::Base before_filter :set_dd_param, :except => :index def index session[:dd] = params[:dd] # Here you write the session @current_user ||= User.find(params[:dd]) || User.new end # ... protected def set_dd_param params[:dd] = session[:dd] || -1 # Here you read the session a write the params variable end end Sorry for the delay. | Low | [
0.525842696629213,
29.25,
26.375
] |
Kogota Station is a railway station in the town of Misato, Miyagi, Japan, operated by East Japan Railway Company (JR East). Lines Kogota Station is served by three lines: the Tōhoku Main Line, the Ishinomaki Line, and the Rikuu East Line. It is located 395.0 rail kilometers from the terminus of the Tōhoku Main Line at Tokyo Station. It is the eastern terminus of the Rikuu East Line and the western terminus of the Ishinomaki Line. Most Kesennuma Line trains use Kogota station as their operating terminus, although the line physically ends at Maeyachi Station. Station layout Kogota Station has two island platforms serving four tracks. The platforms are connected by a footbridge. The station has a "Midori no Madoguchi" staffed ticket office. Platforms History Kogota Station opened on April 16, 1890 on what would become the Tōhoku Main Line. The Ishinomaki Line opened on October 28, 1912, and the Rikuu Line (Rikuu East Line) opened on April 20, 1913. The station was absorbed into the JR East network upon the privatization of JNR on April 1, 1987. Passenger statistics In fiscal 2016, the station was used by an average of 2,097 passengers daily (boarding passengers only). Surrounding area Kogota Post Office National Route 108 See also List of Railway Stations in Japan References External links Category:Railway stations in Miyagi Prefecture Category:Tōhoku Main Line Category:Rikuu East Line Category:Ishinomaki Line Category:Railway stations opened in 1890 Category:1890 establishments in Japan Category:Misato, Miyagi Category:Stations of East Japan Railway Company | Mid | [
0.552462526766595,
32.25,
26.125
] |
Newcastle manager Rafa Benitez is said to be a long-term admirer of the 23-year-old centre-back. And according to Portuguese outlet O Jogo, Semedo is set to be subject of a £13million bid by newly-promoted Newcastle this summer. Sporting Lisbon are reportedly looking to secure at least £17m to consider selling Semedo, who is also a target for French outfit Lille. The Magpies appear to be leading the race for Semedo, with the defender said to prefer a move to England over France. | Mid | [
0.64390243902439,
33,
18.25
] |
Portable filtering systems such as U.S. Pat. No. 4,298,475 to Gartner are known which provide an elongate tube through which water is to be drawn in the manner of a straw. Such filtering systems suffer a number of disadvantages. Firstly, they typically require very strong suction to draw water through them with the result that they are only really suitable for emergency use and cannot conveniently be used to drink fluids. Secondly, the tubes are of a relatively complex structure and are difficult to manufacture. | Low | [
0.47925311203319504,
28.875,
31.375
] |
Rotating sample magnetometer for cryogenic temperatures and high magnetic fields. We report on the design and implementation of a rotating sample magnetometer (RSM) operating in the variable temperature insert (VTI) of a cryostat equipped with a high-field magnet. The limited space and the cryogenic temperatures impose the most critical design parameters: the small bore size of the magnet requires a very compact pick-up coil system and the low temperatures demand a very careful design of the bearings. Despite these difficulties the RSM achieves excellent resolution at high magnetic field sweep rates, exceeding that of a typical vibrating sample magnetometer by about a factor of ten. In addition the gas-flow cryostat and the high-field superconducting magnet provide a temperature and magnetic field range unprecedented for this type of magnetometer. | High | [
0.678048780487804,
34.75,
16.5
] |
Q: MongoDB increase disk on the VM My problem is with Mongo eating up space on the disk. Reading a few blogs no the web - I was certain - a repair would save me time as this would free up mongo's reserved space. But attempting a repair throws this error because I am at 90% disk usage : db.repairDatabase() { "ok" : 0, "errmsg" : "Cannot repair database my_d_b having size: 347673198592 (bytes) because free disk space is: 42874580992 (bytes)" } Then I tried the next step which is compacting every collection in the database using : db.getCollectionNames().forEach(function (collectionName) { print('Compacting: ' + collectionName); db.runCommand({ compact: collectionName }); }); This reduced my disk usage by just 1%. Now I can easily pause my apps from writing to this mongo database. I don't want to use any replset approach etc. I want to just move it to a bigger disk and move forward. I have already mounted an extra disk which 2.5times the size. I am not finding concrete steps to move the data and change mongo configuration and then start mongo process. My repairs and compactions may be failing because they need space to operate as per my understading. If I can move this data to new disk and point mongo to the new disk, I will be good. This is what I want to achieve - would appreciate a little direction. A: If you have a standalone MongoDB server and can tolerate downtime, the most direct approach would be to copy the contents of your current dbPath to a directory on the new disk: Stop mongod Copy the contents of your dbPath to a directory on the new disk Update dbPath in your configuration file to point to this new directory Finally, restart mongod | High | [
0.658227848101265,
32.5,
16.875
] |
Judy Bennett (historian) Judith Ann Bennett (born 1944) is a New Zealand historian. She is currently a full professor at the University of Otago. Academic career Bennett wrote a 1979 PhD thesis at Australian National University titled, 'Wealth of the Solomons: a history of trade, plantations and society, Solomon Islands, c.1800–1942' studying the colonial history of the Solomon Islands and has spent much of her career researching, writing and teaching about the Pacific and its history. Bennett has received two Marsden grants, the first to research the children of American servicemen and pacific women and the second to research the history of the coconut and its trade. Selected works Bennett, Judith A. Wealth of the Solomons: A history of a Pacific archipelago, 1800–1978. Vol. 3. University of Hawaii Press, 1987. Bennett, Judith. Roots of conflict in Solomon Islands-though much is taken, much abides: legacies of tradition and colonialism. State, Society and Governance in Melanesia, Discussion Paper 2002/5, Australian National University, Canberra 2002, (2002). Bennett, Judith A. Pacific forest: A history of resource control and contest in the Solomon Islands C. 1800–1997. Brill, 2000. Bennett, J. A. with Russell, K. J. (eds), Journeys in a Small Canoe: the life and times of a Solomon Islander, Lloyd Maepeza Gina, Canberra, Pandanus Press, ANU (2003), 300 p. Bennett, Judith A. Natives and exotics: World War II and environment in the Southern Pacific. University of Hawaii Press, 2009 Bayliss-Smith, T and J.A.Bennett (eds),(2012). An Otago storeman in Solomon Islands: The diary of William Crossan, copra trader, 1885-86. Canberra, Australia: ANU E Press, 95p. Bennett, J. A. (Ed.). Oceanian journeys and sojourns: Home thoughts abroad. Dunedin, New Zealand: Otago University Press, (2015) 408p. Bennett, J.A. and Wanhalla, A (eds) Mothers’ Darlings of the South Pacific: the children of Indigenous Women and US Servicemen in World War Two, Honolulu: University of Hawaii Press and Dunedin: University of Otago Press. 2016. 379 p Bennett, J. A. (2018) Pacific Coconut: Comestible, Comfort and Commodity, Journal of Pacific History, 53: 4, 353-37; Bennett, J. A. (2018) Voices of Rotuma: Enduring refrain, Journal of Pacific History, 53: 4, 502-520; Bennett, J. A. (2017) Fluid frontiers and uncertain geographies: US controls on immigration from the Pacific (c. 1880-1950), Journal of Pacific History, DOI:10.1080/00223344.2017.1406319; Bennett, J. A. (2013) Meditations: new directions in the study of the decolonization of Melanesia. Journal of Pacific History, 48: 3, 323-329. Bennett, J. A. (2013) Introduction to Pacific Research Protocols at the University of Otago, The Contemporary Pacific, 25 (1), 95-124, References External links Category:Living people Category:New Zealand women academics Category:New Zealand historians Category:Australian National University alumni Category:University of Otago faculty Category:1944 births Category:Women historians | High | [
0.7079365079365081,
27.875,
11.5
] |
The present invention relates generally to the field of calibrating a multi-axis machining system, and more particularly, to a system and method for virtually calibrating automated equipment running on an xyz-coordinate system. Multi-axis machining systems such as Computer Numeric Controlled (CNC) machining systems can be used to precisely machine and fabricate a workpiece from a set of instructions. Such systems typically include a table for supporting the workpiece, and a toolhead positioned vertically above the table and moveable relative thereto along one or more of x, y and z linear axes, as well as rotational axes. Movement of the toolhead along the axes can be controlled by instructions implemented, for example, by Computer Aided Design (CAD) software. One well known format of CNC instruction codes is known as “g-codes”. G-codes are translation instructions in which G0 represents a linear movement, and G02 and G03 represent circular or arcuate movements for the toolhead. The process for creating a g-code file involves defining a series of g-codes that represent various contours of the finished product, such as from a model, and defining the requirements of the CNC machine. CNC machine requirements include identifying and labeling features of the model, selecting cutting tools for the toolhead, determining machining speeds, defining an orientation of the workpiece, etc. After the instruction codes defining the finished model are formulated, the instruction codes are passed to the CNC controller of the CNC machine. The CNC controller uses the instruction codes comprising the g-codes to precisely control the toolhead and cutting tool to machine the workpiece into the finished product. Before machining, it has been necessary to calibrate the machine to ensure that the mechanical components are in alignment to achieve satisfactory performance from the machine. Machine components can move out of alignment over time as a result of physical contact, machine transport, component wear and normal use. Conventional methods for calibrating a CNC machine to bring components back into alignment include mechanically adjusting the toolhead path along the y-axis, adjusting perpendicularity between the adjusted y-axis and x-axis (i.e., squaring), adjusting the z-axis relative to the y-axis, x-axis and x-y plane, as well as adjustments of rotational axes perpendicular to the x-y plane, among other adjustments. Such mechanical calibration methods are disadvantageous because they are time consuming and result in significant downtime for the machine. Accordingly, what is needed is a method of virtually calibrating a CNC machine that ensures that the machine performs satisfactorily without the need for mechanical calibration methods. | Mid | [
0.636363636363636,
36.75,
21
] |
I wonder what the world would be like if we could talk about mental illness the same way we talk about physical illness. Not that I’m convinced that these are neatly separated categories, but it is a useful basic distinction. Imagine if you could walk into a party and say, “don’t hug me, I’ve been suffering from traumatic flashbacks all day & I can’t take being that close to another person right now.” Like you would if you had a cold — you’d say “don’t hug me, I have a cold & don’t want to pass it along.” If you say you have a cold, the other person might mostly ignore it & move on, saying that they hope you feel better. Or they might be moved to offer some sort of sympathy or help — “oh no, that sucks — let me give you some tissues & soup and a get well soon card.” But what would they say if you tell them you are sorry for missing their party, but you couldn’t leave the house because the panic attack was too intense? What would they say the tenth time you tell them that? The lack of ability to talk about mental illness is an extremely isolating phenomenon. Mental illness is just as prevalent as physical illness, but we have to hide it. We have to make excuses for missing events & reacting to things in less-typical ways because to tell the truth is considered shameful. We are not supposed to reveal that our parents tortured us, or that we’re not over the horrors we saw in war, or that our genes are messed up & we can’t be happy. We are not supposed to be vulnerable to abuse, or admit that it happened, or that it had an effect on us. I don’t believe people are bad. I have an almost endless supply of faith in the potential redemption of every person. I am almost always willing to believe that someone does not mean to do harm. And yet I don’t see the kind of compassion in the world that I think we need to have for other people. Mental illness does not always manifest as a diagnosis in the DSM. Sometimes it’s temporary or situational — something terrible happens that overwhelms our sense of self & our capacity to relate to others. That seems like something we should be able to see & recognize in other people, not something we should punish & sweep under the rug. Even when these situations arise out of events that are societally acceptable, such as losing a spouse or other close person, we still struggle with extending compassion & understanding. We don’t even have a system for letting people know that we’re grieving a loved one, and once we’ve named our grief, others feel awkward & don’t know how to respond. I wish we could talk about mental illness as easily as we talk about physical illness. I wish that there were better ways to incorporate the reality of mental illness into our public lives, instead of hiding it away because we are supposed to feel ashamed. ** trigger warning: this post is mostly talking about sept. 11, some dark dream content & trauma. I don’t know if it rises to the level of triggering, but just in case** Lo the long months of summer are over. I haven’t written here for a long, long time. And now, instead of updating you on my life, I am going to write a somewhat long meditation on the events of September 11, 2001, which will a) reveal a lot of personal history and b) bring a lot of google searchers to my blog. Whatever. I am not too concerned with anonymity here any more. I’ve been looking at the NYT special report on Sept. 11 and it’s bringing up a lot of memories of that time in my life. So. July 2001. M and I moved to CA, fresh out of undergrad, thinking we were going to break free of the ties that bound us (to our uncomfortable families, mostly, but we didn’t put it quite that way at the time) and start on our shiny new adult lives. We had been joking about how people ‘settled…like sediment in a bottle’ and scoffed at their bourgeois aspirations of kids and houses and stable jobs. Neither of us wanted that, at least I knew I didn’t want it at all. I was watching high school friends & acquaintances make choices that seemed to emulate our parents’ lives, but I was certain that youth was for other things, like seeing the world & raising hell. We just up and left Boston, to the dismay of family & what few friends & coworkers we had. We traveled out west & found an apartment, got some jobs. But once in CA, we didn’t do so well. We got there & immediately faced some classic struggles: our new bank put a two-week hold on a five figure cashier’s check that was our combined life savings (as a result, we bounced our first rent check), our rental agent tried to renege on the pet allowance (non negotiable, we had just driven our two beloved kitties from Boston to Berkeley by rental car), M’s new job was mind-numbingly boring, and my new coworkers decided I was a ‘stuck up east-coaster’ and shunned me. By the time September rolled around, we were deep into a profound funk. We didn’t have a car, so we started to look into buying one. Neither of us realized how minimal the public transportation was in the Bay Area — in order to visit someone we knew in Napa, we either had to go into San Francisco & take a 2-hour bus, or ride the BART to the end of the line & get picked up & driven for another hour. We were isolated. Eventually all we ever did was cook massive dinners & drink copious amounts of beer or wine while eating them. In the midst of this, I was planning a stressful visit from my mother. The night of Sept. 10, I stood at the stove cooking eggplant parmesan, one of my specialties, in preparation for her arrival the next day. I finished frying the eggplant & assembling the dish with a massive headache — I felt so unwell I sat on the bathroom floor for an hour, crying because my head hurt so bad & convinced I was going to throw up from headache-induced nausea. I couldn’t figure out why I felt so terrible — was it the smoke from the frying? Anticipatory stress from my mother’s visit? The beets I had for dinner the night before? So perhaps it’s not surprising that to me, the events of September 11 felt like a terrible blow to an already wounded body. We woke up that morning to a phone call from M’s mother, telling us that something bad had happened & we should check the news. She said she knew my mother was flying that day & was she okay. I turned on the television (back when we had one) to see the first tower crumple. I called my mother, who picked up the phone. She was fine, they cancelled her flight, she was going to stay in town with my father at his place of work. I watched the second tower crumple with M at my side. I said, ‘oh…they’re showing it fall again.’ and she said ‘no. that’s the other one.’ I think my mouth opened with shock. Then we pulled ourselves together & went to work, only to find the city of San Francisco in total chaos. After arriving at work to realize that nothing was going to get done that day, we walked toward each other from our offices & met up in what felt like an apocalyptic war zone. We took the BART home amidst armed police & bomb-sniffing dogs. *** My mother was lucky. She had booked her flight through a travel agent (old school!) and had been given the option of two different flights to CA from Boston. One was routed through Newark, flight 93 that crashed in PA. The other was routed through Chicago. She chose Chicago, and lived. Needless to say I freaked out. I didn’t know what to do. I was 23, and my mother had just almost died. My world was upside down. No one around me seemed to care about me (remember the shunning?) and my family was worlds away, reachable only by rental car or amtrak. I can see very clearly now that this was the beginning of the end of us living in CA. After that our eyes were only focused on the east coast. We had decided we would move back to the east coast within a year sometime either right before or right after the attacks. Neither of us could stomach the vaunted easy living of the Bay Area. We couldn’t figure out how to connect to the queer scene. We had terrible awful jobs. We were planning an agonizing trip back home over the holidays, a trip that involved two weeks and $2000 worth of Amtrak tickets. I finally broke down & suggested we just move back permanently as soon as my winter break began, in the first week of December. We hired more movers, they came & took our stuff, & we drove across the country for the second time in six months in a rented pickup truck. Everywhere we looked we saw american flags. *** The effects of Sept. 11 on my life were not only geographic. Since my third year of college, I had been having terrible nightmares; ones that involved lots of scary bugs & rats infesting things. But after Sept. 11 these dreams intensified. One in particular was incredibly vivid & terrifying. I entered a public bathroom, very dark & filled with creepy crawlies. At the end of the hall, the first stall in a long bank of them had its door partly open. It swung further open as I approached & seated on the toilet was a fully clothed man, staring at me. He looked like a corpse, though he was still a little bit alive, and in that moment it came to me that he was filled with ground glass, that he was bleeding to death inside because he had swallowed it. The image is still burned into my brain. Versions of that dream haunted me for months afterward. I wish I had known about trauma back then. How it works, where it comes from, the effects it can have on lives. I wish I had known that there were words to talk about it, that it was a whole field of study. That dream was triggered by September 11, no question. But it was really about my father, and the incredibly problematic relationship I had with him (details of which I will not go into here). *** We moved back to Boston briefly, just long enough to get married & discover that the job market was less than hopping in Massachusetts. Then we moved to Manhattan. This might seem surprising, given everything that’s gone before in this narrative. Sept. 11 scared me out of CA and back home to Boston. Why on earth did we then move to the epicenter of doom? Not even Brooklyn, but Manhattan? But it didn’t seem like a big deal to me. We joked about NY being safer than ever — what are the chances of two such catastrophes striking in a row? But what I didn’t say, couldn’t yet say, was that the trauma of Sept. 11 was not the first horrible, life-changing, completely random & awful thing that happened in my life. I already knew about trauma, already knew that horrible things happen to good people for no reason, & all we can do is survive & move forward. I doubted that Manhattan was more dangerous than Berkeley or Boston because I knew that random senseless tragedy happens everywhere. In a sense I was already in the place that many people got to after those events. This is not meant to minimize the trauma & horror that people felt because of those events — I have often grappled with a sense of alienation about them, precisely because it all seemed so logical and inevitable to me. This is not to say that moving to Manhattan was good for me. Living in NY took its toll. I was prepared for the huge attacks, the inevitable crises, but I wasn’t prepared for the day-to-day interpersonal disdain of NY. The countless rude comments, the doors swung shut in my face, dozens of baby strollers rolled across my toes, the lack of ability to make friends and form intimate relationships with my peers — all of these things were an incredible drain on my sense of self. I found myself becoming meaner, less caring, less tolerant of other people. But when the blackout of 2003 rolled around, I was cool as a cucumber. Our apartment was in an old tenement building on the first floor, so we had running water & our gas stove worked. I cooked lighting the stove with a match & heated water for a bath, congratulating myself on my survival skills. *** I don’t think that the events of Sept. 11, 2001 really changed my life that much. We would have left CA regardless, I’m almost sure. We would probably have moved to NYC. At that time I worked in theatre and I doubt that I would have been satisfied before trying out the bright lights of Broadway. Needless to say I found them sorely lacking, & changed careers so I could feel a sense of doing good in the world. Just like all the other people my age that the Economist writes about. Of all the things I regret about Sept. 11, 2001, the thing I have the most horror about is the US response to the attacks. We have lost so much — I believe what we’ve lost as a country far outstrips whatever those people who flew those planes into those buildings imagined we would. We lost our collective way. Who remember the gorgeous summer of 2001? The weather was beautiful. We were worried about shark attacks. Jobs were everywhere, for everyone. I miss that time. It wasn’t an innocent time — but it was a productive time. Sept. 11 was supposed to bring us together, but it didn’t. The gap between rich and poor has widened considerably since then. Young people go into tremendous debt & graduate to no prospect of gainful employment. Our credit rating slipped as a nation so badly that other superpowers no longer want to invest in our currency. I know we will survive this, just like we survive everything. But I wish that we could go back & do it over. Tonight, I made eggplant parmesan for dinner as a sort of commemoration. But also because eggplants and tomatoes are in season right now. I will probably always make eggplant parmesan at this time of year, because it makes sense. Over the past 10 years, I have made a lot of progress thinking through & recovering from the trauma in my life. It’s an ongoing process, as different parts of my life come into better focus. Time passes and I achieve distance from the hard stuff. I hope that we as a society & culture start recovering from the trauma of Sept. 11 soon. my secret favorite holiday of the year is beltaine. there are a few reasons for this, which i will enumerate: 1. it is about sex. outrageous outdoor sex by blazing bonfires. or off in a leafy dell in the woods. the only day of the year where you’re supposed to stay out all night & partake in pure unadulterated joyous sex. 2. in a similar vein, it is about flowers. [similar because flowers=plant sex. yes, it’s a theme.] flowers are another one of my favorite things ever. 3. it is the first day of my birth month, which i think should be celebrated instead of my birthday. to hell with birthdays. may is full of beautiful weather and flowers all month long — what better way to celebrate my birth than dedicate a whole month to it? so on beltaine, unfortunately once again, i did not have an opportunity to drive a herd of cattle between two bonfires and then sneak off to the woods with my beloved. sigh. really all may festivals are about sex. young girls dancing around a flower-bedecked phallic pole? clearly about sex. in spite of my lack of bonfire exposure, i have been making use of this lovely month by spending lots of time in the lovely park by our house, eating ice cream (i’m looking forward to my free birthday sundae courtesy of here), and training for long walks in the hills when we take off and visit our friends in the UK. yup, you heard me. all three of you who still read this blog might remember that its roots are in the UK. after we bought our tickets i said to M, ‘it’s the first time we’ve been back since we left!’ and then we both cracked up. thank you captain obvious! what i meant was, it’s the first time we’ve been back since we lived there back in 2008. and it means a lot to us. it also means a lot to us that we’ll be staying with our amazing friends, my first ever dyke friends. in other news, this completes one full year post-grad-school, and i couldn’t be happier. seriously. i never, ever, EVER want to do that again. phew. or maybe it is really just that i swing wildly back and forth between wanting to pour my heart out here, in positive and negative realms, and wanting not to expose myself. the fear of my distant associates finding me here holds me back, and the pain-in-the-arse-ness of the passworded post keeps me from that route right now…sigh. in lieu of a) suspending my blog and b) writing reams about the latest wounds with salt in them, here are some random bullets greg-style: i brought home a gorgeous loud musical instrument, which forced me to completely rearrange my room to fit it in. i will have to obtain mute pads before i can play it but i am SO HAPPY. i got a good deal on craigslist. i had an awful run-in with straight culture this past weekend — an evil straight dude basically came on to me with his wife IN THE SAME ROOM. GROSS. i had a terrible femme fashion moment — due to the pouring rain i had succumbed to the dreaded temptation to wear my sneakers to my new employee training, which culminated in lunch at the faculty club. i’m happily munching my grilled cheese sandwich when all of a sudden the dean of my [former] graduate school walks in and sits at the table next to us. this is a person who has a high opinion of me, and even higher expectations. AND I WAS WEARING SNEAKERS WITH MY WORK CLOTHES. epic fail. i tried to hide my face but she was on the side of me that has less hair (i’m parting my hair on the side these days) and so all i could do was try to hide my feet under the table & hope she didn’t notice me. i’m calling this a lesson learned for good. i’ve been re-connecting with the music scene here in boston and going out more, and it feels so so good. i feel like i lost sight of how much i love going to rock shows and watching people make music. a main motivation for having just made my extravagant and awesome purchase is to bring it home even more personally and have an opportunity to do it as well as watch. yay. March is a big deal month in my household. M and I celebrate two anniversaries in March — the relationship anniversary and the wedding anniversary. 17 years and 9 years respectively. I was at work yesterday and one of my coworkers came in all excited because she got engaged the night before, and it was one of those strange moments where I felt really old and really queer and really out of the mainstream. They went around the group and told their engagement stories, and I thought I wouldn’t join in until the last minute when the coworker I’m closest to jumped into the lull at the end of the story and said ‘FG…it’s your turn!’ So I told my story, and felt even older. ‘back in the day before debit cards, M went to the bank & took out a lot of cash, then she went to the jewelry store & said she wanted to buy a diamond ring for a friend…because this was back in the day when people just weren’t that out…then we got on a plane & went to Paris and she proposed on her knee in the mud in the Jardin du Luxembourg…’ Yeah. January 5, 2000. Back when this group was still in grade school. Sometimes life feels a little surreal. So M and I will figure out some way to celebrate appropriately this month. It makes it all the more meaningful that last year at this time we were basically not speaking to each other. Honestly though if it’s not one thing it’s another. The relationship realm feels much more stable to me right now, but I’m struggling with some really intense personal stuff that feels like it’s sometimes winning. There are times when I feel like there’s no amount of support that could even begin to keep me on my feet. Part of me wants to say that it’s the weather, the winter, the transition to working full time — but deep down I know it’s more to do with the ghosts that are haunting me than anything environmental. In happier and more exciting news, we signed up for a farm share. It feels like a really significant investment in the future. It’s a statement of intent in a way — we plan to be here this summer and maybe always. We plan to be together sharing food. We are investing in our local community — the farm is literally right down the street, an outpost of urban farming. We are deepening our roots in this place. We are also signing up for WAY MORE VEGETABLES than we will easily be able to eat. Stay tuned for hilarious late summer posts about how to deal with the deluge. someone posted this meme on that terrible blue and white social networking media, and i am embarrassingly still part of it. so…i am bored and posting it. here goes: Lovers: Tonight Lovers: Dead Deer Yeah Yeah Yeahs: Hysteric The National: Bloodbuzz Ohio Arcade Fire: Wake Up The Cliks: Not Your Boy Hunter Valentine: She Only Loves Me When She’s Wasted The Damned: Life Goes On Lady GaGa: Paparazzi The Go-Betweens: Quiet Heart Lovers: Igloo for Ojos Arcade Fire: Crown of Love New Order: Ceremony Joy Division: Atmosphere Lovers: Peppermint (from Darklight, a remix of a song originally on Star Lit Sunken Ship) Hunter Valentine: Youthful Existence MGMT: Time To Pretend Scissor Sisters: Don’t Feel like Dancin Echo & The Bunnymen: Bring on the Dancing Horses M.I.A.: Paper Planes Lovers: Perpetual Motion, Perpetual Sound Lovers: From A Highway Yeah Yeah Yeahs: Turn Into Depeche Mode: The Sinner In Me Lady GaGa: Bad Romance since there’s heavy representation on this list from Lovers, which (surprise!) is my favorite band, here’s their website: www.holdmyclothes.com what’s funny about this meme is that the 25 most played songs are indeed mostly my favorites. but it also reflects a series of really difficult times in my life, when i put various of these songs on repeat for hours as i tried to calm myself down. i won’t walk you through them all, but it’s a funny thing to keep track of in a way. sometimes i listen to this list at not-sad times to desensitize myself to them. some new faves: still Lovers (of course) but also Sharon Van Etten, i’m on a huge New Order kick right now, and i’m actually listening to the radio a fair amount. i feel as though i should write the second december post (more musing, this time on the phrase ‘letting oneself go’) but instead i’ll update you on my life. fun times! today is a holiday, and instead of working from home, i’m doing laundry & other household errands. because my remote desktop access isn’t really working. and i’m not cool enough to know how to fix it. also i’m rather less inspired to work today than i thought i would be, money be damned! so: house is clean, laundry is washing, my grocery list is made, & when i get home i’m going to make a frangipane tart for the first time ever with some of the many pears in my fridge. a relative gave us a very large amount of pears for the holidays, and we bravely ate most of them, but there’s several left and it’s getting to be that time… let’s see…i don’t do year in review posts, but those of you who know me & followed my leaving & returning to this space know that it was QUITE a year. part of me thinks that 2011 had better be a good one. because i’m going to need some time to recover. but the rest of me knows that the more you state intentions and wishes for time and life the more the universe gets to come around and kick you in the ass. so i’ll leave it at this: i hope that the healing and growing that i’m doing every day becomes both easier and more successful. and that the relationships that sustain me grow deeper and stronger. i saw in a local cafe a box with a sign that said, ‘what do you want NOT to change about yourself in the coming year?’ and there was a stack of notecards that you could write on and add them. i don’t know what they were planning to do with these intentions, but what a cool idea. i’m still pondering this — but i know a couple of things i don’t want to change about myself, either now or ever: anyone want to add what they are NOT going to change about themselves? i’m not really into missions of self-improvement, unless there’s something about yourself that makes you think less of yourself. i’m more interested in what makes you great. | Mid | [
0.641975308641975,
32.5,
18.125
] |
News and Events AVILA # Project - Cyber Crime Awareness Camp. # By [email protected] Golden Jubilee Project Public Announcements August 06, 2016 Friday, 5.8.2016. Conducted by - Dr.P.N. Rajan.,Inspector of Police,Cyber Crime Cell,Coimbatore. Cyber Crime is emerging as a very serious threat in today’s world. We are concerned about our students, falling prey to antisocial elements who would exploit their innocence and ignorance. Hence we gave awareness resulting in crime prevention. The student community ( Age group 13 to 16 ) are enlightened on the greatest menace of the use and misuse of the communication network and social media. The school takes pride – with due reverence and obeisance to her patron saint, Saint Teresa of Avila – in being christened with the name of a province in Spain, which has given to the world Saint Teresa – the unparalleled advocate of the spirit of true Christianity and who carries the title – The Doctor of the Church with unquestionable aptness. | Mid | [
0.582608695652173,
33.5,
24
] |
Q: Scalable Kinetic.JS vector map I have an flash application with colossal interactive scalable vector worldmap seperated by extra large amount of selectable layers (such as population map, resource map, etc) which i need to port into html5 Kinetic.JS. So, all layer graphic goes in swf/swc/fla. What is the perfomance best practices for such application here in htmlt5? Should i convert all graphics to svg (is it possible for vector swf?) and simple scale it on runtime, or would it be better to rasterize it as some mipmap (premade scaled versions of graphic) and draw premaded images instead of scaling? A: KineticJS is canvas based and canvas can use .SVG images for scaling with less pixelizing. Better Visual Results For best visual results, you should stick with Kinetic.Image using .SVG image source if possible. Better Performance The most recent release of Kinetic (5.1.0) has added a Kinetic.FastLayer which increases drawing performance by eliminating the overhead of the eventing system. For better performance you can use FastLayers+scaling for all map+overlay layers except the user interactivity layer. | High | [
0.6815476190476191,
28.625,
13.375
] |
Circadian rhythms of the spontaneous meal pattern, macronutrient intake, and mood of humans. Circadian (24-hour) rhythms in the feeding behavior of humans were investigated using diary self-reports of spontaneous food intake. Eight male and 30 female undergraduate students recorded what they ate, when they ate it, and their mood at the time of ingestion in a diary over a consecutive nine day period. Self-ratings of depression, energy, and anxiety were made at the beginning of each meal on three seven-point scales. The total amount of food energy in each meal as well as the amount of protein, carbohydrate, and fat, the intervals prior to and following the meals, and the satiety and deprivation ratios were calculated. The food energy contained in the stomach at the beginning and end of each meal was estimated with a mathematical model. These variables were evaluated in relation to the time of meal occurrence during the day. Fluctuations in the levels of self-rated energy and anxiety, but not depression, were detected during the day. Clear 24-hour rhythms were identified for the amount eaten and the macronutrients ingested during the day with decreases for males and increases for females. The amount eaten per meal and the meal's content of carbohydrate or fat, but not protein, varied over the day with peaks at the lunch and dinner periods. A clear sex difference without circadian variation was apparent with the deprivation ratios. This suggests that males eat larger meals than females because of a heightened responsivity to deprivation and not to a smaller response to the satiating properties of food. Preprandial correlations were found for meals occurring either during the breakfast or the dinner periods. No postprandial correlations were found. These data demonstrate that the preprandial correlations are not an artifact produced by the 24-hour rhythm and suggests that they reflect a basic regulatory strategy employed by humans. As the day progressed, postmeal intervals and satiety ratios decreased, while premeal intervals increased. This suggests that humans obtain less satiety from a given amount of food later in the day than earlier. It is postulated that this represents eating which anticipates the overnight fast. These data clearly demonstrate the efficacy of the approach and the orderly, analyzable nature of the spontaneous eating behavior of humans. | High | [
0.6617283950617281,
33.5,
17.125
] |
The busses drive to a specific location on the border. Here the cargo is unloaded and the process of walking across the border begins. Each of the human cargo is given information on what to do once they reach the other side, including a phone number of someone to call. The number is not necessarily a local number. It may be a location in Virginia, or Maine or Utah. Anywhere in the U.S. The person on the other end gives instructions on how to gain transportation to their location where they will be brought into the illegal community in that city. And so the journey across the border begins. Somewhere in the middle, between Mexico and the U.S. is a tree. From the branches of that tree hang women's panties. It's called the panty tree. Why? Trophies from the raped women of previous journeys. It's just the cost of doing business with the "Coyotes," the murderous thugs who run the illegal immigrant trade. They don't care who lives or dies. These are the ones who will leave illegals locked in trucks without food or water or ventilation. They charge enormous fees - up front. To them the cargo is all the same. They carry the drugs with the humans. They make deals with terrorists for the same trip. They rape, maim and kill. And go back for another load. Business is booming. Once the cargo is inside the U.S., more busses are there to pick them up and transport them to drop off points. Here the phone calls are made for arrangements of more transportation across the nation. And in that highly organized manner, illegal aliens make their way into American cities. Some are "Sanctuary Cities" where politicians have decided it's good for the community to encourage illegals to live. In such communities no one can ask for the country of origin, even if a crime as horrible as murder is committed. The sanctuaries permit 20 million illegals, drug smugglers, child sex rings, ID forgery networks, and an assortment of run of the mill criminals to live lawlessly inside the United States. They are provided with income, identification, driver's licenses, credit, housing, education, and medical care at taxpayer expense. As stated, it's a $300 billion a year industry. That buys a lot of politicians. Along the Border States no one talks about it. And, no surprise, a lot of politicians do nothing to stop it. Our fear and their greed are destroying the American dream. MEANWHILE IN YOUR LOCAL COMMUNITY… How a community treats the illegals is key as to how many come there. The main magnet is the establishment of a day labor center. The nation-wide illegal network knows where to send them. If a community opens its arms, of course they flock there. If a community stands up to them, they leave. But that is easier said than done. First, federal laws or lack of enforcement hampers efforts against the illegals, no matter the sentiment of the community. Federal courts strike down local laws, such as just happened in Hazleton, Pennsylvania when a federal judge degreed that laws the community had passed to crack down on illegals were unconstitutional. Federal agencies say it is illegal for local police to ask if anyone is an illegal. The federal government argues that immigration is a federal issue and for local communities to take action interferes with U.S. foreign policy. On the local level too, there is great pressure on elected officials to do nothing. Strong lobbying arms protect the illegals. The ACLU, of course, threatens lawsuits. But many Americans would be surprised to learn of the Hispanic forces behind much of the pressure applied to their local officials. Many immigrant groups are joined together through the La Raza movement. These are the groups which organized the massive demonstrations in cities across the nation last year. It is past time for all Americans to know what is at the root of those demonstrations and the extent to which our nation is at risk to the La Raza movement. One of the most prominent Hispanic organizations pushing for "immigrant rights" is the National Council of La Raza - the Council of "the Race." The mainstream media and most members of Congress depict La Raza as little more than a Hispanic Rotary Club. In 2005, La Raza received $15.2 million in federal grants, of which $7.9 million was in U.S. Department of Education grants for Charter Schools, and undisclosed amounts to get-out-the-vote efforts supporting La Raza political positions including lobbying for open borders and amnesty for illegals. Had the Senate's immigration bill passed, several million more dollars were budgeted for La Raza. Behind the respectable front of the National Council of La Raza lies the real agenda of the La Raza movement. This radical agenda, pushed by secondary groups contains the reasons behind the demonstrations and the strong lobbying efforts in our communities. Key among those secondary groups is the radical racist group Movimiento Estudiantil Chicano de Aztlan, or Chicano Student Movement of Astlan (MEChA). MEChA seeks to carve a racist nation out of the American West. MEChA opposes assimilation into American society. MEChA is a leader in the effort to "Reconquista" or reconquest our western states. MEChA's founding principles state: "In the spirit of a new people that is conscious not only of its proud historical heritage but also of the brutal gringo invasion of our territories, we, the Chicano inhabitants and civilizers of the northern land of Aztlan from whence came our forefathers, reclaiming the land of their birth and consecrating the determination of our people of the sun, declare that the call of our blood is our power, our responsibility, and our inevitable destiny... Aztlan belongs to those who plant the seeds, water the fields, and gather the crops and no to the foreign Europeans... For La Raza to do. Fuera de la Raza nada." That closing two-sentence motto is chilling to everyone who values equal rights for all. It says: "For The Race everything. Outside The Race, nothing." These words don't come from a fringe radical element. These come straight from the official MEChA sites at Georgetown University, the University of Texas, UCLA, University of Michigan, University of Oregon, and many other colleges and universities around the country. Another leading Hispanic group involved in community organization, promoting the pro illegal position is Mexicanos Sin Fronteras. The translation of the name means "Mexicans Without Borders." This group is active throughout the country and many times works with the "Zapatista Army of National Liberation." These groups seek to radicalize the Latino community. The official website of the Mexicanos Sin Fronteras states that it is "anti-capitalist, anti-imperialist in the capital of the most terrorist country of world-wide history" (Washington, DC). It goes on to say it pledges its support to "other campaigns" of the radical illegal Hispanics with material and financial assistance. In Manassas, Virginia the Mexicanos Sin Fronteras and the Zapatista Army of National Liberation are the two most prominent "pro-Hispanic" voices. In fact, these two groups are spearheading the illegal alien lobby in Prince William County, where Manassas is located. This is the "mainstream opposition" to efforts to curb illegal immigration in that community. Together, these groups are holding rallies and calling for boycotts and even the violent overthrow of the United States. Again, these groups are not fringe radicals. They are the most prominent voices for the illegals. The photo on this page is of a meeting in Mexico with many of these groups. It is interesting to note that speaker in this picture, with his face covered, is Arnoldo Borjas a member of Mexicanos Sin Fronteras and a resident of Woodbridge, Virginia. He is one of the main leaders in that local movement. Further, in Prince William County, there are several candidates running for local office as well as the state legislature who are closely aligned with these two radical organizations. FIGHTING BACK While Congress fiddles and the Bush Administration issues meaningless pronouncements on "get tough" programs it never intends to enforce, local communities and state legislatures are beginning to fight back. And they are meeting with success. State Legislatures, forced to deal with the failure of the federal government to fix the immigration laws, have considered 1,404 immigration bills this year and enacted 170 of them. These laws are aimed at curbing employment of illegals and making it more difficult to obtain state identification documents like driver's licenses. In May, Oklahoma passed the "Taxpayer and Citizen protection Act" which denies illegals state identification, and requires all state and local agencies to verify citizenship status of all applicants before authorizing benefits. On the local level incredible success is being achieved in Northern Virginia. Last year two residents of Herndon, Virginia, with no prior political experience, began an effort called Save Herndon. The issue was the establishment of a day labor center in the community. The center would give illegals a gathering place in the community to help them get jobs, identification and benefits from the community. The two began a campaign that at once made a major issue out of the establishment of the center. When the mayor and the city council moved forward and voted to establish the center over the objections of a majority of the citizens, Save Herndon began a campaign to assure these representatives were not re-elected. They succeeded beyond their wildest expectations, helping to out the mayor and everyone on the city council who voted for the center. Now the movement is growing across the Northern Virginia area. There is now Help Save Manassas, Help Save Loudoun (County), Help Save Fairfax, Help Save Virginia and Help Save Maryland. Together these purely grassroots movements have succeeded in enacting legislation in Loudoun County (the nation's fastest growing county) and in its neighbor, Prince William County which stops county tax-payer services to illegals. Incredibly, under challenge from federal and state officials, the members of county commissioners are holding tough behind the laws. The key, as stated earlier, is the day labor centers. If your city has one, then the message has gone out to the illegal infrastructure that your community welcomes them. Get rid of it and send the message that they are no longer welcome. If faced with lawsuits from the ACLU and La Raze, welcome them. Tell them you will gladly have a news conference to discuss their suit in front of the cameras. Do not be afraid. Here are a few guidelines to help organize locally and face the coming onslaught of charges of racism. DON'T express anger at what is happening to your community. DON'T express annoyance because illegals refuse to assimilate into your community or abide by your customs. DON'T make the issue economic and safety issues. Overcrowded housing and commercial vehicle zoning violations or that specific individuals are illegal aliens. The pro-illegals will try to tell the public that there is uncertainty as to who is illegal, creating doubt. They will talk about how impossible it is to check everyone's legal status. It will be easy to charge racism. Subscribe to the NewsWithViews Daily News Alerts! Enter Your E-Mail Address: Instead, make the issues about the abrogation of law. Focus your efforts against the individuals, businesses and politicians who create this problem and cheat honest business owners and workers by allowing illegal hiring practices under the table. In short, make the issue about enforcement of the law, cost and corruption. It's working in Virginia. Today, we have the chance to not only stop the flood of illegal aliens, but in the process, deflate the size and power of the federal government in the process. It's time to organize Help Save America. For part one click below. Most Americans understand that new laws are not needed to stop illegal immigration. What is necessary is repeal of some laws granting taxpayer-financed services to illegals along with enforcement of existing laws. | Mid | [
0.5431578947368421,
32.25,
27.125
] |
Q: Removing duplicates from a list in Haskell without elem I'm trying to define a function which will remove duplicates from a list. So far I have a working implementation: rmdups :: Eq a => [a] -> [a] rmdups [] = [] rmdups (x:xs) | x `elem` xs = rmdups xs | otherwise = x : rmdups xs However I'd like to rework this without using elem. What would be the best method for this? I'd like to do this using my own function and not nub or nubBy. A: Both your code and nub have O(N^2) complexity. You can improve the complexity to O(N log N) and avoid using elem by sorting, grouping, and taking only the first element of each group. Conceptually, rmdups :: (Ord a) => [a] -> [a] rmdups = map head . group . sort Suppose you start with the list [1, 2, 1, 3, 2, 4]. By sorting it, you get, [1, 1, 2, 2, 3, 4]; by grouping that, you get, [[1, 1], [2, 2], [3], [4]]; finally, by taking the head of each list, you get [1, 2, 3, 4]. The full implementation of the above just involves expanding each function. Note that this requires the stronger Ord constraint on the elements of the list, and also changes their order in the returned list. A: Even easier. import Data.Set mkUniq :: Ord a => [a] -> [a] mkUniq = toList . fromList Convert the set to a list of elements in O(n) time: toList :: Set a -> [a] Create a set from a list of elements in O(n log n) time: fromList :: Ord a => [a] -> Set a In python it would be no different. def mkUniq(x): return list(set(x))) A: Same as @scvalex's solution the following has an O(n * log n) complexity and an Ord dependency. In difference to it, it preserves the order, keeping the first occurences of items. import qualified Data.Set as Set rmdups :: Ord a => [a] -> [a] rmdups = rmdups' Set.empty where rmdups' _ [] = [] rmdups' a (b : c) = if Set.member b a then rmdups' a c else b : rmdups' (Set.insert b a) c Benchmark results As you can see, the benchmark results prove this solution to be the most effective. You can find the source of this benchmark here. | Mid | [
0.6014492753623181,
31.125,
20.625
] |
<template lang="html"> <div class="popup-container"> <wd-header title="Popup" fixed> <router-link to="/" slot="left" class="link"> <span class="iconfont icon-zuosanjiao"></span> </router-link> </wd-header> <br> <br> <br> <br> <wd-button type="primary" @click.native="bottom = true">Popup bottom</wd-button> <br> <wd-button type="primary" @click.native="top = true">Popup top</wd-button> <br> <wd-button type="primary" @click.native="left = true">Popup left</wd-button> <br> <wd-button type="primary" @click.native="right = true">Popup right</wd-button> <br> <br> <wd-button type="primary" @click.native="right70 = true">Popup left 70%</wd-button> <br> <wd-button type="primary" @click.native="left300 = true">Popup left 300px</wd-button> <br> <wd-button type="primary" @click.native="close = true">Popup 点击 model 关闭</wd-button> <br> <wd-button type="primary" @click.native="closeMask = true">Popup 点击 mask 关闭</wd-button> <wd-popup class="popup" v-model="bottom"> <wd-button type="gray" @click.native="bottom = false">close bottom</wd-button> </wd-popup> <wd-popup class="popup" v-model="top" position="top"> <wd-button type="gray" @click.native="top = false">close top</wd-button> </wd-popup> <wd-popup class="popup" v-model="left" position="left"> <wd-button type="gray" @click.native="left = false">close left</wd-button> </wd-popup> <wd-popup class="popup" v-model="right" position="right"> <wd-button type="gray" @click.native="right = false">close right</wd-button> </wd-popup> <wd-popup class="popup" v-model="right70" position="left" cover="70%"> <wd-button type="gray" @click.native="right70 = false">close left 70%</wd-button> </wd-popup> <wd-popup class="popup" v-model="left300" position="left" cover="300px"> <wd-button type="gray" @click.native="left300 = false">close left 300px</wd-button> </wd-popup> <wd-popup class="popup" v-model="close" position="bottom" cover="50%" closeWhenClicked> <p>点击 model 关闭</p> </wd-popup> <wd-popup class="popup" v-model="closeMask" position="bottom" cover="50%" @maskClick="closeMask = false"> <p>点击 mask 关闭</p> </wd-popup> <br> </div> </template> <script> export default { data() { return { bottom: false, top: false, left: false, right: false, right70: false, left300: false, close: false, closeMask: false } } } </script> <style lang="sass"> .popup-container{ position: relative; display: flex; flex-direction: column; align-items: center; width: 100%; height: 100%; .popup { display: flex; flex-direction: column; align-items: center; .wd-button, p { margin-top: 50px; text-align: center; width: 90%; } } .app-header-container { position: absolute; top: 0; left: 0; right: 0; } } </style> | Low | [
0.529761904761904,
22.25,
19.75
] |
Introduction ============ Heart failure is a clinical manifestation of various cardiovascular diseases. It is a devastating disease characterized by interstitial fibrosis, ventricular remodeling and decreased ventricular compliance. During the pathology of cardiac remodeling, activation of cardiac fibroblasts (CFs) results in excessive deposition of extracellular matrix (ECM) protein, decreased tissue compliance and accelerated heart failure [@B1], [@B2]. After myocardial injury, the secretion of various proinflammatory cytokines and fibrotic factors increase, leading to fibroblast proliferation and activation into myofibroblasts[@B3], [@B4]. In myofibroblasts, alpha-smooth muscle actin (α-SMA) is assembled into stress fibers that can remodel the surrounding ECM and then contribute to pathologic cardiac remodeling [@B5]. Therefore, the development of drugs targeting fibroblasts is essential for reducing cardiac remodeling and delaying the development of heart failure. During the pathological process of various cardiovascular diseases, the sources of activated fibroblasts include the presence of fibroblasts, vascular origin cells, hematopoietic cells and pericytes[@B6]. Of these cells, cardiac endothelial cells undergoing endothelial-mesenchymal transition (EndMT) have been shown to contribute 27\~33% of all cardiac fibroblasts following pressure-overload[@B7]. During the EndMT process, endothelial cells lose polarity and expression of intercellular adhesion complexes, such as CD31 and E-Cadherin, but activate the expression of additional mesenchymal genes and proteins, such as α-SMA, collagen I and III, and vimentin[@B8]. Inhibition of EndMT/EMT is a promising target for clinical therapeutic applications in cardiac fibrosis[@B9], [@B10]; thus, drugs targeting EndMT may become a new strategy for the treatment of cardiac fibrosis. Saikosaponin A (SSA) is a triterpenoid saponin isolated from Radix Bupleuri (Rb). At present, SSA has been reported to have many pharmacological activities, such as anti-inflammatory and antioxidant effects. During activation of hepatic stellate cells, SSA was reported to regulate the expression of bone morphogenetic protein 4 (BMP-4)[@B11]. In the chemical-induced liver inflammation and fibrosis rat model, SSA was also reported to exert protective effects[@B12]. Moreover, in human umbilical vein endothelial cells, SSA inhibited oxidative stress and inflammation by suppressing TLR4 translocation into lipid rafts[@B13]. These data suggest a protective effect of SSA on tissue fibrosis as well as on endothelial cells. Thus, we suppose SSA would exert some extension of these effects on cardiac fibrosis. In this study, aortic banding surgery was used to establish the mouse cardiac fibrosis model. The effects of SSA on cardiac fibrosis as well as the effect of SSA on fibroblast and endothelial cells were investigated. Materials and Methods ===================== Materials --------- National Institutes for Food and Drug Control (Beijing, China) supplied the Saikosaponin A. Antibodies specific for GAPDH, TGFβ, smad2, smad3, smad4, Wnt, β-catenin, GSK3β and laminin B came from Cell Signaling Technology (Beverly, MA). Antibodies including VE-cadherin, CD31, α-SMA and vimentin came from Abcam (Cambridge, CB4 0FL, UK). SRI-011381 and WAY-262611 were purchased from MechemExpress (Monmouth Junction, NJ 08852, USA). Animal and Animal models ------------------------ We followed the Guide for the Care and Use of Laboratory Animals, which was published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). The Animal Care and Use Committee of The First Affiliated Hospital of Zhengzhou University approved our experiment. The Institute of Laboratory Animal Science, CAMS& PUMC (Beijing, China) supplied us with male C57BL/6 mice that were 8-10 weeks old. The animals were randomly assigned to four groups: a. sham surgery group; b. vehicle-aortic banding (AB) group; c. SSA-low dosage (LD)-AB group (intraperitoneal injection, 5 mg/kg/d) after 2 weeks of AB for 28 consecutive days. d. SSA-high dosage (HD)-AB group (intraperitoneal injection, 40 mg/kg/d) after 2 weeks of AB for 28 consecutive days. Echocardiography and Hemodynamics --------------------------------- Echocardiography was performed as described in a previous study with MyLab 30CV ultrasound (Biosound Esaote, Genoa, Italy) and a 10-MHz linear array ultrasound transducer[@B10]. Hemodynamics were measured with a microtip catheter transducer (SPR-839; Millar Instruments, Houston, TX) as described in a previous study[@B10]. The PVAN data analysis software was used to process data. Histology and Immunofluorescence -------------------------------- HE and PSR staining were performed according to the protocol in our previous study[@B10]. For immunofluorescence, the antigen was heated by pressure cooker, incubated with anti-CD31 and alpha-SMA, and then incubated with goat anti-mouse / rabbit secondary antibody. DAPI was used to stain nuclear material and prevent fading. RT-PCR and Western blot ----------------------- RNA and RT-PCR were performed according to the protocol in our previous study [@B10]. A LightCycler 480 SYBR Green 1 Master Mix (Roche, 04707516001) was used for amplification prior to PCR. GAPDH gene expression was used as a reference. Western blotting was performed according to the protocol in our previous study [@B10]. Protein samples were separated with SDS electrophoresis and transferred to immobilon-FL transfer membranes (IPFL00010, Millipore, Billerica, MA). After blocking with 5% milk, membranes were incubated with primary antibodies. Goat anti-rabbit (LI-COR) IgG or anti-mouse IgG (LI-COR) were used. A two-color infrared imaging system (Odyssey, LI-COR, Lincoln, NE) was used to scan the blots. Cell culture ------------ ### Neonatal rat cardiomyocytes (NRCMs) NRCMs were isolated according to the protocol in our previous study[@B14]. Briefly, 1- to 3-day-old Sprague-Dawley rat hearts were harvested. Ventricles were digested four times for fifteen min each in 0.125% trypsin-EDTA in PBS. Following centrifugation, cells were resuspended and incubated for 90 min in a 100-mm dish to allow noncardiac myocytes (mainly cardiac fibroblasts) to adhere to the plastic. After culture with 1% bromodeoxyuridine for 48 h, NRCMs were treated with AngII (1 μM) for 24 h and then with SSA (1, 3, 10, 30, 50 μM) for 12 h. ### Mouse adult CF culture Mouse adult CFs were isolated according to the protocol in our previous study [@B15]. Briefly, 0.125% trypsin and collagenase were used to digest the left ventricles from 8-week-old mice. DMEM/F12 medium containing 10% FBS was used to suspend and culture adult CFs. Ninety minutes after attachment, the attached CFs were cultured and passaged. Cells were cultured in serum-free DMEM/F12 for 8 h and then stimulated with TGFβ1 (10 ng/ml) for 24 h. SSA (1, 3, 10, 30 and 50 μM) was applied for another 12 h. To activate TGFβ/smad signaling, after culturing with TGFβ1 for 24 h, the cells were treated with SSA (30 μM) and SRI-011381 (10 μM) for another 12 h. ### Primary mouse heart EC (MHEC) culture MHECs were isolated as described in the previous study [@B16]. Briefly, mouse hearts were cut in Hanks\' balanced salt solution buffer. Collagenase A was used to digest the heart tissue, and 10% FBS-DMEM was used to stop digestion. After filtering with a nylon mesh (70-mm pores), cells were resuspended in Hanks\' solution. CD31 beads were used to bind ECs. ECs were then washed and cultured in dishes precoated with 2% gelatin (Sigma, Oakville, ON, Canada) in endothelial basal medium with 10% FBS. MHECs were starved for 12 h and then cultured with TGFβ1 (10 ng/ml) for 24 h. SSA (1, 3, 10, 30 and 50 μM) was applied for another 12 h. To activate Wnt/β-catenin signaling, after culture with TGFβ1 for 24 h, cells were treated with SSA (1 μM) and WAY-262611(1 μM) for another 12 h. Cell viability detection ------------------------ The MTT assay was used to detect cell viability. Briefly, after treatment, cells were incubated with MTT (5 mg/ml) at 37°C for 4 h. Following additional incubation with dimethyl sulfoxide, an ELISA reader was used to measure absorbance at 495 nm. Immunofluorescence ------------------ After being washed with PBS and fixed in 4% polyoxymethylene, cells were permeabilized with 0.1% Triton X-100 (Amresco). The following primary antibodies were used to stain the cells: anti-actin (in NRCMs), anti-α-SMA (in fibroblasts), or anti-CD31 and vimentin (in MHECs). After incubation with Goat anti-Mouse/Rabbit IRdye 800CW secondary antibody for 60 min, cells were cultured with DAPI to stain nuclear material and prevent fading. Statistical analysis -------------------- All data are expressed as the mean ± standard deviation (SD). The differences between groups were evaluated by one-way ANOVA and post-tests. Student\'s unpaired t test was used to compare differences between the two groups. P \< 0.05 had statistical significance. Results ======= The effects of SSA on cardiac hypertrophy *in vivo* --------------------------------------------------- Six weeks after surgery, severe cardiac hypertrophy was observed in vehicle-treated mice with increased HW/BW, HW/TL, LW/BW, and LW/TL ratios, increased cell surface area (CSA), and increased transcription of hypertrophy markers. The extent of cardiac hypertrophy in both the LD and HD SSA-treated mice showed no significant difference from that in the vehicle-treated mice since the extent of HW/BW, HW/TL, LW/BW, LW/TL, and CSA was the same for all three groups (Fig. [1](#F1){ref-type="fig"}A-F). The transcription levels of ANP and BNP, but not β type-MHC and α type-MHC, were reduced by both LD and HD SSA treatment (Fig. [1](#F1){ref-type="fig"}G-J). These data indicate that SSA exerted a limited effect on cardiac hypertrophy. The effects of SSA on cardiac fibrosis *in vivo* ------------------------------------------------ The perivascular and interstitial fibrosis levels were increased in vehicle-treated AB mice compared with the sham group. Both LD and HD SSA decreased perivascular and interstitial fibrosis levels as well as LV collagen volume compared with those of the vehicle-treated mice (Fig. [2](#F2){ref-type="fig"}A, B). Moreover, the increased expression level of fibrosis markers was reduced by both LD and HD SSA treatment (Fig. [2](#F2){ref-type="fig"}C-G). These data suggest that SSA affected cardiac fibrosis. The effects of SSA on cardiac function -------------------------------------- Cardiac dysfunction is the basic characteristic of heart failure. Thus, echocardiography and hemodynamics measurement were used to evaluate cardiac function. Increased ventricular wall thickness (increased IVSd, LVPWd), dilatation (increased LVEDd, LVESd) and systolic (decreased EF, FS, dp/dtmax, dp/dtmin) and diastolic dysfunction (increased Tau value) were observed in vehicle-treated mice after 6 weeks of AB. Both LD and HD SSA treatment did not change the increased ventricular wall thickness but did ameliorate the ventricular dilatation (decreased LVEDd, LVESd) and improved systolic (increased EF, FS, dp/dtmax, dp/dtmin) and diastolic function (decreased Tau value)(Table [1](#T1){ref-type="table"}). Collectively, our results suggest that SSA protects against cardiac fibrosis and improves cardiac function. The effects of SSA on AngII-induced cardiomyocyte hypertrophy in NRCMs ---------------------------------------------------------------------- To determine the effect of SSA on cell types, NRCMs were stimulated with AngII to induce cardiomyocyte hypertrophy. Cell viability in the 1\~30 μM SSA groups revealed no significant difference from the control group, though the 50 µM group did differ (Fig. [3](#F3){ref-type="fig"}A). Thus, we chose 1 and 30 μM SSA for further study. AngII induced deteriorated hypertrophy as assessed by the increase in CSA and increased transcription levels of hypertrophic markers. Nevertheless, none of the concentrations of SSA could attenuate AngII-induced increased CSA and transcription of β-MHC (Fig. [3](#F3){ref-type="fig"}B, C, E). However, both 1 and 30 μM SSA attenuated the transcription of ANP (Fig. [3](#F3){ref-type="fig"}D). SSA relieves TGFβ1-induced fibroblast activation and function in adult mouse CFs -------------------------------------------------------------------------------- To determine whether SSA directly affected CFs to protect against cardiac fibrosis, CFs were isolated and cultured with TGFβ1 and then treated with SSA (1, 3, 10, 30 and 50 μM). Different concentrations of SSA did not affect cell viability except for 50 μM SSA (Fig. [4](#F4){ref-type="fig"}A). Thus, 1, 3, 10 and 30 μM SSA were used. TGFβ1 induced remarkable proliferation of CFs, but only 10 and 30 μM SSA decreased TGFβ1-induced cell proliferation (Fig. [4](#F4){ref-type="fig"}B). Increased expression of α-SMA and transcription of collagen I, collagen III, and CTGF were observed in CFs after TGFβ1 stimulation, suggesting a myofibroblast transition and function after TGFβ1 stimulation. Treatment with 10 and 30 μM SSA, but not 1 and 3 μM SSA, inhibited CF transition and function (Fig. [4](#F4){ref-type="fig"}C-F). SSA suppresses TGFβ1-induced EndMT in MHECs ------------------------------------------- EndMT is an important source of CFs in the pressure overload induced cardiac fibrosis model. Thus, we investigated whether SSA affected EndMT in endothelial cells. MHECs were isolated and cultured with TGFβ1 and then treated with SSA (1, 3, 10, 30 and 50 μM). Different concentrations of SSA did not affect cell viability except 50 μM SSA (Fig. [5](#F5){ref-type="fig"}A). Thus, 1, 3, 10, 30 μM SSA were used. TGFβ1 induced remarkable EndMT in MHECs as assessed by increased CF markers (α-SMA and vimentin) and decreased endothelial cell markers (VE-cadherin and CD31), as well as increased transcription levels of EndMT markers (snail1, snail2, twist1, and twist2). Interestingly, only low concentrations (1 and 3 μM), but not higher concentrations (10 and 30 μM), of SSA ameliorated the increased EndMT induced by TGFβ1 as evidenced by decreased CF markers and increased endothelial cell markers and decreased transcription levels of EndMT markers (Fig. [5](#F5){ref-type="fig"}B-H). SSA attenuates EndMT *in vivo* ------------------------------ To confirm the influence of SSA on EndMT *in vivo,* EndMT markers were evaluated in mouse hearts after 6 weeks of AB. Increased EndMT was observed in vehicle-treated mouse hearts with increased CF markers (α-SMA and vimentin) and decreased endothelial cell markers (VE-cadherin and CD31) (Fig. [6](#F6){ref-type="fig"}A, B), as well as increased transcription levels of EndMT markers (snail1, snail2, twist1, and twist2) (Fig. [6](#F6){ref-type="fig"}D). Consistent with the *in vitro* study, only LD SSA treatment attenuated these EndMT transitions in mouse hearts (Fig. [6](#F6){ref-type="fig"}A-D). These data indicate that different concentrations of SSA may target different cell types to protect against cardiac fibrosis. The effects of SSA on TGFβ/smad and Wnt/β-catenin pathway --------------------------------------------------------- To evaluate the protective effects of SSA on CFs and MHECs, the associated signaling pathways were screened by western blot. As a result, 30 μM SSA treatments decreased the phosphorylation level of smad2, smad3 and nuclear expression levels of smad4, while 1 μM SSA treatment did not affect this pathway (Fig. [7](#F7){ref-type="fig"}A, B). In MHECs, 1 μM SSA treatment decreased the expression of Wnt, β-catenin, the phosphorylation level of GSK3β as well as the nuclear expression of β-catenin; 30 μM SSA treatments did not affect this pathway (Fig. [7](#F7){ref-type="fig"}C, D). The effects of smad activator on fibroblast activation and function in CFs or Wnt activator on EndMT in MHECs ------------------------------------------------------------------------------------------------------------- To confirm the effect of SSA on smad signaling in CFs, CFs were stimulated with TGFβ1 and then treated with 30 μM SSA and SRI-011381. The Smad activator SRI-011381 eliminated the protective effects of high concentrations of SSA on CFs as shown by the same expression levels of α-SMA, collagen I and collagen III in the TGFβ group and the TGFβ +SSA+SRI-011381 group (Fig. [8](#F8){ref-type="fig"}A-C). To confirm the effect of SSA on Wnt/β-catenin signaling in MHECs, MHECs were stimulated with TGFβ1 and then treated with 1 μM SSA and WAY-262611. The Wnt activator WAY-262611 eliminated the protective effects of low concentrations of SSA on EndMT in MHECs as shown by the same expression levels of increased vimentin, snail1 and snail2 and decreased expression levels of VE-cadherin in the TGFβ group and the TGFβ +SSA+ WAY-262611 group (Fig. [8](#F8){ref-type="fig"}D-F). Discussion ========== In this study, we found that SSA alleviated long-term stress overload in cardiac dysfunction and cardiac fibrosis. Supplementation with high-dose SSA can block the transformation of CFs to MFs, inhibit the proliferation and activation of fibroblasts induced by TGF-beta, and inhibit collagen secretion. Supplementation with low dosages of SSA blocked the EndMT process in TGF-β-treated MHECs and pressure overload-induced heart remodeling. High dosages of SSA inhibited phosphorylation and activation of Smad signaling in CFs. Smad activators can make these protective effects vanish. We also found that low doses of SSA inhibited the activation of Wnt/ β-catenin signaling in MHECs, while the protective effect of LD SSA was eliminated by a Wnt/β-catenin activator. Therefore, our current research finds that SSA is a new therapeutic agent for cardiac fibrosis. More and more evidence indicates that SSA may play a role in cardiac remodeling due to its pleiotropic biological activity, including powerful antioxidant and anti-inflammatory effects[@B17], [@B18]. SSA protects lung tissue against inflammation induced by cigarette smoke by inhibiting NF-kappa B and upregulating Nrf2 and HO-1 expression[@B17]. By activating LXRα, SSA protects human osteoarthritis chondrocytes from injury induced by IL-1β[@B19]. However, our study shows that the protective effect of SSA on cardiac fibrosis is not related to these factors. The antifibrosis effect of SSA does not depend on cardiomyocytes because we show negative results in the NRCM experiments. ECM derived from CFs provides the structural scaffold for cardiomyocytes in heart tissue[@B6]. However, during various pathologies, increased ECM enhanced ventricular stiffness and can lead to cardiac dysfunction[@B5]. In addition, excessive ECM and fibroblasts damage the electromechanical coupling of CMS, thereby reducing the risk of cardiac contractions and increasing the occurrence and mortality of arrhythmias[@B20]. Herein, we found that a higher dosage of SSA prevented against cardiac fibrosis via directly inhibiting CFs activation and function. The TGF-beta growth factor family may be the most extensively activated mediator of fibroblasts, and TGF-beta 1 may play the most important role in pathological fibrosis[@B21]. The signal transduction pathway of TGF-beta 1 includes the phosphorylation of Smad 2/3, and the binding of Smad2 and Smad4 leads to the migration of Smad4 to the nucleus[@B21]. The complex acts as a transcription factor to induce the activation of many fibroblast genes[@B22]. In this setting, we found that the effect of the higher dosage of SSA on CF activation and function was dependent on the inhibition of TGFβ/smad signaling since a smad activator eliminated the protective effects of SSA on CFs. Evidence implicating EndMT in cardiac fibrosis has been mounting for several years[@B8]. In a landmark publication in 2007, Kalluri and co-workers demonstrated that EndMT makes a significant contribution to myocardial fibrosis in the adult heart[@B7]. Many findings suggest that the inhibition of EndMT/EMT may be a promising target for clinical therapeutic applications in cases of cardiac fibrosis[@B9], [@B10]. In this study, we found that lower dosages of SSA, but not higher ones, could inhibit TGFβ1-induced EndMT both *in vitro* and *in vivo*. Wnt/β-catenin plays a major causal role in EndMT in endothelial cells[@B7]. Under inactivation, cytoplasmic β-catenin is bound to APC, Axin and GSK3β, leading to the phosphorylation, ubiquitination and decomposition of β-catenin. The binding of Wnt to its receptor Frizzled and LRP inhibited the degradation of the complex and induced the signal transduction of β-catenin[@B23]. Binding of nuclear β-catenin to members of the transcription factor TCF/LEF family promotes EndMT[@B24]. Studies have found that by downregulating AXIN2, TGFβ activation primes canonical Wnt signaling in fibroblasts[@B25]. In our study, we found that in endothelial cells, TGFβ1 induced activation of the Wnt/β-catenin pathway. Lower dosages of SSA did not affect smad signaling (data not given) but inhibited the Wnt/β-catenin pathway. These anti-EndMT effects of lower dosages of SSA were dependent on inhibition of the Wnt/β-catenin pathway since a β-catenin activator eliminated the protective effects of SSA on MHECs. The target of SSA in cardiac fibrosis was unclear. Studies have reported that SSA stimulates bone marrow stromal cells to differentiate into osteoblasts by activating the Wnt/β-catenin pathway[@B18]. However, in our study, lower dosages of SSA inhibited EndMT in heart endothelial cells by blocking the Wnt/β-catenin pathway. These results suggested diverse effects of SSA on different cell types at different dosages. Further studies are needed to determine why different dosages of SSA exert different effects on diverse cell types. In conclusion, this study shows that supplementation with SSA reduces cardiac dysfunction and inhibits cardiac fibrosis after prolonged stress overload *in vivo*. The beneficial effects of SSA on cardiac fibrosis may be attributed to its inhibition of TGFβ/Smad signaling in CFs when using higher dosage treatment and inhibition of the Wnt/β-catenin signaling in endothelial cells when using lower dosage treatment. This work was supported by grants from the National Natural Science Foundation of China (No: 81600189, 81600191) and the Scientific and Technological Project of Henan province (NO: 172102310531 and 182102310495). Authors\' contributions ======================= Yuan Liu, Lina Li, and Haibo Yang contributed to the conception and design of the experiments; Yuan Liu, Lu Gao, Xiaoyan Zhao and Sen Guo carried out the experiments; Yuzhou Liu, Ran Li and Cui Liang analyzed the experimental results. Ling Li, Jianzeng Dong and Lina Li revised the manuscript; Lina Li and Yuan Liu wrote and revised the manuscript. AngII : angiotensin II ANP : atrial natriuretic peptide α-SMA : alpha-smooth muscle actin BMP-4 : bone morphogenetic protein 4 BNP : brain natriuretic peptide BW : body weight CFs : cardiac fibroblasts CTGF : connective tissue growth factor dp/dtmax : maximum descending rate of left ventricular pressure dp/dtmin : minimum descending rate of left ventricular pressure ECM : extracellular matrix ECs : endothelial cells EF : ejection fraction EndMT : endothelium-mesenchymal transition FS : fractional shortening HE : hematoxylin and eosin HW : heart weight IVSd : interventricular septal end diastolic dimension LV : left ventricular LVEDd : left ventricular end-diastolic dimension LVESd : left ventricular end-systolic dimension LVPWd : left ventricular end diastolic posterior wall dimension LW : lung weight MHC : myosin heavy chain MHECs : mouse heart endothelial cells PSR : PicroSirius red SSA : Saikosaponin A TGFβ : transforming growth factor β TL : tibia length. {#F1} {#F2} {#F3} {#F4} {#F5} {#F6} {#F7} {#F8} ###### Echocardiography and hemodynamics measurement data for different groups after 6 weeks of AB. --------------------------------------------------------------------------------- Sham\ Vehicle-AB\ LD-AB\ HD-AB\ (n=15) (n=15) (n=15) (n=15) ----------------------- ----------- ------------- --------------- --------------- **HR (bpm)** 465±6.4 457±11 463±10 470±11 **IVSd (mm)** 0.64±0.01 0.84±0.01\* 0.85±0.01\* 0.86±0.01\* **LVPWd (mm)** 0.67±0.03 0.87±0.01\* 0.86±0.01\* 0.86±0.01\* **EF (%)** 65.2±0.77 36.7±0.53\* 52.3±0.88^\#^ 53.8±0.69^\#^ **LVEDd (mm)** 3.51±0.04 4.31±0.03\* 3.95±0.02^\#^ 3.93±0.03^\#^ **LVEDs (mm)** 2.18±0.03 2.84±0.03\* 2.55±0.03^\#^ 2.49±0.02^\#^ **FS (%)** 41.0±0.60 28.1±0.62\* 31.6±0.41^\#^ 33.6±0.82^\#^ **dp/dtmax (mmHg/s)** 10241±230 6426±153\* 8040±149^\#^ 7804±2443^\#^ **dp/dtmin (mmHg/s)** -9316±213 -6704±135\* -7455±214^\#^ 7576±120^\#^ **Tau (Weiss; ms)** 8.77±0.34 17.1±1.56\* 10.6±0.34^\#^ 11.6±0.94^\#^ --------------------------------------------------------------------------------- HR, heart rate; IVSd, interventricular septal thickness at diastole; LVPWd, left ventricular posterior wall thickness at end-diastole; LVEDd, left ventricular end-diastolic diameter; LVESd, left ventricular end-systolic diameter; EF, left ventricular ejection fraction; FS, fractional shortening; dp/dtmax, maximal rate of pressure development; dp/dtmin, maximal rate of pressure decay; Tau, time constant of LV pressure decay \*P\<0.05 for difference from sham group. \#P\<0.05 vs vehicle-AB group. [^1]: Competing Interests: The authors have declared that no competing interest exists. | Mid | [
0.63517060367454,
30.25,
17.375
] |
@Imports ROOT_PROJECT_NAMESPACE.Areas.HelpPage.ModelDescriptions @ModelType SimpleTypeModelDescription @Model.Documentation | Mid | [
0.593516209476309,
29.75,
20.375
] |
AFTER an emergency meeting was called this evening, the LNP party room has voted to ask State President Bruce McIver to consider Yeerongpilly MP Carl Judge's disendorsement. 8.17pm: "I was hopeful a resolution would be achieved," Mr Judge said. "Clearly they are seeking to have me expelled. "I would have liked to have had the opportunity to address the party room." 8.10pm: Mr Judge said he was committed to the LNP despite the decision and would await the party's final call. "Campbell Newman and Jeff Seeney run the parliamentary wing... They certainly don't run the party," he said. Mr Judge said he had sought a meeting with the Premier before the party room meeting but was denied one. He called on Mr Seeney to substantiate the allegations against him and afford him natural justice. 8.05pm: Yeerongpilly MP Carl Judge is expected to call a press conference soon after the LNP party room voted to recommend his disendorsement during an emergency meeting earlier this evening. 7.30pm: "There was a whole range of behavior we found unacceptable," Deputy Premier Jeff Seeney said. "The team has decided to take action." He said the party would ask State President Bruce McIver to consider Mr Judge's disendorsement. Mr Seeney said the party room had voted "without dissent" on a motion asking Mr McIver to take action against the Yeerongpilly MP. "We don't believe the member for Yeerongpilly... any longer deserves the endorsement of the LNP in that position." Mr Seeney said the party room did not have the power to expel him. "All the party room can do is exclude him from our ranks," he said. As for Gaven MP Alex Douglas' fate, Mr Seeney said he was confident he and Premier Campbell Newman would come to a resolution. "They are both experienced politicians and I think they will settle their differences tonight," Mr Seeney said. Mr Newman, Mr Douglas and several other MPs remain locked in a meeting tonight, attempting to resolve those issues. Mr Douglas said he was still a member of the LNP and would "probably die one". 6.40pm: LNP MPs had called an emergency party room meeting this evening amid speculation rogue backbenchers Carl Judge and Alex Douglas could be punted from the party. Water Minister Mark McArdle, asked as he entered the meeting if the two should go, answered only "Yes" before closing the door. Dr Douglas also entered the meeting, saying only: "I'll always be an LNP MP." Mr Newman said their membership was: "A matter for the party room". But Howard Hobbs, who some had speculated could follow former colleague Ray Hopper and defect to Katter's Australian Party, said: "The LNP's a great party to be with", adding "My word" when asked if he wanted to stick with the Newman team. - additional reporting by Steven Scott, Robyn Ironside, Koren Helbig EARLIER, sidelined Gold Coast MP Alex Douglas planned to stay put in the LNP if he is allowed to, despite being kicked off another committee for speaking out against the government. The Member for Gaven today demanded to be reinstated to the Ethics Committee and sought a retraction of comments made by Manager of Government Business Ray Stevens, regarding his honesty and integrity. The pair attacked each other on radio this morning, over events leading up to his removal from the Ethics Committee. In parliament, Premier Campbell Newman said he was disappointed to hear two members of his government at loggerheads on radio, but he believed Mr Stevens over Dr Douglas, who was also discharged from the Legal Affairs Committee. Mr Newman told parliament Dr Douglas had assured him - in a meeting with witnesses on Tuesday - that he was happy with the move. Mr Newman attacked the integrity of his MP and said it was right that he be stripped of his new committee role. "Perhaps that speaks volumes about why there does need to be a change, because if you don't have the integrity to tell the truth about a meeting with the leader of your party ... then perhaps you shouldn't be doing that job," the premier said. He said that during Tuesday's meeting, he told Dr Douglas: "Alex, there will be no move if you are unhappy." The premier said the MP replied: "I'm perfectly happy to do this and move." After Question Time, Dr Douglas said he planned to remain in the LNP but conceded he could face similar treatment to Carl Judge who has been banned from the LNP party room, for disloyalty. "The normal sorts of procedures to be banned, would require a vote of the party room and it would have to be very strongly supported," he said. Manager of Government Business Ray Stevens told Parliament moments after today's sitting started, that Dr Douglas would be discharged as chairman of the Legal Affairs Committee, and Ian Berry appointed in his place. Independent Peter Wellington spoke against the motion, saying it was a "get square" by the government because it had the numbers to do so. A division was called and the motion was passed with all LNP MPs voting in favour, and the Opposition, Katter Australian Party and Mr Wellington voting against. Wavering MP Carl Judge was not in the chamber. The move is a significant blow to Dr Douglas who also lost his place on the Parliamentary Crime and Misconduct Committee yesterday. It effectively means a $21,000 pay cut. Mr Berry is the Member for Ipswich, a seat he holds with a four per cent margin. Earlier, Mr Judge criticised the removal of Ethics Committee chairman Alex Douglas, comparing the treatment to that of his own at the hands of the LNP. Three days after Mr Judge was locked out of the LNP party room for not publicly declaring his allegiance to the Premier, he is still to make up his mind whether to remain with the party, or leave. He said he expected to announce a decision tomorrow, but it was proving very difficult. "If I need a bit longer, I'll take a bit more time. It's a difficult decision to make," said Mr Judge. "There's no reverse gear on this." In relation to the removal of Dr Douglas from the Ethics and Parliamentary Crime and Misconduct Committees, Mr Judge said it was "not the approach he would've taken to deal with somebody". "We all operate differently. That's the course of action they've taken, so be it," he said. "I'm sure it's been upsetting for Dr Douglas, likewise when I was approached by the Deputy Premier and (Manager of Government Business) Ray Stevens, I wasn't impressed with their manner. "We didn't have a cup of tea, put it that way. There could've been another approach taken." Responding to the events of the last few days, Opposition leader Annastacia Palaszczuk said there was "something rotten" in the State of Queensland. "I believe Alex Douglas to be a very ethical man, a man of integrity, a man who understands the nature of handling an Ethics and PCMC committee," she said. "There's a lot of explaining at needs to happen today not only by the Premier but also by the Leader of the House. "I am very concerned that we have very serious matters before the Ethics Committee and why now has Alex Douglas been pushed aside." This morning, it was reported that axed Ethics Committee chairman Alex Douglas would demand to be immediately reinstated to his post in a personal statement to the parliament. Dr Douglas said he had received new information about the reasons for his removal - which he did not request, despite Premier Campbell Newman telling the Parliament he had. “I’m very very uncomfortable with what the Premier said in parliament yesterday,” said Dr Douglas. Asked if he believed the Premier had misled the house, he said “people will make up their own minds about that”. Campbell Newman told Parliament, he understood Dr Douglas had indicated he wanted a change from the Ethics Committee and the Parliamentary Crime and Misconduct Committee. Mr Newman said if he had not wanted to change, he did not have to. Dr Douglas said he was only told shortly before parliament sat of the decision, and he had not got the full details of why he was moved at that time. “I am now aware of other things that have transpired and these things give me great concern as the exiting chairman of the Ethics Committee,” he said. “You don’t go and change the chairman. You only change the chairman if you’re trying to set a different type of agenda, and if you haven’t told the chairman it beholds the chairman to take action. “I’m not trying to build myself up. There’s something very, very odd about what has occurred.” But Manager of Government Business Ray Stevens described the ongoing dramatics in Parliament as "cheap show business". Mr Stevens claimed Dr Douglas was being "loose with the truth" and insisted he was happy with the changes. He told ABC Radio, he reported his conversation to the Premier which led to his statement to parliament that Dr Douglas had asked for the change. "Alex likes to talk on the media regularly and we found out later he was unhappy, he has been very unhappy about not being on Cabinet," Mr Stevens said. He went on to say if he was disgruntled, he should resign from his new post as chairman of the Legal Affairs and Community Safety Committee. Mr Stevens insisted the appointment only came about because of the defection of Ray Hopper from the LNP to the Katter Australian Party. Dr Douglas has suggested other motivations were in play to move him out of the powerful Ethics Committee which was in the process of investigating accusations Transport and Main Roads' Director-General Michael Caltabiano misinformed an Estimates hearing about his work history. ' The Ethics Committee had just suspended a number of inquiries into matters relating to Mr Caltabiano. Yesterday the government claimed the reasons for the change was because of the defection of Ray Hopper to the Katter Australian Party. Mining magnate Clive Palmer, who threw in his Liberal National Party life membership last week after a long-running war of words with government, says the premier should resign for misleading parliament. "The premier has no alternative but to resign for misleading parliament and the good people of Queensland over this grubby affair," he said in a statement on Wednesday. Mr Palmer has also called for Katter's Australian Party's Queensland leader Rob Katter and Labor leader Annastacia Palaszczuk to refer Mr Newman to the ethics committee. Meanwhile, the divisions within Campbell Newman's Government have sparked concerns in the Coalition ranks in Canberra. One senior figure has told the Premier he needs to better manage the renegades in his parliamentary team. Despite public assurances from Tony Abbott that he was not worried about the threats of more defections, one of Mr Abbott's closest allies said Mr Newman needed to learn from the way Mr Abbott managed outspoken federal MPs and Senators such as Alby Schultz, Bill Heffernan and Barnaby Joyce. "You've got to manage people, keep them on side," the senior source said. "If you can't manage them, all people see is bits and pieces falling off the machine." Senior federal members of the Liberal National Party said they feared the fallout damaging their merged party's brand and one warned that "they could blow it apart". "They have got to get their sh*t together. This is amateur hour stuff," the source said. "It's not just Campbell, it's the whole leadership team." The anonymous attack from very senior levels reflects a growing anxiety in the federal party about being tarnished by the infighting within the state LNP. It is designed to send a message to the State Government of anger from within the federal Coalition, the source said. But another senior federal Coalition figure defended Mr Newman, saying "only one defection" was insignificant given the size of his back bench. The same person said Clive Palmer should wear the blame for the turmoil. Some in the Coalition are warning they need to view Bob Katter as more of a threat than Labor and have predicted his party could win a Senate seat from either one of the main parties at next year's election. Mr Abbott has avoided commenting on the fallout in the LNP, saying it is "a matter for the party in Queensland". He has publicly denied suggestions the LNP is "falling apart" and laughed off suggestions the threatened defections were hurting the party. "If we get the kind of election result that Campbell Newman got in Queensland, I'd be a very happy man," Mr Abbott said on Monday. - additional reporting by Steven Scott, Robyn Ironside, Koren Helbig Originally published as LNP asks party to disendorse 'rogue' MP | Mid | [
0.570776255707762,
31.25,
23.5
] |
Owaisi, Lok Sabha member from Hyderabad, referred to media reports, quoting officials, that a new law to curb lynching is unlikely as existing laws were enough to combat crimes like lynching and all it required was "enforcement." He had earlier favoured bringing in a law against lynching. | Low | [
0.5038759689922481,
32.5,
32
] |
Q: Unable to dump mysql tables to local I was trying to dump my mysql table using the below command mysqldump --tab=/home/username/Desktop/basic/ --user myusername -p mysql user; But it returned an error saying mysqldump: Got error: 1: Can't create/write to file '/home/username/Desktop/basic/user.txt' (Errcode: 13) when executing 'SELECT INTO OUTFILE' I use Ubuntu 14.04. I have tried to disable apparmor as explained here. But still the error exists. Any other solutions? Edit I get the .sql file but not the .txt file A: First make sure that mysql can write to /home/username/Desktop/basic/; if you're planning to do multiple dumps in the same directory, a pretty clean way to do it would be to set the ownership of the folder to mysql and to set the SGID permission on the folder (thanks to muru for this suggestion): this way mysqldump will be able to write to the folder, but new files will inherit the the group from the parent directory; this has the advantage of leaving to your user read, write, and execute permissions on the dumps. sudo chown mysql /home/username/Desktop/basic/ && sudo chmod g+s /home/username/Desktop/basic/ Additionally, make sure that there isn't any file named user.sql or user.txt present in the target directory before issuing the command; if either mysql can't write to the target directory or a file with the same name of one of the expected output files exists before issuing the command, mysqldump is going to fail. | Mid | [
0.6139534883720931,
33,
20.75
] |
John Terry and Gary Cahill: Helped Chelsea keep most clean sheets this season Jose Mourinho's backline boasts a league-high of 14 clean sheets this season, conceding just once in their last four games in all competitions, while their hosts, Crystal Palace, have scored just 19 goals all season. The Blues are the only side considered odds-on to keep a clean sheet this weekend by the number crunchers at Sky Bet, while the free-scoring nature of their backline makes them increasingly appealing. John Terry (£7m) and Branislav Ivanovic (£7.8m) look good investments, with the former leading the points scoring charts for defenders this season with 143. With points shared around Mourinho's attacking options, Terry is his side's second highest points scorer as Eden Hazard leads the way, having become just the third player to join the double centurion club with his 14th goal of the season against Arsenal last Saturday. Only Luis Suarez (£9.9m) and Yaya Toure (£8.6m) trump the Belgian's tally, with 280 and 224 apiece, having both bagged hat-tricks last weekend, making them also the game's most in-form players with 57 and 52 points from the last five weeks. Toure actually racked up 31 of his 52 during the double gameweek just gone as he also scored at Manchester United on Tuesday. The Ivorian midfielder has now scored 12 goals in his last 15 league games heading into their Saturday Night Football clash with Arsenal, who have conceded eight goals in their last two games. Edin Dzeko (£8.5m), who has been charged with leading City's line due to Sergio Aguero's injury and Alvaro Negredo's goal drought, took his tally to six goals in seven starts with a brace at Old Trafford. City's backline has also found some impressive form, with five successive clean sheets, although the combination of injuries and squad rotation means Pablo Zabaleta (£7.4m) is their only defender to have reached triple figures. Looking to Anfield, Liverpool's stars look worth backing to inflict further misery on Tottenham Hotspur, having demolished them 5-0 at White Hart Lane. Steven Gerrard (£8.1m) took his points tally to 170 with his 11th goal of the season on Wednesday, although 10 of those have come from set-pieces, while Daniel Sturridge (£9.2m) has scored 11 goals in as many home games this season. Super Sunday also sees Romelu Lukaku (£8.6m) look to maintain his fine form, having netted three in four, when Everton visit basement side Fulham. Elsewhere, Jay Rodriguez (£7.9m) will be full of confidence heading to Newcastle United after scoring in his last three as well as in the reverse fixture with the Magpies. Southampton's backline also looks worth backing given Alan Pardew's side have netted just once in eight games in the absence of the injured Loic Remy. Meanwhile, Wilfried Bony (£8m), who has eight goals in 13 Premier League appearances at the Liberty Stadium, is worth backing to continue to enjoy home comforts when poor travellers Norwich City head west. | Mid | [
0.6074766355140181,
32.5,
21
] |
The large scale introduction of sophisticated electronic technology into the automobile began in the 1981 model year. Since that time, the electronic content of the average new car has steadily increased. The use of engine computers and other sophisticated electronic systems has enable automobile manufactures to meet a number of important objectives, particularly with regard to the industry's attempt to maximize fuel economy and minimize engine emissions. The increased use of automotive electronics has created a corresponding need for automotive service technicians who can diagnose, and maintain "high tech"electronic systems. Such technicians must possess a level of technical competence which encompasses more than the skills required for utilizing manufacturer designed "on board diagnostics" or specialized testing equipment useful only for specific automotive electronic applications. Unfortunately, not every conceivable electronic system malfunction can be detected by an on-board computer or by specialized testing equipment. When these types of failures occur, a service technician must be able to independently trouble shoot an electronic system to isolate, identify and repair the particular electronic malfunction which is the cause of the system's problem. | Mid | [
0.6504424778761061,
36.75,
19.75
] |
A fisherman thought to be missing at sea for more than 12 hours is found safe and asleep inside a compartment of the commercial fishing vessel. The search efforts included dozens of people, eight helicopters and two planes. A father and son who couldn't swim drowned after wading into Airlie Beach's beachside lagoon on Sunday afternoon. Police say despite the crowds of people and lifeguards on duty it was six minutes before they were spotted. A Tasmanian tourist survives a shark attack in the Whitsundays after being pulled onto a nearby yacht that happened to have an emergency department doctor on board. Rescue personnel say the actions of the doctor saved her life. An inquest into the death of a British tourist who died while scuba-diving in the Whitsundays three years ago hears the lead dive instructor strayed from her normal route and took her eyes off the introductory divers before turning back and realising one was missing. | Low | [
0.49027237354085607,
31.5,
32.75
] |
Differential modulation of clock speed by the administration of intermittent versus continuous cocaine. The roles that psychostimulant sensitization and tolerance play in temporal perception in the seconds-to-minutes range were assessed in rats. Cocaine (20 mg/kg/day) was administered for 2 weeks either intermittently via daily injections (induces sensitization) or continuously via an osmotic minipump (induces tolerance). Interval timing was evaluated throughout administration and withdrawal. Injections of cocaine caused immediate, proportional, leftward shifts in peak times, indicating an increase in the speed of an internal clock. These shifts grew progressively larger with repeated administration, indicating that stimulant-induced increases in clock speed can be sensitized. Continuous cocaine administration produced no reliable effects. These results suggest that the mechanisms of sensitization may play a considerable role in drug-induced alterations of the perception of time. | High | [
0.657824933687002,
31,
16.125
] |
Bilateral pulmonary agenesis. Two cases of bilateral pulmonary agenesis in infants of 31 and 41 weeks gestation are reported. In addition to absence of both lungs, major abnormalities not previously reported were also found in other systems. It is concluded that these abnormalities are not due to chromosomal abnormality but no alternative can be offered. | Mid | [
0.638820638820638,
32.5,
18.375
] |
Background ========== Sepsis or bacteraemia requiring hospital admission is rare, however it is a significant cause of high mortality and serious complications such as septic shock and multi organ dysfunction syndrome \[[@B1]-[@B3]\]. Currently, little data is available about the causal factors of sepsis or bacteraemia in children in the population. The available studies in this field deal particularly with adults or with children belonging to high-risk groups such as neonates and those who are immunocompromized due to HIV infection and children with underlying malignancies \[[@B4]-[@B7]\]. The few studies which have been performed on sepsis or bacteraemia in children from the general population are case series \[[@B8]-[@B10]\] or deal with specific causative bacterial agents \[[@B1],[@B11]-[@B13]\]. Three previous studies of which only one performed in children reported that from the identifiable primary focus in patients with sepsis or bacteraemia most often (22--37%) an infection of the skin was detected \[[@B1],[@B2],[@B12]\]. Children suffering from atopic dermatitis are chronic carriers of *Staphylococcus Aureus*and run therefore a higher risk to develop sepsis or bacteraemia \[[@B9],[@B14]\]. Skin infections are almost always curable, but some may lead to serious complications such as nephritis, carditis, arthritis and sepsis if the diagnosis is delayed and/or treatment is inadequate \[[@B15]\]. A Dutch study performed in children aged 0--14 years reported that 28% of those with skin diseases consulted the general practitioner (GP) \[[@B16]\]. Hence, for this reason, we hypothesize that children who were admitted to hospital due to sepsis or bacteraemia suffered more often from skin diseases, especially skin infections, and therefore visited their GP for this reason more often prior to their admission compared to their controls. If our hypothesis is true and given the fact that skin diseases account for 23% of the total morbidity in children in general practice \[[@B17]\], the GP may be able to reduce the risk of sepsis or bacteraemia by recognizing skin diseases in time and treating them adequately. To test this hypothesis we performed a case-control study, aiming to answer the following research question: \- Did children who were admitted to a hospital for sepsis or bacteraemia visit their GP more often for skin diseases before their admission, compared to matched controls? Methods ======= We used data of the second Dutch National Survey of general practice performed by NIVEL (Netherlands Institute for Health Services Research) in 2001 and data of the LMR (National Medical Registration in the Netherlands). Second Dutch National Survey ---------------------------- In the Netherlands, general practices have a fixed list size and all inhabitants are listed with a general practice, and GPs have a gate-keeping role. Usually, the first contact with health care, in a broad sense, is the contact with the general practitioner. This survey included a representative sample of the Dutch population. Data about all physician-patient contacts, prescriptions and referrals during 12 months in 2001 were extracted from electronic medical records of all listed patients of 104 practices (195 GPs) \[[@B18]\]. All diagnoses were coded using the International Classification of Primary Care (ICPC) \[[@B19]\]. Different health problems within one consultation were recorded separately. Socio-demographic characteristics such as age, gender, region and urbanization level of all patients listed to the participating GPs were derived from the GP\'s computerized patient file. The degree of urbanization was derived from the general practice\'s postal code and categorized into four classes \'under 30,000 inhabitants\', \'30,000--50,000 inhabitants\', \'over 50,000 inhabitants\' and \'the three large Dutch cities Amsterdam, Rotterdam and The Hague\'. The Netherlands were divided into a Northern, Central and Southern region. Childrens\' socioeconomic status (SES) and ethnic origin were obtained by a questionnaire filled out by parents or by the children themselves if they were older than 12 years (response rate 76%). SES was based on the father\'s occupation, which was categorized into five classes \"non-manual work high (class I)\", \"non-manual work middle (class II)\", \"non-manual low and farmers (class III)\", \"manual work high/middle (class IV)\" and \"manual work low (class V)\". Ethnicity was derived from the country of birth of either parent. If either parent was born in Turkey, Africa, Asia (except Japan and Indonesia) and Central or South America, their children were considered to be children of non-Western origin (in accordance with the classification of Statistics Netherlands). All other children were defined as Western. Eight practices were excluded from analysis because of insufficient quality of data registration. LMR (National Medical Registration in the Netherlands) ------------------------------------------------------ This continuous registration contains information about hospital admissions, diagnostic and therapeutic interventions of all hospitals in the Netherlands. All diagnoses were coded using the International Classification of Diseases 9^th^revision (ICD-9) \[[@B20]\]. Previous research revealed that about 87% of the patients referred by the GP to a specialist can be linked to a record of the hospital register \[[@B21]\]. Cases and controls ------------------ Cases were defined as being diagnosed with sepsis or bacteraemia at discharge. The corresponding ICD-9 codes for sepsis and bacteraemia are listed in a separate table \[see [Additional file 1](#S1){ref-type="supplementary-material"}\]. Cases were only selected when their admission date was at least 14 days after the start and before the end of the one-year registration period of the survey in general practice. If cases had more than one admission within a week concerning the same health problem only the first admission was selected. We excluded all children who were primarily admitted to a hospital for skin diseases (N = 29), but assessed GP consultations of these children 14 days prior to their hospital admission. We selected two control groups by matching each case with six controls. Cases and controls were matched on age group (table [1](#T1){ref-type="table"}), gender and region. The first control group was randomly selected from the GP patient lists irrespective of hospital admission and GP consultation, the so called GP controls. The second control group was composed by drawing a random sample from those children who were admitted to a hospital for other reasons than sepsis or bacteraemia, the so called hospital controls. This second control group was added because we can not rule out that some of our severely ill cases bypassed the general practitioner prior to their hospital admission which might lead to an under-estimation of contacts with the GP in this group. ###### Baseline characteristics in percentages of cases and controls Cases (N = 101) GP Controls^1^(N = 597) Hospital Controls^2^(N = 583) ------------------------------ ----------------- ------------------------- ------------------------------- **Age group** 0 -- 3 months 8.9 7.7 9.3 3 -- 6 months 6.9 6.9 5.8 6 -- 24 months 27.7 30.2 28.3 24 -- 72 months 27.7 26.8 26.8 6 -- 17 years 28.7 28.5 29.8 **Gender** Boys 63.4 63.7 64.3 Girls 36.6 36.3 35.7 **Urbanization** \< 30,000 36.6 38.0 36.4 30,000 -- 50,000 18.8 15.9 17.5 \> 50,000 37.6 39.2 36.9 Big cities^3^ 6.9 6.9 9.3 **Region** Northern 19.8 20.1 18.0 Central 61.4 60.8 62.4 Southern 18.8 19.1 19.6 **SES**^**4**^ Non-manual high 34.1 37.4 38.8 Non-manual middle 31.8 31.3 35.6 Non-manual low & farmers 15.9 13.5 5.0 Manual high/middle 2.3 7.5 9.6 Manual low 15.9 10.3 11.0 **Ethnicity** Natives & Western immigrants 85.7 89.8 87.2 Non -- Western immigrants 14.3 10.2 12.8 1 = control group randomly sampled from the general practitioners\' (GP) patient lists irrespective of hospital admission and GP consultation 2 = control group randomly sampled from those children who were hospitalized for other reasons than sepsis or bacteraemia 3 = Amsterdam, Rotterdam, The Hague 4 = according to fathers occupation Ethical approval ---------------- The study was carried out according to Dutch legislation on privacy. The privacy regulation of the study was approved by the Dutch Data Protection Authority. According to Dutch legislation, obtaining informed consent is not obligatory for observational studies. Data-analysis ------------- We analyzed data of all children aged 0--17 years and assessed whether a higher proportion of cases visited the GP with any disease, especially skin disease as listed in the S-chapter of the ICPC \[see [Additional file 2](#S2){ref-type="supplementary-material"}\], within 14 days prior to their admission than controls (GP controls and hospital controls). We calculated odds ratios for the presence of GP consultations for all diseases, skin diseases and other diseases than skin diseases (cases/controls) and 95% confidence intervals (CI) using a conditional logistic regression model. We performed the same analysis for skin diseases within 30 days prior to the hospital admission of the cases. We repeated the latter analysis in a more strictly defined group (N = 44) of cases suffering from sepsis or severe bacteraemia and their matched controls. These cases were explicitly defined as being admitted to hospital due to sepsis, meningitis, acute osteomyelitis, acute pyelonefritis, acute mastoiditis, infectious arthritis or pneumonia. A two-sided p-value less than 0.05 was considered significant in all tests. Results ======= Study population ---------------- The total general practice population included 88,307 children aged 0--17 years. We found 101 cases that could be matched with 597 GP controls and 583 hospital controls. Table [1](#T1){ref-type="table"} shows the baseline characteristics of cases and both control groups. Cases were comparable to their controls regarding socio-demographic characteristics. GP consultations ---------------- Sixty eight cases (67%) consulted the GP 161 times within 14 days prior to their hospital admission; five cases (5%) consulted the GP for a skin disease. Among the GP controls 67 consultations were made by 53 (9%) children within 14 days prior to the admission of the case they were linked to; nine controls (1.5%) consulted the GP for a skin disease. In the same period 255 (43.7%) children among the hospital controls consulted their GP 477 times; of these children 20 (3.4%) presented a skin disease. Table [2](#T2){ref-type="table"} shows which skin diseases were presented to the GP by cases and controls. ###### GP consultation for skin diseases within 14 days prior to hospital admission of cases Diagnoses ICPC^1^ Cases (N = 101) GP Controls^2^(N = 597) Hospital Controls^3^(N = 583) ------------------------------- --------- ----------------- ------------------------- ------------------------------- Pruritis **S02** 0 1 0 Rash localized **S06** 0 0 1 Skin infection post-traumatic **S11** 0 0 1 Insect bite/sting **S12** 0 1 0 Burn/scald **S14** 0 3 1 Bruise/contusion **S16** 0 0 1 Laceration/cut **S18** 0 0 1 Dermatophytosis **S74** 1 0 1 Moniliasis/candidiasis skin **S75** 1 2 4 Naevus/mole **S82** 0 0 1 Impetigo **S84** 0 1 2 Dermatitis seborrhoeic **S86** 0 0 2 Dermatitis/atopic eczema **S87** 2 2 4 Dermatitis contact/allergic **S88** 0 0 2 Diaper rash **S89** 0 0 2 Sebaceous cyst **S93** 1 0 0 Molluscum contagiosum **S95** 0 1 0 Urticaria **S98** 0 0 1 1 = International Classification of Primary Care 2 = control group randomly selected from the general practitioners\' (GP) patient lists irrespective of hospital admission and GP consultation 3 = control group randomly sampled from those children who were hospitalized for other reasons than sepsis or bacteraemia Children who were primarily admitted to hospital for a skin disease (N = 29) and excluded from analysis had the following diagnosis at discharge: skin abscesses, cellulitis, erysipelas, impetigo, infected finger/toe, paronychia and local skin infections. Of these children 14 (48%) consulted the GP 28 times within 14 days prior to their hospital admission. Eight children (28%) consulted the GP for a skin disease. Strengths of relationships -------------------------- Table [3A](#T3){ref-type="table"} shows the odds ratios (cases/controls) for whether or not a GP was consulted stratified for skin diseases and other diseases than skin diseases within 14 days prior to the hospital admission of the cases for children aged 0--17 years. Compared to their controls, more cases consulted the GP. The odds ratio for skin diseases (cases/GP controls) was 3.4 (95% CI: \[1.1--10.8\], p = 0.03) and 1.4 (95% CI: \[0.5--3.9\], p = 0.44) for cases versus hospital controls. ###### A: GP consultations of children aged 0--17 years admitted for bacterial infections and matched controls: odds ratios, 95% confidence intervals and p-values B: GP consultations of children \< 3 months admitted for bacterial infections and matched controls: odds ratios, 95% confidence intervals and p-values C: GP consultations of children aged 3 months to 17 years admitted for bacterial infections and matched controls: odds ratios, 95% confidence intervals and p-values --------------------------------------------------------------------------------------------------------- **(A)** -------------------------------- ------------------------------------- ---------------------------------- Diagnoses according to ICPC^1^ Cases (N = 101)\ Cases (N = 101)\ vs\ vs\ GP controls (N = 597) Hospital controls (N = 583) **Skin diseases (S01 -- S99)** OR^2^3.4 \[1.1--10.8\], p = 0.03 OR 1.4 \[0.5--3.9\], p = 0.44 **Other diseases** OR 33.0 \[16.4--66.7\], p \< 0.0001 OR 2.8 \[1.8--4.5\], p \< 0.0001 **All diseases** OR 25.9 \[13.6--49.4\], p \< 0.0001 OR 2.7 \[1.7--4.2\], p \< 0.0001 **(B)** Diagnoses according to ICPC^1^ Cases (N = 9)\ Cases (N = 9)\ vs\ vs\ GP controls (N = 46) Hospital controls (N = 54) **Skin diseases (S01 -- S99)** OR^2^9.2 \[0.81--106.1\], p = 0.07 OR 4.0 \[0.67--23.9\], p = 0.12 **Other diseases** OR 19.2 \[2.2--164.0\], p = 0.007 OR 5.8 \[1.13--30.3\], p = 0.03 **All diseases** OR 15.3 \[1.8--130.1\], p = 0.012 OR 5.9 \[1.13--30.3\], p = 0.03 **(C)** Diagnoses according to ICPC^1^ Cases (N = 92)\ Cases (N = 92)\ vs\ vs\ GP controls (N = 551) Hospital controls (N = 529) **Skin diseases (S01 -- S99)** OR^2^2.5 \[0.7--9.9\], p = 0.17 OR 1.0 \[0.3--3.5\], p = 0.98 **Other diseases** OR 34.8 \[16.6--73.2\], p \< 0.0001 OR 2.6 \[1.6--4.2\], p \< 0.0001 **All diseases** OR 27.2 \[13.7--53.2\], p \< 0.0001 OR 2.4 \[1.5--4.0\], p = 0.002 --------------------------------------------------------------------------------------------------------- 1 = International Classification of Primary Care 2 = Odds ratio Table [3B](#T3){ref-type="table"} and [3C](#T3){ref-type="table"} show the odds ratios of skin diseases and other diseases for children younger than three months and for children aged three months to17 years respectively. Cases younger than three months showed an odds ratio (cases/GP controls) of 9.2 (95% CI: \[08.1--106.1\], p = 0.07). In this age group the odds ratio (cases/hospital controls) was 4.0 (95% CI: \[0.67--23.9\], p = 0.12). In all age groups significantly more cases consulted the GP for other diseases than skin diseases 14 days prior to their hospital admission compared to matched controls. Repeated analysis of consultations for skin diseases within 30 days prior to the hospital admission of the cases showed similar results, as did repetition of the analysis restricted to the most severe cases (N = 44) and their controls. Discussion ========== We tested the null hypothesis that there is no difference between children admitted for sepsis or bacteraemia and other children as to consulting a GP for skin diseases in a period of 14 days before admission to hospital. We found that there is an association between skin diseases presented to the GP and subsequent hospitalization for sepsis or bacteraemia among GP controls but not for hospital controls. We performed the same analysis in cases and controls younger than three months and found an even stronger relationship, though not significant. This lack of significance is probably due to the small number of cases in this age group. From a clinical point of view the difference between cases and controls may not be very relevant. The probability that a case consulted the GP for skin diseases prior to their hospital admission is only about 5% and therefore not a point of departure for GPs to reduce the risk of sepsis and/or bacteraemia considerably by diagnosing and treating skin diseases appropriately. However, considering cases younger than 3 months (N = 9) about 22% consulted the GP for skin diseases prior to their hospital admission which means that GPs may have possibilities in this age group to reduce the risk of sepsis and/or bacteraemia considerably by diagnosing and treating skin diseases appropriately. We recommend replication of our study in a larger dataset for this age group. Compared with both control groups our cases visited the GP about two times as high with both infectious skin diseases and atopic skin diseases as well, which could support the association between sepsis or bacteremia and infectious and atopic skin diseases \[[@B1],[@B2],[@B9],[@B12],[@B14]\]. In all age groups we found odds ratios concerning GP consultations for other diseases than skin diseases that are considerably high and significantly different (p \< 0.0001) compared to the odds ratios for skin diseases. This finding indicates that there is a very strong association between GP consultations for other diseases than skin diseases, 14 days prior to hospital admission, and being hospitalized for sepsis or bacteraemia. These two large and representative datasets enabled us to assess accurately odds ratios among cases and their matched controls and to test our hypothesis. By matching our cases and controls on age, gender and region we adjusted for differences concerning these variables and also for other socio-demographic characteristics (table [1](#T1){ref-type="table"}). To limit the seasonal variation of the GP consultations we selected only the consultations that took place within 14 days prior to the admission date of the case to whom the controls were linked to. Overall the odds ratio for a GP consultation concerning skin diseases among cases versus GP controls 14 days prior to the admission of the cases is higher compared to the odds ratio among cases versus hospital controls. Our findings are in accordance with an earlier finding by Infante-Rivard \[[@B22]\] that inferences of severe childhood diseases using hospital controls in comparison with population controls resulted in odds ratios closer to the null value. Conclusion ========== There is evidence that children who were admitted due to sepsis or bacteraemia consulted the GP more often for skin diseases prior to their admission, than other children, but the differences are not clinically relevant which means that there is little opportunity for GPs to reduce the risk of sepsis and/or bacteraemia considerably by diagnosing and treating skin diseases appropriately. Competing interests =================== The author(s) declare that they have no competing interests. Authors\' contributions ======================= RSAM and JCvdW designed the study. RSAM and SPW carried out the analyses, RSAM drafted the paper. All authors commented on draft versions and approved the final manuscript. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1471-2296/7/52/prepub> Supplementary Material ====================== ###### Additional File 1 ICD-9 codes used for selection of sepsis and bacteraemia cases. discharge diagnoses related to sepsis or bacteraemia according to ICD-9 classification, used for selecting cases. ###### Click here for file ###### Additional File 2 Chapter S (skin diseases) of the International Classification of Primary Care (ICPC). tabulation of all codes in chapter S (skin diseases) of the International Classification of Primary Care (ICPC). ###### Click here for file Acknowledgements ================ The authors thank all participating GPs and their staff members for providing data. Funding: The Dutch ministry of Health, Welfare and Sports mainly funded the surveys directly or indirectly. In addition, the \"Stichting Centraal Fonds RVVZ\" contributed financially to the second Dutch National Survey. The analysis reported in this paper was made possible through internal funding of the department of General Practice, Erasmus MC-University Medical Center Rotterdam. | Mid | [
0.5954825462012321,
36.25,
24.625
] |
Effects of several vasoactive drugs on the vascular resistance of MT-W9B tumors in W/Fu rats. These experiments were designed to study the effects of vasoactive drugs on normal and malignant tissue in W/Fu rats. The increase in resistance to tumor blood flow elicited by a bolus injection of 10 microgram of norepinephrine was greater than that elicited in the surrounding mammary gland tissue. A 10-fold increase in the resistance to tumor blood flow was sustained for 30 min by the infusion of norepinephrine at the rate of 1.39 microgram/min, whereas a smaller initial increase in mammary gland vascular resistance decreased with time. In contrast, the increase in resistance to tumor blood flow caused by a bolus injection of angiotensin II was less than that observed in the mammary gland tissue. A 20-fold increase in mammary gland vascular resistance could be maintained for at least 5 min by infusion of angiotensin II at the rate of 1.39 microgram/min. In comparison, such treatment caused only a 3-fold increase in the resistance to tumor blood flow. A bolus injection of 1 microgram of isoproterenol decreased the vascular resistance in all normal tissues studied, but the resistance to blood flow in the tumor remained unchanged. The results of these experiments indicate that there may be methods whereby the tumor blood flow can be manipulated for therapeutic purposes and to assist radiographic visualization of tumors. | Mid | [
0.650259067357512,
31.375,
16.875
] |
Q: How can I link to a particular image in a lightbox slideshow? I think I may be way in over my head here... I'm using a WP custom post type and attachments in conjunction with FancyBox to create a slideshow/gallery. Nothing fancy, I don't think. You can see it here: http://photo.convoke.info/galleries/test-gallery/ Except, I want to be able to link to a particular image. So, in that particular gallery, there are two images. I'd like to be able to give someone a link like http://photo.convoke.info/galleries/test-gallery#1 and have it open up the gallery page with the first image already open in the lightbox. #2 for the second image, etc. Is this possible? It doesn't have to be #1... could be any sort of identifier. I'm pretty noob at javascript/jQuery stuff, so please forgive me... I tried googling around but couldn't find anything of use. Thanks! A: Whelp, after a few weeks of mucking around, I finally figured it all out. I needed a few functions: $(document).ready(function() { if (window.location.hash) { // if there is a hash $.fancybox.open($('.fancybox'), {index : parseInt(location.hash.substring(1))}); } }); This badboy checks for a hash, and opens the image corresponding to said hash using fancy box ONLY WHEN THE PAGE IS LOADED. function sethash(id) { top.document.location.hash = id; } This little guy is called by the links to each image in the gallery markup. It sets tthe hash of the page equal to the index of whatever image you've clicked on. <a onclick="sethash('$count')>Image</a> This isn't REAL code, but you get the idea. I have a variable called count that I use to index each image in the gallery. This number corresponds to the index of the image in the fancybox slideshow (i.e. it starts at 0 for the first image in the gallery) It was a lot of work, but it's finally working (almost) perfectly. The last thing I'm going to try is to get the hash to change/update when you click on the previous/next arrows in fancybox. But frankly, if that doesn't work, I don't really care. | High | [
0.6970128022759601,
30.625,
13.3125
] |
Occupants heard a smoke detector alarming and found a fire in the basement. They attempted to extinguish the fire with water, but it intensified and they called 911. Fire personnel arrived and put out the fire. A small dog and a lizard were removed from the home by firefighters, and the occupants — a 19-year-old, a 13-year-old, a 3-year-old and an 11-month-old — self-evacuated the residence, the press release said. The cause remains under investigation. The Red Cross was notified to provide assistance to the family. Two Rivers Police Department also assisted at the scene. | Low | [
0.5088888888888881,
28.625,
27.625
] |
/* run.config STDOPT:+"-machdep gcc_x86_32" */ typedef struct __S { int i; } STR; STR A[] = { { }, { }, { } }; STR D[] = { { }, { 1 }, { } }; int E[][3] = { { }, { } }; int f () { STR B[] = { { }, { }, { } }; STR C[] = { { }, { 3 }, { } }; int F[][4] = { { }, { 23, 45 }, { } }; return B[1].i; } | Low | [
0.523696682464455,
27.625,
25.125
] |
public class ContosoChatHub : Hub { public async Task NewContosoChatMessage(string name, string message) { await Clients.All.addNewMessageToPage(name, message); } } | Low | [
0.5149253731343281,
25.875,
24.375
] |
'use strict'; var constants = require('../../../lib/constants'), ErrorCondition = require('../../../lib/types/error_condition'); module.exports = { Client: require('./client'), Server: require('./server'), Connection: require('./connection'), Session: require('./session'), SenderLink: require('./sender_link'), ReceiverLink: require('./receiver_link'), // useful default options Defaults: { begin: { remoteChannel: 1, nextOutgoingId: 0, incomingWindow: 100000, outgoingWindow: 2147483647, handleMax: 4294967295 }, attach: { handle: 1, role: constants.linkRole.sender, source: {}, target: {}, initialDeliveryCount: 0 }, flow: { handle: 1, deliveryCount: 1, nextIncomingId: 1, incomingWindow: 2147483647, nextOutgoingId: 0, outgoingWindow: 2147483647, linkCredit: 500 }, close: { error: { condition: ErrorCondition.ConnectionForced, description: 'from mock server' } } } }; | Mid | [
0.5846153846153841,
33.25,
23.625
] |
Kris made this adorable quilt as a gift using a pattern by Rabbits Haven. The colours are very soft and pretty, and the embroidery is just wonderful. I am probably not patient enough to even attempt something like this. We decided to leave the embroidered blocks unquilted, I just stitched around them in the ditch. The background is filled with free motion flowers and loops. | Low | [
0.502958579881656,
31.875,
31.5
] |
Postnatal cerebellar defects in mice deficient in methylenetetrahydrofolate reductase. Patients with severe deficiency of methylenetetrahydrofolate reductase (MTHFR) suffer from a wide variety of neurological problems, which can begin in the neonatal period. MTHFR is a critical enzyme in folate metabolism; the product of the MTHFR reaction, 5-methyltetrahydrofolate, is required for homocysteine remethylation to methionine and synthesis of S-adenosylmethionine (SAM). To understand the mechanisms by which MTHFR deficiency leads to significant neuropathology, we examined early postnatal brain development in mice with a homozygous knockout of the Mthfr gene. These mice displayed a dramatically reduced size of the cerebellum and cerebral cortex, with enlarged lateral ventricles. Mthfr deficiency affected granule cell maturation, but not neurogenesis. Depletion of external granule cells and disorganization of Purkinje cells were mainly confined to the anterior lobules of mutant cerebella. Decreased cellular proliferation and increased cell death contributed to the granule cell loss. Reduced expression of Engrailed-2 (En2), Reelin (Reln) and inositol 1,4,5-triphosphate receptor type 1 (Itpr1) genes was observed in the cerebellum. Supplementation of Mthfr(+/-) dams with an alternate methyl donor, betaine, reduced cerebellar abnormalities in the Mthfr(-/-) pups. Our findings suggest that MTHFR plays a role in cerebellar patterning, possibly through effects on proliferation or apoptosis. | High | [
0.676616915422885,
34,
16.25
] |
Josh Reviews Netflix’s Season Three of Black Mirror! I adored the original six episodes made of the British TV show Black Mirror. Series creator Charlie Brooker had made a riveting modern/day Twilight Zone, with each episode a completely stand-alone installment presenting a look at the ways that technology has the potential to be terribly destructive to our lives. Those first six episodes, made between 2011-13, are brilliant, and if you haven’t yet seen them I implore you to drop everything and go check them out — they are available to stream on Netflix. I was very excited when I read that Netflix would be resurrecting the show, allowing Mr. Brooker to create six new episodes. I took my time watching the new episodes, both because I didn’t want them to be over too quickly and also because these episodes are very intense and I couldn’t handle too many too quickly! But now I have completed the new season and am eager to share my thoughts. While there is nothing here in season three that equals the best of the original six episodes, I enjoyed most of these new episodes very much. Mr. Brooker has brought in some talented people to help create this new season, and it’s interesting to see the resulting slightly-different spins on the show. (Though, rest assured, these new episodes all thoroughly feel like Black Mirror.) None of these new episodes reach the genius level that so many of the original six episodes did, and a few are weakened by some flaws I’d have preferred to have seen corrected along the way. But all six episodes are interesting and have a lot to enjoy. While this third season might just be “very good” rather than “genius,” that is still something for us to be thankful for. I am very glad that six more episodes of Black Mirror now exist! (With the possibility of more on the way!) Here is my episode-by-episode rundown. I’ll avoid major SPOILERS but, still, I highly advise stopping here if you haven’t yet seen these episodes. Nosedive — the new season gets off to a somewhat shaky start with this first installment. “Nosedive” has a brilliant, terrifying-in-its-possibility premise, but it suffers somewhat in execution. In the not-too-distant future, everyone can use their cell-phones to rate their interactions with every person they meet, and those scores accumulate into a person’s average score that is constantly visible (because of special contact lenses that everyone wears) whenever you see anyone else. Bryce Dallas Howard is spectacular as a young woman, Lacie, trying to nudge up her personal score. As the story unfolds it becomes clear that these scores classify each individual into a certain social class. (The story is instigated because Lacie wants to live in a new housing development only affordable to individuals with a certain social score, and as the episode continues we see the dark side to what happens to anyone who drops below a certain score.) It’s horrifying how plausible this scenario is. This is a classic Black Mirror premise, in terms of how short a distance there is from our world to the one depicted in this episode, and it’s nightmarish to contemplate this ever becoming our reality. The problem with the episode is that its basic idea is clear after the first few minutes (and in case you had any doubts what was going to happen to Lacie, the episode is calked “Nosedive” so you know exactly where this story is going), but the episode runs over an hour in length. So it becomes excruciating after a while as we watch Lacie’s life get worse and worse and worse. There’s no twist in the episode’s second half, we’re just watching the slow collapse of Lacie’s carefully-constructed life. By the end, when she’s literally rolling around in dirt and mud, I was rolling my eyes. I think the episode would have been stronger with a much tighter runtime. Still, this is a classic Black Mirror premise and a very interesting way to start to the new season. Nice work by talented Black Mirror newbies Rashida Jones and Mike Schur (the Parks and Recreation showrunner) and director Joe Wright (Pride and Prejudice, Atonement, Hanna), and I enjoyed the appearances of supporting cast-members Alice Eve and Cherry Jones. Playtest — In contrast to the first episode, this second installment (skillfully directed by 10 Cloverfield Lane‘s Dan Trachtenberg) was riveting from start to finish, and I genuinely had no idea where the story was going. A broke young man, Cooper, takes a job testing out a project for a video-game company and finds himself trapped in a horrifying virtual reality scenario. Wyatt Russell is a young actor who I don’t recall ever seeing on-screen before (and apparently he used to be a hockey player!), but he’s terrific in lead role as Cooper. (Wunmi Mosaku is also lovely as the voice in Cooper’s ear for most of the episode.). This one was great until the final few minutes. I didn’t care overmuch for the series of fake-out “is this real or is this fantasy” endings. That was clever ten or twenty years ago, when Star Trek did it in episodes like TNG’s “Future Imperfect” or even the Doctor-focused episode of Voyager, “Projections”. But at this point it felt overplayed and cliche to me, and this narrative trickery diluted the impact of the final ending that showed what actually happened to Cooper. Shut Up And Dance —In this episode, an internet hacker (or group of hackers? We never find out) blackmails a number of every-day people into doing his/her/their bidding. For most of the episode we follow Kenny, a teenage boy who made the unfortunate decision to masturbate to internet porn on his hacked laptop. The hacker filmed him using his own laptop’s camera, and sends Kenny an email threatening to send the video to every one of his contacts if he doesn’t do as ordered. With no apparent choice but to follow those instructions, Kenny begins following a series of tasks that at first seem just bizarre but eventually escalate to something much more serious. Along the way, he meets up with Hector ( Jerome Flynn, who plays Bronn on Game of Thrones!), another unfortunate soul being blackmailed by the mysterious on-line entity (or entities). This is a gripping installment as you watch poor Kenny get sucked further and further down the blackmail rabbit hole, hoping he’ll find a way out of his situation but knowing he probably won’t. I though this episode was pretty spectacular until the twist ending. STOP NOW FOR SPOILERS!! Still here? OK, at the very end we discover that Kenny is far from the innocent boy we thought he was. That shock was effective and horrifying but, to me, it totally diluted the point of the episode. I’d thought this was a story about how so many people have online secrets they’d like to protect — emails they don’t want others to see, browsing history they don’t want exposed, etc. — and the dangers that can lead to, how easily someone’s life could get turned upside down if someone got access to those things they’d prefer be kept private. For most of this episode as we watch Kenny go through this ordeal it seems that this could happen to almost anyone. But when you learn that Kenny really did have this coming, suddenly I was left unsure of the point of this whole episode. That everyone is horrible?? San Junipero — In the 1980’s, we follow the gentle story of the flowering relationship between Yorkie (The Martian‘s Mackenzie Davis), a tentative young woman first taking ownership of her being a lesbian, and Kelly (Gugu Mbatha-Raw), a friendly and outgoing bisexual party girl. This is a gorgeous story, one that strikes an unusually sweet tone for Black Mirror and even — shockers!! — has a (mostly) happy ending!! I loved this episode, written by series creator and showrunner Charlie Brooker. This is a beautiful episode, and a wonderful example of how expansive Black Mirror’s anthology structure can be. I was not expecting an episode like this, and so I was delighted by the surprise. Both Ms. Davis and Ms. Mbatha-Raw are wonderful, endearing and with a depth of character that you discover as the episode unfolds. I loved the charisma between the two, and the gentle way we watch their relationship blossom while also peeling back the onion of their individual back-stories. I’d like to write a whole separate blog piece just analyzing the ending of this episode. At first blush it seems happy, but is the idea of these two people being together for all eternity really happy? Could that eventually become nightmarish? Not to mention the religious implications of a human-created afterlife… “San Junipero” was a highlight of this new season. Men Against Fire — in the not too distant future, we follow Stripe (Malachi Kirby, who recently starred as Kunta Kinte in the remake of Roots), a rookie soldier fighting monsters called Roaches somewhere in what looks like Europe. After Stripe gets his first kill, something appears to start going wrong with the implant that all the soldiers have, through which they get military directives, targeting assistance, and apparently even implanted dreams. Is his breakdown a technological problem, or a psychological breakdown? It’s actually something else entirely, and I adored the twist ending. This episode has a powerful message about the ease with which we dehumanize our enemies. Like “Nosedive” and “Shut Up and Dance”, this feels horrifyingly possible in the very near future. The episode’s weakness is that, while the ultimate twist is great, the episode up to that point is a bit flat. I like Mr. Kirby’s work in the lead role and he’s a capable audience-surrogate character, but once Stripe gets zapped by that mysterious object held by one of the Roaches, you pretty much know how things are going to go. Hated in the Nation — the season concludes with this extended episode. Clocking in at almost an hour and a half long, this sort of feels like a Black Mirror movie. Kelly Macdonald (No Country For Old Men, Brave, Boardwalk Empire) stars as Karin Parke, a homicide detective tasked with investigating the death of journalist Jo Powers. Powers had been the subject of a social media outcry in response to an article she’d written. Was she murdered? Or did her internet humiliation drive her to take her own life? Parke’s investigation is complicated when, the next day, another individual facing a social media firestorm — in this case, the rapper “Tusk” — is also murdered. Parke and her new partner Blue (Faye Marsay, who played “the Waif” on Game of Thrones), along with National Crime Agency officer Shaun Li (Benedict Wong, from The Martian and Doctor Strange) soon discover that the Twitter hashtag #DeathTo is being used to allow anonymous social media users across the UK to vote on who will die at the end of each day. Much of “Hated in the Nation” unfolds like a Black Mirror version of a police procedural, as we follow Parke and her team through their investigation, as the widening horror of what they have discovered unfolds. There are some magnificently tense sequences in this episode, particularly the assault on the safehouse in which Parke, Blue, and Shaun Li attempt to safeguard marked-victim number three. While the episode does feature a typically gruesome Black Mirror finish, I was surprised that the very end gave us a glimpse of hope — the second ray-of-light ending that this season gave us! The great Kelly Macdonald carries this episode on her shoulders, as we discover this story through her character’s eyes. This isn’t the most groundbreaking episode of Black Mirror ever made, but it’s a strong, enjoyable finish to the season. I’m delighted that Netflix chose to resurrect Black Mirror, and very happy that Charlie Brooker was able to give us these six new terrifying stories. This is innovative television at its best, with remarkable talent assembled in front of and behind the camera. I am hoping this is not the end of Black Mirror! | Mid | [
0.608076009501187,
32,
20.625
] |
In the past, pilferage detection systems have been provided in which a magnetic or electromagnetic (resonant circuit) marker is placed in or on an article to be protected. If the marker is not removed or deactivated, the marker is detected by an electronic system located at the exit from the protected area. While a great variety of antipilferage systems exist for the utilization of a magnetic or resonant circuit marker, all of the present systems have troublesome false alarms due to the high level of magnetic and electromagnetic noise in the environment. Such alarms are due to transient electromagnetic noise generated, for instance, by fluorescent lamps, the turning on and off of electrical machinery and, in general, by any unshielded electromagnetic radiation which reaches the detector portion of the system. As a result of such unwanted noise, George Lichtblau and others developed a number of filtering and signal discrimination systems to eliminate noise due to electromagnetic transients in the protected area. Representative Lichtblau systems are described in U.S. Pat. Nos. 3,810,147; 3,828,337; 3,863,244; 3,913,219; 3,938,044; 3,961,322; 3,967,161; 4,021,705; 4,117,466; 4,168,496; 4,243,980; 4,251,808; 4,260,990 and 4,498,076. The problems associated with the utilization of a magnetic marker are, in many respects, similar to those problems associated with the utilization of a resonant circuit (radio frequency) marker. FIG. 1 1A illustrates the typical antipilferage system which uses a magnetic marker and FIG. 1B illustrates a similar system using a resonant circuit marker. In both cases, one antenna system produces an electromagnetic time varying field in the area of interest and a second antenna system monitors this field for disturbances caused by the specific type of "marker". In both types of systems, the disturbance caused by a real marker is much shorter in time than the modulation period of the applied electromagnetic field. In the magnetic case, the field is amplitude modulated and in the resonant circuit system the radio frequency field is frequency modulated. In both cases, the basic modulation rate (and radio frequency carrier) must be removed from the monitor signal prior to further signal processing and signal discrimination. The resonant circuit (swept radio frequency) systems are subject to problems due to spurious resonances in nearby electrical and mechanical equipment, beat-notes due to local radio transmitters and noise from fluorescent lamps, high frequency noise from nearby computers and point-of-sale case registers, and high frequency impulse noise from arcing electric motors. On the other hand, there are very few objects in retail stores which closely resemble a high "Q" resonant circuit. Magnetic based antipilferage systems are subject to many of the same type of noise sources as the resonant circuit systems. Such noise sources as arcing electric motors, point-of-sale cash registers, laser scanners, and computer printers generate large amounts of low frequency electrical noise which fall in the same frequency range as the signals produced by the magnetic markers. In addition, the magnetic based systems are constantly subject to disturbances caused by nearby magnetic materials which are present in retail stores. Supermarket checkout counters and shopping carts are almost always made of steel and other magnetic materials. The unwanted signals are not only due to the presence of magnetic materials other than the markers in the protected area, but also due to vibration of nearby magnetic materials caused, for instance, by rolling supermarket carts. The physical vibrations are then translated in spurious signals within the detection portion of the system. There have been many systems developed and patented to detect the signal produced by a resonant circuit within a swept radio frequency field. The Lichtblau earlier patents illustrate many of the problems and solutions. Likewise there have been many systems developed and patented to detect the signal produced by a magnetic marker. A very early technique was suggested in French Pat. No. 763,681 issued to P. A. Picard in 1934. Picard detected the marker by first filtering out many of the lower order harmonics of the field generating signal and then detecting a single harmonic i.e., the 13th harmonic of 50 Hertz. Picard also suggested comparing the amplitude ratio of several harmonics rather than just the amplitude of a single harmonic. Lastly he suggested that the phase of the signal produced by the magnetic marker be compared with the phase of the field producing means to aid in further discrimination. In U.S. Pat. No. 3,631,442 issued to R. E. Fearon on Dec. 21, 1971, and U.S. Pat. No. 3,747,086 issued to G. Peterson on July 17, 1973, the magnetic field was generated using two separate frequencies and the marker served as a nonlinear mixer which gave rise to a third frequency which was the sum and difference between the two applied frequencies. The signal received by the magnetic field sensor was passed through a very narrowband filter which passed the difference (or sum) frequency. Similar to Picard in U.S. Pat. No. 3,820,103, Fearon suggested detcting harmonics of the applied signal; however, the harmonics were detected in a synchronous detector phase-locked to the field generator so that any external noise not synchronized in frequency and phase with the magnetic field generator would be averaged out to zero. In U.S. Pat. No. 3,665,449 issued to T. J. Elder, et al on May 23, 1972, it was recognized that the signal generated by a magnetic marker normally occurs slightly after the applied magnetic field passes through zero. Therefore, the detection system was turned on (gated) only during the portion of the modulation period when the magnetic field was near zero. In addition, the shape of the marker signal as a function of time was examined as compared to the harmonics representing the same signal. In U.S. Pat. No. 3,983,552 issued to P. Bakeman and A. Armstrong on Sept. 28, 1976, a special magnetic marker was required and the detection system looked for only even harmonics of the applied field. In all of the above systems, only a small part of the actual signal produced by the marker was used for signal discrimination. In addition, none of the previous systems for either resonant circuit or magnetic marker systems addressed techniques for removing high level impulse noise from the monitor systems or for automatically maintaining a minimum signal to noise ratio prior to signal discrimination. It is quite clear that the limiting factor in sensitivity to detect a resonant circuit or magnetic marker is the relationship between the signal and the noise. If there were no noise, signal discrimination would be extremely simple. All of the previous systems looked only for the signal produced by the marker and did not examine the nature of the noise. All of the filters described in the previous patents were linear and therefore subject to high level ringing if driven by impulse type noise (automobile ignitions, etc). In addition, none of the previously described patents suggested any way to automatically adjust the sensitivity of the detection system to compensate for external noise picked up by the system. | Mid | [
0.563981042654028,
29.75,
23
] |
1. Technical Field The present invention relates to an electrically switchable optical device operating in transmission for manipulating an incident light wave or light waves passing through the device. The invention also relates to a method for forming electrically switchable optical devices for forming such an optical switching device. 2. Discussion of Related Art Optical signals in different forms are today increasingly utilized in many different types of devices and applications. In order to take full advantage of systems including optical signals or beams, it must be possible to direct the optical signal or beam coming in on a guided optical conduit, or on some other type of optical system in a desired electrically controlled manner to another optical conduit or to another optical system. The aforementioned optical conduit can be, for example, an optical fiber or other type of optical waveguide. There exists a wide variety of optical systems, which work under fast changing operational conditions, and thus require capability to perform optical functions in an efficient and electrically controlled manner. Especially the recent rapid development of optical telecommunication and optical data processing systems creates increasing needs for versatile electrically switchable optical devices. In addition to the act of simply switching the optical signal/beam on or off, the term “optical switching” above and hereinbelow also refers to more complex optical functions, i.e. transformations of the optical signal/beam and/or its path. These include, for example, dividing, redirecting or modulating the amplitude or phase of the optical signal/beam in a desired manner. In the following, some prior art solutions for electrically controlled optical switching are shortly discussed. However, methods which are based on first converting optical signals into electrical signals for switching and then reconverting said electrical signals back into optical signals for outputting are not included in the following discussion as they are not relevant to the present invention. A conventional method for electrically controlled optical switching is to mechanically move the optical components, for example mirrors, beamsplitters or beam attenuators in order to affect the propagation of the optical signal/beam. Said mechanical movements can be realized using various kinds of electrical actuators. However, such optical components together with the required electrical actuators cannot be easily made very compact in size and they are also rather difficult and expensive to manufacture, especially as mass-produced articles. Silicon-surfacemicromachining is a recent technology for fabricating miniature or microscopic devices. This technology has also been used for manufacturing optical microelectromechanical systems (optical MEMS). U.S. Pat. No. 5,867,297 discloses an oscillatory optical MEMS device including a micromirror for deflecting light in a predetermined manner. Small physical sizes and masses of these micromachined silicon “machine parts” make them more robust and capable of faster operation than conventional macroscopic mechanical devices. Grating Light Valve™ devices by Silicon Light Machines, USA represent another type of optical MEMS devices. U.S. Pat. No. 5,311,360 discloses a light modulator structure, which consists of parallel rows of reflective ribbons. Alternative rows of ribbons can be pulled down by electrostatic attraction forces a distance corresponding to approximately one-quarter wavelength to create an electrically controlled grating like structure, which can be used to diffractively modulate the incident light wave. The electrical switching of the ribbons can be realized by integrating bottom electrodes below the ribbons, and by applying different voltages to the ribbons and said bottom electrodes to create the required electrostatic forces. U.S. Pat. No. 6,130,770 discloses another type of solution, where instead of using physical electrical connections to charge the predetermined ribbons of the light modulator structure, selected ribbons are electrically charged with an electron gun. In principle, silicon optical MEMS technology uses processing steps derived from the integrated circuit (IC) fabrication techniques of photolithography, material deposition and chemical etching to produce the movable mechanical structures on a silicon chip. The aforementioned manufacturing process is, however, fairly difficult and thus expensive. Further, the optical MEMS devices operate mainly only in reflection and thus the capabilities of such devices of more complex transformations of the optical signal/beam and/or its path are limited. Material fatigue may also become significant in certain applications. Birefringence, also known as double refraction, is a property which can be found in some transparent materials, for example in crystals. Such optical materials have two different indices of refraction in different directions. This can be used to create Pockels effect, an electro-optical effect in which the application of an electric field produces a birefringence which is proportional to the electric field applied to the material. The Pockels effect is well known in the art and it is commonly used to create, for example, fast optical shutters. However, because the use of birefringence requires use of polarized light, this severely limits its use as a general method in realizing optical switching devices. U.S. Pat. No. 5,937,115 describes switchable optical component structures based on a holographic polymer dispersed liquid crystal. These are electronically controlled Bragg grating structures which allow to electronically switch on and off the diffractive effect of the transparent grating structures, which have been optically recorded or otherwise generated in the material. These electronically switchable Bragg grating (ESBG) devices can be used for various filtering or lensing applications. The major drawback of the ESBG technology is the complex manufacturing process required. Environmental concerns and hazards generally related to liquid crystal materials apply also to the ESBG devices. U.S. Pat. No. 4,626,920 discloses a semiconductor device, which has an array of spaced charge storage electrodes on semiconductor material (Si) and an elastomer layer disposed on said electrodes. At least one conductive and light reflective layer is disposed over the elastomer layer. When voltages are applied between the charge storage electrodes and the conductive layer, this causes the deformation of the conductive/reflective layer and the elastomer layer from a flat surface to a form having a sinusoidally cyclically varying cross-section. Thus, the reflective front surface of the conductive layer can be utilized as an electrically switchable reflective grating. GB patent 2,237,443 describes another light modulating device, where a reflective elastomer or viscoelastic layer is utilized for light modulation. In this arrangement an electron gun (cathode ray tube) is used instead of direct electrical connections/electrodes (cf. U.S. Pat. No. 4,626,920) to generate the electrical pattern needed to deform the elastomer layer. An important aspect in the above described type of systems (U.S. Pat. No. 4,626,920 and GB 2,237,443) is the operation of the conductive/reflective layer or layers which is/are mounted on the deformable elastomer layer. Said conductive/reflective layer or layers must reliably and repeatably provide precise patterns of deformations which correspond to the charge pattern modifying the elastomer layer. This, together with the fact that said devices operate only in reflection, limits the use of such devices due to the limited selection of suitable conductive and reflective materials as well as due to the overall response characteristics (sensitivity to the applied voltages/charges, temporal response characteristics) of the device. Yury P. Guscho “Physics of Reliofography” (Nauka, 1992, 520 p. in Russian) describes in chapter 7 a number of light modulator structures, in which a transparent viscoelastic layer is electrically deformed to manipulate the light passing through said viscoelastic layer. These devices can be taken to present the closest prior art with respect to the current invention, and they are therefore shortly described below with reference to the appended FIGS. 1a and 1b. FIGS. 1a and 1b correspond to FIG. 7.1 in chapter 7 of “Physics of Reliofography” and show the two basic schemes of the light modulator structures. In the first scheme in FIG. 1a, the driving signal (U) for deforming the viscoelastic layer G is applied from the free side of the viscoelastic layer G using driving electrodes ES1, which electrodes ES1 are formed on the lower surface of a top glass substrate SM1. A gap is left between the free surface of the viscoelastic layer G and the lower surface of the top glass substrate SM1, allowing the viscoelastic layer G to deform without contacting the opposite structure. The aforementioned gap can be for example air, gas or vacuum. The electric field deforming the viscoelastic layer G is generated between the driving electrodes ES1 and the conductive substrate electrode ES2. In the second scheme in FIG. 1b, the viscoelastic layer G is disposed on the driving electrode structure ES1, which in turn is formed on a glass substrate SM1. The electric field deforming the viscoelastic layer G is generated by applying alternating voltages to the neighbouring electrode zones in the driving electrode structure ES1. In both of the aforementioned schemes, the free surface of the viscoelastic layer G can be coated with a conductive reflecting layer (sputtered metal film). According to our best understanding, all the light modulator structures presented in the chapter 7 of “Physics of Reliofography” and discussed shortly above are based on the basic idea of deforming the viscoelastic layer into a surface structure having a substantially sinusoidally varying cross-section. This allows to use the viscoelastic layer as an electrically controlled sinusoidal grating in order to modulate the incident light wave. | Low | [
0.49894736842105203,
29.625,
29.75
] |
Q: Purpose of debian "sites-available" and "sites-enabled" dirs Can anyone tell me—in a nutshell—what the purpose of these two directories are in Debian? /etc/apache2/sites-enabled /etc/apache2/sites-available I notice that diffing sites-available/000-default and sites-enabled/default shows they are identical. What gives? A: sites-available contains the apache config files for each of your sites. For example: <VirtualHost *:80> ServerName site.mysite.com ServerAdmin [email protected] DirectoryIndex index.php DocumentRoot /home/user/public_html/site.mysite.com/public LogLevel warn ErrorLog /home/user/public_html/site.mysite.com/logs/error.log CustomLog /home/user/public_html/site.mysite.com/logs/access.log combined </VirtualHost> When you want to add a new site (for example, site.mysite.com), you add it here, and use: a2ensite site.mysite.com To enable the site. Once the site is enabled, a symlink to the config file is placed in the sites-enabled directory, indicating that the site is enabled. A: More important than the mechanics of the system is the rationale... Debian provides the two separate directories so that if you're automatically managing your Apache configs, you can just have all of the vhosts drop into sites-available on all your machines, and then individual vhosts can be enabled on the server that will actually serve them. It also means you can near-instantaneously disable a site if it's causing problems (a2dissite example.com; /etc/init.d/apache2 reload). A: Important information: You should edit files only in sites-available directory. Do never edit files inside the sites-enabled directory, otherwise you can have problems if your editor runs out of memory or, for any reason, it receives a SIGHUP or SIGTERM. For example: if you are using nano to edit the file sites-enabled/default and it runs out of memory or, for any reason, it receives a SIGHUP or SIGTERM, then nano will create an emergency file called default.save, inside the sites-enabled directory. So, there will be an extra file inside the sites-enabled directory. That will prevent Apache or NGINX to start. If your site was working, it will not be anymore. You will have a hard time until you find out, in the logs, something related to the default.save file and, then, remove it. In the example above, if you were editing the file inside the sites-available directory, nothing bad would have happened. The file sites-available/default.save would have been created, but it wouldn't do any harm inside the sites-available directory. | High | [
0.6803278688524591,
31.125,
14.625
] |
Red River system The Red River system is a network of rivers surrounding the main river - Red River in North Vietnam. These branches of the system contribute to or receive water from Red River. Red River system, joining with the Thái Bình river system in the northeast, creates the Red River Delta - the second largest delta in Vietnam. Because of the close relation between Red River system and Thái Bình river system, the two system are known as the common name Red and Thai Binh rivers system. Alluvium of the Red River system creates the central and south Red River Delta. Two banks of the rivers are protected by a great dyke system. Rivers of the system Main river: Red River Confluences: Da River Lô River Besides that, confluences of another river - River Đáy, a river starts from mountainous area of Hòa Bình and Ninh Bình provinces, including Bôi river, Hoàng Long river, Vạc river although not contribute water to Red River, but for several reasons, they are still considered as Red River confluences. Branches: River Đáy and its branches Nhuệ River Đuống River Phủ Lý River (or Châu Giang River) Luoc River linking Red River with Thái Bình River Trà Lý River, flowing eastward through Thái Bình Province Diêm Hộ River Ninh Cơ River flowing southward through Nam Định Province Nam Định River So River Lân River River mouth Ba Lat, main river mouth, located in the border between Thái Bình provinces and Nam Định provinces Diêm Hộ, Trà Lý, Lân (Thái Bình Province) So, Lach Giang (Nam Định Province) Đáy, located in the border between Ninh Bình and Nam Định provinces. Category:Geography of Vietnam | High | [
0.68018018018018,
37.75,
17.75
] |
Dollar Keeper Way back in 1997 a company named Bullfrog productions created a game called “Dungeon Keeper” . It was published by Electronic arts back when games were written for DOS, the word “Playstation” didn’t have any numbers after it and Xbox was but a dream. To some the game was, and is still, considered a classic. What happens when Mythic Entertainment (or is it still Bioware-Mythic?) brings the classic game to mobile platforms? What happens is what is fast becoming the rule, rather than the exception in mobile gaming. Imagine you walk into your favorite fast food restaurant to order a hamburger and are greeted with a banner advertising “FREE HAMBURGERS.” That sounds great, right? It is what you wanted in the first place! You walk up to the windows to get your hamburger and what the nice person behind the counter hands you is an empty bun – nothing but cold hard bread. You look up and are greeted with the following sign: Hamburger: FREE!! Hamburger with meat: $20.00 Pickles (per slice): $5.00 Mustard: $10.00 per ounce Catsup: $15.00 per ounce Lettuce (without mold): $6.00 per leaf You decide you are hungry and begin to take your stale empty bun and walk away. As you do the person behind the counter berates you for being a cheapskate for not ordering anything extra. Being a bit low on cash you ask if there is any way you can earn at least a slice of pickle. “Sure,” replies the manager. With a broad smile he suggests that you sweep out the parking lot and hands you a toothbrush with which to accomplish the task. Think that is farfetched? Read the following excerpt. “It started in the game’s very tutorial. The grasping. The harassing. The demands for money. As I was being taught about how gems can speed up the building and excavating of dungeons, the game’s narrator – a twee redesign of the once iconic Horned Reaper – openly mocked me, making fun of how “polarizing” in-app purchases were before shamelessly telling me how spending my real money will grease the wheels and get things accomplished.” – Jim Sterling , Escapist Magazine, DUNGEON KEEPER MOBILE REVIEW – WALLET REAPER If you don’t recognize the author’s style of writing, watch a few episodes of Jimquisition and you soon will – we are sure you will love it like we do. PC gamers have yet to experience the level of greed that seems to be a growing trend in the mobile gaming industry. When we see “free to play” we often think of companies like Turbine (whom we have lauded often on our show). This is the company that brings you Lord of the Rings Online and Dungeons and Dragons Online. This is a company that produces a perfectly playable game that really is free to play – not “free to play” as long as you are willing to spend excruciatingly boring evenings at tasks that would make a stretch in solitary look like a weekend in Vegas . This is what we hear at No Prisoners, No Mercy have come to call games that are “Greed to Play”. To be sure not all game developers are like this. 505 Games brought us Terraria . For just five dollars I received a game that was both innovative and restored my interest in 2d scrollers. Rubicon Development brought us Great Big War Game. For just three dollars I received a top down, three d strategy game that doesn’t ask for anything but time to have fun. But the greed to play games are, as Jim Sterling calls the mobile edition of Dungeon Keeper “a cancer that is eroding the market and has already destroyed the credibility of the once promising mobile gaming sector”. Jim Sterling couldn’t be more right. Greed will kill any company, any industry, faster than three bullets to the head. As a professional project manager I have seen it destroy more than one career. If it weren’t for government bailouts it would have killed the saving and loan industry, Wall Street and the American Automobile Industry. Don’t get us wrong. There is nothing wrong with free to play when it is done correctly. Some companies know how – Mythic, it seems, doesn’t. What is more judging by the reception of the gaming community of their latest offering, the company that brought us War Hammer Online (another fantastic IP damaged by mishandling) might be doomed to repeat itself. | Low | [
0.5263157894736841,
28.75,
25.875
] |
Tag Archives: Pacific Northwest Post navigation (Vancouver, Sept. 23, 2014) – The Coastal First Nations supports a federal NDP [New Democratic Party] bill aimed at putting in place a law that would prohibit supertankers from on the North Coast. Skeena-Bulkley Valley NDP MP Nathan Cullen introduced a private members bill, An Act to Defend the Pacific Northwest, that would also give communities a stronger voice in pipeline reviews and consider impacts of projects on jobs. Executive Director Art Sterritt said for too long the concerns of our people and the majority of British Columbians have been ignored. “The bill addresses some of our major concerns with Enbridge’s Northern Gateway Pipeline.” The pipeline review process with First Nations has been lacking. “This bill will ensure that our voices and concerns are heard.” Sterritt said the bill will allow for more sustainable and long-term jobs. “We have spent more than a decade developing a sustainable economy.” The Coastal First Nations are an alliance of First Nations that includes the Wuikinuxv Nation, Heiltsuk, Kitasoo/Xaixais, Nuxalk, Gitga’at, Haisla, Metlakatla, Old Massett, Skidegate, and Council of the Haida Nation working together to create a sustainable economy on British Columbia’s North and Central Coast and Haida Gwaii. Native Americans, environmentalists, and fed-up citizens unite to keep corporations from turning the region into a fossil fuel corridor On August 4, a dam holding back mining wastewater burst open in Likely, B.C., gushing roughly 6,604,301,309 gallons of toxic waste into the nearby lakes—a spill 78 percent larger than initial estimates. Only a month after the incident, Imperial Metals, the corporation responsible, declared the water safe to drink again. “One of my friends caught a salmon alive and kicking there last week,” Sundance Chief Rueben George from the Tsleil-Waututh Nation said to a packed Seattle crowd at the Daybreak Star Indian Cultural Center on Sunday. “But when my friend picked it up, the fish’s skin slid off in his hands.” Salmon have long been spiritual symbols of the Pacific Northwest—aquatic residents of the Salish Sea that have given life to Coast Salish people for 14,000 years and white settlers for 150. That the skin of the Northwest’s spirit animal is melting off is just one of many reasons organizers say they are forming the brand-new Nawt-sa-maat Alliance, a group that has vowed to defeat oil and coal corporations bent on turning the Pacific Northwest into a fossil-fuel corridor. Photo by Kelton Sears Nawt-sa-maat, a Coast Salish word that means “One house, one heart, one prayer,” is an unprecedented trans-border coalition of Coast Salish indigenous nations, environmentalists, interfaith groups, and youth activists that met for the first time this past weekend in Discovery Park. The Alliance’s goal? “To protect the sacredness of the Salish Sea.” “The tribes are the original environmentalists,” Annette Klapstein, a member of the Seattle Raging Grannies and a new member of the Nawt-sa-maat Alliance, said at the initial meeting on Sunday. Klapstein was one of three protesters who sat on train tracks in Anacortes to block the controversial “exploding” oil trains in July. It was her first direct action after years of fruitless writings to the Seattle City Council and visits to Olympia to persuade politicians to do something about the influx of dangerous rail cars. “It was always very iffy for tribes to work with environmental organizations because these organizations were arrogant,” Klapstein said. “They would tell tribes what to do, which didn’t go over very well. This new alliance, based on respect and understanding, is so important because these different groups’ goals are much the same, and we are so much more powerful together.” Chief George, one of the three main founders of the Nawt-sa-maat, presided over the initial meeting and made it clear that one of its biggest enemies was the massive energy company Kinder Morgan. “We stand as one, and together we will protect and restore the sacredness of the Salish Sea,” he said. “Together, we are stronger than those who wish to use our home and waters as a mere highway for dirty oil and coal. Together, we will stop them. Kinder Morgan will not win this battle.” Formed by Richard Kinder, an ex-Enron employee, the oil mega-corporation is proposing a massive $5.4 billion oil pipeline connecting the Alberta tar sands to the Pacific through Burnaby, B.C., tripling current capacity and creating the potential for enormous spills in the North Salish that would directly affect us in Washington. Canadian Prime Minister Stephen Harper has been pushing the project despite massive backlash from British Columbian activists and the indigenous Tsleil-Waututh, who are now taking the project to court for failing to consult with the First Nations tribe on the federal review. The mood at the meeting was intensely spiritual at times. Four local religious leaders, a United Methodist, a Buddhist, a Sufi, and an Interspirit, came together to bless the gathering in their respective traditions, ending with an indigenous cedar-bough blessing that the crowd happily lined up to receive. Many of the religious groups present vowed to convert their houses of worship to solar energy in an act of good faith. Being a member of the Nawt-sa-maat effectively means a couple of things. Members are expected to join in a “4 Days of Action” campaign, starting on Sept. 19, that ranges from a salmon homecoming celebration to a climate-change rally at the Canadian border and ends with an international treaty signing that will effectively ratify the new trans-border Nawt-sa-maat Alliance. Members are then expected to join in future actions and work to build the nascent network, which will soon expand its scope to tackle the proposed coal-extraction sites at Cherry Point, sacred land to the people of the Lummi Nation near Bellingham. “I just want to make this very clear,” Chief George said as he doled out salmon to the Nawt-sa-maat near the meeting’s end, “this Alliance isn’t just for one group. It’s for everyone. The Salish Sea is for everyone, not just corporations. We will win this fight.” As more oil trains travel along the Columbia River and Puget Sound, conservation groups worry that cleanup plans could harm sensitive wildlife, like endangered salmon and shorebirds. That concern is prompting legal action. The Center for Biological Diversity and Friends of the Columbia Gorge Thursday filed a 60-day notice to sue the U.S. Coast Guard and the Environmental Protection Agency. The conservation groups say the oil spill response plan needs to be updated to account for endangered species. Jared Margolis, an attorney for the center, said the response plan hasn’t been updated in 10 years. That means the plan doesn’t include new wildlife habitat and new species on the Endangered Species List, like smelt, also known as eulachon. “If those spill response plans aren’t up-to-date, they could boom the oil right into critical habitat for endangered species, which can really impact the salmon and sturgeon.” Margolis said. Portland, Oregon: Dozens of social, economic and climate justice organizers from across the Pacific Northwest have been meeting for the past 16 months to bring the Pacific Northwest Social Forum to Portland, Oregon, September, 26th-28th, 2014. The three-day event will feature music; a fundraiser/solidarity action for a computer center in Burundi, Africa; and assemblies and panels on topics including Indigenous Treaty Rights, Climate Justice, Housing and Homelessness and Democracy. The overall goal of the event is to create a Pacific Northwest People’s Plan for Social, Economic and Climate Justice with strategy and actions for the next two years. The event will conclude with a direct action on Sunday that is also the kick-off to the implementation of the Pacific Northwest People’s Plan for Justice. The Pacific Northwest Social Forum is one of many events taking place across the country in 2014 that are connected to and building toward larger gatherings in 2015 for the US Social Forum. The US Social Forum (USSF) is a national and international movement building process that is connected and accountable to the World Social Forum. After gathering 100,000 people in Porto Alegre, Brazil in 2005, the International Council of the World Social Forum decided the following year there would be regional social forums. The USSF is one of these regional forums, stating that it was strategic to hold a gathering of peoples and movements within the “belly of the beast” that were against the ravages of globalization and neoliberal policies in the US and worldwide. The USSF is not a conference rather it is a space to come up with the peoples’ solutions to the economic and ecological crisis. The USSF is a next most important step in the struggle to build a powerful multi-racial, multi-sectoral, inter-generational, diverse, inclusive, internationalist movement that transforms this country and changes history. “We hope to gather as many folks from the Pacific Northwest as we can from all walks of life,” reported Shamako Noble, National Coordinator with the USSF and organizer for the event. “We have buses coming from the North, South and East to the Forum, with reps from Hip Hop Congress, Move to Amend, Montana based Indian Peoples Action, and (folks from North), and groups from Seattle like the Multi-Media Center. This is shaping up to be a historic event, a game changer in working together to reclaim our region in a way that makes sense for the people and the planet. We’re excited to come together for this motion forward.” Alyssa Macy, an organizer with the International Indian Treaty Council has been mobilizing Indigenous Peoples to participate in the forum. She stated, “This is an excellent opportunity to educate those individuals and organizations working for a most just society on Treaty Rights here in the Northwest and our shared responsibility in ensuring that the US honors them. Our struggles are related and it is only together that we can realize the society we envision.” Registration is now open for this historic event at www.pnwsf.org and offers a sliding scale of $10-$100 with the opportunity to do 2-hours of barter work in exchange for registration. Courtesy of ‘Kwel Hoy: A Totem Pole Journey’A 19-foot pole carved by Lummi master carver Jewell James and the House of Tears Carvers is being taken on a journey to 21 Native and non-Native communities in four Northwest states and British Columbia. James carved the pole to compel people to speak out against coal and oil transport projects that could have a devastating impact on the environment. The pole will be raised at Beaver Lake Cree First Nation on September 6. LUMMI NATION, Washington—At each stop on the totem pole’s journey, people have gathered to pray, sing and take a stand. They took a stand in Couer d’Alene, Bozeman, Spearfish, Wagner and Lower Brule. They took a stand in Billings, Spokane, Yakama Nation, Olympia and Seattle. They took a stand in Anacortes, on San Juan Island, and in Victoria, Vancouver and Tsleil Waututh. They’ll take a stand in Kamloops, Calgary and Edmonton. And they’ll take a stand at Beaver Lake Cree First Nation, where the pole will be raised after its 5,100-mile journey to raise awareness of environmental threats posed by coal and oil extraction and rail transport. “The coal trains, the tar sands, the destruction of Mother Earth—this totem [pole] is on a journey. It’s calling attention to these issues,” Linda Soriano, Lummi, told videographer Freddy Lane, Lummi, who is documenting the journey. “Generations yet unborn are being affected by the contaminants in our water.… We need people to take a stand. Warrior up—take a stand, speak up, get involved in these issues. We will not be silent.” The 19-foot pole was crafted by Lummi master carver Jewell James and the House of Tears Carvers. The pole and entourage left the Lummi Nation on August 17 for 21 Native and non-Native communities in four Northwest states and British Columbia. The itinerary includes Olympia, the capital of Washington State, and Victoria, the capital of British Columbia. The pole is scheduled to arrive at Beaver Lake Cree on September 6. The journey takes place as U.S. energy company Kinder Morgan plans to ship 400 tanker loads of heavy crude oil each year out of the Northwest; a refinery is proposed in Kitimat, British Columbia, where heavy crude oil from Enbridge’s Northern Gateway pipeline would be loaded onto tankers bound for Asia; and as Gateway Pacific proposes a coal train terminal at Cherry Point in Lummi Nation territory. Cherry Point is a sacred and environmentally sensitive area; early site preparation for the terminal was done without permits, and ancestral burials were desecrated. In a guest column published on August 11 in the Bellingham Herald, James wrote that Native peoples have long seen and experienced environmental degradation and destruction of healthy ecosystems, with the result being the loss of traditional foods and medicines, at the expense of people’s health. “We wonder how Salish Sea fisheries, already impacted by decades of pollution and global warming, will respond to the toxic runoff from the water used for coal piles stored on site,” he wrote. “What will happen to the region’s air quality as coal trains bring dust and increase diesel pollution? And of course, any coal burned overseas will come home to our state as mercury pollution in our fish, adding to the perils of climate change.” James wrote that the totem pole “brings to mind our shared responsibility for the lands, the waters and the peoples who face environmental and cultural devastation from fossil fuel megaprojects.… Our commitment to place, to each other, unites us as one people, one voice to call out to others who understand that our shared responsibility is to leave a better, more bountiful world for those who follow.” ‘This Is the Risk That Is Being Taken’ Recent events contributed to the urgency of the totem pole journey’s message. Two weeks before the journey got under way, a dike broke at a Quesnel, British Columbia, pond that held toxic byproducts left over from mining; an estimated 10 million cubic meters of wastewater and 4.5 million cubic meters of fine sand flowed into lakes and creeks upstream from the Fraser River, a total of four billion gallons of mining waste. A Sto:lo First Nation fisheries adviser told the Chilliwack Progress of reports of fish dying near the spill, either from toxins or asphyxiation from silt clogging their gills; and First Nation and non-Native fisheries are bracing for an impact on this year’s runs. On July 24, a Burlington Northern train pulling 100 loads of Bakken crude oil derailed in Seattle’s Interbay neighborhood. The railcars didn’t leak, but the derailment prompted a statement from Fawn Sharp, president of the Quinault Indian Nation and the Affiliated Tribes of Northwest Indians and Area Vice President of the National Congress of American Indians. “People need to know that every time an oil train travels by, this is the risk that is being taken,” she said. “These accidents have occurred before. They will occur again. … The rail and bridge infrastructure in this country is far too inadequate to service the vast expansion of oil traffic we are witnessing.” A year earlier, on July 6, 2013, an unmanned train with 72 tank cars full of Bakken crude oil derailed in a small Quebec village, killing 47 people. An estimated 1.5 million gallons of oil spilled from ruptured tank cars and burned; according to the Washington Post, it was one of 10 significant derailments since 2008 in the United States and Canada in which oil spilled from ruptured cars. Some good news during the journey: As the totem pole and entourage arrived at the Yankton Sioux Reservation in Wagner, South Dakota, word was received that the Oregon Department of State Lands rejected Ambre Energy’s application to build a coal terminal on the Columbia River; the company wants to ship 8.8 million tons of coal annually to Asia through the terminal. One of the concerns that communities have about coal transport is exposure to coal dust; those concerns are shared by residents of Plaquemines Parish, Louisiana, where proponents of a coal terminal on the Mississippi River forecast an increase in Gulf Coast coal exports from seven million tons in 2011 to 96 million by 2030. “I think the risk is real. I think there is a lot of potential harm from multiple sources,” Maumus told the Times-Picayune. James said there are alternatives to coal and oil—among them energy generated by wind, sun and tides. “But we’re not going to move toward those until we move away from fossil fuels,” he said. In his Nation’s territory, Yakama Chairman JoDe L. Goudy told videographer Lane he hopes the pole’s journey will help the voice of Native people “and the voice of those people across the land that have a concern for the well-being of all” to be heard. “May the journey, the blessing, the collective prayers that’s [being offered] and the awareness that’s being created lift us all up,” he said, “lift us all up to find a way to come against the powers that be … whether it be coal, whether it be oil or whatever it may be.” Albert Redstar, Nez Perce, advised young people: “Remember the teachings of your people. Remember that there’s another way to look at the world rather than the corporate [way]. It’s time to say no to all that. It’s time to accept the old values and take them as your truths as well.… They’re ready for you to awaken into your own heart today.” To Unite and Protect The totem pole journey is being made in honor of the life of environmental leader and treaty rights activist Billy Frank Jr., Nisqually. Frank, chairman of the Northwest Indian Fisheries Commission, walked on in May. James said the pole depicts a woman representing Mother Earth, lifting a child up; four warriors, representing protectors of the environment; and a snake, representing the power of the Earth. The pole journey has been undertaken in times of crisis several times this century. In 2002, 2003 and 2004, to help promote healing after the 9/11 terrorist attacks, James and the House of Tears Carvers journeyed across the United States with healing poles for Arrow Park, New York, 52 miles north of Ground Zero; Shanksville, Pennsylvania, where the hijacked United Airlines Flight 93 crashed; and Washington, D.C.’s Congressional Cemetery, seven miles from the Pentagon. And In 2011, James and a 20-foot healing pole for the National Library of Medicine visited nine Native American reservations en route to Bethesda, Maryland. At each stop on the three-week cross-country journey, people prayed, James said at the time, “for the protection of our children, our communities and our elders, and generally helping us move along with the idea that we all need to unite and protect the knowledge that we have, and respect each other.” Scott Terrell photoTribal fisherman Randy Fornsby hoists a chinook salmon on the bank of the Skagit River west of Mount Vernon, Wash., Sept. 2, 1987. The Swinomish and Upper Skagit tribes shared a fishing area just upriver from where the Skagit breaks into its north and south forks. LA CONNER, Wash. – With 95 percent of the Swinomish Indian Tribal Community’s reservation borders on the water, the tribe is concerned about the rise in sea level and storm surges expected as the planet warms. As sea level rise pushes high tides and winter storm surges farther inland, coastal tribes in the Northwest worry that their archaeological sites will be wiped out, Swinomish Tribal historic preservation officer Larry Campbell said. They also worry that traditional food sources like salmon and oysters may be affected. Campbell said food and medicine resources used by tribes around the country have moved or disappeared altogether in some places from where they were traditionally gathered, which is believed to be a result of the changing climate and shifting weather patterns. Those changes affect not only physical access to the natural resources, but the cultural well-being of the tribes. “It’s important when you look at overall health to look at not just the foods and the resources, but the gathering,” Campbell said. “There’s a process of gathering these things that’s traditional in nature.” Traditions are passed down through generations as elders share family gathering secrets with their next of kin, he said. The Swinomish tribe has gained national recognition for its commitment to protecting the culture and natural resources of the Skagit Valley in the face of climate change and is gearing up to begin a new research project. Building off past studies, the tribe will evaluate both the physical and social impacts climate change may have on local near-shore environments. Swinomish environmental health analyst Jamie Donatuto said the study will build upon earlier research by looking at indigenous health indicators, which take into account cultural, familial and emotional aspects of the impacts climate change may have on the natural resources the tribe values. Over the course of the three-year study, Swinomish environmental specialist Sarah Grossman will lead efforts to monitor waves and winds on the shorelines during the winter, when storm surges roll in. She will also lead beach surveys to document characteristics like sediment, wood debris and eelgrass cover. Donatuto will lead the social science side, organizing a series of spring workshops to invite the community to review and discuss the scientific data collected. “You can’t assess health without actual conversations with community members,” she said. A $756,000 U.S. Environmental Protection Agency Science to Achieve Results program grant was awarded in June to support the multiyear project. Swinomish intergovernmental affairs liaison Debra Lekanof said the Swinomish have invested $17 million in collaborative work on the nation’s natural resources over the past 10 years. “We’re protecting the universal resource rather than the tribal resource. We’re doing a lot more for the state and the county, and then in the end the tribe benefits by taking care of the whole,” Campbell said. “We’re a very aggressive tribe when it comes to our environment.” The tribe has also been chosen as a finalist for the Harvard Project on American Indian Economic Development’s Honoring Nations Program. The program, run by the John F. Kennedy School of Government at Harvard University, “identifies, celebrates and shares excellence in American Indian tribal governance.” This year, the tribe gained its place among 18 finalists in the running for the single “High Honor” because of its climate change initiative. The winner will be announced in October. The Swinomish Indian Senate passed a proclamation on its climate change initiative Oct. 2, 2007, that marked the start of the tribe’s commitment to addressing the potential effects of climate change. The tribe developed an Impact Assessment Technical Report in 2009 and a Climate Adaptation Plan in 2010 that have provided a framework for other tribes to follow, and has continued to conduct related research, Donatuto said. Associated Press photoA tribal canoe, in view of the Space Needle, arrives July 20, 2011, at Seattle’s Alki Beach. The landing of about a dozen canoes marked one leg of an annual journey of tribal canoes from the Salish Sea, heading to Swinomish, Wash. The Lummi Nation, a Native American tribe in the Pacific Northwest, has taken an uncompromising stand against the largest proposed coal export terminal in the country: the Gateway Pacific Terminal. If completed, it would export 48 million tons of coal mined from Montana and Wyoming’s Powder River Basin, and in the process threaten the Lummi’s ancestral fishing grounds and their economic survival. On Aug. 17 the Lummi people launch a totem pole journey — both a monument to protest and a traveling rally that will bring together imperiled locals, citizen groups, and other indigenous tribes for a unified front against Big Coal and Big Oil. Grist fellow Amber Cortes visited the Lummis in the run-up to the pivotal protest to find out how they’ve been able to push back against the terminal. The result is a rich story about activism, alliances, and small victories that add up to a big resistance. If you listen closely, you can hear Dan Cornelius singing his favorite Willie Nelson theme song—“I’m on the road again…”—as his Mobile Farmers Market vehicle heads down the highway. Cornelius, of Wisconsin’s Oneida Nation, is general manager of a three-month-long, 10,000-mile foodie road show designed to showcase Native American foods in conjunction with a reconnection of tribal trade routes. “A lot of native communities are remote, literally food deserts, and don’t have good access to healthy traditional fresh foods. Part of our mission is to access food resources, take those great products and distribute them as part of a tribal trade reintroduction,” he says. “There’s a lot of product that is traditionally grown, harvested and processed—lots of time and labor that goes into that—but the traditional foods aren’t made available to the general public as a sustainable economic resource.” The interest is there, but the connection still needs to be made. “It’s about health issues, maintaining our traditions, and turning the effort into a form of economic development by selling excess product for profit.” The “Reconnecting the Tribal Trade Routes Roadtrip” is an effort to bring attention to the unique Native food products and artwork from across the country. The Mobile Farmers Market van started the roadtrip in mid-December when it picked up wild rice, maple syrup, and other products in northern Minnesota. The roadtrip officially kicked off in early January, making the drive from Wisconsin to Louisiana before heading to Oklahoma, New Mexico, Arizona, and the West Coast. The trip then visited Montana and the Dakotas en route to concluding during March back in Minnesota. (Intertribal Agriculture Council) The Mobile Farmers Market traveled across the country earlier this year as part of the Intertribal Agriculture Council‘s efforts to improve Indian agriculture by promoting Indian use of Indian resources. “Prior to our founding in 1987, American Indian agriculture was basically unheard of outside reservation boundaries,” notes the group’s web page. ”The Mobile Farmers Market utilized a large capacity fuel-efficient cargo van to transport a number of products across a region, all the while providing support to start farmers markets in interested tribal communities,” says Market Manager Bruce Savage. The vans’ insulated interior lining ensured correct temperature control, and a chest freezer allowed for transport of frozen goods. “For a variety of reasons, traditional native products are frequently difficult to obtain, and the Mobile Farmers Market hoped to change that by making things more accessible to tribal communities,” says Cornelius. In the Pacific Northwest, canned and smoked salmon were frequently obtainable items while the Southwest offered up cactus buds and syrup. The Great Plains provided a prairie-grown protein-packed wild turnip. In the Great Lakes region it was sumac berries. “Soak them in water, add honey or syrup, and you get a tea-like lemonade that you won’t find commercially,” Cornelius says. Coyote Valley Tribe’s community and Head Start garden and greenhouse (Intertribal Agriculture Council) Success of the project was contingent on cultivating supportive relationships with local partners and that part of the plan came together nicely, very reminiscent of the early trade and barter days. “Trade routes once connected regional tribes across the continent where different local areas produced unique resources,” says Cornelius. “As an example, the Objiwe exchanged meat and fish for corn from the Huadenosaunee in the Northeast. And, of course, the Three Sisters combination of corn/beans/squash gradually moved from South and Central America throughout all of the North American Continent. “ The Reconnecting the Tribal Trade Routes Roadtrip got underway in December 2013 by first picking up wild rice, maple syrup, and other products in Minnesota before heading off to Wisconsin, Louisiana, Oklahoma, New Mexico, Arizona, and the West Coast and finally heading home to Minnesota earlier this year via Montana and the Dakotas. The Mobile Farmers Market’s main focus is food, but it also supports Native artisan by carrying a small selection of jewelry, crafts, and artwork. Pictured here: inlaid earrings from Santa Domingo Pueblo. (nativefoodnetwork.com) As Cornelius and crew bought and sold the wares of North America’s indigenous communities, the grocery list grew to include tepary beans from the Tohono O’odham people to chocolate produced by the Chickasaw Nation. The mobile van discovered a gold mine at Ramona Farms in Sacaton, Arizona, on the Gila River Indian Reservation. Ramona and Terry Button have been growing crops for small ethnic grocers on the reservation for over 40 years and still have plenty to share with the outside world, everything from Southwestern staples like garbanzo and Anasazi beans to white Sonoran and Pima club wheat as well as alfalfa and cotton. “Part of our mission was to build an awareness and an excitement of all the things available ‘out there’ and we succeeded,” Cornelius says. “One of the great things about our initial effort (discussions are currently underway to find funding for more vans and an increased regional visability) was the ground level opportunity to talk with community growers face-to-face discussing products, challenges, and opportunities to introduce traditional items to a larger world.” ThinkstockThe ocean’s acidity is rising and dissolving seashells, which could spell doom for Northwest tribes’ way of life as well as their livelihood in the shellfish industry and sustenance harvesting. The ancestral connections of tribal coastal communities to the ocean’s natural resources stretch back thousands of years. But growing acidification is changing oceanic conditions, putting the cultural and economic reliance of coastal tribes—a critical definition of who they are—at risk. It’s a big challenge to tribes in the Pacific Northwest, said Billy Frank Jr. (Suquamish) back in 2010, addressing the 20 tribes that make up the Northwest Indian Fisheries Commission. “It’s scary,” he said in a video posted at the fisheries commission website. “The State of Washington hasn’t been managing it. The federal government hasn’t been managing it. We’ve got to bring the science people in to tell them what we’re talking about.” What they were talking about are the decreases in pH and lower calcium carbonate saturation in surface waters, which together is called ocean acidification, as defined by the National Oceanic and Atmospheric Administration (NOAA). Some 30 percent of the carbon, or CO2, released into the atmosphere by human activities has dissolved straight into the sea. There it forms the carbolic acid that depletes ocean waters of the calcium that shellfish, coral and small creatures need to make their calcium carbonate shells and skeletons. Its impacts are felt by Native and non-Native communities in Washington State that rely on oysters and shellfish. Disastrous production failures in oyster beds caused by low pH-seawater blindsided the oyster industry in 2010, prompting a comprehensive 2012 investigation by Washington State. Earlier this month Governor Jay Inslee took the issue to the media in order to jump-start climate change action in his state, The New York Times reported on August 3. The Quinault Indian Nation on Washington’s coast is part of one of the most productive natural areas in the world and is especially involved in the ocean acidification issue. The rivers in Quinault support runs of salmon that have in turn supported generations of Quinault people. The villages of Taholah and Queets are located at the mouth of two of those great rivers. The Pacific Ocean they flow into is the source of halibut, crab, razor clams and many other species that are part of the Quinault heritage. “Since the summer of 2006, Quinault has documented thousands of dead fish and crab coming ashore in the late summer months, specifically onto the beaches near Taholah,” Quinault Marine Resources scientist Joe Schumacker told Indian Country Today Media Network. “Our science team has worked with NOAA scientists to confirm that these events are a result of critically low oxygen levels in this ocean area.“ The great productivity of this northwest coast is driven by natural upwelling, in which summer winds drive deep ocean waters, rich in nutrients, to the surface, Schumacker explained. This cycle has been happening forever on the Washington coast, and the ecosystem depends on it. But now, “due to recent changes in summer wind and current patterns possibly due to climate change, these deep waters, devoid of oxygen, are sometimes not getting mixed with air at the surface,” Schumacker said. “The deep water now comes ashore, taking over the entire water column as it does, and we find beaches littered with dead fish—and some still living—in shallow pools on the beaches, literally gasping for oxygen. Normally reclusive fish such as lingcod and greenling will be trapped in inches of water trying to get what little oxygen they can to stay alive.” The Quinault, working with University of Washington and NOAA scientists determined these hypoxia events were also related to ocean acidification. “Now Quinault faces the potential for not just hypoxia impacts coming each summer, but also those same waters bring low-pH acidic waters to our coast,” Schumacker said. “Upwelling is the very foundation of our coastal ecosystem, and it now carries a legacy of pollution that may be causing profound changes unknown to us as of yet. The Quinault Department of Fisheries has been seeking funding to better study and monitor these potential ecosystem impacts to allow us to prepare for an unknown future.” Schumacker noted that tribes are in a prime position to observe and react to these changes. “The tribes of the west coast of the U.S. are literally on the front line of ocean acidification impacts,” he said. “Oyster growers from Washington and Oregon have documented year after year of lost crops as tiny oyster larvae die from low pH water. What is going on in the ecosystem adjacent to Quinault? What other small organisms are being impacted, and how is our ecosystem reacting? We have a responsibility to know so we can plan for an uncertain future.” Scientists from NOAA and Oregon State University studied ocean waters off California, Oregon and Washington shorelines in August 2011, and found the first evidence that increasing acidity was dissolving the shells of a key species of minuscule floating snails called pterapods that lie at the base of the food chain. Their study, published in the April 4, 2014, edition of the British scientific journal Proceedings of the Royal Society B, found that 53 percent of pterapods “are already dissolving,” said NOAA’s Feely. “Pteropods are only a canary in this coal mine,” the Quinault’s Schumacker said. “They are a critical component of salmon diets, but what other creatures in the ecosystem are being affected?” It’s a concern too, for the Yurok Tribe on the northern California coast. Micah Gibson, director of the Yurok Tribe Environmental Program, told ICTMN, “We’ve done some research, but no monitoring yet.” The Passamaquoddy Tribal Environmental Department in Maine is monitoring ocean acidification, according to a letter the tribe sent to the U.S. Environmental Protection Agency (EPA). They reported that the pH of Passamaquoddy, Cobscook Bays and the Bay of Fundy was around 8.03 during the 1990s and had dropped to 7.92. The lower the pH value, the more acidic the environment. If, or when, the Passamaquoddy letter stated, the level in bays falls to 7.90, shellfish—including clams, scallops and lobster, all economic mainstays—will die. In Alaska, coastal waters are particularly vulnerable because colder water absorbs more carbon dioxide, and the Arctic’s unique ocean circulation patterns bring naturally acidic deep ocean waters to the surface, according to recent research funded by National Oceanic and Atmospheric Administration (NOAA) awaiting publication in the journal Progress in Oceanography. Ocean acidification spells even more trouble for the Inuit subsistence way of life. “New NOAA-led research shows that subsistence fisheries vital to Native Alaskans and America’s commercial fisheries are at-risk from ocean acidification,” NOAA said in the report. “Emerging because the sea is absorbing increasing amounts of carbon dioxide, ocean acidification is driving fundamental chemical changes in the coastal waters of Alaska’s vulnerable southeast and southwest communities.” The pH of the ocean’s surface waters had held stable at 8.2 for more than 600,000 years, but in the last two centuries the global average pH of the surface ocean has decreased by 0.11, dropping to 8.1. That may not sound like a lot, but as of now the oceans are 30 percent more acidic than they were at the start of the Industrial Revolution 250 years ago, according to NOAA. If humans continue emitting CO2 at the level they are today, scientists predict that by the end of this century the ocean’s surface waters could be nearly 150 percent more acidic, resulting in a pH the oceans haven’t experienced for more than 20 million years. The ocean acts as a carbon sink, greatly reducing the climate change impact of CO2 in the atmosphere. When scientists factor in our increasingly acidic oceans their studies show that global temperatures are set to rise rapidly, according to a study of ocean warming published last year in the journal Geophysical Research Letters. These frightening scenarios illustrate the point made by Frank in his talk on ocean acidification: Humanity must meet this challenge. So too must Inslee’s persistence in trying to place a high priority on climate change in Washington DC. We are moving into the Anthropocene Age, a new geological epoch in which humanity is influencing every aspect of the Earth on a scale akin to the great forces of nature, according to the journal Environmental Science & Technology. The Anthropocene challenges American Indians, but if traditional knowledge could foresee the tremendous challenges posed by ocean acidification, Indigenous knowledge can surely find solutions to the impacts of climate change, starting with how we use energy, and how much carbon we emit. “Have a little courage, and get out of some boxes,” the environmentalist and writer Winona LaDuke told ICTMN. “Put in renewable energy and re-localize our economies, from food to housing, health and energy.” A dam break at a central British Columbia mine could threaten salmon fisheries in the Pacific Northwest. Mount Polley is an open-pit copper and gold mine roughly 400 miles north of Seattle. A dam holding back water and silt leftover from the mining process broke Monday. It released enough material to fill more than 2,000 Olympic-sized swimming pools. Government regulators have not yet determined its content. But documents show it could contain sulfur, arsenic and mercury. Imperial Metals, the mine’s owner, issued a statement that only said the material was not acidic. Emergency officials told residents not to drink or bathe in water from affected rivers and lakes. The spill area is in the watershed of the Fraser River, which empties into the Pacific Ocean at Vancouver, B.C. The river supports a large sport and commercial fishery in Washington state. Brian Lynch of the Petersburg, Alaska, Vessel Owners Association says some of those fish also swim north. “The United States has a harvest-sharing arrangement for Fraser sockeye and pink salmon through provisions of the Pacific Salmon Treaty. So any problem associated with salmon production on the Fraser will affect U.S. fishermen,” he says. Imperial Metals did not respond to requests for comment. Its website says the mine is closed and damage is being assessed. Provincial officials have ordered the corporation to stop water from flowing through the dam break. Imperial could face up to $1 million in fines. Environmental groups in Canada and Alaska say Mount Polley’s dam is similar to those planned for a half-dozen mines in northwest British Columbia. They say a dam break there would pollute salmon-producing rivers that flow through Alaska. That could also affect U.S.-Canada Salmon Treaty allocations, including for waters off Washington state. | Mid | [
0.5688073394495411,
31,
23.5
] |
Time-correlation between membrane depolarization and intracellular calcium in insulin secreting BRIN-BD11 cells: studies using FLIPR. Cytoplasmic Ca(2+) ([Ca(2+)](i)) and membrane potential changes were measured in clonal pancreatic beta cells using a fluorimetric imaging plate reader (FLIPR). KCl (30 mM) produced a fast membrane depolarization immediately followed by increase of [Ca(2+)](i) in BRIN-BD11 cells. l-Alanine (10 mM) but not l-arginine (10 mM) mimicked the KCl profile and also produced a fast membrane depolarization and elevation of [Ca(2+)](i). Conversely, a rise in glucose from 5.6 mM to 11.1 or 16.7 mM induced rapid membrane depolarization, followed by a slower and delayed increase of [Ca(2+)](i). GLP-1 (20 nM) did not affect membrane potential or [Ca(2+)](i). In contrast, acetylcholine (ACh, 100 microM) induced fast membrane depolarization immediately followed by a modest [Ca(2+)](i) increase. When extracellular Ca(2+) was buffered with EGTA, ACh mobilized intracellular calcium stores and the [Ca(2+)](i) increase was reduced by 2-aminoethoxydiphenyl borate but not by dantrolene, indicating the involvement of inositol triphosphate receptors (InsP(3)R). It is concluded that membrane depolarization of beta cells by glucose stimulation is not immediately followed by elevation of [Ca(2+)](i) and other metabolic events are involved in glucose induced stimulus-secretion coupling. It is also suggested that ACh mobilizes intracellular Ca(2+) through store operated InsP(3)R. | High | [
0.6769230769230771,
33,
15.75
] |
Tuesday, April 2, 2013 1. Give Wilton Lopez a fair shake: Denver sports fans aren’t the most forgiving people when professional athletes struggle wearing their team’s uniform or decide to skip town for greener pastures, but it’s only one outing. Ugly, horrendous and disastrous, yes, but still only one outing. The Rockies brought Lopez in to be their 8th inning guy (if you hate set roles in the bullpen, I understand but we'll have to cover that later) and one magnified bad outing on opening day isn’t going to change that. Nor should it. 2. It wasn’t Walt’s fault: Yes, Matt Belisle only threw one pitch in the game. (It was a damn fine pitch, too.) But when you spend all spring establishing roles you don’t just change them on opening day for no reason. Belisle did his job. The 8th inning is entrusted to Lopez. Everyone on the team knows this. Why would you then change that for the sake of changing it on opening day? There’s no logic in that. Lopez had done nothing yet to lose the role coming in, so you roll with him as planned. Did Weiss stick with him too long? Maybe. Maybe he should have had Rafael Betancourt or someone else ready. That could have worked. And maybe next time he will. But you can’t panic and stray from the gameplan on Day 1. Especially when you're a BRAND new manager just establishing yourself. That’s not an impression you want to leave on players because they‘ll start second guessing him quickly. When Walt Weiss feels like he needs to change a player's role, I don't think he'll hesitate to do it. It's just not going to happen in the middle of Game 1. 3. Jhoulys Chacin: The offense packed a nice punch. That was encouraging. Of course we also had a lot of the same lousy base running and poor execution in run scoring situations, but the potential to score runs in bunches will be there. I have little doubt about that. As good as that was though, I think we all had to be pretty pleased and encouraged by Jhoulys Chacin’s performance. Granted, it could have ended up a lot different had Milwaukee not made three strange outs on the bases, but he looked great once he settled down and those middle innings into the 7th were fun to watch. If we could just get him to bottle that up and hold on to it, we’d had no worries at the top of the rotation. But it’s one step at a time, so we’ll say he moved forward here and leave it at that. Monday, April 1, 2013 Well folks, it seems I've been busier than even I anticipated I'd be since the beginning of the year so I didn't even have a chance to weigh in on spring training. I don't think there was much to talk about anyway aside from maybe Tyler Colvin getting shipped to minors after a rough, rough March. I probably wouldn't have reacted that way, but after seeing how lost he became in 2011, I guess I see the Rockies reasoning. I just hope he gets it together quick. Yorvit Torrealba beat out Ramon Hernandez. No surprise there. They inked Jon Garland. Big fan of that move. Aaron Cook is back on a minor league deal. That's fine. The rest of the starting pitching has been all over the map. Duh. Todd Helton looked like his old self over the past week. That's always nice to see. But that's all behind us now. It's time to look forward, which is what I intend to do here with a few predictions. Just remember... these predictions won't matter a week from now and will likely be forgotten six months from now. Unless they're correct, of course. Wins: 73 Some people think they can get to .500 this season. ESPN's Keith Law says 53 wins. I'm going in between with a learn towards optimism. They're going to struggle to pitch again, and they probably won't succeed within the division, but a healthier season should eliminate some of the misery. All-Stars: If Dexter Fowler isn’t an all-star, we’ll all be complaining that he should have been. I think he finally breaks out. Meanwhile, Troy Tulowitzki is a given and Carlos Gonzalez should be, too. Team leader in wins: Jon Garland... even if he’s traded in July or August. I'm thinking 11-12. Team leader in saves: Rafael Betancourt... again, even if he's traded in July or August. Todd Helton's numbers: .280, 10 home runs, 55 RBI in 92 games. Wouldn't be a bad way to go out. Wilin Rosario home runs: 27 Wilin Rosario: passed balls: 11 Date Nolan Arenado arrives: No sooner than June 15 and no later than July 15. He’ll be a breath of fresh air. Walt Weiss status: He'll earn a second year. I assume he'll get it, too, but I'm more certain he'll earn it than receive it. Public Enemy No 1 (AKA the Frankin Morales/Felipe Paulino/Esmil Rogers/Jeremy Guthrie on the team): Hands down this will be Chris Volstad. Rockies fans tend to sour on new guys quickly and I'm afraid Volstad will make himself an easy target. Thursday, January 10, 2013 Stunning how little significant activity we've seen from the Rockies this offseason, isn't it? Well, unless you consider the Manny Corpas signing on Wednesday an impact signing, which of course it isn't. But hey, I like Manny a lot and will always appreciate his efforts from the days before Jim Tracy blew his arm up, so I can't complain about it and certainly hope it ends up working out better than expected. Anyway, the blog certainly won't be as silent as it has been during the offseason once spring training gets underway, but it also won't be as active as past seasons. That's because other writing opportunities and work assignments will require a lot of attention, making it increasingly difficult for me to write recaps - or recraps - after each game. Honestly, I'm very proud of the fact I haven't missed a single recap since the blog opened three years ago and have been able to offer something resembling a fresh take every time, but to be at my best here and to be at my best elsewhere, I'll need to change things up and take a different approach to the site. What that means exactly is still up in the air, but you'll still read plenty of thoughts from me in one form or another. That much is guaranteed. I look at the changes two different ways. 1) The games I am able to watch live I will actually be able to watch intently instead of half-watch and mostly listening while preparing my recaps. 2) It will allow me to be more of a fan and actually interact with other fans on Twitter during games. I'm actually very excited about both of those things, and feel the changes will help keep my perspective fresher and my sanity more completely intact. The former far more likely than the latter, obviously. So that's where we are right now. Players rankings, screen grabs, lineup cards and all the other fun things will remain. Dissecting of Walt Weiss press conferences may become a thing, too, depending on how overwhelmed he becomes by the unfortunate circumstances he's been placed into. It will likely be another mostly frustrating, often painful season, but we'll still try to make it as fun as possible, since that's kinda the point of the game anyway. Wednesday, November 21, 2012 Regardless of size or significance, every single trade a team makes in this social media and blog driven world is met with reactions (often overreactions). Here's mine to the trade Colorado Rockies made on Tuesday, which sent left-hander reliever Matt Reynolds to the division rival Arizona Diamondbacks in exchange for 24-year-old corner IF/OF Ryan Wheeler. *Shrug* I always liked Matt Reynolds for his durability, versatility and the fact he attended the same high school as my cousins in St. Charles, IL. I also realize the importance of left-hander relievers, but he's totally replaceable, just as most bullpens arms are. Not that the Rockies have or will acquire upgrades, but there's a better chance of stumbling in production in middle relief (see Josh Roenicke and Adam Ottavino) than any other position. That said, I'm not so sure we're getting a meaningful piece back here in Ryan Wheeler. It's a little frustrating, too, because it seems like Reynolds would have been more valuable in a package for something a little more significant. This one has the feel of the typical Rockies trade that doesn't maximize the value of the talent involved and ultimately turns into a throwaway, but it will certainly take time to figure that out for sure. The Diamondbacks likely were willing to trade Wheeler in large part because of his perceived defensive shortcomings. Scouts have had concerns about the big-bodied Wheeler’s mobility at third base for years now, and Wheeler has worked hard to try to become more agile. But defense and athleticism seem to be turning into an enormous factors in most Diamondbacks acquisitions lately, so it’s not a big surprise that they don’t view Wheeler as their archetypal third baseman. The other question with him is whether he’ll be able to hit for enough power in the majors; he’s more of a natural opposite-field hitter, and the Diamondbacks’ coaches were working with him this season on pulling the ball more regularly, driving it with more authority. He’s headed to the best hitter’s ballpark in baseball, so we’ll see if he’ll be able to hit enough to make up for whatever defensive shortcomings may exist. The other thing is, he has a tremendous work ethic and makeup, so there’s little question he’ll put in the time and effort to improve. It sounds like there's some work to do here on both sides of the field, but based on that information I'm going to guess the Rockies will give Wheeler a long look at first base this spring. Links Speaking of trades, Chris Jaffe over at the Hardball Times posted a couple recent historical items on the Rockies, including the Mike Hampton-Juan Pierre deal from 2002. Wednesday, November 14, 2012 Dante Bichette was my favorite player growing up. There really wasn't a close second, though Vinny Castilla would have been the choice until Todd Helton came along. With that out of the way, I've obviously been hoping for many years that Dante would be back in the Rockies fold in some capacity before all was said and done. That it's happening now as the hitting coach is really very exciting. Forgot the fact that this coaching staff could be in place for just one season — that won't be the case because they will inevitably improve with better health, and ownership will be convinced things are headed in the right direction regardless of the truth — I'm just happy to have a guy in place who truly understands the unique situation he's walking into, and can draw on past experiences to aid his teaching. But as I mentioned on Twitter after the announcement was made... I have little doubt Dante Bichette will give great hitting advice. Who listens and how it's used is up the players. The end. #rockies — Mark Townsend (@Townie813) November 13, 2012 Don Baylor had experience at Coors Field, too, and seemed to struggle putting gameplans together for Rockies hitters. What that means, if anything, I honestly don't know, but he's done at least a decent job in Arizona and obviously knows hitting, The sure difference, though, is with Bichette you have a guy who has stood in that batter's box at Coors Field hundreds of times, has made his own adjustments on the road, and has his own feel for the proper mental approach. That's a positive step up. Despite some really ugly swings when his best guess was wrong, Bichette also had great instincts. But Bichette's greatest quality was that he never gave away an at-bats, especially with two strikes. Bichette, for my money, is the best two strike hitter in last 20 years. As great as Helton is in the same situation I'm not sure he ever surpassed Bichette. I don't care how wrong that is, either, because it's money. But the reason Bichette and Helton excel with two strikes is because they value each and every opportunity they get. They make the adjustments they need to on the fly just to prolong an at-bat and maybe capitalize on a mistake. That really is and was the art and beauty of their game. Now, when you hear and read scouting reports for Dante Jr. and even Beau Bichette, you know it's either in the genes or Senior is really good at getting his message across. Bottom line, under Bichette, there will be no excuses on offense. He will have them prepared as best he can. He'll send the right messages. You can bet he's going to have them watching a lot of video. And it wouldn't surprise me if their first assignment at spring training is reading The Science of Hitting by Ted Williams.(Dante read that book countless times throughout his career.) It will be up to the players to listen, learn, adjust when necessary and execute. Now we just need to find a pitching coach/director/instructor/whatever that can boast the same experience and success from the pitching side of things. Sadly, that guy isn't out there, but I'm feeling really good about the lineup. Oh, and let's also trade for Dante Bichette Jr. just to cover all the bases here. | Mid | [
0.5714285714285711,
32,
24
] |
Cookie-carrying crook robs business on 6th Street San Francisco police are looking for a man who ordered a cookie before robbing a business along the city's Sixth Street corridor on Thursday morning. The robbery was reported at about 10:50 a.m. in the 100 block of Sixth Street. The suspect, described as a man around 40 years old, entered the business and ordered a cookie, then paid for it. But as the employee opened the cash register, the suspect leapt over the counter and grabbed money out of the register, according to police. A struggle ensued between the employee and suspect, who was eventually able to flee with some cash and was last seen headed north on Sixth Street toward Mission Street, police said. Anyone with information about the robbery is encouraged to call the Police Department's anonymous tip line at (415) 575-4444 or send a tip by text message to TIP411. | Mid | [
0.5570093457943921,
37.25,
29.625
] |
Why 6’4″ Lt. Saru on ‘Star Trek: Discovery’ Walks Like Supermodel In the new series Star Trek: Discovery “new worlds and civilizations are explored by new members of the Star Trek universe.” The premiere episode is titled “The Vulcan Hello” and Kelpien (a new alien race!) Lt. Saru is the science officer aboard the Discovery who is easily compared to Spock and Data from previous Star Trek series. Lt. Saru is portrayed by Doug Jones. The nearly 6’4” tall actor says Saru’s walk is inspired by supermodels (walking on the balls of his feet), thanks to the boots he has to wear as his character has hooved feet. Jones is accustomed to wearing lots of makeup and unusual costumes for his roles including The Strain (The Ancient), Falling Skies (Cochise), The Neighbors (Dominique Wilkins), among others. Jones is also well recognized for his roles in Spike Jonze’s Adapation. (Augustus Margary), Guillermo del Toro’s Pan’s Labyrinth, the Fantastic 4 movies (The Silver Surfer) and Hellboy (Abe Sapien) — see link above — among others. Fun Fact: Jones had a recurring role on The Weird Al Show in 1997 as a contortionist. Star Trek: Discovery premieres on CBS on Sunday, September 24 at 7:30pm, and then will be available on CBS All-Access. | Mid | [
0.6008403361344531,
35.75,
23.75
] |
Supreme Court: Decision Nears on 'Obamacare' WASHINGTON -- The Supreme Court is expected to announce its ruling on the Affordable Care Act (ACA) this month and speculation about the impact of that decision is heating up on both sides of the "Obamacare" debate. And both sides predict disaster for doctors -- massive disruption if the law is struck down -- or if it is upheld. If the court decides to go with something in between, confusion is likely to be the short-term result. Under this scenario, the law's most controversial provision -- the mandate that everyone must have health insurance or else pay a penalty -- would be ruled unconstitutional, but everything else in the law -- including the insurance market reforms, health insurance exchanges, and subsidies for those who can't afford insurance -- would remain. The states that are suing the government want the Supreme Court to strike down the entire law if the individual mandate is found to be unconstitutional. The Obama administration counters with a "half a loaf" argument: if the mandate is found to be unconstitutional, the law should be able to stand, with the exception of two provisions -- the guaranteed-issue provision, which bans insurers from refusing to offer coverage due to a preexisting medical condition, and the community rating provision, which bars insurers from charging higher premiums based on a person's medical history. Most agree that the guaranteed issue and community rating provisions would be difficult to enforce absent the requirement that everyone have health insurance. During oral arguments on the issue -- known as the mandate's "severability" -- the Supreme Court justices enunciated these differing positions. No, said Paul Clement, the lawyer for the 26 states that are suing the federal government over the law. Sometimes no loaf is indeed better than half a loaf, he said. In the case of the ACA, the mandate is too integral to the overall survival of the whole law. "If you don't have the individual mandate to force people into the market, premiums will skyrocket," Clement said during oral arguments in March. Clement and the Obama administration agree that without forcing young and healthy people into the insurance market, many would not buy insurance. That would mean the insurance pool would largely be comprised of less-healthy people, which would cause insurance to be more expensive for everyone. A brief about the different decision scenarios issued by consulting firm Deloitte said the mandate being struck down but other parts remaining is a "distinct possibility." Leonardo Cuello, an attorney and director of health reform for the National Health Law Program, which advocates for low-income individuals, gave it 50/50 odds. The Entire Law Is Struck Down If the mandate is found to violate the Constitution and the justices also decide it's too enmeshed in the larger law to be separated, they could overturn the entire law. This outcome would be the most disruptive to doctors, said Ron Pollack, executive director of Families USA, a liberal consumer group that supports the ACA. That's because they've already been working to prepare for the law -- for example, by taking steps to form accountable care organizations encouraged under the law. Hospitals, meanwhile, may be bearing the brunt in preparing for major changes under the ACA. Hospitals are already cutting costs to absorb the $155 billion the industry agreed to give up to fund the expansion of health insurance under the ACA, the Deloitte brief said. Aside from affecting doctors directly, it's U.S. citizens as a whole who have benefited from provisions of the law that have already been implemented, according to the Deloitte consultants. Some 27.8 million people have already been impacted, including seniors who have received doughnut hole rebates and young adults under 26 who are now covered by their parents' insurance plan. Consultants at Deloitte predicted the entire law would likely not be overturned. The Entire Law Remains As Is "If you want chaos, this is a good way to do it," Joe Antos of the American Enterprise Institute, a right-leaning think tank, said of this option. He added that he thinks the court will go this route and either uphold the law, or else rule the mandate unconstitutional -- but it won't repeal the whole thing. "If everything is allowed to continue, there's a lot of uncertainly about how the law will actually be implemented," Antos said. Grace Marie Turner, president of the Galen Institute, a free-market think tank, predicted that even if the law remains as is, many provisions will have to be tweaked once they are deemed unworkable. For instance, many states are not ready to start health insurance exchanges in 2014, so that provision may have to be substantially delayed. She also predicted that states may not have the capacity to treat new patients that would be brought into the system by the ACA's expansion of Medicaid in 2014, so the start date on that could very well be pushed back as well. Pollack disagrees with Antos and Turner and said if the law remained as is, it would be the least disruptive for doctors and for patients. Medicaid Expansion is Removed from Law Another option -- striking down the ACA's Medicaid expansion, is thought to be an unlikely outcome of the Supreme Court challenge. Starting in 2014, the ACA expands Medicaid to cover nearly all people under age 65 with household incomes at or below 133% of the federal poverty level. Currently, most states' Medicaid programs only cover pregnant women and children who are very poor, as well as certain low-income, disabled adults. Congress has never required mandatory coverage criteria for childless adults who are not within the covered categories, but it has expanded the Medicaid program a number of times. The 26 states that are suing the federal government over the law argue that the Medicaid expansion is a violation of the Spending Clause of the Constitution largely because it's coercive -- it conditions receipt of all federal Medicaid funds on the states' expanding Medicaid. "How can they claim that this is coercive?" asked Antos. "It doesn't seem reasonable to me. " Cuello also said he'd be surprised if the court ruled the Medicaid expansion unconstitutional. The Anti-Injunction Act Is Ruled Applicable and the Court Defers its Decision Finally, the court must decide whether an 1867 federal law called the Anti-Injunction Act, which prohibits a lawsuit from being brought over a particular tax until that tax actually takes effect, applies in the case of the ACA. Under the ACA, everyone is required to have health insurance starting in 2014, or else pay a penalty in 2015. If the court were to decide the Anti-Injunction Act bars the issue from being heard now because 2015 is still several years away, the Supreme Court could postpone a decision on the controversial healthcare law until after 2015 -- the year in which the penalty would first be collected. Both sides -- the Obama administration and the 26 states suing the federal government -- agree that the old tax law doesn't apply to the ACA and shouldn't stand in the way of a court ruling on the case. Based on oral arguments, and the fact that no side is pushing for the tax law to apply, it is unlikely the court would defer a decision based on the Anti-Injunction Act, experts agree. More in Washington-Watch MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals. Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities. | Mid | [
0.593607305936073,
32.5,
22.25
] |
What’s private might not be so private anymore Facebook- the social media site that has taken the world by storm. With 1 million users in 2004 to over 400 million users in 2010, Facebook has become one of the most common ways to communicate with people not only on the other side of the world but next door too. Despite the number of users, Facebook has recently been taking slack from many of its followers. It has slowly been increasing the amount of data that can be shared with “friends” on Facebook. Between December 2004 and April 2010, Facebook has increased the amount of items that are available for public viewing from 4 to over 8. This means that information that is put up on Facebook has gone from being available for viewing for Facebook users, to available for the world to see. Not a good thing if your mate put pictures up of that time you passed out drunk, hugging the toilet bowl. Facebook suicide There was recently a website formed, www.quitfacebook.com, that petitioned the privacy settings. The plan that was to follow was for Facebook users to “kill off” their social network profiles. Quit Facebook Day on the 31st May 2010 had almost 30 000 members who planned to say goodbye to the addictive site forever. They felt violated by Facebook’s privacy policy and settings. However not all of the angry users did delete their profiles. The creator and CEO of Facebook, Mark Zuckerberg, and the rest of the team have nothing to worry about should more people decide to cut ties with the popular social site. Facebook is gaining a monstrous 35 000 users an hour. To break that down for you, that’s about 10 users every second, all over the world. Privacy control on Facebook With so many complaints about Facebook privacy settings there have been changes made to try decrease the amount of personal information and data that is available to the public. A privacy setting has been added to all content. It applies to contact details, photos and status updates. Facebookers can now decide whether or not they want to share their information with Facebook friends, friends- of- friends or everyone on the internet. Less information will be available to the public from now on and games applications on Facebook will have to ask the Facebook account holder for permission to access private information. Over the last few months, Facebook has received harsh criticism from regulators. The European Commission and advocacy groups such as Electronic Frontier Foundation have made remarks and complaints about Facebook’s privacy settings. Facebook was accused of steering users towards sharing private information instead of keeping it private. Mark Zuckerberg says that because so many new applications and features have been added to Facebook, it became almost impossible for users to control the privacy settings. They became complicated and difficult to use. Let’s just hope that they have overcome this hiccup and that we can continue posting those crazy weekend pics up without the rest of the world having a good laugh at us. | Mid | [
0.582750582750582,
31.25,
22.375
] |
Thousands of Dead Fish Baffle Residents in North Carolina Community Residents near High Rock Lake in North Carolina are scratching their heads wondering what killed thousands of fish strewn about the shores of the lake, reported the Salisbury Post. State water quality officials said the event was just a natural occurrence, according to the Salisbury Post report; but Dean Naujoks, the Yadkin riverkeeper, told the Salisbury Post he believes the fish deaths were connected to a 15.9 million gallon sewage spill that occurred earlier this year in Thomasville, N.C.: Since early August, the sewage had been spilling into North Hamby Creek, which feeds into High Rock Lake, the Salisbury Post reported. Naujoks said the sewage likely settled into the sediment near the High Rock dam, according to the report. But Dr. JoAnn Burkholder, a water quality expert at North Carolina State University, disputed the possibility of this, and according to the Salisbury Post, said a sewage spill of that magnitude would linger on the lake bottom for up to six months. Still, Naujoks is convinced something disturbed the water to churn up the sewage, which could deplete oxygen in the water and kill the fish, the Salisbury Post reported. "There's no way to prove it,” he told the Salisbury Post. “But, in my opinion, when you have a sewage spill of 15 million gallons, it's going to rob this lake, which is already struggling, of oxygen; and it likely contributed to this fish kill." The water quality officials attributed the fish deaths to a “turnover” event when low dissolved oxygen goes through the entire water column, due to changing temperatures and storms; and fish suddenly are caught in low oxygen areas, officials told the Salisbury Post. Further, the Salisbury Post reported that, according to the North Carolina Division of Water Quality, a state investigator tested the water on the lake following the fish deaths, and found no evidence that wastewater was the culprit. | Low | [
0.51578947368421,
30.625,
28.75
] |
package com.palmergames.bukkit.towny.utils; import com.palmergames.bukkit.towny.object.CellBorder; import com.palmergames.bukkit.towny.object.WorldCoord; import java.util.ArrayList; import java.util.List; /** * @author Chris H (Zren / Shade) * Date: 4/15/12 */ public class BorderUtil { public static List<CellBorder> getOuterBorder(List<WorldCoord> worldCoords) { List<CellBorder> borderCoords = new ArrayList<CellBorder>(); for (WorldCoord worldCoord : worldCoords) { CellBorder border = new CellBorder(worldCoord, new boolean[] { !worldCoords.contains(worldCoord.add(-1, 0)), !worldCoords.contains(worldCoord.add(-1, -1)), !worldCoords.contains(worldCoord.add(0, -1)), !worldCoords.contains(worldCoord.add(1, -1)), !worldCoords.contains(worldCoord.add(1, 0)), !worldCoords.contains(worldCoord.add(1, 1)), !worldCoords.contains(worldCoord.add(0, 1)), !worldCoords.contains(worldCoord.add(-1, 1)) }); if (border.hasAnyBorder()) borderCoords.add(border); } return borderCoords; } public static List<CellBorder> getPlotBorder(List<WorldCoord> worldCoords) { List<CellBorder> borderCoords = new ArrayList<CellBorder>(); for (WorldCoord worldCoord : worldCoords) { CellBorder border = getPlotBorder(worldCoord); borderCoords.add(border); } return borderCoords; } public static CellBorder getPlotBorder(WorldCoord worldCoord) { return new CellBorder(worldCoord, new boolean[] { true, true, true, true, true, true, true, true }); } } | Mid | [
0.550607287449392,
34,
27.75
] |
Queletia Queletia is a genus of fungi in the family Agaricaceae. The genus was described by Elias Magnus Fries in 1872. Fruit bodies of Queletia species are roughly spherical with a stipe-like base. They have a thin outer skin (peridium) and a harder inner skin that breaks into small pieces with age. The genus is named after French mycologist Lucien Quélet. See also List of Agaricales genera List of Agaricaceae genera References Category:Agaricaceae Category:Agaricales genera | High | [
0.6744730679156901,
36,
17.375
] |
Records smashed at new velodrome as Britain delight AFP, LONDON France’s Gregory Bauge, left, Michael D’Almeida, center, and Kevin Sireau compete during the qualification round for the team sprint at the UCI Track Cycling World Cup at the Olympic velodrome in London on Friday. Photo: AFP Olympic champion Victoria Pendleton and Jess Varnish inspired Britain to two world record-winning performances on Friday as Britain underscored their gold winning potential at the London velodrome. However, on the second day of the World Cup meeting, which doubles as an Olympic test event, the Olympics kings from Beijing were given plenty of food for thought ahead of this summer’s Games. After earlier seeing Australian pair Anna Meares and Kaarle McCulloch improve their own world record by clocking 32.828 seconds for the two-lap event, Pendleton and Varnish rose to the challenge in the final to set an improved mark of 32.754 seconds. This London Olympics will be Pendleton’s last and the Englishwoman — who is set to compete in the individual and team event in August — was in bullish mood. “We were pleased this morning, so I can’t even explain to you how good it feels to have the world record. The Australians took it for a while, then we took it back,” Pendleton said. Meares will be among the biggest threats to Pendleton’s Olympic title in the individual sprint in London, having beaten the Englishwoman to the world title for the first time this year. Racing alongside McCulloch, gold medal expectations will also be high in the team sprint, which this year will join the keirin and the individual sprint on the women’s five-race Olympic program. Despite having to settle for team sprint silver on Friday, Meares and McCulloch — the three-time defending world champions — promise to redress the balance at the world championships in Melbourne in April. “We would have loved to have won here, it’s just not happened, but what we can take from this is riding in front of a very large British crowd, against the British team and we can go from strength to strength,” Meares said. “At the end of the day it’s about Anna and I putting the best performance we can out on the track and we did that tonight,” McCulloch added. “But you know what? This is only a stepping stone for us. We’ll be better at the worlds and we’ll be better in London, you can bet your bottom dollar on it.” Australia’s women were celebrating for the second time when their pursuit trio of Josephine Tomic, Amy Cure and Annette Edmondson beat the US’s world record of 3 minutes, 19.569 seconds on their way to bronze in 3 minutes, 19.164 seconds. Minutes later, Britain’s Laura Trott, Danielle King and Joanna Rowsell showed impressive form over 12 laps to win the event and regain their world record in 3 minutes, 18.148 seconds. “We knew it was on,” Rowsell said. “From training we’ve been riding above world record pace for the last few training sessions. We knew it was in the tank. We’re really pleased we’ve got that world record back.” Meanwhile, world champions Germany put their Olympic gold winning credentials on display by outclassing the French in the men’s team sprint final. Frenchman Kevin Sireau, who is battling compatriot Gregory Bauge for the sole individual sprint spot, said their team was buoyed by their first ride together since winning the world title last year. “The Germans have been working at this event all season and we haven’t so it’s a pretty good sign for us finishing second on the podium,” Sireau said. Olympic champions in the event, Britain had to settle for third after finishing only fourth in qualifying. Sir Chris Hoy, who also won sprint and keirin gold in Beijing, said their plans to defend their Olympic title were well on track. | Mid | [
0.556354916067146,
29,
23.125
] |
<?php declare(strict_types=1); namespace GraphQL\Language; /** * List of available directive locations */ class DirectiveLocation { // Request Definitions const QUERY = 'QUERY'; const MUTATION = 'MUTATION'; const SUBSCRIPTION = 'SUBSCRIPTION'; const FIELD = 'FIELD'; const FRAGMENT_DEFINITION = 'FRAGMENT_DEFINITION'; const FRAGMENT_SPREAD = 'FRAGMENT_SPREAD'; const INLINE_FRAGMENT = 'INLINE_FRAGMENT'; // Type System Definitions const SCHEMA = 'SCHEMA'; const SCALAR = 'SCALAR'; const OBJECT = 'OBJECT'; const FIELD_DEFINITION = 'FIELD_DEFINITION'; const ARGUMENT_DEFINITION = 'ARGUMENT_DEFINITION'; const IFACE = 'INTERFACE'; const UNION = 'UNION'; const ENUM = 'ENUM'; const ENUM_VALUE = 'ENUM_VALUE'; const INPUT_OBJECT = 'INPUT_OBJECT'; const INPUT_FIELD_DEFINITION = 'INPUT_FIELD_DEFINITION'; /** @var string[] */ private static $locations = [ self::QUERY => self::QUERY, self::MUTATION => self::MUTATION, self::SUBSCRIPTION => self::SUBSCRIPTION, self::FIELD => self::FIELD, self::FRAGMENT_DEFINITION => self::FRAGMENT_DEFINITION, self::FRAGMENT_SPREAD => self::FRAGMENT_SPREAD, self::INLINE_FRAGMENT => self::INLINE_FRAGMENT, self::SCHEMA => self::SCHEMA, self::SCALAR => self::SCALAR, self::OBJECT => self::OBJECT, self::FIELD_DEFINITION => self::FIELD_DEFINITION, self::ARGUMENT_DEFINITION => self::ARGUMENT_DEFINITION, self::IFACE => self::IFACE, self::UNION => self::UNION, self::ENUM => self::ENUM, self::ENUM_VALUE => self::ENUM_VALUE, self::INPUT_OBJECT => self::INPUT_OBJECT, self::INPUT_FIELD_DEFINITION => self::INPUT_FIELD_DEFINITION, ]; /** * @param string $name * * @return bool */ public static function has($name) { return isset(self::$locations[$name]); } } | Mid | [
0.587991718426501,
35.5,
24.875
] |
Q: Meaning of Agda level error message: ... : .Agda.Primitive.Level I'm trying to decipher an error message concerning levels. In Haskell, I can write the following stream function, twist, in a straightforward fashion: data Stream a = a :> Stream a twist :: (a -> (b , (Either a c))) -> (c -> (b , (Either a c))) -> (Either a c) -> Stream b twist lt rt (Left a) = b :> twist lt rt ac where (b , ac) = lt a twist lt rt (Right c) = b :> twist lt rt ac where (b , ac) = rt c So far, so good. Now, when I attempt to define the analogous function in Agda, I get an error message about levels that I don't understand. Specifically, I get this error message: _a_41 : .Agda.Primitive.Level [ at ...snip.../MinimalStream.agda:20,34-35 ] _b_42 : .Agda.Primitive.Level [ at ...snip.../MinimalStream.agda:20,34-35 ] It seems to be complaining about the level of type variables a and b in the type declaration of twist, but I am not sure I understand what the problem is. Any pointers or explanation that anyone could provide would be greatly appreciated! Thanks, Bill Here's the Agda code that generates thin its entirety: module MinimalStream where open import Data.Product using (_×_; _,_; proj₁) open import Data.Sum -- using (_⊎_) case_of_ : ∀ {a b} {A : Set a} {B : Set b} → A → (A → B) → B case x of f = f x record Stream A : Set where coinductive field headStr : A tailStr : Stream A open Stream; S = Stream -- standard kinds of stream functions work as expected. unzip₁ : ∀ {a b : Set} → Stream (a × b) → Stream a headStr (unzip₁ sab) = proj₁ (headStr sab) tailStr (unzip₁ sab) = unzip₁ (tailStr sab) twist : ∀ {a b c} → (a → (b × (a ⊎ c))) → (c → (b × (a ⊎ c))) → (a ⊎ c) → Stream b headStr (twist lt rt (inj₁ a)) = case lt a of λ { (b , (inj₁ _)) → b ; (b , (inj₂ _)) → b } headStr (twist lt rt (inj₂ c)) = case rt c of λ { (b , (inj₁ _)) → b ; (b , (inj₂ _)) → b } tailStr (twist lt rt (inj₁ a)) = case lt a of λ { (_ , (inj₁ a')) → twist lt rt (inj₁ a') ; (_ , (inj₂ c)) → twist lt rt (inj₂ c) } tailStr (twist lt rt (inj₂ c)) = case rt c of λ { (_ , (inj₁ a)) → twist lt rt (inj₁ a) ; (_ , (inj₂ c')) → twist lt rt (inj₂ c') } A: Welcome to Stack Overflow! This sort of error indicates an unsolved metavariable, which means that Agda has failed to infer an implicit argument. The error message indicates the metavariable's (autogenerated) name and its type. In this case, the issue is probably with the types {a, b, c} in twist: It is unclear which level these should be at. To fix this, specify the level: {a b c : Set}. | Mid | [
0.621983914209115,
29,
17.625
] |
Severe adenovirus pneumonia requiring extracorporeal membrane oxygenation support--Serotype 7 revisited. Adenovirus causing severe fatal pneumonia has been well described in infants, children, and patients with immunocompromised function, but reports in previously healthy adults are rare. We report 3 cases of severe adenovirus pneumonia in whom conventional mechanical ventilation failed and required extracorporeal membrane oxygenation support. Retrospective case records review of 3 patients admitted to the medical intensive care unit, Singapore General Hospital, a tertiary care university-affiliated hospital, with severe adenovirus pneumonia requiring extracorporeal membrane oxygenation support from February to March 2013. All 3 patients were previously healthy immunocompetent adults from the community with negative HIV serology. Duration prior to development of respiratory failure requiring intubation and invasive mechanical ventilation was 2, 8 and 3 days. Veno-venous extracorporeal membrane oxygenation (ECMO) support as rescue ventilation was instituted in all 3 patients after 2, 16, and 5 days of conventional mechanical ventilator support. Duration on ECMO support was 16, 22, and 9 days and mechanical ventilation was 18, 62, and 19 days respectively. Length of stay in intensive care unit was 18, 68, and 21 days, and length of stay in hospital was 20, 70, and 31 days respectively. Two of the 3 patients died. The mainstay of treatment for patients with severe adenovirus pneumonia is still supportive, with the use of antivirals not apparently effective. Whilst ECMO support for rescue ventilation may be considered, the outcomes do not appear as promising as other viral pneumonias, mirroring that previously described in the paediatric population. | Mid | [
0.64824120603015,
32.25,
17.5
] |
Body contouring remains among the most common cosmetic surgical procedures performed in the United States. Data from the American Society for Aesthetic Plastic Surgery indicate that liposuction replaced breast augmentation as the most popular surgical procedure in 2013, with 363,912 procedures performed. Its popularity has grown considerably because of advantages such as aesthetic improvements as well as numerous metabolic benefits.^[@R1],[@R2]^ Despite its popularity, there remain rare but significant risks regarding liposuction, including complications from anesthesia, infections, and even death.^[@R3]^ Clinical studies have reported a 21.7 percent incidence of minor complications as well as a 0.38 percent incidence of major complications.^[@R4],[@R5]^ Similarly, Fischer et al. showed that the incidence of minor wound complications was 6.3 percent, and the incidence of a major morbidity was 6.8 percent within 30 days after a surgical body contouring procedure.^[@R6]^ Although liposuction is an effective therapeutic option for the removal of excess adipose tissue, it remains an invasive procedure and carries the inherent risks associated with surgery. In recent years, new modalities have been developed to address body contouring from a less-invasive perspective. These modalities primarily target the physical properties of fat that differentiate it from the overlying epidermis and dermis, thus resulting in selective destruction of fat. Devices using high-frequency ultrasound, radiofrequency energy, and laser light have the potential to improve efficiency, minimize adverse consequences, and shorten postoperative recovery time. Through thermal destruction, cavitational destruction, or creation of a temporary adipocyte cell membrane pore, the final result is that the number of adipocytes is reduced, which, when translated over millions of fat cells, results in a measurable reduction of fat.^[@R7]^ Cryolipolysis is one of the most recent forms of noninvasive fat reduction to emerge. The development behind cryolipolysis stems from the clinical observation of cold-induced panniculitis.^[@R8]--[@R10]^ In 1970, Epstein and Oren coined the term popsicle panniculitis after reporting the presence of a red indurated nodule followed by transient fat necrosis in the cheek of an infant who had been sucking on a popsicle.^[@R9]^ Initially described in infants, cold-induced panniculitis has also been observed in adult patients. These observations led to the concept that lipid-rich tissues are more susceptible to cold injury than the surrounding water-rich tissue. With these historical observations in mind, Manstein et al. introduced a novel noninvasive method for fat reduction with freezing in 2007, termed cryolipolysis.^[@R11]^ This technique is performed by applying an applicator to the targeted area set at a specific cooling temperature for a preset period of time. This targets adipocytes while sparing the skin, nerves, vessels, and muscles. Initial preclinical and clinical studies have demonstrated the efficacy of cryolipolysis for subcutaneous fat layer reduction. However, the exact mechanism of action for cryolipolysis is not yet completely understood. In addition, the techniques of cryolipolysis treatment are not uniformly applied. Studies have suggested that the addition of posttreatment manual massage may enhance the effectiveness of a single cryolipolysis treatment, and that multiple treatments may lead to further improvement.^[@R12],[@R13]^ Finally, we are currently still unaware of the long-term side effects and outcomes of this treatment. The aim of the present review was to give an overview of cryolipolysis with emphasis on the efficacy (volume reduction), methods, safety, and complications. PATIENTS AND METHODS ==================== Search Strategy, Article Selection, and Data Extraction ------------------------------------------------------- A systematic review of the MEDLINE and Cochrane databases was performed with the search algorithm cryolipolysis OR cool sculpting OR fat freezing OR lipocryolysis. Two investigators independently reviewed article titles and abstracts to identify studies that assessed outcomes of cryolipolysis. Selected articles that met these inclusion criteria then underwent full article review by the two investigators. Additional articles were then identified by manual review of the references of the articles that were initially identified via the primary search. Review papers and animal studies were eliminated. A third investigator reconciled disagreements. The Cohen Kappa coefficient was calculated to demonstrate the level of agreement between the two initial investigators. The same two investigators performed data extraction independently, and any discrepancies were again reconciled by the third. Table [1](#T1){ref-type="table"} lists the information extracted from each article. ###### Data Extracted from Reviewed Articles  RESULTS ======= Search Strategy and Article Selection ------------------------------------- The primary literature search returned 319 articles (Fig. [1](#F1){ref-type="fig"}). The references of articles identified in the primary search were reviewed, yielding a total of 37 articles. Review papers and animal studies were eliminated, yielding a final number of 19 articles, including 12 prospective studies, three retrospective studies, one study with both prospective and retrospective groups, and three case reports. The Kappa coefficient was calculated at 0.885, indicating very good agreement between the investigators. {#F1} Efficacy -------- Common treatment areas included the abdomen, brassiere rolls, lumbar rolls, hip rolls/flanks, inner thighs, medial knee, peritrochanteric areas, arms, and ankles (Table [2](#T2){ref-type="table"}). Follow-up length generally ranged from 2 to 6 months, although one study presented case reports on two patients at 2 and 5 years after treatment,^[@R14]^ noting persistent reduction at these time points when comparing pretreatment and posttreatment photographs. Objective outcome measures included fat caliper measurements, ultrasound measurements, and three-dimensional imaging (VECTRA M3; Canfield Scientific, Inc., Fairfield, N.J.). Every study that evaluated clinical outcomes using these outcome measures noted a significant reduction in fat volume in treatment areas (Table [3](#T3){ref-type="table"}). Although outcomes varied greatly based on treatment site and study design, average reduction in caliper measurement ranged from 14.67 percent to 28.5 percent. Average reduction by ultrasound ranged from 10.3 percent to 25.5 percent (Table [3](#T3){ref-type="table"}). Three studies evaluated lipid levels and liver function tests (Table [3](#T3){ref-type="table"}).^[@R15]--[@R17]^ No significant impact was noted on lipid levels or liver function tests after cryolipolysis treatments in any study. ###### Reported Reduction in Caliper and Imaging Measurements after Cryolipolysis, Organized by Location  ###### Study Design, Demographics, Methods, Follow-Up, and Final Outcomes from Reviewed Articles  Subjective assessments included both patient satisfaction rates and investigator assessments. In all cases, high satisfaction rates were noted, as demonstrated by posttreatment patient satisfaction surveys.^[@R13],[@R15],[@R16],[@R18]--[@R20]^ Only one of the reviewed studies used a validated survey to assess patient satisfaction.^[@R20]^ A clinically apparent difference was noted by posttreatment investigator assessments.^[@R13],[@R15],[@R16],[@R18],[@R20],[@R21]^ Investigator assessments were based on whether or not there was an appreciable fat reduction. Blinded investigators were able to correctly differentiate between pretreatment and posttreatment images in 89 percent of cases in one study^[@R22]^ and 79 percent of cases in another.^[@R19]^ None of the studies reviewed included investigator assessments that specifically evaluated other factors, such as contour or texture. The effect of posttreatment massage was evaluated in two studies. Sasaki et al. evaluated 5 minutes of posttreatment massage, noting an average fat reduction of 21.5 percent in treated areas by caliper measurement at 6 months.^[@R20]^ Another study by Boey and Wasilenchuk compared patients receiving 2 minutes of posttreatment manual massage to a control group receiving only the standard cryolipolysis treatment.^[@R12]^ At 2 months after treatment, average fat layer reduction was 68 percent greater on the massaged side (12.6 percent on the nonmassaged side versus 21.0 percent on the massaged side, *p* = 0.0007). However, at 4 months, average fat layer reduction was only 44 percent greater on the massaged side (10.3 percent on the nonmassaged side versus 14.9 percent on the massaged side, *p* = 0.1).^[@R12]^ The effect of multiple treatments has also been evaluated. In one study, patients receiving two treatments in the peritrochanteric area yielded an average fat layer reduction of 28.5 percent, compared with 19.7 percent in patients receiving only one treatment (*p* = 0.046).^[@R23]^ The effect of multiple treatments was evaluated on love handles and abdomens of patients in another study demonstrating different outcomes. Although a second treatment yielded a significant decrease in caliper measurements on the abdomen (*p* = 0.020), a statistically significant difference was not produced with a second treatment on the love handles (*p* = 0.084) (Table [3](#T3){ref-type="table"}).^[@R13]^ Histologic outcomes were evaluated in a handful of studies. No evidence of fibrosis was noted in one study.^[@R12]^ Most studies demonstrate an inflammatory response at different stages after cryolipolysis, with inflammatory cell infiltrates peaking at 30 days,^[@R12]^ which led to adipocyte apoptosis.^[@R15]^ Biopsy specimens of peripheral nerve cells showed no long-term changes in peripheral nerves, with equal and normal numbers of epidermal nerves.^[@R21]^ Complications ------------- Common complications noted after cryolipolysis included erythema, bruising, swelling, sensitivity, and pain (Table [4](#T4){ref-type="table"}). These side effects are generally resolved within a few weeks after treatment. No persistent ulcerations, scarring, paresthesias, hematomas, blistering, bleeding, hyperpigmentation or hypopigmentation, or infections have been described. One isolated case report described paradoxical adipose hyperplasia after cryolipolysis treatment.^[@R24]^ ###### Complications and Complication Rates for Cryolipolysis from Reviewed Articles  DISCUSSION ========== Recently, a surge of novel technologies involving noninvasive, energy-based techniques have been introduced to the market, signaling a potential paradigm shift in fat reduction and body contouring practices. The major goal of these novel therapies includes volume reduction of tissue, with a possible end point of noninvasive body contouring.^[@R25]^ With more than 450,000 procedures performed thus far, cryolipolysis is becoming one of the most popular alternatives to liposuction for spot reduction of adipose tissue.^[@R26]^ Because of its ease of use and limited adverse effects, this procedure is becoming the leading technology in noninvasive techniques as well. This review sought to explore the efficacy, methods, safety, and complications of cryolipolysis in the current literature. Although its mechanism is not fully understood, it is believed that vacuum suction with regulated heat extraction impedes blood flow and induces crystallization of the targeted adipose tissue when cryolipolysis is performed.^[@R11],[@R27]^ The temperatures induced in cryolipolysis have no permanent effect on the overlying dermis and epidermis. However, this cold ischemic injury may promote cellular injury in adipose tissue via cellular edema, reduced Na-K-ATPase activity, reduced adenosine triphosphate, elevated lactic acid levels, and mitochondrial free radical release.^[@R20]^ Another mechanism proposes that the initial insult of crystallization and cold ischemic injury induced by cryolipolysis is further compounded by ischemia reperfusion injury, causing generation of reactive oxygen species, elevation of cytosolic calcium levels, and activation of apoptotic pathways.^[@R20]^ Ultimately, crystallization and cold ischemic injury of the targeted adipocytes induce apoptosis of these cells and a pronounced inflammatory response, resulting in their eventual removal from the treatment site within the following several weeks.^[@R7],[@R11],[@R25]^ Histological studies show that within 3 months, macrophages are mostly responsible for clearing the damaged cells and debris.^[@R26],[@R28]^ With the removal of the adipocytes internally, there has been concern that cryolipolysis may cause rising blood lipid levels and elevations in liver enzymes that may put the patient at additional risk, particularly for cardiovascular parameters. However, multiple studies have demonstrated that cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, aspartate transaminase/alanine transaminase, total bilirubin, albumin, and glucose remained within normal limits during and after cryolipolysis.^[@R15]--[@R17]^ With the relatively recent emergence of cryolipolysis, many factors still need to be considered and investigated, including what type of patient would benefit most from this procedure. Ferraro et al. suggested that patients who require only small or moderate amounts of adipose tissue and cellulite removal would benefit most from cryolipolysis treatment.^[@R15]^ Contraindications to cryolipolysis include cold-induced conditions such as cryoglobulinemia, cold urticaria, and paroxysmal cold hemoglobinuria.^[@R29]^ Cryolipolysis should not be performed in treatment areas with severe varicose veins, dermatitis, or other cutaneous lesions.^[@R23],[@R27]^ Although all studies reviewed showed a fat reduction in every area examined, it is still unknown what areas are most responsive to cryolipolysis. Various factors may play a role in the degree of fat reduction observed after cryolipolysis. The vascularity, local cytoarchitecture, and metabolic activity of the specific fat depots in question may play a role. Because of the limited size and number of studies evaluating cryolipolysis in clinical populations, it is unclear which treatment sites are most amenable to cryolipolysis. Future comparative outcome studies should be adequately powered to determine which treatment sites are most suitable for fat reduction with this modality. Because cryolipolysis is still a relatively new procedure, treatment protocols have yet to be optimized to maximize results. Recent studies have focused on maximizing the reduction of adipose tissue by adjusting treatment protocols. Three studies assessed the theoretical enhanced efficacy with multiple treatments in the same anatomic area and demonstrated that a second successive course of cryolipolysis treatment led to further fat reduction.^[@R13],[@R23]^ It is important to note that although a subsequent treatment leads to further fat reduction, the extent of improvement was not as dramatic as the first treatment. Interestingly, one study demonstrated that a second treatment enhanced fat layer reduction in the abdomen area but not the love handles.^[@R13]^ One hypothesis for the diminished effect of the second treatment may be that the fat exposed to the second heat extraction is closer to the muscle layer. The vascular supply to the muscle layer may impede the efficiency of heat extraction so that the fat closer to the muscle layer may not reach the intended optimal temperature of 4°C. Another hypothesis is that adipocytes that survived the first treatment have a higher tolerance to cold. Boey and Wasilenchuk evaluated whether the addition of a posttreatment manual massage enhanced the efficacy of a single cryolipolysis treatment.^[@R12]^ Immediately after treatment, patients received a 2-minute manual massage. This consisted of 1 minute of vigorous kneading of the treated tissue between the thumb and fingers followed by 1 minute of circular massage of the treated tissue against the patient's body. To examine the effects of massage on subcutaneous tissue over time, histological analysis was completed through 4 months after treatment. Although the difference at 2 months after treatment was statistically significant, the difference at 4 months after treatment was not. One hypothesis for potentially improved efficacy with manual massage is that manual massage caused an additional mechanism of damage to the targeted adipose tissue immediately after treatment, perhaps from tissue-reperfusion injury. Histological analysis revealed no evidence of necrosis or fibrosis resulting from the massage, thus showing posttreatment manual massage to be a safe and effective method to further reduce the fat layer after cryolipolysis. Sasaki et al. described cryolipolysis with 5 minutes of posttreatment integrated preset mechanical massage using the device applicator with excellent outcomes.^[@R20]^ A low profile of adverse effects is one of the main advantages with cryolipolysis, especially when compared with more invasive measures. Only mild, short-term side effects, such as erythema, bruising, changes in sensation, and pain, were reported in the studies reviewed. Erythema was noted in multiple studies immediately after the treatment and subsided within a week.^[@R18]--[@R20]^ This is most likely because of the strength of the vacuum and the temperature at which the tissue is kept for extended durations and poses no threat to the patients. Swelling and bruising of the area were shown to a slightly lesser extent than erythema, but are believed to be because of the same processes. These complications also subsided shortly after.^[@R13],[@R16],[@R18],[@R19]^ Hypersensitivity and hyposensitivity were shown in studies but were never debilitating nor persisted beyond 1 month. Coleman et al. demonstrated that patients exhibiting reduction in sensation recovered normal sensation in 3.6 weeks.^[@R21]^ This study also showed that a nerve biopsy taken at 3 months after treatment showed no long-term changes to nerve fibers, concluding that temperature and duration of cryolipolysis have no permanent effect on nervous tissue.^[@R21]^ In one study, pain during the procedure was generally nonexistent to tolerable 96 percent of the time.^[@R18]^ Rare side effects that have been described include vasovagal reaction^[@R18]^ and paradoxical adipose hyperplasia.^[@R24]^ Jalian et al. estimated an incidence of 0.0051 percent, or approximately one in 20,000, for paradoxical adipose hyperplasia.^[@R24]^ Affected patients exhibit fat loss after therapy and then develop a large, demarcated, tender fat mass at the site 2 to 3 months later. The hypothesized pathogenesis includes recruitment of stem cells and hypertrophy of existing fat cells in the area.^[@R24]^ However, compared with traditional liposuction side effects, cryolipolysis poses a minor threat to patients, with a very low incidence of complications. Of note, the reviewed studies used a variety of different modalities to determine the degree of fat reduction after cryolipolysis treatments. Various studies have compared caliper, ultrasound, three-dimensional imaging, and manual tape measurements. Although no single study has compared all of these modalities, the available data suggest that these techniques correlate well with one another.^[@R30],[@R31]^ Studies that used more than one of these modalities to assess outcomes after cryolipolysis also demonstrated that these measurements corresponded well.^[@R19],[@R20]^ A drawback of this work is the limited number of high-quality, prospective, randomized clinical studies. Cryolipolysis was first described in 2007, and although its popularity has increased dramatically, the available literature remains limited. Tremendous variability exists in study design, machinery used, and outcome measures. Because of this lack of uniformity, comparing effect size becomes challenging, and the value of a meta-analysis of the available data is limited. The variations in the available studies make it difficult to control for any bias present in the discussed studies. Despite these limitations, clinical data demonstrate consistent fat reduction in treated subjects, which supports the clinical utility of this technique. CONCLUSIONS =========== This study presents the first systematic review of the available data on cryolipolysis. Although the body of evidence is limited because of the nascence of this procedure, cryolipolysis is a promising procedure for nonsurgical fat reduction and body contouring. While the outcomes of cryolipolysis are rather modest, this technology is well suited for patients who desire nonsurgical spot reduction at modestly sized adiposities. Cryolipolysis appeals to both men and women and is an effective means by which new patients can be drawn to the aesthetic surgery practice.^[@R32]^ Although the specific mechanism of cryolipolysis has not been completely elucidated, this procedure appears to be effective and safe in the short term, with a limited side effect profile. Posttreatment manual massage has the potential to improve the efficacy of cryolipolysis. Multiple treatments in the same anatomic area may lead to further fat reduction, although the efficacy of cryolipolysis appears to be attenuated with successive treatments. The efficacy of this technique in areas that have been treated previously with liposuction remains to be studied. Future studies should address which treatment sites are most amenable to cryolipolysis to enhance treatment stratification for body contouring patients and should evaluate a potential role for cryolipolysis in skin tightening and the treatment of cellulite. **Disclosure:** Gordon H. Sasaki, M.D., is a consultant for ZELTIQ Aesthetics, Inc. (Pleasanton, Calif.). The other authors have no financial interest to declare in relation to any of the products or devices mentioned in this article. No funding was used for the preparation of this article. {#FU1} | Mid | [
0.5743707093821511,
31.375,
23.25
] |
Liu Chengming Liu Chengming (born 20 March 1987) is a Paralympian athlete from China competing mainly in T54 classification sprint events. Athletics career Liu first represented China as a wheelchair racer at the 2010 Asian Para Games in Guangzhou, winning an individual gold in the 400m (T54) and a team gold with the men's 4 × 400 m relay (T53/54). The next year he competed at the 2011 IPC Athletics World Championships in Christchurch, New Zealand. In Christchurch he took two more gold medals, again in the 400m sprint and the men's 4 × 400 m (T53/54). The next year Liu appeared at his first Summer Paralympic, the 2012 Games in London. He was again part of the Chinese team that took gold in the men's 400 metre relay, and also won an individual medal; bronze in the 100m sprint. Further success came at the 2015 World Championships in Doha, with a relay gold and two individual medals a gold in the 800m race and a silver in the 400m sprint. Personal history Liu was born in Chaoyang, China in 1987. When he was six months old Liu contracted polio which resulted in muscle atrophy in his legs. Notes Category:Paralympic athletes of China Category:Athletes (track and field) at the 2012 Summer Paralympics Category:Athletes (track and field) at the 2016 Summer Paralympics Category:Paralympic gold medalists for China Category:Paralympic silver medalists for China Category:Living people Category:1987 births Category:Medalists at the 2012 Summer Paralympics Category:Medalists at the 2016 Summer Paralympics Category:Chinese male sprinters Category:People from Chaoyang, Liaoning Category:Chinese male wheelchair racers Category:Runners from Liaoning | High | [
0.721461187214611,
29.625,
11.4375
] |
Prevalence and burden of bipolar disorders in European countries. A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5-1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5-2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization. | High | [
0.6675977653631281,
29.875,
14.875
] |
SINGAPORE - The revamped Funan mall and office complex will open months ahead of schedule by the second quarter of next year and use facial recognition technology to offer shoppers recommendations. The launch of its co-living serviced residence component lyf Funan, managed by The Ascott, will meanwhile be brought forward from 2020 to the fourth quarter of next year. These were announced by owner CapitaLand Mall Trust on Friday (Sept 28) at a ceremony to mark Funan's structural completion. Finance Minister Heng Swee Keat said at the event that the new Funan mall will be Singapore's first "online and offline mall", powered by an ecosystem of sensors, data analytics and facial recognition tools to better understand consumer shopping habits and preferences. Funan mall will be the first here to use technology such as a smart directory that uses facial recognition to provide shoppers with customised recommendations, said CapitaLand. The mall will have a touch screen directory, equipped with a camera, that can scan the faces of shoppers to sort them into general profiles such as young female and senior male, and recommend stores that target that demographic. The facial recognition function of these directories, which will also be rolled out to other CapitaLand malls, does not capture or store personal data, CapitaLand Retail's chief executive Wilson Tan told The Straits Times on Friday. Related Story New Funan to focus on fun and creativity Related Story Underground walkway will link the new Funan mall to City Hall MRT The new six-storey Funan mall will also utilise video analytics to study shopper traffic and crowd density, which will help CapitaLand to adjust tenant mix and placement. Shoppers will also be able to search for their car in the carpark using a video system that can scan licence plates. The former Funan DigitaLife Mall in North Bridge Road, which closed in July 2016, has been undergoing a $560 million transformation into an integrated development centred on lifestyle, technology, and the arts. About 70 per cent of Funan's retail space has already been leased to tenants such as Golden Village, FairPrice Finest and theatre company Wild Rice. New tenants announced on Friday include foldable bike brand Brompton Bicycle, which will be opening its flagship Singapore store, a farm-to-table restaurant concept by Spa Esprit Group and gaming store GamePro, which will host eSports tournaments in a dedicated eSports zone in the mall. CapitaLand Group's president and group chief executive Lee Chee Koon said that with the growing market share of online sales, brick-and-mortar businesses must go beyond passively selling products and services and create quality retail experiences and emotional connections. "We are taking a close examination of our retail portfolio in Singapore and abroad to identify areas for reinvention," he said. Elaborating on the use of facial recognition technology, Mr Tan said some may choose to have their faces scanned to receive personal recommendations. For instance, CapitaStar loyalty programme members who provide consent may in the future have their faces scanned to receive personal recommendations based on their purchase history. "The idea is that a retailer has a digital screen or wall that can recognise I am a CapitaStar member and have been a previous customer of that store, and the screen will be customised for me," said Mr Tan, who added that facial recognition technology may also be used for entry at Funan's office complex as well as lyf Funan. Other plans for the CapitaStar programme, which has about 920,000 members, include having data captured from receipts provided to members as insights into their spending patterns, he said. | High | [
0.667560321715817,
31.125,
15.5
] |
<UserControl x:Class="Demo.UserControls.UserControl3" xmlns="http://schemas.microsoft.com/winfx/2006/xaml/presentation" xmlns:x="http://schemas.microsoft.com/winfx/2006/xaml" xmlns:mc="http://schemas.openxmlformats.org/markup-compatibility/2006" xmlns:d="http://schemas.microsoft.com/expression/blend/2008" mc:Ignorable="d" d:DesignHeight="300" d:DesignWidth="300"> <Grid Margin="30,10"> <Grid.RowDefinitions> <RowDefinition Height="Auto" /> <RowDefinition Height="Auto" /> <RowDefinition Height="*" /> </Grid.RowDefinitions> <Label Content="{Binding TabName}" FontSize="18" /> <TextBlock Text="{Binding MyStringContent}" Grid.Row="1" Margin="0,0,0,20" TextWrapping="Wrap" /> <Image Source="{Binding MyImageUrl}" Grid.Row="2" Stretch="Uniform" /> </Grid> </UserControl> | Mid | [
0.5862068965517241,
25.5,
18
] |
Cellular cadmium uptake mediated by the transport system for manganese. The mechanism of cellular cadmium (Cd) uptake has been poorly understood. Recently, we developed Cd-resistant cell lines from metallothionein null mouse cells and showed that the Cd resistance of these cells was conferred primarily by a reduced Cd accumulation. Surprisingly, the uptake rate of manganese (Mn) was also markedly reduced in Cd-resistant cells. Subsequent studies on the kinetics of Cd and Mn uptake by Cd-resistant and parental cells revealed that the Mn transport system with high affinity for Mn is used for cellular Cd uptake, and that this pathway is suppressed in Cd-resistant metallothionein null cells. This is the first indication that the transport system for Mn is used for Cd uptake in mammalian cells. Divalent metal transporter 1 (DMT1) is the only known mammalian transporter involved in the uptake of both Cd and Mn. However, the high-affinity Mn/Cd transport system we found seems to be distinct from DMT1 because of the difference in optimal pH and substrate specificity. On the other hand, various types of Mn transporters have been shown to play an important role in cellular Cd uptake in non-mammalian species such as yeast, plants and bacteria, suggesting the existence of Mn transporters other than DMT1 in mammals. | High | [
0.6666666666666661,
33.75,
16.875
] |
Les voyants sont au vert pour la démographie d'entreprises. Selon le dernier bulletin de la Banque de France publié ce mercredi 13 novembre, le nombre de défaillances d'entreprises sur un an a diminué de 0,7% en glissement annuel. À la fin du mois d'août dernier, le nombre cumulé de défaillances sur les douze derniers mois s'établit à 52.893 contre 53.241 en août 2018. D'après des chiffres encore provisoires, le cumul sur les douze derniers mois s'élève à 52.398, soit une baisse de 1,9% entre septembre 2018 et septembre 2019. Des disparités entre les secteurs L'enquête fournie par l'institution bancaire montre que tous les secteurs ne sont pas logés à la même enseigne. L'information-communication (-4,4%), le commerce (-2%), les activités immobilières (-1,9%) et la construction (-1,4%) ont enregistré des baisses par rapport à août 2018. Les défaillances reculent également dans le domaine des conseils et services aux entreprises (-0,8%) et dans l'industrie (-0,2%), pourtant confrontée à une conjoncture très instable. À l'opposé, d'autres secteurs ont connu des périodes plus troublées. Il s'agit des transports (6,6%), des activités financières et d'assurance (4,6%), ou encore de l'enseignement, la santé et les services aux ménages (1,6%). Des défaillances en recul pour les microentreprises Par taille d'entreprise, les défaillances cumulées sur les douze derniers mois sont en recul de 1% pour les microentreprises, à 49.963 contre 50.450 en août 2018. Les entreprises de taille intermédiaires (ETI, entre 250 et 5.000 salariés) et les grandes entreprises ont également connu une baisse de défaillances sur la même période bien plus marquée (-17%). En revanche, les petites et moyennes entreprises (moins de 250 personnes avec un chiffre d'affaires inférieur à 50 millions d'euros) ont enregistré une hausse respective des défaillances de 9% et 18%. Elles sont en légère hausse de 1,3% pour les très petites entreprises (TPE) de moins de 20 salariés qui réalisent moins de 10 millions d'euros de chiffre d'affaires. Une baisse de la croissance à prévoir Malgré ces résultats favorables, la trésorerie des entreprises pourrait connaître des tensions dans les mois à venir. En effet, la plupart des instituts de statistiques anticipent un ralentissement de l'économie en 2020. Lors d'une récente réunion organisée par l'observatoire français des conjonctures économiques (OFCE), la plupart des institutions publiques et privées invitées tablent sur une croissance de 1,2% en 2020 contre 1,3% en 2019 et 1,4% en 2018. "Le consensus s'oriente vers une contribution de la demande intérieure hors stocks à la croissance moins importante qu'en 2019 (en particulier de l'investissement des entreprises non financières et celui des administrations publiques) ainsi qu'une contribution négative du commerce extérieur"explique une note de blog. Outre les nombreuses incertitudes sur la scène internationale, de nombreux économistes s'interrogent sur la consommation à venir des Français. Après avoir connu une hausse importante du pouvoir d'achat en 2019, beaucoup de ménages français ont privilégié l'épargne à la consommation cette année. Pour l'année prochaine, certains conjoncturistes font le pari d'une légère transformation des moteurs de la demande intérieure, passant de l'investissement des entreprises à la consommation des ménages. | High | [
0.6558891454965351,
35.5,
18.625
] |
h1 { @nest a & { <warning descr="Nested ruleset selector should start with '&'">div</warning> { } } } | Low | [
0.44219653179190704,
19.125,
24.125
] |
Q: Vagrantfile for Centos 6 LAMP stack I need assistance putting together a Vagrantfile. I am trying to setup a virtual machine on my Windows desktop for working on an existing PHP/MySQL application. I've been instructed to use Vagrant and VirtualBox. I've been going through the documentation for Vagrant and found this to be over my head with a lot of information out of date. I have some background in general Linux usage, but none in setting up LAMP servers on them. What I have: Vagrant 2.1.2 VirtualBox 5.2.18 Things I need in the VM: Centos 6 Apache MySQL 5.5 PHP 5.6 MySQLi/Mysqlnd (PDO optional) Curl DOM/SimpleXML Any PHP extensions needed for a typical PHP application A: It has taken a few weeks and a lot of wading through out of date tutorials, but I got it done. I am sharing so others on the LAMP service stack have a place to start in crafting their vagrantfile. Note that this was not done for elegance. It is a quick starter that is easy-ish to understand and adjust to one's needs. A few small deviations of note were made from the above original post: I went with Ubuntu/bionic64 instead of Centos 6, mostly because of the abundance of tutorial material I was able to find. Modifying this file for CentOS 6 shouldn't be too hard. CentOS uses Yum instead of Apt-get for package management. I'm not entirely certain what else is different. I went with PHP 7.2 instead of 5.6. I found PHP 7.2 comes with MySQLi and the native driver already installed out of the box. Working vagrantfile and shell bootstrapper included, heavily commented for comprehension: https://pastebin.com/Eqvhq8KZ # -*- mode: ruby -*- # vi: set ft=ruby : VAGRANTFILE_API_VERSION = '2' ######################################################################### # VM Setup for LAMP stack application # # - Install PHP and packages # - Install Apache # - Configure /vagrant as document root # - Config PHP for development and logging # - Install MySQL # - Setup database and permissions (username and password are "vagrant") # - Install Composer ######################################################################### @script = <<SCRIPT #################### PHP #################### apt-get install -y apt-utils php7.2 php7.2-bcmath php7.2-bz2 php7.2-cli php7.2-curl php7.2-intl php7.2-json php7.2-mbstring php7.2-opcache php7.2-soap php7.2-sqlite3 php7.2-xml php7.2-xsl php7.2-zip unzip #################### APACHE2 #################### apt-get install -y apache2 libapache2-mod-php7.2 # Remove /var/www default rm -rf /var/www # Symlink /vagrant to /var/www ln -fs /vagrant /var/www # Add ServerName to httpd.conf echo "ServerName localhost" > /etc/apache2/httpd.conf # Setup hosts file VHOST=$(cat <<EOF <VirtualHost *:80> DocumentRoot "/vagrant" ServerName localhost <Directory "/vagrant"> Options Indexes FollowSymLinks MultiViews Includes AllowOverride All Require all granted Order allow,deny Allow from all AddType text/html .shtm .shtml AddOutputFilter INCLUDES .htm .html .shtm .shtml </Directory> </VirtualHost> EOF ) echo "${VHOST}" > /etc/apache2/sites-enabled/000-default.conf # Enable mod_rewrite a2enmod rewrite # Put PHP into development configuration mv /etc/php/7.2/apache2/php.ini /etc/php/7.2/apache2/php.ini.back cp /usr/lib/php/7.2/php.ini-development /etc/php/7.2/apache2/php.ini # Enable PHP extensions in php.ini #sed -i 's/;extension=mysqli/extension=mysqli/' /etc/php/7.2/apache2/php.ini # PHP will log its errors in a /log/error_log file sed -i 's:;error_log = php_errors.log:error_log = /vagrant/log/error_log:' /etc/php/7.2/apache2/php.ini # Restart apache systemctl restart apache2.service #################### MYSQL #################### apt-get install -y mysql-server mysql-client-core-5.7 php7.2-mysql systemctl start mysql.service # Reset root password #/usr/bin/mysqladmin -u root password 'root' mysqladmin -u root password 'root' # Setup database from root user and setup the application user mysql -uroot -proot -e "CREATE DATABASE IF NOT EXISTS app" mysql -uroot -proot app < /vagrant/db/schema.sql mysql -uroot -proot -e "GRANT ALL PRIVILEGES ON *.* to 'vagrant'@'localhost' IDENTIFIED BY 'vagrant'" mysql -uroot -proot -e "GRANT ALL PRIVILEGES ON *.* to 'vagrant'@'%' IDENTIFIED BY 'vagrant'" mysql -uroot -proot -e "FLUSH PRIVILEGES" # Allow remote connections for MySQL Workbench MYSQLCONF=$(cat <<EOF [mysqld] bind-address = 0.0.0.0 EOF ) echo "${MYSQLCONF}" >> /etc/mysql/my.cnf # Restart mysql /etc/init.d/mysql restart #################### COMPOSER #################### curl -sS http://getcomposer.org/installer | php mv composer.phar /usr/local/bin/composer # Run composer install cd /vagrant && composer install #################### FINISHED! #################### echo "** [PHP] Visit http://localhost:8080 in your browser for to view the application **" SCRIPT Vagrant.configure(VAGRANTFILE_API_VERSION) do |config| config.vm.box = 'ubuntu/bionic64' config.ssh.insert_key = false config.vm.network "forwarded_port", guest: 80, host: 8080 config.vm.network "forwarded_port", guest: 443, host: 8081 config.vm.network "forwarded_port", guest: 3306, host: 3307 #config.vm.synced_folder '.', '/var/www/html' # Provision runs only on the first "Vangrant up" command config.vm.provision 'shell', privileged: true, inline: @script config.vm.provider "virtualbox" do |vb| vb.customize ["modifyvm", :id, "--memory", "2048"] vb.customize ['modifyvm', :id, "--natdnshostresolver1", "on"] end end | Mid | [
0.6497326203208551,
30.375,
16.375
] |
Armageddon adventure aims for authentic thrills, chills Cameron DiVella, of Kent, is celebrating the Halloween season with his new adventure "Undead Armageddon Haunted Forest," located behind the Iron Horse Saloon on Main Market Road in Burton Township. Divella plans to capitalize on the current zombie craze by combining an intense experience with a beautiful location in Geauga County. Freddy Krueger? Forget about it. A drooling Dracula? No way. Don’t expect to find either of these standard scary figures lurking in the shadows at Undead Armageddon, a haunted forest experience set for the upcoming Halloween season in Burton Township. Instead, owner and creator Cameron Divella, who claims that most monster maneuvers are a tad trite, says he wants to ensure that seekers of eerie encounters become “immersed into the Apocalyptic nightmare where the dead have risen.” The Ohio native, who now lives in Florida where he owns a martial arts studio, said he envisioned the idea about three years ago after visiting one too many similar-style haunted houses. “I wanted to see something new, something that hasn’t been done before,” he said. Divella added that he chose to build the cataclysmic attraction in Northeast Ohio because haunted venues during Halloween “are a way of life here.” His main hurdle was finding the right locale. Not everyone owning suitable property was open to the idea. He credits Kathy Holmes, a real estate broker from All Points Realty in Chardon, for helping him land the perfect spot. “I want to take this beautiful property and turn it into an apocalypse,” he said when first eyeing the site. Chris Kanieski, who owns the property along with the Iron Horse Saloon which fronts the forest on Main Market Road, welcomed Divella and the impending “end of the world” adventure. He’ll even be offering zombie-inspired spirits and discounted menu items throughout the run of the event — Sept. 28 through Nov. 2. Earlier this week, carpenters were busy building structures to be erected along freshly cut trails winding through several acres. About $30,000 is being spent on the project. Those choosing to embark on the creepy quest won’t have long to wait before shock value sets in. They’ll be met in the parking lot by … (shh! not all details being revealed here) and escorted through decontamination tents where cringe-inducing revelations await. Divella’s counting on visitors to feel as if they’re part of the action rather than mere observers and plans on accomplishing the feat by treating them as true “survivors.” Undead Armageddon is recommended for ages 12 and older. Those ages 12 through 15 must be accompanied by a parent and identification will be requested from those ages 16 and older. On Fridays and Saturdays, tickets can be purchased from 6 to 10 p.m.; on Sundays from 6 to 9 p.m. A friendlier trek (no zombies) through the forest will be offered for youngsters accompanied by parents from 5 to 6 p.m. Sundays. Cost is $5 for children; free for parents. Children may come in costume and trick-or-treat along the way. Cost of the event is $20 and $2 discount tickets can be found at local outlets.For more details, visit www.undeadohio.com. | Mid | [
0.6103286384976521,
32.5,
20.75
] |
xmlns "http://ballerinalang.org/ns1" ns1; | Low | [
0.45575221238938,
25.75,
30.75
] |
Q: Vectorizing an operation between all pairs of elements in two numpy arrays Given two arrays where each row represents a circle (x, y, r): data = {} data[1] = np.array([[455.108, 97.0478, 0.0122453333], [403.775, 170.558, 0.0138770952], [255.383, 363.815, 0.0179857619]]) data[2] = np.array([[455.103, 97.0473, 0.012041], [210.19, 326.958, 0.0156912857], [455.106, 97.049, 0.0150472381]]) I would like to pull out all of the pairs of circles that are not disjointed. This can be done by: close_data = {} for row1 in data[1]: #loop over first array for row2 in data[2]: #loop over second array condition = ((abs(row1[0]-row2[0]) + abs(row1[1]-row2[1])) < (row1[2]+row2[2])) if condition: #circles overlap if true if tuple(row1) not in close_data.keys(): close_data[tuple(row1)] = [row1, row2] #pull out close data points else: close_data[tuple(row1)].append(row2) for k, v in close_data.iteritems(): print k, v #desired outcome #(455.108, 97.047799999999995, 0.012245333299999999) #[array([ 4.55108000e+02, 9.70478000e+01, 1.22453333e-02]), # array([ 4.55103000e+02, 9.70473000e+01, 1.2040000e-02]), # array([ 4.55106000e+02, 9.70490000e+01, 1.50472381e-02])] However the multiple loops over the arrays are very inefficient for large datasets. Is it possible to vectorize the calculations so I get the advantage of using numpy? A: The most difficult bit is actually getting to your representation of the info. Oh, and I inserted a few squares. If you really don't want Euclidean distances you have to change back. import numpy as np data = {} data[1] = np.array([[455.108, 97.0478, 0.0122453333], [403.775, 170.558, 0.0138770952], [255.383, 363.815, 0.0179857619]]) data[2] = np.array([[455.103, 97.0473, 0.012041], [210.19, 326.958, 0.0156912857], [455.106, 97.049, 0.0150472381]]) d1 = data[1][:, None, :] d2 = data[2][None, :, :] dists2 = ((d1[..., :2] - d2[..., :2])**2).sum(axis = -1) radss2 = (d1[..., 2] + d2[..., 2])**2 inds1, inds2 = np.where(dists2 <= radss2) # translate to your representation: bnds = np.r_[np.searchsorted(inds1, np.arange(3)), len(inds1)] rows = [data[2][inds2[bnds[i]:bnds[i+1]]] for i in range(3)] out = dict([(tuple (data[1][i]), rows[i]) for i in range(3) if rows[i].size > 0]) | Mid | [
0.563002680965147,
26.25,
20.375
] |
1. S.1655 — 108th Congress (2003-2004)A bill to ratify the authority of the Federal Trade Commission to establish the do-not-call registry.Sponsor:Sen. Ensign, John [R-NV] (Introduced 09/25/2003) Cosponsors: (63)Committees:Senate - Commerce, Science, and TransportationLatest Action:09/25/2003 Read twice and referred to the Committee on Commerce, Science, and Transportation. (All Actions)Notes:For further action, see H.R. 3161, which became Public Law 108-82 on 9/29/2003.Tracker: | Mid | [
0.5703125,
27.375,
20.625
] |
/* pages/view/pages/notice-bar/index.wxss */ .container{ display: flex; flex-direction: column } | Low | [
0.32480000000000003,
12.6875,
26.375
] |
In a profile piece on Joanne Chang published this week, the Boston Globe learned the baker and restaurateur has two new projects in the works: She is scouting out locations for a fifth Flour Bakery + Café, and she and husband Christopher Myers, co-owners of Myers + Chang, are “in talks to open a second restaurant … on the Novartis research campus just outside Kendall Square.” While Chang was preparing to open the fourth Flour in Back Bay in 2012, she told Boston magazine that a fifth bakery wasn’t her priority. “If there happens to be another location at some point in the future, that works for our management team and for me, I am certainly not going to rule it out. But it’s not a goal,” she said. In yesterday’s Globe piece, she said the forthcoming location could be somewhere in Harvard Square. The current cafés are in the South End, Central Square in Cambridge, Back Bay, and Fort Point, and Chang’s preferred mode of transportation is bicycle. “I can’t imagine a Flour I couldn’t get to all the time,” she told the Globe. Flour recently opened a commissary kitchen in Allston, which will help the company efficiently continue growing, the Globe reports. About 15 years after opening the first Flour in the South End, Chang said finally created a plan for the company about a year ago. “Until now, it was relatively seat-of-your-pants,” she told the Globe. Among the reasons she has expanded the brand into different neighborhoods is to give her staff growth opportunities within Flour, and she also feels confident in her staff to focus on growing the brand. Chang said. The company “should be something that makes the lives of her customers and staff better,” according to the Globe. Chang credits her husband with having the vision to grow both her brands: “If it weren’t for [Myers], I’d still be living above the first Flour. He’s the one who kind of saw the potential to do more—and encouraged me to think bigger.” In the 2012 interview with Boston, Chang said she and Myers believe their Asian restaurant is “an idea that would do well in other places.” Boston magazine has reached out to Joanne Chang to learn more about her plans for the new venture with Myers. | Mid | [
0.5626373626373621,
32,
24.875
] |
Q: C# LINQ create month and year list I have a collection of flyers with a property FlyerDate as datetime and I want to create a dropdown list with month and year, such "nov 2015, dec 2015, jan 2016"... This is my code: var monthList = flyers.Where(i => i.FlyerDate != DateTime.MinValue && i.FlyerDate.Year >= 2013) .GroupBy(i => i.FlyerDate.Month) .Select(g => new { Month = g.Key, Year = g.First(i => i.FlyerDate != DateTime.MinValue).FlyerDate.Year, FullDate = String.Concat(DateTimeFormatInfo.CurrentInfo.GetMonthName(g.Key), " ", g.First(i => i.FlyerDate != DateTime.MinValue).FlyerDate.Year), Total = g.Count(i => i.FlyerID > 0) } ); I would that the GroupBy works both on month and year as in my case the list contains only the first occurrence of each months. Any hints? A: You need to group by an anonymous type containing both, the year and the month: var monthList = flyers.Where(i => i.FlyerDate.Year >= 2013) .GroupBy(i => new { i.FlyerDate.Year, i.FlyerDate.Month }) .Select(g => new { Year = g.Key.Year, Month = g.Key.Month, FullDate = DateTimeFormatInfo.CurrentInfo.GetMonthName(g.Key.Month) + " " + g.Key.Year }); Btw, if you want the abbreviated month-name as your desired result suggests you need to use DateTimeFormatInfo.CurrentInfo.GetAbbreviatedMonthName instead of GetMonthName. | High | [
0.692771084337349,
28.75,
12.75
] |
There has been a great deal of interest in recent years in the use of bio-oxidation to recover metals from sulfide ores. In such ores, the sulfides trap, or occlude, the metal particles within sulfide minerals, such as iron pyrite for example. The bio-oxidation techniques use natural microorganisms to catalyze the oxidation of sulfides in the ore into soluble sulfates, in order to adequately expose the metal in the ore for subsequent extraction. Typical metals which may be recovered in this way include gold, silver, copper, zinc, nickel or cobalt. In recent years, the gold industry has shown a particular interest in the use of bio-oxidation techniques for the recovery of gold, in large part because of the high value of gold. The primary goal of the gold mining industry is cost-effective recovery of gold from ore, and the most commonly used techniques for gold recovery from ore are smelting and cyanidation. However, a great deal of ore is to be found in ore which is naturally resistant to conventional recovery techniques. Such ore is called “refractory,” and usually contains gold particles which are locked, or occluded, within sulfide minerals. To obtain adequate gold recovery from such refractory ore, the ore must first be subjected to a pre-treatment process in which the sulfide minerals are degraded by oxidation. The ore may then be treated by a traditional reagent such as cyanide to dissolve the gold, in order to recover the gold from the treated ore. Such bio-oxidation techniques are particularly useful for pre-treatment of mine tailings, which are the byproducts of mining operations. Not only does this allow gold extraction from highly refractory ores, but it provides the added benefit of removing a barrier to redevelopment and a potential environmental hazard. Bio-oxidation is particularly well suited to the pre-treatment of tailings, as the low gold concentrations found in such tailings are not a problem for the microorganisms involved. The microorganisms simply ignore the waste products in the ore, and proceed to oxidize the sulfides surrounding the gold, often resulting in ultimate extraction recoveries not achievable by other methods One method of bio-oxidation used to pre-treat sulfide-refractory gold ores is heap bio-oxidation, which is described in U.S. Pat. No. 5,246,486 to Brierley et al. In this method, coarsely ground (P80>¼″)1 refractory ores are first agglomerated while being inoculated with a microorganism slurry, then heaped onto a leach pad with aeration and drain lines. This is referred to as a “free-drained” system; i.e., one in which there is no water table within the bed, no part of the bed is flooded, and the water leaves the system drained by gravity. Initially the inoculum is grown in a tank, but after the heap oxidation process matures, the solution draining from the heap contains the organisms and is used as the inoculum. The bio-oxidation continues until the predetermined target level of sulfide oxidation has been achieved. The ongoing sulfide oxidation levels are determined by the analysis of sulfate concentration in the bioreactor effluent solution and the bioreactor effluent cumulative mass flow. Once the bio-oxidation is complete, the ore is removed from the pad and lime is added to neutralize the ore. This makes the microorganisms in the ore become dormant, and also conditions the bio-oxidized ore for cyanide leaching to extract the gold. 1“P80” is a commonly used abbreviation in the mining industry, and means that 80% of the ore particles are finer than the specified size—in this case, ¼ inch. Heap bio-oxidation can permit ultimate gold recoveries in the range of 60-70% from refractory ore. In addition, it uses inexpensive pond liners and allows air addition via high-volume blowers, which are relatively efficient and low-cost. However, heap bio-oxidation suffers from certain inefficiencies, primarily due to the large particle sizes, typically with a P80 of approximately ½ inch and no finer than a P80 of ¼ inch, with −150 [Tyler] mesh2 (106 microns) fines totaling less than 10% by weight of the total ore (expressed in the industry as P80=¼″, <10% −150 mesh). This large particle size causes “channeling,” in which water and solution seek large gaps between particles, and thus tend to flow by the ore without making substantial contact. To counter this channeling effect, a relatively high solution application rate is utilized in order to maintain contact with the ore. However, such high solution application rates result in a relatively thick layer of solution around each ore particle which impedes air flow through the heap, so that the oxidation rate is significantly slowed. 2A minus sign in front of a size designator, such as mesh or microns, followed by a percentage, is a standard abbreviation used in the mining industry to indicate that the specified percentage of the ore particles are finer than the specified size. In this case, the abbreviation is used to signify that less than 10% of the particles are smaller than 150 mesh (106 microns). Further, it has long been known that the more finely ground an ore, the more efficiently it may be oxidized and the higher the ultimate gold recoveries would be in the subsequent gold recovery process. This is because as a given quantity of ore is ground into smaller particles, the overall surface area of that quantity of ore is increased. Since an increased surface area increases the contact with the oxidizing solutions, the oxidation proceeds at a faster rate, and is also more complete. However, a great deal of experience with heap leach gold cyanidation led to the conclusion that particle sizes less than P80=¼ inch tended to migrate through the heap, until ultimately they bind together into a clay-like mass, thereby “plugging” the flow of both solution and air through the heap. Since such plugging would render the heap bio-oxidation extremely inefficient, no use of particle sizes smaller than P 80=¼ inch has traditionally been attempted. Unfortunately, this perceived inability of heap bio-oxidation to utilize smaller particle sizes has greatly limited the efficiency and thoroughness of the oxidation achievable with the process. Notably, the typical 60-70% overall gold recovery could potentially be significantly higher if the oxidation were more thorough. In addition, the time for completing the heap bio-oxidation process is typically in the range of 180-360 days, thereby adding substantially to the heap bio-oxidation capital and operating costs. This heap retention time could also potentially be greatly reduced, if smaller particles could be accommodated by the heap bio-oxidation process. One attempted solution to the above-mentioned problems with heap bio-oxidation has been agitated tank bio-oxidation. Agitated tank bio-oxidation is an alternative to heap bio-oxidation which allows for the utilization of much smaller particles (<100 microns). In this process, large quantities of oxygen and carbon dioxide are dissolved into a finely ground slurry of ore. Plugging problems which might otherwise be associated with such fine particles are avoided by utilizing a mechanically agitated tank to house the process. While such tanks are an effective way to allow very fine particles to be used in the process, they are highly expensive to purchase and to operate, and thus add greatly to the cost of the oxidation. Air addition into the agitated tank is also expensive and difficult to achieve, as the air must be added as extremely fine bubbles, and under sufficient pressure to overcome the pressure associated with the solution depth of the flooded tank. In addition to being costly, the air addition and the tank agitation render the whole process much more complex than traditional heap bio-oxidation. Ultimately, agitated tank bio-oxidation typically results in an accelerated retention time of 5-8 days, with an overall ultimate gold recovery of 85-90%. There is thus a need for a pre-treatment bio-oxidation process for refractory gold ore which would allow significantly smaller particle distributions to be utilized, thereby greatly improving overall gold recovery and shortening bio-oxidation retention times. Ideally, the process would utilize a free-drained system, and thus would avoid the cost and complexity of agitated tank bio-oxidation. | Mid | [
0.6405867970660141,
32.75,
18.375
] |
UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas. The UbcH10 gene codes for a protein that belongs to the ubiquitin-conjugating enzyme family. Previous studies of our group suggest UbcH10 expression as a valid indicator of the proliferative and aggressive status of thyroid carcinomas. Therefore, to better understand the process of ovarian carcinogenesis, and to look for possible tools to be used as prognostic markers in these neoplasias, we decided to extend the analysis of the UbcH10 expression to the ovarian neoplastic disease. We found that the UbcH10 gene was upregulated in some ovarian carcinoma cell lines analysed. Then, immunohistochemical studies demonstrate that UbcH10 expression significantly correlates with the tumor grade and the undifferentiated histotype of the ovarian carcinomas. Furthermore, a significant relationship between UbcH10 expression and overall survival was observed. Finally, the block of UbcH10 protein synthesis by RNA interference inhibited the growth of ovarian carcinoma cell lines, suggesting a role of UbcH10 overexpression in ovarian carcinogenesis. Therefore, all these data taken together suggest the possibility to use UbcH10 detection as a marker for the diagnosis and prognosis of these neoplastic diseases and open the perspective of a therapy of some ovarian carcinomas based on the suppression of the UbcH10 synthesis and/or function. | High | [
0.6749379652605461,
34,
16.375
] |
This invention relates generally to pressure regulating devices for use with irrigation equipment and, more particularly, to a device for regulating the downstream pressure of a remotely controlled water supply valve. As is well known in the art, it is highly desirable for an irrigation sprinkler, or other irrigation equipment such as a trickle irrigation emitter, to be supplied with water at a constant predetermined pressure. In this way, the irrigation device can be operated at a pressure which provides optimum performance and efficiency and the user of the device can accurately plan and control the amount of irrigation water applied. One way in which this has been accomplished is by providing a pressure regulator adjacent the inlet of each sprinkler. Naturally, this arrangement accomplishes the desired result, but the expense of providing and maintaining a separate pressure regulator for each sprinkler may not be justified by the advantages gained. Another method for regulating the pressure supplied to irrigation devices is to interpose a pressure regulator in the supply line to the devices immediately downstream of the remotely controlled valve. Although this method also functions satisfactorily, the pressure regulator must be relatively large in order to conduct the large volume of water supplied to several irrigation devices, and again, the expense of providing and maintaining a larger number of such pressure regulators can be prohibitive. Accordingly, there has existed a need for a convenient and effective device for regulating the pressure supplied to an irrigation device, such as a conventional sprinkler or a trickle irrigation emitter, which is relatively inexpensive to manufacture and can be adapted for use with conventional remotely controlled supply valves. As will become apparent from the following, the present invention satisfies that need. | Mid | [
0.6509635974304061,
38,
20.375
] |
488 S.W.2d 50 (1972) The CONTINENTAL INSURANCE COMPANY et al., Appellants, v. CITY OF KNOXVILLE, Appellee. Supreme Court of Tennessee. November 20, 1972. *51 Jerry A. Farmer, Knoxville, for appellants; Poore, Cox, Baker, McAuley, Ray & Byrne, Knoxville, of counsel. Norman B. Jackson, Knoxville, for appellee; Marsh, Thompson & Jackson, Knoxville, of counsel. OPINION CHATTIN, Justice. This appeal is from a decree of the Chancellor awarding indemnity against appellants in favor of the appellee. The facts were stipulated. On March 22, 1967, Mrs. Martha B. Rose sustained personal injuries when she tripped and fell on a metal trapdoor located in the sidewalk at 304 Wall Avenue in the City of Knoxville. The trapdoor constituted a part of the sidewalk and protruded above it. The trapdoor provided access to the basement of the building located at 304 Wall Avenue, and had been installed for the exclusive benefit of the building. At the time of the accident the building was under a lease to Leasing Company No. 1, Inc., from the owners of same. Mrs. Rose and her husband filed suit in Circuit Court against the City and Leasing in November 1967. For the consideration of payment to them of $4,250.00, they gave Leasing a covenant not to sue and dismissed the suit as to Leasing. As a result of the trial, Mrs. Rose was awarded damages in the amount of $10,000.00 and Mr. Rose the sum of $5,000.00. The trial judge suggested a remittitur of $2,500.00 in each case, which was accepted. Thereafter, the City made a motion for a reduction of judgment pursuant to the provisions of T.C.A. 23-3105, a part of the Uniform Contribution Among Tort-Feasors Act. The motion sought a credit of the $4,250.00 paid by Leasing against the judgment against the City. The trial judge overruled the motion on the ground it came too late since it was made after the motion for a new trial. The parties appealed. The Court of Appeals restored the amount of Mrs. Rose's remittitur and then deducted the $4,250.00 paid for the covenant not to sue from the judgments by sustaining the City's assignment of error the trial judge erred in refusing to grant its motion for a reduction in judgment. One-fifth of the $4,250.00 was deducted from Mr. Rose's judgment of $2,500.00 and four-fifths from Mrs. Rose's judgment of $10,000.00. It was stipulated that Leasing surrendered its charter on February 15, 1968; and that pursuant to T.C.A. 48-516 trustees were appointed to hold the assets of the corporation for the benefit of its creditors and stockholders. As a result of the judgments recovered by Mr. and Mrs. Rose against the City, this suit was instituted against Leasing, the named trustees and Continental Insurance Company, the public liability insurance carrier for Leasing at the time of the accident, for indemnity or in the alternative contribution. The Chancellor found the City entitled to indemnity. Appellants have perfected an appeal and assigned five alleged errors. We will consider the first two assignments jointly. The first assignment insists the Chancellor erred as a matter of law in overruling Continental's demurrer on the ground no cause of action had been stated against it. The second assignment contends the Chancellor erred as a matter of law in overruling Leasing's demurrer on the ground its corporate existence was dissolved and liquidated on February 15, 1968, and it was not subject to suit. We disagree. The pertinent statute at the time of *52 the dissolution was T.C.A. Section 48-514, which provides: "The filing of said certificate in the office of the secretary of state shall operate as a surrender to the state by the corporation of all its corporate franchises and privileges, and shall have effect to annul the charter of said corporation, and its right to continue the corporate business shall thereupon cease and determine; provided, however, that the rights of the creditors of said corporation to the satisfaction of their debts out of the corporate assets shall not be prejudiced thereby; and provided, also, that the corporation shall continue to exist for the purpose of winding up its affairs so long as may be necessary for that purpose, but no longer, or otherwise." This statute operates to prolong the life of the corporation until its corporate affairs are completed. Leasing existed for the purpose of this suit, notwithstanding its charter had been surrendered. The statute makes it clear a corporation may not avoid its obligations by simply dissolving. Although trustees were appointed to wind up the corporate affairs, they act in the place and stead of the board of directors and officers of the corporation, it was not a duplication of parties. The corporation was in existence for the purpose of liquidating its affairs. The second assignment of error is overruled. It is argued in support of the first assignment by Continental that only a party to the insurance policy can institute an action on it. Therefore, it is argued this suit is a direct action by the City for the alleged failure of Continental to perform its obligation under the policy, although the City was not a party or a third party beneficiary thereunder. We must disagree with this argument. This suit is not a direct action against Continental to perform its obligation under its policy. The parties stipulated and the Chancellor found the insurance policy was an asset of Leasing. The action is by a party secondarily liable to recover indemnity from the assets of the party (Leasing) primarily liable for the same obligation. The assignment is overruled. We will consider the third and fifth assignments together. The third assignment insists the Chancellor erred, as a matter of law, in overruling the demurrers of each appellant on the ground the City is not entitled to recover indemnity after having accepted a reduction of judgment pursuant to T.C.A. Section 23-3105 in the original suits of Mr. and Mrs. Rose. The fifth assignment contends the Chancellor erred, as a matter of law, in finding the City was not estopped from seeking indemnity in this action because of its acceptance and reliance upon the Uniform Contribution Among Tort-Feasors Act in the original suits. As hereinabove stated, the Court of Appeals allowed the City's motion for a reduction of the judgments in the original suits. Appellants argue since there was a reduction of the judgments, the City should be estopped from recovering indemnity. We agree with the Chancellor there is no evidence in the record to indicate appellants relied to their detriment on the action taken by the City; and that a good argument exists that the City was required, in order to mitigate damages, to seek reduction of the judgments in the amount paid by Leasing for the covenant not to sue. Had the City paid the entire judgment of $12,500.00 and obtained indemnity of that amount, the Roses would have been the beneficiaries of a windfall of $4,250.00 which would be unjust. *53 Since the City obtained only partial relief because of the reduction of the judgments, there is no reason to prevent it from recovering complete relief by way of indemnity. Secondly, the Uniform Contribution Among Tort-Feasors Act provides in part: "This chapter does not impair any right of indemnity under existing law." T.C.A. Section 23-3102(f) * * * "When a release or covenant not to sue or not to enforce judgment is given in good faith to one (1) or two (2) or more persons liable in tort for the same injury or the same wrongful death; * * * * * * (b) It discharges the tort-feasor to whom it is given from all liability for contribution to any other tort-feasor." T.C.A. Section 23-3105. The foregoing makes it clear the relief afforded under the Uniform Contribution Among Tort-Feasors Act does not estop the party afforded the relief from later enforcing a right of indemnity. Both assignments are overruled. Appellants' fourth assignment of error contends the Chancellor erred, as a matter of law, in finding the City is entitled to indemnity under the record. In Southern Coal and Coke Co. v. Beech Grove Mining Co., 53 Tenn. App. 108, 381 S.W.2d 299 (1963), the Court said: "* * * a person who, in whole or in part, has discharged a duty which is owed by him but which as between himself and another should have been discharged by the other is entitled to indemnity from the other, unless the payor is barred by the wrongful nature of his conduct." While the courts of this State have generally made a determination as to whether or not the one seeking indemnity was guilty of active negligence, the rule seems to be that only one guilty of passive rather than active negligence can recover indemnity. Cohen v. Noel, 165 Tenn. 600, 56 S.W.2d 744 (1933); Graham v. Miller, 182 Tenn. 434, 187 S.W.2d 622 (1944). The Chancellor took note of this rule in his memorandum opinion, but properly went beyond it due to the particular circumstances of this case. He said: "I think that there was a distinction of active and passive negligence here, if that is necessary for the quantum to give the city the right to recover under the indemnity. But I would hold, regardless of the active and passive question, that inasmuch as the trapdoor and the manner in which it caused the injury was for the exclusive benefit of the landowner, that as between the two that should put the burden of indemnifying the city upon the landowners." We think legal justification, as well as logic, exists for concurring with the Chancellor and that the primary responsibility should not be placed upon the City under the particular facts of this case. In determining the primary responsibility in this case, the following ordinances of the City are pertinent: "It shall be the duty of the abutting property owner or agent of any house or property to maintain or repair sidewalks or driveways adjoining the property." Knoxville City Ordinance, Section 36-6. "All cellar doors upon any of the streets, parks, or squares of the city shall be of strong material, and be uniform and flush with the pavement or sidewalk." Knoxville City Ordinance, Section 36-66. The City contends the ordinances are sufficient to effectively impose the primary responsibility for the maintenance of the *54 trapdoor on Leasing. However, the appellants cite numerous cases which state the primary responsibility for safe streets rests with the municipality and this duty cannot be shifted by ordinance to the abutting landowners. Harbin v. Smith, 168 Tenn. 112, 76 S.W.2d 107 (1934); Hale v. City of Knoxville, 189 Tenn. 491, 226 S.W.2d 265 (1949); City of Knoxville v. Ferguson, 34 Tenn. App. 585, 241 S.W.2d 612 (1951); City of Winchester v. Finchum, 201 Tenn. 604, 301 S.W.2d 341 (1957). We are of the opinion all these cases are inapplicable under the facts of this case. Since the artificial structure, a trapdoor, was placed in the sidewalk exclusively for the benefit of the abutting landowner and not the City, it is only just that the City be reimbursed. This is not an attempt to burden the abutting landowner with the responsibility of general repairs; the abutting landowner's burden here is only for that which exists exclusively for his benefit, the trapdoor. This is in accordance with the general rule as stated in 39 Am.Jur.2d, Highways, Streets, and Bridges, Section 383, page 777: "Where an adjoining property owner, for the exclusive benefit of his own property, places in a public street or sidewalk some artificial structure and the public authority is compelled to pay compensation in damages to a member of the public injured thereby, the public authority may recover the amount so paid from the property owner by way of indemnity." Accordingly, we overrule the fourth assignment of error. The decree of the Chancellor is affirmed. Appellants will pay the costs. DYER, C.J., HUMPHREYS and McCANLESS, JJ., and WILSON, Special Judge, concur. | Low | [
0.527649769585253,
28.625,
25.625
] |
Login using You can login by using one of your existing accounts. We will be provided with an authorization token (please note: passwords are not shared with us) and will sync your accounts for you. This means that you will not need to remember your user name and password in the future and you will be able to login with the account you choose to sync, with the click of a button. It is of great importance to identify quantitative trait loci (QTL) controlling fiber quality traits and yield components for future marker-assisted selection (MAS) and candidate gene function identifications. In this study, two kinds of traits in 231 F6:8 recombinant inbred lines (RILs), derived from an intraspecific cross between Xinluzao24, a cultivar with elite fiber quality, and Lumianyan28, a cultivar with wide adaptability and high yield potential, were measured in nine environments. This RIL population was genotyped by 122 SSR and 4729 SNP markers, which were also used to construct the genetic map. The map covered 2477.99 cM of hirsutum genome, with an average marker interval of 0.51 cM between adjacent markers. As a result, a total of 134 QTLs for fiber quality traits and 122 QTLs for yield components were detected, with 2.18–24.45 and 1.68–28.27% proportions of the phenotypic variance explained by each QTL, respectively. Among these QTLs, 57 were detected in at least two environments, named stable QTLs. A total of 209 and 139 quantitative trait nucleotides (QTNs) were associated with fiber quality traits and yield components by four multilocus genome-wide association studies methods, respectively. Among these QTNs, 74 were detected by at least two algorithms or in two environments. The candidate genes harbored by 57 stable QTLs were compared with the ones associated with QTN, and 35 common candidate genes were found. Among these common candidate genes, four were possibly “pleiotropic.” This study provided important information for MAS and candidate gene functional studies. Introduction Cotton is an important cash crop that provides major natural fiber supply for textile industry and human daily life. Four species in Gossypium, namely G. herbaceum (A1), G. arboreum (A2), G. hirsutum (AD1), and G. barbadense (AD2), are cultivated ones. G. hirsutum (2n = 4x = 52, genome size: 2.5 Gb) (Li et al., 2014, 2015; Wendel and Grover, 2015; Zhang et al., 2015), also called upland cotton, has a high yield potential, whereas fair fiber quality attributes (Cai et al., 2014), thus making it most widely cultivated and utilized worldwide, approximately accounting for 95% of global cotton fiber production (Chen et al., 2007). Along with the progress of technologies in textile industry and improvement of human living standard, the demand for cotton fiber supply not only increases in quantity but also is required in a diverse combination of various qualities such as high strength, natural color, various lengths, and fineness. Fiber quality traits and yield components are quantitative and controlled by multiple genes (Said et al., 2013), yet most of which were negatively correlated with each other (Shen et al., 2007; Wang H. et al., 2015). Therefore, it is difficult to improve all these traits simultaneously by traditional breeding programs, even after time-consuming and laborious efforts were put (Shen et al., 2005; Lacape et al., 2009; Jamshed et al., 2016; Zhang et al., 2016). The rapid development of applied genome research provides an effective tool for improving plant breeding efficiency, a typical example of which is the marker-assisted selection (MAS) and genome selection through the molecular markers closely linked to target genes or quantitative trait loci (QTLs). Materials and Methods Plant Materials An RIL population of 231 lines was developed from a cross between two homozygous upland cotton cultivars, Lumianyan28 (LMY28), a commercial transgenic cultivar with high yield potential and wide adaptability developed by the Cotton Research Center of Shandong Academy of Agricultural Sciences as a maternal line, and Xinluzao24 (XLZ24), a high fiber quality upland cotton cultivar with long-staple developed by XinJiang KangDi company as a paternal line. The RIL development was briefed as follows: the cross between LMY28 and XLZ24 was made in the summer growing season in 2008 in Anyang, Henan Province. F1 were planted and self-pollinated in the winter growing season in 2008 in Hainan Province. In the spring of 2009, 238 F2 plants were grown and self-pollinated, and F2:3 seeds were harvested in Anyang (Kong et al., 2011). Of the 238 F2:3 lines, 231 were self-pollinated in each generation until F2:6. Then single plant selection was made from each of the 231 F2:6 lines to form the F6:7 population. The F6:7 population was planted in plant rows and self-pollinated to construct the F6:8 RIL population. All the generations beyond F6:8 are regarded as F6:8 for convenience of analysis. The target traits of the F6:8 RIL population were evaluated in Henan (Anyang, 2013, 2014, 2015, and 2016, designated as 13AY, 14AY, 15AY, and 16AY, respectively), Shandong (LinQing, 2013 and 2014, designated as 13LQ and 14LQ, respectively), Hebei (Quzhou 2013, designated as 13QZ), and Xinjiang (Kuerle 2014 and Alaer 2015, designated as 14KEL and 15ALE, respectively), and a randomized complete block design with two replications was adopted in all nine environmental evaluations. A single-row plot with 5-m row length, 0.8-m row spacing, and 0.25-m plant spacing was adopted in 13AY, 13LQ, 13QZ, 14AY, 14LQ, 15AY, and 16AY, whereas a two-narrow-row plot with 3-m row length, 0.66/0.10-m alternating row spacing, and 0.12-m plant spacing were adopted in 14KEL and 15ALE. One-way analysis of variance (ANOVA) between parents and the descriptive statistics for the RIL population was conducted using Microsoft Excel 2016, and correlation analysis was performed using SPSS 20.0 (SPSS, Chicago, IL, United States). Integrated ANOVA across nine environments along with the heritability of all the traits was conducted using ANOVA function in the QTL IciMapping software. DNA Extraction and Genotyping Genomic DNA was extracted from fresh leaves of parents and 231 RILs with a modified cetyltrimethyl ammonium bromide (CTAB) method (Song et al., 1998). The DNA was used both for SSR screening and CottonSNP80K array hybridization. A total of 9668 pairs of SSR primer pool, which contained a variety of sources including NAU, BNL, DPL, CGR, PGML, SWU, and CCRI, were used to screen the polymorphisms between parents. The primer information was also available at the CottonGen Database1. PCR amplification and product detection were conducted according to the procedures described by Zhang et al. (2005). The polymorphic primers between the parents were used to genotype the population, and the SSR markers that were codominant and had a unique physical location in the reference genome were used to construct the linkage map. The cottonSNP80K array, which contained 77,774 SNPs (Cai et al., 2017), was used to genotype the parents and the 231 RILs. The genotyping was conducted according to the Illumina suggestions (Illumina Inc., San Diego, CA, United States) (Cai et al., 2017). After genotyping, the raw data were filtered based on the following criteria (Zhang Z. et al., 2017): first, any or both of the SNP loci of parents were missing (69,395 SNPs were remained after filtering); second, the loci had no polymorphism between parents (15,128 loci were remained); third, the loci of any of the parent were heterozygous (7480 SNPs were remained); forth, the missing rate of SNPs in the population was more than 40% (Hulse-Kemp et al., 2015) (7479 loci were remained); and finally, the segregation distortion of SNPs reached criteria of P < 0.001 (5202 loci were remained). Subsequently, the remaining SNP markers were applied to the genetic map construction after converting into the “ABH” data format as SSR. Genetic Map Construction The remaining SSR and SNP markers were divided into the 26 chromosomes based on their position on the physical map of the upland cotton (TM-1) genome database (Zhang et al., 2015). Then, the genetic linkage map was constructed using the HighMap software with multiple sorting and error-correcting functions (Liu et al., 2014). Map distances were estimated using Kosambi’s mapping function (Kosambi, 1943). The significance of segregation distortion markers (SDMs; P < 0.05) was detected using the chi-square test. The regions containing at least three consecutive SDMs were defined as segregation distortion regions (SDRs) (Zhang et al., 2016). The distribution of SDMs and SDRs, and the size of SDRs on the map were analyzed. QTL Mapping and Genome-Wide Association Studies The Windows QTL Cartographer 2.5 software (Wang et al., 2012) was employed using the CIM method with a mapping step of 1.0 cM and five control markers (Zeng, 1994) for QTL identification. The threshold value of the logarithm of odds (LOD) was calculated by 1000 permutations at the 0.05 significance level. QTLs, identified in different environments and had fully or partially overlapping confidence intervals, were regarded as the same QTL. The QTL detected in at least two environments was regarded as a stable one. Nomenclature of QTL was designated following Sun’s description (Sun F.D. et al., 2012). MapChart 2.3 (Voorrips, 2002) was used to graphically represent the genetic map and QTL. Quantitative trait nucleotides for the target traits were identified by four multilocus GWAS methods. The first one is mrMLM (Wang et al., 2016), in which calculate Kinship (K) matrix model was used, with critical P-value of 0.01, search radius of the candidate gene of 20 kb, and critical LOD score for significant QTN of 3. The second one is FASTmrEMMA (Wen et al., 2017), with restricted maximum likelihood, in which calculate K matrix model was used, critical P-value of 0.005, and critical LOD score for significant QTN of 3. The third one is ISIS EM-BLASSO (Tamba et al., 2017), with critical P-value of 0.01. The fourth one is pLARmEB (Zhang J. et al., 2017); each chromosome selected 50 potential associations at a critical LOD score of 2 with variable selection through LAR. QTL Congruency Comparison With Previous Studies Previous QTLs for the target traits were detected and downloaded in the CottonQTLdb database2 (Said et al., 2015). The QTLs sharing similar genetic positions (spacing distance < 15 cM) were regarded as common or same QTL. The physical positions of a QTL were identified in the CottonGen database3. When a QTL in the current study shared the same physical region as the previous QTL, it was regarded as a repeated identification of the previous QTL; otherwise, the QTL in the current study was regarded as a new one. The Candidate Genes Identification Candidate genes harbored in the stable QTLs were searched and identified based on their confidence intervals in the following steps: The markers including the closest flanking ones in the confidence interval of a QTL were identified. The physical interval of that QTL was determined based on the physical position of its markers in the upland cotton (TM-1) genome4 (Zhang et al., 2015). All the genes in the physical interval were identified as candidate genes. Candidate genes associated with QTNs in the multilocus GWAS analysis were confirmed based on the location of QTNs in the upland cotton (TM-1) reference genome (Zhang et al., 2015). The gene in which the QTL was located was considered as the candidate gene. But when the physical location of a QTN was between two genes, both of the genes were considered as candidate genes. Results Phenotypic Evaluation of the RIL Populations The one-way ANOVA between parents in nine environments showed that a significant difference for FS at the 0.001 level and no significant differences for the other traits were observed (Table 1). The descriptive statistical analysis showed that all traits in the RIL population performed transgressive segregations, with approximately normal distribution in all the nine environments (Table 1). The integrated ANOVA of the RILs across nine environments also revealed significant variations for all traits among the RILs (Supplementary Table S1). TABLE 1 TABLE 1. The results of the statistical analysis of the parents and the RIL population. Most of the traits exhibited medium–high heritability across nine environments (Supplementary Table S2). Correlation analysis showed that significant or very significant positive correlations were observed between the trait pairs of FL–FS, FL–SI, FS–SI, FM–LP, FM–BW, and SI–BW; and significant negative correlations were observed between the pairs of FL–FM, FL–LP, FS–FM, FS–LP, BW–LP, and SI–LP. In addition, FL–BW showed a significant or very significant positive correlation in three environments, whereas no significant correlation was observed in the remaining six environments (Table 2). Genetic Map Construction The genetic linkage map totally covered 2477.99 cM of the upland cotton genome with an average adjacent marker interval of 0.51 cM (Figure 1 and Table 3). It contained 4851 markers, including 4729 SNP and 122 SSR loci, with uneven distributions in the At and Dt subgenomes as well as on 26 chromosomes. A total of 3300 markers were mapped in the At subgenome, covering a genetic distance of 1474.63 cM with an average adjacent marker interval of 0.45 cM. On the other hand, a total of 1551 markers were mapped in the Dt subgenome, covering a genetic distance of 1003.36 cM with an average adjacent marker interval of 0.65 cM. At the chromosome level, chr08 contained the maximum number of markers (481 markers), spanning a genetic distance of 142.55 cM with an average adjacent marker interval of 0.32 cM. chr17 contained the minimum number of markers (19 markers), spanning a total genetic distance of 60.60 cM with an average adjacent marker interval of 3.56 cM. Gap analysis revealed that there were 33 gaps (≥10 cM), of which 19 were in the At subgenome with the largest of 22.68 cM on chr07, whereas 14 were in the Dt subgenome with the largest of 42.23 cM on chr17. chr11, chr16, chr19, chr20 and chr24 had no gap larger than 10 cM. Segregation Distortion There were a total of 1,563 SDMs (32.22%) (P < 0.05), which were unevenly distributed at both subgenome and chromosome levels (Tables 3 and Supplementary Table S3). One thousand and sixty-one SDMs were found in the At subgenome, whereas 502 in the Dt subgenome. chr08 had the maximum number of SDMs of 237 (15.16% of total SDMs). The SDMs formed 110 SDRs, of which 66 were in the At subgenome whereas 44 in the Dt subgenome. chr05 contained the maximum number of SDRs of 10. There was no SDR in chr03 and chr17. Collinearity Analysis The reliability of the genetic map was usually assessed by comparing it with the physical maps of the upland cotton (TM-1) reference genome (Zhang et al., 2015). The results of the collinear analysis are shown in Figure 2. The results revealed an overall good congruency between the linkage map and its physical one, while there also existed some discrepancies between the two on chr03, chr06, chr08, and chr13 in the At subgenome and on chr15, chr16, chr17, chr19, chr22, chr23, and chr26 in the Dt subgenome. The collinearity in subgenomes revealed that the At subgenome showed a better compatibility between the linkage and the physical maps than the Dt subgenome did. FIGURE 2 FIGURE 2. Collinearity between the genetic map (left) and the physical map (right). At, collinearity of the At subgenome; Dt, collinearity of the Dt subgenome. QTL Mapping for Fiber Quality Traits and Yield Components A total of 256 QTLs (Supplementary Table S4), 134 for fiber quality traits, and 122 for yield components, were identified across nine environments using the CIM algorithm, with 1.68–28.27% proportions of the phenotypic variance (PV) explained by each QTL. Fifty-seven stable QTLs (Figure 3 and Supplementary Table S4) were identified in at least two environments, of which 32 were for fiber quality traits and 25 for yield components. Fiber Length A total of 36 QTLs for FL were identified on 21 chromosomes except chr02, chr04, chr09, chr10, and chr25, among which 7 were stable (Figure 3 and Supplementary Table S4). In these stable QTLs, qFL-chr17-1 was identified in three environments, and could explain 3.95–5.36% proportions of the observed PV. In its marker interval of TM53503–TM53577, there harbored 88 candidate genes. The stable QTLs, qFL-chr05-1, qFL-chr06-2, qFL-chr11-1, qFL-chr16-1, qFL-chr19-1, and qFL-chr26-1, could explain 12.13–13.83, 6.35–6.62, 5.15–9.41, 5.24–6.23, 4.65–5.07, and 4.56–5.59% proportions of the observed PVs, respectively. In their marker intervals of CICR0262, TM18200–TM18321, TM39956–TM39953, TM66757–NAU3563, TM57055–TM5 7082, and TM77259–TM77261, there harbored 2, 141, 15, 309, 65, and 1 candidate genes, respectively. Fiber Strength Forty-six QTLs for FS were identified on 19 chromosomes except chr02, chr03, chr14, chr17, chr18, chr22, and chr23, among which 10 were stable (Figure 3 and Supplementary Table S4). In these stable QTLs, qFS-chr07-2 was identified in all nine environments, and could explain 5.81–19.47% proportions of the observed PV. In its marker interval of DPL0852–DPL0757, eight candidate genes were harbored. qFS-chr16-3 was identified in five environments, and could explain 4.28–6.45% proportions of the observed PV. In its marker interval of SWU2707–DPL0492, 342 candidate genes were harbored. qFS-chr01-2 and qFS-chr20-5 were identified in three environments, and could explain 5.32–8.86 and 4.50–5.90% proportions of the observed PVs, respectively. In their marker intervals of TM379–TM404 and NAU4989–TM73152, 20 and 7 candidate genes, respectively, were harbored. qFS-chr07-1, qFS-chr11-1, qFS-chr11-2, qFS-chr13-1, qFS-chr20-1, and qFS-chr24-1 were identified in two environments, and could explain 5.97–6.21, 4.87–5.59, 5.26–7.21, 5.74–10.69, 2.91–8.18, and 5.11–5.43% proportions of the observed PVs, respectively. In their marker intervals of TM19848–TM19875, TM37826–TM37828, TM37897–TM37935, TM43230–TM43229, TM75088–TM75100, and TM67152–TM67146, 4, 1, 29, 1, 8, and 6 candidate genes, respectively, were harbored. Fiber Micronaire Fifty-two QTLs for FM were identified on 21 chromosomes except chr02, chr12, chr17, chr23, and chr26, among which 15 were stable (Figure 3 and Supplementary Table S4). In these stable QTLs, qFM-chr07-1 and qFM-chr13-1 were identified in six environments, and could explain 5.51–24.45 and 4.73–8.88% proportion of the observed PV, respectively. In their marker intervals of DPL0852–DPL0757 and TM43230–TM43241, 8 and 15 candidate genes, respectively, were harbored. qFM-chr01-2 was identified in five environments, and could explain 3.94–6.17% proportions of the observed PVs. In its marker interval, one marker of TM3451 was exclusively contained and two candidate genes were harbored. qFM-chr19-1 and qFM-chr19-2 were identified in four environments, and could explain 4.57–8.54 and 5.19–8.20% proportions of the observed PVs, respectively. In their marker intervals of TM57055–TM57057 and TM56813–TM56753, 4 and 161 candidate genes, respectively, were harbored. qFM-chr14-1, qFM-chr15-1, and qFM-chr24-2 were identified in three environments, and could explain 4.18–6.53, 4.45–5.35, and 4.25–4.69% proportions of the observed PVs, respectively. In their marker intervals of TM50241–TM50231, CGR5709–TM50087, and TM67152–TM67125, 13, 1, and 18 candidate genes, respectively, were harbored. qFM-chr03-1, qFM-chr05-1, qFM-chr10-1, qFM-chr11-4, qFM-chr14-3, qFM-chr15-2, and qFM-chr20-2 were identified in two environments, and could explain 3.89–5.18, 4.13–4.42, 4.66–5.16, 4.22–4.30, 4.52–4.54, 3.75–5.95, and 4.47–5.02% proportions of the observed PVs, respectively. In their marker intervals of TM7008–TM7102, TM10798–TM10805, TM33784–TM33813, TM39510–TM39490, TM52033–TM52031, TM50087–TM50082, and TM75041–TM75030, 125, 6, 100, 8, 1, 5, and 44 candidate genes, respectively, were harbored. Boll Weight A total of 53 QTLs for BW were identified on 25 chromosomes except chr15, among which 7 were stable (Figure 3 and Supplementary Table S4). In these stable QTLs, qBW-chr24-1 was identified in three environments, and could explain 4.13–6.99% proportions of the observed PVs. In its marker interval of TM67152–TM67127, 18 candidate genes were harbored. qBW-chr04-2, qBW-chr05-5, qBW-chr06-3, qBW-chr07-4, qBW-chr20-1, and qBW-chr21-4 were identified in two environments, and could explain 3.77–5.74, 4.28–6.42, 3.87–4.07, 7.62–8.08, 5.56–8.12, and 6.05–7.26% proportions of the observed PVs, respectively. In their marker intervals of TM9831–TM9827, TM10953–TM10979, TM14514–TM14509, DPL0852, NAU4989–CICR0002, and TM76018–TM75887, 6, 59, 23, 2, 7, and 119 candidate genes were harbored, respectively. Lint Percentage A total of 39 QTLs for LP were identified on 20 chromosomes except chr02, chr12, chr15, chr17, chr23, and chr24, among which nine were stable (Figure 3 and Supplementary Table S4). In these stable QTLs, qLP-chr10-1 was identified in five environments, and could explain 4.44–8.80% proportions of the observed PVs. In its marker interval of DPL0468–CGR5624, 148 candidate genes were harbored. qLP-chr04-1 was identified in four environments, and could explain 3.81–4.50% proportions of the observed PVs. In its marker interval of TM9862–TM9831, 217 candidate genes were harbored. qLP-chr26-2 was identified in three environments, and could explain 3.98–5.34% proportions of the observed PVs. In its marker interval of TM77259–TM77267, 3 candidate genes were harbored. qLP-chr03-1, qLP-chr06-2, qLP-chr08-1, qLP-chr11-1, qLP-chr22-1, and qLP-chr25-3 were identified in two environments, and could explain 2.69–2.83, 3.76–6.32, 4.43–6.02, 3.91–4.75, 3.61–4.26, and 4.77–7.64% proportions of the observed PVs, respectively. In their marker intervals of TM6006–TM6010, TM18161–TM18322, TM29470–TM29463, TM39443–TM39427, TM55461–TM55466, and TM63143–TM63142, 1, 141, 26, 12, 16, and 1 candidate genes, respectively, were harbored. Seed Index A total of 30 QTLs for SI were identified on 16 chromosomes except chr01, chr14, chr15, chr18, chr21, chr22, chr23, chr24, chr25, and chr26, among which nine were stable (Figure 3 and Supplementary Table S4). In these stable QTLs, qSI-chr07-2 was identified in five environments, which could explain 4.83–28.27% of the observed PVs. In its confidence interval of DPL0852–DPL0757, there harbored 8 candidate genes. qSI-chr16-1 was identified in four environments, which could explain 4.24–6.91% of the observed PVs. In its confidence interval of TM66717–TM66737, there harbored 19 candidate genes. qSI-chr10-1, qSI-chr10-2, and qSI-chr11-2 were identified in three environments, which could explain 6.67–7.83%, 4.28–6.50%, and 4.35–6.01% of the observed PVs, respectively. In their confidence intervals of DPL0468, TM36374–TM36487, and TM37826–TM37828, there harbored 2, 87, and 1 candidate genes, respectively. qSI-chr04-2, qSI-chr07-1, qSI-chr11-3, and qSI-chr13-2 were identified in two environments, which could explain 4.57–5.23%, 5.59–8.50%, 5.52–5.66%, and 3.37–5.29% of the observed PVs, respectively. In their confidence intervals of TM9702–TM9697, TM19691–TM19898, TM37970–TM39953, and TM43247–TM43263, there harbored 8, 39, 73, and 11 candidate genes, respectively. GWAS for Fiber Quality Traits and Yield Components A total of 209 and 139 QTNs were identified by four multilocus GWAS methods to be associated with fiber quality and yield component traits, respectively, in the current study (Supplementary Table S6). Among these QTNs, 74 were simultaneously found by at least two algorithms or in two environments (Supplementary Table S6), each with 0.15–47.17% proportions of the observed PVs explained, and a total of 104 candidate genes were mined. Fiber Quality Traits A total of 68, 65, and 76 QTNs were found to be associated with FL, FS, and FM, respectively, and the corresponding 110, 99, and 126 candidate genes were identified. In these QTNs, 11 for FL, 17 for FS, and 22 for FM were simultaneously associated by at least two algorithms or in two environments, and each could explain 0.15–29.10, 1.43–47.17, and 2.54–41.39% proportions of the observed PVs, respectively. Yield Components A total of 51, 50, and 38 QTNs were found to be associated with BW, LP, and SI, respectively, and the corresponding 82, 83, and 65 candidate genes were identified. In these QTNs, 9 for BW, 5 for LP, and 10 for SI were simultaneously associated by at least two algorithms or in two environments, and each could explain 3.41–28.76, 3.00–22.49, and 1.21–38.73% proportions of the observed PVs, respectively. Candidate Genes Annotation A total of 2133 candidate genes, among which 621 were for FL, 426 for FS, 510 for FM, 234 for BW, 565 for LP, and 323 for SI, were identified from stable QTL (Supplementary Table S5), and 506 candidate genes, among which 110 for FL, 99 for FS, 126 for FM, 82 for BW, 83 for LP, and 65 for SI, were identified from GWAS (Supplementary Table S6). Annotation analysis of the 35 common genes from these two candidate gene pools revealed that 33 of them had annotation information, whereas 8 had unknown function (Supplementary Table S7). In the gene ontology (GO) analysis of the candidate gene for fiber quality (Supplementary Table S8), 24, 17, and 29 candidate genes were identified in the cellular component, molecular function, and biological process category, respectively. In the cellular component category, three main brackets of cell (six genes), cell part (six genes), and organelle (five genes) were enriched, whereas in the molecular function category, two main brackets of binding (eight genes) and catalytic activity (six genes), and in biological process category, four main brackets of metabolic process (seven genes), single-organism process (seven genes), cellular process (five genes), and response to stimulus (five genes) were, respectively, enriched (Figure 4A). In gene ontology (GO) analysis of the candidate gene for yield components (Supplementary Table S10), 19, 13, and 27 candidate genes were identified in the cellular component, molecular function, and biological process category, respectively. In the cellular component category, three main brackets of cell (five genes), organelle (five genes), and cell part (five genes) were enriched, whereas in the molecular function category, two main brackets of binding (six genes) and catalytic activity (five genes), and in the biological process category, four main brackets of single-organism process (seven genes), metabolic process (five genes), cellular process (five genes), and localization (four genes) were, respectively, enriched (Figure 4B). Kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that six candidate genes for fiber quality were involved in 10 pathways and two candidate genes for yield were involved in six pathways (Supplementary Tables S9, S11). The reliability of the genetic map is also estimated by gap size, collinearity, and segregation distortion analyses (Figure 2 and Table 3). Although the development of SNP markers was based on the CottonSNP80K array, a few chromosomes still had a large gap or uneven distribution of makers (Li et al., 2016; Zhang Z. et al., 2017). Totally, there were 33 gaps larger than 10 cM, of which the largest one was of 42.23 cM on chr17 and there were only 19 markers mapped on it. The result of collinearity between the genetic map and the G. hirsutum (TM-1) reference genome indicated accuracy and quality of the map. The segregation distortion is recognized as strong evolutionary force in the process of biological evolution (Taylor and Ingvarsson, 2003), which was also a common phenomenon in the study of genetic mapping (Shappley et al., 1998; Ulloa et al., 2002; Jamshed et al., 2016; Zhang et al., 2016; Tan et al., 2018). The current study observed that 32.22% of the total mapping markers were SDMs (P < 0.05). The maximum SDMs were on chr08, where there were 237 SDMs of the total 481 markers, forming five SDRs (Figure 1). This was in consistency with the SSR map constructed from the F2 population of the same parents of the current study (Kong et al., 2011). However, some studies observed an increase of the SDM ratio from F2 generation to the completion of RILs (Tan et al., 2018). This phenomenon was influenced by plenty of factors, including genetic drift (Shen et al., 2007) of mapping population, pollen tube competition, preferential fertilization of particular gametic genotypes, and others (Zhang et al., 2016; Zhang Z. et al., 2017; Tan et al., 2018). In the current study, some chromosomal uneven distribution of QTLs in SDR versus normal regions was also observed in chr01, chr06, chr07, chr10, chr16, chr19, and chr20. These facts implied an impact of the selections being imposed during the construction of the RIL population. The QTLs detected in this study were compared with those in previous studies. As a result, 22 QTLs for FL, 25 QTLs for FS, 31 QTLs for FM, 36 QTLs for BW, 22 QTLs for LP, and 19 QTLs for SI in this study were coincided in the same physical regions of QTLs identified in previous studies (indicated with asterisks in Supplementary Table S4). The remaining could possibly be novel QTLs, of which 21 were stable ones, namely qFL-chr11-1, qFL-chr16-1, qFL-chr19-1, qFL-chr26-1, qFS-chr01-2, qFS-chr16-3, qFS-chr20-1, qFS-chr20-5, qFM-chr01-2, qFM-chr03-1, qFM-chr10-1, qFM-chr14-1, qFM-chr19-1, qBW-chr20-1, qLP-chr03-1, qLP-chr22-1, qLP-chr25-3, qLP-chr26-2, qSI-chr07-1, qSI-chr10-1, and qSI-chr16-1. Even though in the phenotypic evaluations of the population, the phenotypic differences between the two parents did not reach the significant level except that of FS, transgressive segregation in the RILs and significant differences among RILs indicated that the parents might harbor different favorable alleles for the target traits. QTL identification results well illustrated such presuppositions as these different favorable alleles contributed greatly to the similarity or nonsignificant differences between the two parents. These alleles could be addressed through map construction and detected in QTL identification. The high heritability of the target traits also enhanced the reliability of the QTL identification. In addition, four multilocus GWAS algorithms were applied to the association of QTNs with the target traits, and their results were compared with the previous identified QTLs (Said et al., 2015). The results confirmed that quite a ratio of QTNs were coincided in the physical regions of the confidence intervals of reported QTLs in the database, namely 43 QTNs for FL, 44 QTNs for FS, 51 QTNs for FM, 40 QTNs for BW, 34 QTNs for LP, and 25 QTNs for SI (indicated with asterisks in Supplementary Table S6). The remaining QTNs could possibly be novel QTNs, of which 27 were associated by at least two algorithms or in two environments. These loci could be of great significance for cotton molecular-assisted breeding, particularly the loci of TM9941 and TM54893, which were identified both by multiple algorithms and in multiple environments for more than one target trait. Based on linkage disequilibrium, GWAS is an effective genetic analysis method to dissect the genetic foundation of complex traits in plants in natural populations. The four multilocus GWAS algorithms provided promising alternatives in GWAS. Usually, GWAS needed a large panel size with sufficient marker polymorphism (Bodmer and Bonilla, 2008; Manolio et al., 2009), and was effective to identify major loci while ineffective to rare or polygenes (Asimit and Zeggini, 2010; Gibson, 2012) in the population. Linkage analysis in segregating populations could effectively eliminate the false-positive results, which was a built-in defect of GWAS in natural populations. But linkage analysis usually identified large DNA fragments, which made it difficult to further study the initial identification results. In the current study, both GWAS and linkage analysis were applied in the segregating RILs to study the correlations between genotypes and phenotypes. When comparing the results of GWAS to the QTLs of both previous studies (Said et al., 2015) and current study, common loci (genes) (Supplementary Table S7) demonstrated the effectiveness and feasibility of multilocus GWAS methods to address the correlation between genotypes and phenotypes in segregating RILs. Especially under the condition of increased marker density and improved genome coverage, the accuracy of QTN identification in GWAS would also increase. The increased accuracy probably rendered the application of GWAS in segregating population to have a higher effect on the observed PVs, sometimes even higher than that of QTL on the PVs in linkage analysis, which was usually low in natural populations. Congruency and Function Analysis of Candidate Genes In this study, candidate genes were identified independently both from the physical region in the marker intervals of the QTLs, which were identified by CIM (Zeng, 1994) in WinQTL Cartographer 2.5 (Wang et al., 2012), and from the physical position of the QTNs, which were associated by multilocus GWAS algorithms. As the CIM algorithm gave not only the QTL position where the highest LOD value located, but also a marker interval of that QTL, the physical regions where the marker interval resided by QTL/QTN were used to search the candidate genes around the QTLs. To avoid redundant genes, the markers, which resided far away from the physical positions of the rest in the same confidence interval, were discarded for consideration of candidate gene searching. This increased the accuracy of the functional analysis of the candidate genes harbored in the confidence intervals of QTLs. When comparing both candidate gene lists, even if they were not completely consistent, they still revealed a good congruency of candidate gene identification from both algorithms of QTL/QTN; namely, three congruent candidate genes for FL, seven for FS, nine for FM, five for BW, eight for LP, and nine for SI were identified (Supplementary Table S7). Further analysis of these candidate genes indicated that 1 for FL, 17 for FS, and 2 for FM (indicated with asterisks in Supplementary Table S6) were congruent with some previous reports (Huang et al., 2017; Sun et al., 2017). Two candidate genes, Gh_D102255 (a protein kinase superfamily gene) and Gh_A13G0187 (actin 1 gene), which were for fiber quality, were also reported to participate in fiber elongation (Li et al., 2005; Huang et al., 2008). Gh_A07G1730 and Gh_D03G0236 belonged to a WD40 protein superfamily were mainly involved in yield formation in the current study, and might be related to a series of functions (Sun Q. et al., 2012; Gachomo et al., 2014). Gh_D11G1653 (myb domain protein 6) functioned in BW formation, whereas reports indicated that several members of MYB family were involved in fiber development (Suo et al., 2003; Machado et al., 2009; Sun et al., 2015; Huang et al., 2016). Findings in the current study also indicated that some candidate genes could possibly be “pleiotropic,” namely Gh_A07G1744 for FS, FM, and SI; Gh_A07G1745 for FS and FM; Gh_A07G1743 for BW and SI; and Gh_D08G0430 for FM and BW. These candidate genes could be of great significance for further studies including functional gene cloning as well as cultivar development. Conclusion The enriched high-density genetic map, which contained 4729 SNP and 122 SSR markers, spanned 2477.99 cM with a marker density of 0.51 cM between adjacent markers. A total of 134 QTLs for fiber quality traits and 122 for yield components were identified by the CIM, of which 57 are stable. A total of 209 and 139 QTNs for fiber quality traits and yield components were, respectively, associated by four multilocus GWAS algorithms, of which 74 QTNs were detected by at least two algorithms or in two environments. Comparing the candidate genes harbored in 57 stable QTLs with those associated with the QTN, 35 were found to be congruent, 4 of which were possibly “pleiotropic.” Results in the study could be promising for future breeding practices through MAS and candidate gene functional studies. Author Contributions WG and YY initiated the research. WG, RL, and QC designed the experiments. RL, XX, and ZZ performed the molecular experiments. JG, JL, AL, HS, YS, QG, QL, MI, XD, SL, JP, LD, QZ, XJ, XZ, and AH conducted the phenotypic evaluations and collected the data from the field. RL, WG, YY, and HG performed the analysis. RL drafted the manuscript. YY and WG finalized the manuscript. All authors contributed in the interpretation of results and approved the final manuscript. Funding This work was funded by the National Key R&D Program of China (2016YFD0100500), the Fundamental Research Funds for Central Research Institutes (Y2017JC48), the National Key R&D Program of China (2017YFD0101600 and 2016YFD0101401), the Natural Science Foundation of China (31371668, 31471538), the National High Technology Research and Development Program of China (2012AA101108), and the National Agricultural Science and Technology Innovation Project for CAAS and the Henan province foundation with cutting-edge technology research projects (142300413202). Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments The authors thank the Biomarker Technologies Corporation (Beijing, China) for providing the software Highmap and help in the genetic map construction with Highmap. | Mid | [
0.646766169154228,
32.5,
17.75
] |
1. Field of the Invention The present invention relates to a carton, and more particularly, to a carton that is used for packaging precision equipment, such as a digital camera. 2. Description of the Related Art In a carton for packaging precision equipment, such as a digital camera, partition plates, which are formed integrally with a body of the carton, are conventionally used for partitioning a space in the carton into a plurality of sections. For example, in a carton for use as a packaging box described in Japanese Patent Application Laid-Open (JP-A) No. 6-263181, the space in the carton is partitioned into a section for accommodating electronics and a section for accommodating a manual by a partition wall connected to a box body. Further, in a carton described in Japanese Utility Model Application Laid-Open (JP-U) No. 6-69119, the space in the carton is partitioned into a section for accommodating a body of an object to be packaged and a section for accommodating a manual by an inner bottom wall, a first partition plate and a second partition plate, which are connected to a body of the carton. In these cartons, the body and the partition plates (the partition wall, the inner bottom wall, the first partition plate, and the second partition plate) are integrally formed, and therefore, the cartons have advantages in that production thereof is easy and in that a number of parts can be reduced. However, since the partition plates of the cartons described in the above-cited documents are fixed at predetermined positions, the partition plates cannot be pulled out from, and then pushed into the cartons. | Mid | [
0.554166666666666,
33.25,
26.75
] |
A Stepwise Embolization Strategy for a Bronchial Arterial Aneurysm: Proximal Coil and Distal Glue with the Optional Use of a Microballoon Occlusion System. This study aimed to demonstrate a transcatheter embolization strategy for bronchial artery aneurysms (BAAs) using coils for the proximal lesion and glue (n-butyl-2-cyanoacrylate [NBCA]) embolization for the distal lesion with or without the use of a microballoon occlusion catheter. Five patients with BAAs presenting with hemoptysis were enrolled in this study. A bronchial angiogram indicated a mediastinal BAA near the orifice, accompanied by dilated distal branches with or without intrapulmonary BAA. A stepwise procedure was performed. First, the intrapulmonary branches were embolized with glue, with or without the use of a microballoon catheter depending upon the anatomical and local flow hemodynamic conditions. Second, the mediastinal BAA was tightly packed with detachable coils. Glue embolization of intrapulmonary abnormal branches successfully controlled hemoptysis in all patients; microballoon catheters were used in five of the 10 arteries. The volume embolization ratio of coils within the mediastinal BAA ranged from 28 to 59%, and neither coil compaction nor signs of recanalization were observed during follow-up. The stepwise embolization procedure with the sequential use of glue (with or without a microballoon occlusion system) and detachable coils may represent a possible endovascular strategy for the treatment of complex BAAs. Level 4: Case Series. | High | [
0.691588785046728,
37,
16.5
] |
TEWKSBURY -- It's just about that time of year when high school seniors across the region begin to check the mail daily in anticipation of college acceptance letters. For students who are graduating from Tewksbury High School, one of the key reasons for their success is the guidance staff there. "We all have great students and we have outstanding support from our administration team. We work very closely, one on one with every single senior, to make sure each one comes out of here with a plan in place," guidance counselor Cecily Markham said. Over the years, college admission has become more and more competitive, Markham said, so whereas students used to apply to four to six colleges, now it's more like six to eight. "The bar has been raised more and more and it's a little more difficult to get into some schools.," she said. "This past year, our guidance team helped students mail out over 700 college applications," which included letters of recommendation, resumes and official transcripts. The guidance staff organizes things like resume and essay writing workshops and parent/guardian breakfasts. It also works with students to use an Internet-based career resource called Naviance. "As a team, we also do a mini college fair as a part of college career week for juniors in April. We have usually 50 to 60 college representatives and admissions counselors who come to our school. We're particularly proud of the work we do in preparing the students for that," Markham said. Advertisement The guidance staff begins to work with students as early as their freshman year in high school on preparing to take the SAT or ACT exams; for families who are struggling to pay for college, she and her colleagues can them help explore more affordable schools. "Financial aid changes every year. We always bring in experts from both Middlesex Community College and the Massachusetts Education Financing Authority and they go through, step by step, the government's role and available grants," in addition to the forms the students must fill out, Markham said. Another representative from Fitchburg State College visits the school annually to go over with students the dos and don'ts of writing a good essay. Markham said she typically advises students to take the most rigorous courses they can handle without getting behind and to emphasize a strong commitment to extracurricular activities, noting it is often better to do just a few things where they can have a real impact than to try and load up their resumes with an unmanageable number of affiliations. That formula has worked well for students in recent graduating classes, who have earned acceptance to Harvard and other Ivy League schools, as well as institutions like MIT, Merrimack College, all of the UMass campuses and the University of Maine. Last year, 66 percent of the THS graduates went on to four-year colleges, while an additional 20 percent enrolled in two-year colleges, Markham said. "A good college application packet doesn't necessarily need to include having a 4.0 GPA, but it should include strong grades along with evidence of involvement in community service, school activities like drama club and part-time employment. They want a very well-rounded student," she said. For students who plan to enroll in trade schools or technical institutes, THS offers a vocational workshop in fields like automotive technology that can help aid them in selecting a career path, Markham said. College and career planning are just a couple of the areas where the guidance team helps students, who also stop by to visit when they are in any type of personal crisis, whether it's with their school work or relationships that may require peer remediation or faculty intervention, in cases of bullying. David Harne, who is in his first year as a guidance counselor at the school, said he was thrilled to stay on after doing his internship under department director Karen Baker O'Brien, who, he said, is a great boss. The gratitude from students whom she has helped is one of the best parts of the job, sixth-year guidance counselor Tina Sheahan said. "One of the greatest culminations of the year is at scholarship night and at graduation. Once everyone has found their parents, some of them will come over and give you a hug or shake your hand," Sheahan said. Welcome to your discussion forum: Sign in with a Disqus account or your social networking account for your comment to be posted immediately, provided it meets the guidelines. (READ HOW.) Comments made here are the sole responsibility of the person posting them; these comments do not reflect the opinion of The Sun. So keep it civil. | High | [
0.673417721518987,
33.25,
16.125
] |
INTERVISTA ESCLUSIVA SKY. Jorge Mendes, agente di Cristiano Ronaldo, ad Alessandro Alciato svela: "Dalla Cina hanno offerto 300 milioni al Real Madrid e più di 100 all'anno al giocatore. Ma i soldi non sono tutto, il club spagnolo è la sua vita" | Low | [
0.5102040816326531,
31.25,
30
] |
Daily News Channel Neighbors describe man at center of Myanmar political scandal Tucked away in the woods of central Missouri, obscured by tall trees and broken-down cars, is the mobile home of the man at the center of a political scandal rocking the nation of Myanmar. Journalists have been flocking to John Yettaw’s modest residence in the unincorporated community of Falcon for insight into the man who allegedly swam across a lake and sneaked into the home of Myanmar opposition leader Aung San Suu Kyi while she was under house arrest. Yettaw was charged Thursday in Myanmar on two criminal counts: entering the country illegally and staying at a resident’s home without government permission, according to a spokesman for Suu Kyi’s political party. Both charges carry a maximum sentence of five years in prison. Yettaw allegedly stayed overnight in the lakeside home, violating the conditions of Suu Kyi’s house arrest, according to the country’s ruling military junta, which rarely grants her visitors. The 1991 Nobel Peace Prize laureate was subsequently detained and faces trial on Monday. Conversations with Yettaw’s neighbors conjured a blurry image of a man known as a friendly intellect to some and an eccentric recluse to others, deepening the mystery of who he is and what he was doing in Myanmar. “John was always a friendly guy, to me he was,” neighbor Mike Assell said. “He was just a very intelligent man to talk to, he was very literate, he had a good vocabulary and you could talk to him and he understood what you were talking about… he was well-read.” Watch Assell describe his neighbor » Assell described Yettaw as someone who was friendly but did not actively participate in the community. “I think he wasn’t really afraid to talk to folks, but he really was not outgoing,” Assell said. “He has his own — I don’t know if agenda’s the right word — he has his priorities and he is working toward those.” Among those priorities were his family and furthering his career as a medical doctor, Assell said. “He really protected his children, he wanted their best interests worked toward, making sure they were educated, they went to school and that sort of thing. He had some rules and family was high on his list of priorities,” he said. Yettaw’s home, about two miles off the nearest gravel road and nearly half a mile from the closest neighbor, appeared empty Thursday, but neighbors said he lives there with his children, ages 10 to 22. Don’t Miss Aung San Suu Kyi facing trial after American’s swim U.S. Embassy meeting with detained American Myanmar tops list of worst places to be a blogger In depth: Myanmar: Two days, two tragedies He and first wife, Yvonne, divorced about six years ago, but most of their seven children stayed with Yettaw. An older son from Yvonne Yettaw’s first marriage, Craig Dehner, lives in Springfield. He declined CNN’s request for comment. One of Yettaw’s sons died in a motorcycle accident a few years ago, Assell said. Some neighbors who were unwilling to give their names described him as an Army veteran who struggled with drinking and post-traumatic stress disorder. Others said he was an activist type, whose only political agenda was to help others even if it meant charting new territory. Little is known about Yettaw’s role in the Myanmar incident or his intentions, apart from local media reports that said Yettaw, a diabetic, told Suu Kyi’s two housekeepers he was tired and hungry after the swim and they offered him food. The government said Yettaw’s presence violated the conditions of Suu Kyi’s house arrest. She was weeks away from completing six years of house arrest, according to the U.S. Campaign for Burma, a pro-democracy group fighting for her release, which says her detention is a ploy to extend her house arrest. Yettaw’s neighbors said they were unsurprised to find out he was in Myanmar, given his educational background and passion for helping others. Assell speculated that efforts to pursue his career might have sent him to Myanmar. “He probably saw an opportunity to put some of his education to use over there,” Assell said. “That was a way he could expand in those areas.” | Mid | [
0.566523605150214,
33,
25.25
] |
var User = require('../app/models/user'); var Auth = require('../config/middlewares/authorization.js'); module.exports = function(app, passport){ app.set('views', './endpoints/authentication/app/views'); app.set('view engine', 'jade'); /* app.get("/", function(req, res){ if(req.isAuthenticated()){ res.render("home", { user : req.user}); }else{ res.render("home", { user : null}); } }); */ app.get("/login", function(req, res){ res.render("login"); }); app.post("/login" ,passport.authenticate('local',{ successRedirect : "/", failureRedirect : "/login", }) ); app.get("/signup", function (req, res) { res.render("signup"); }); app.post("/signup", Auth.userExist, function (req, res, next) { User.signup(req.body.email, req.body.password, function(err, user){ if(err) throw err; req.login(user, function(err){ if(err) return next(err); return res.redirect("profile"); }); }); }); app.get("/auth/facebook", passport.authenticate("facebook",{ scope : "email"})); app.get("/auth/facebook/callback", passport.authenticate("facebook",{ failureRedirect: '/login'}), function(req,res){ res.render("profile", {user : req.user}); } ); app.get('/auth/google', passport.authenticate( 'google', { scope: [ 'https://www.googleapis.com/auth/userinfo.profile', 'https://www.googleapis.com/auth/userinfo.email' ] }) ); app.get('/auth/google/callback', passport.authenticate('google', { failureRedirect: '/login' }), function(req, res) { // Successful authentication, redirect home. res.redirect('/'); }); app.get("/profile", Auth.isAuthenticated , function(req, res){ res.render("profile", { user : req.user}); }); app.get('/logout', function(req, res){ req.logout(); res.redirect('/login'); }); } | Mid | [
0.61072261072261,
32.75,
20.875
] |
INTRODUCTION ============ Glycogen storage disease type 1b (GSD-1b, MIM 232220) is an autosomal recessive disease caused by a deficiency of microsomal glucose-6-phosphate translocase (G6PT). This protein transports glucose-6-phosphate into the endoplasmic reticulum, where the enzyme glucose-6-phosphatase (G6Pase; EC 3.1.3.9) converts glucose-6-phosphate into glucose and inorganic phosphate. In 1997, Gerin et al. found that a gene coding for the G6PT was mutated in GSD-1b ([@B1]). This gene, *SLC37A4* (formerly called as *G6PT1*), is located on chromosome 11q23.3 and encodes a protein with 429 amino acids ([@B1], [@B2]). Apart from GSD-1b, mutations in the *SLC37A4* gene were also found in essentially all patients previously classified as GSD 1c ([@B2], [@B3]) and 1d ([@B4]). Owing to the discovery, GSD-1b, -1c, or -1d can be diagnosed by the direct mutation analysis of the *SLC37A4* gene, which can spare the patients from invasive liver biopsy. In addition, the genetic causes in a family can facilitate family screening and is essential for prenatal diagnosis ([@B5]). Recently, we experienced a Korean patient with typical clinical features of GSD-1b and performed a mutation analysis to detect the *SLC37A4* gene mutations. In this report, we present the result of the mutation analysis in this patient. CASE REPORT =========== The proband was the first child of non-consanguineous Korean parents. He presented at age 12 yr for failure to thrive and protuberant abdomen. His height and weight was below the third percentile. Physical examination showed an enlarged liver, which was 7 cm below the costal margin. Fasting blood glucose was 40 mg/dL (reference interval: 70-110 mg/dL), blood lactate 5.6 mg/dL (reference interval: 0.7-2.5 mg/dL), serum uric acid 13.1 mg/dL (reference interval: 3.0-8.3 mg/dL), and serum triglyceride 586 mg/dL (reference interval: 50-200 mg/dL). Liver function was within normal limit except a mild elevation of serum ALT 65 U/L (reference interval: \<40 U/L). A glucose-loading test (1.75 g/kg) resulted in rapid decrease in blood lactate and pyruvate. The neutrophil count of the peripheral blood ranged from 0.4×10^9^/L to 0.8×10^9^/L (reference interval: 1.5-9.0×10^9^/L). He had experienced protracted diarrhea and recurrent perianal abscess. On colonoscopic finding, he had an inflammatory bowel disease. He underwent a liver biopsy in suspect of GSD. The biopsy showed an increased glycogen contents (12.3%; reference interval: 1-6%/wet liver), which is compatible to GSD. The G6Pase activities were measured with glucose-6-phosphate as substrate and were incubated in a reaction mixture containing 0.25 M saccharose and 5 mM EDTA buffer, pH 7.2. Microsome permeabilized with sonification and at least two G6P uptake studies were performed for each microsomal preparation. The patient\'s G6Pase activities in liver homogenates showed a very low level, 0.18 and 0.41 (normal range; 5.9-93.0 nM/min/mg protein) in intact microsome and disrupted microsome by sonification, respectively. Based on the clinical and laboratory findings, GSD-1b was considered. But G6Pase activity in disrupted microsome was a very low level, 0.41, but approximately approximately 2.3 times elevated level than that in untreated microsomes. In the first place, we had mutational analysis of the *G6Pase* gene to exclude GSD-1a and observed no mutation. We then analyzed mutations of *SLC37A4* gene because we suspected clinically GSD-1b. Genomic DNA was extracted from whole blood using a Wizard genomic DNA purification kit according to the manufacturer\'s instruction (Promega, Madison, WI, U.S.A.). Informed consent was obtained from the parents. All the exons and intron-exon boundaries of the *SLC37A4* gene were amplified as described previously ([@B3]). Direct sequencing of PCR products was performed on both forward and reverse strands using the same primers for PCR and cycle sequencing was performed with a BigDye Terminator Cycle Sequencing Ready Reaction kit (Applied Biosystems, Foster City, CA, U.S.A.) on the ABI 3,100 Genetic Analyzer (Applied Biosystems). The sequence was compared with the reference sequence NM_001467 in the National Center for Biotechnology Information database (<http://www.ncbi.nlm.nih.gov>). Two different mutations in the *SLC37A4* gene were identified in the proband. One was a heterozygous deletion mutation (c.1042_1043delCT; L348fsX400) in exon 8 and the other was a heterozygous 1-bp substitution mutation (c.443C\>T; A148V) in exon 3 of the *SLC37A4* gene. No other polymorphism was found in the sequencing results. The first mutation, c.1042_1043delCT, has been previously reported in an Italian family with GSD-1b ([@B6]). The second one is a novel mutation, c443C\>T, leading to substitution of alanine by valine at codon 148 (A148V) ([Fig. 1](#F1){ref-type="fig"}). The mother is heterozygous for the A148V mutation and the father is heterozygous for the L348fs mutation. The A148V mutation has been screened in 100 normal chromosomes and none had the same mutation. DISCUSSION ========== GSD1 or von Gierke disease includes a clinically, biochemically, and genetically heterogeneous group of autosomal recessive disorders ([@B7]). The basic defects reside in the impairment of the terminal steps of glycogenolysis and gluconeogenesis, at different levels. Mutations of the glucose-6-phosphatase gene (G6Pase), which lead to the enzyme deficiency, are responsible for the most frequent form of GSD 1, the subtype 1a ([@B7]). This gene is not mutated in patients in which there are biochemical evidences of defects in the glucose-6-phosphate transport system ([@B8]). GSD 1 patients diagnosed as non 1a have been subdivided at least in 1b and 1c subtypes on the basis of clinical and biochemical parameters ([@B7]). In GSD -1a, the WBC count is generally within reference ranges because leukocyte function is unaffected by the defect. In contrast, GSD-1b causes chronic neutropenia due to the impaired function of the neutrophils, particularly in relation to Gram-positive organisms ([@B9]). In GSD-1b, a liver biopsy in which the hepatocytes and their microsomes are intact shows deficient G6Pase activity in enzyme assay, as the defects in the glucose-6-phosphate transport system dose not deliver the required substrate into the microsomal lumen. However, microsomes disrupted by solubilization show normal glucose-6-phosphatase activity, because all substrates have free entry to the enzyme. But G6Pase activity in disrupted microsome by sonification showed a very low level in our enzyme assay, which was not compatible finding to GSD-1b. Since liver biopsy specimen was not left, we could not try to repeat the G6Pase enzyme assay. Our G6Pase enzyme assay result may be caused by insufficient or inadequate sonification procedure for microsome disruption. The recent cloning of the cDNA for a putative endoplasmic reticulum glucose-6-phosphate transporter (G6PT) ([@B1]) has enabled the search for mutations in this gene in non GSD-1a patients ([@B4], [@B6], [@B10]-[@B13]). Recent data from others ([@B4], [@B10]-[@B13]) indicate that mutations in the *SLC37A4* gene are present in both 1b and 1c patients so far investigated. The *SLC37A4* gene product is estimated to function as a transporter for a monophosphate ester by structural comparison to various types of bacterial monophosphate ester transporter proteins ([@B1]). The bacterial transporter proteins as well as a human G6P translocase have 12 transmembrane helices. The genomic structure showed that helix 1 is in exon 1, helices 2-4 in exon 2, helices 5 and 6 in exon 3, helix 7 in exon 4, helix 8 in exon 5, helix 9 in exon 6, helix 10 and the upper region of helix 11 in exon 7, and the lower region of helix 11 and helix 12 in exon 8, indicating close correlation between transmembrane helices and exons ([@B14]). Based on genome sequence data, we analyzed DNA of a patient with GSD-1b. We identified two different mutations in Korean patient. The first mutation at the codon 347 cause a change in reading frame after Ala-347 and premature termination of translation in amino acid 400, which has been previously reported in Italian family with GSD-1b ([@B6]). This can possibly cause an abnormal folding of the transporter in the ER membrane and, consequently, a functional anomaly. On the other hand, nonsense mutations and insertion/deletion mutations cause the synthesis of a truncated protein mussing the two lysines at the carboxy-terminus necessary as a retention signal in the ER membrane and therefore do not allow for glucose-6-phosphate transport. The second mutation at the codon 148, novel mutation was a missence mutation from alanine to valine at codon 148. This alanine locates in the third transmembrane helix. This amino acid change might alter the protein structure at the transmembrane region. All the known missence mutations causing amino acid substitutions in the transmembrane region of the protein are responsible for the conversion of a hydrophobic amino acid to a hydrophilic amino acid. Fifty normal subjects were screened by direct sequencing and none of them carried for the A148V mutation in the *SLC37A4* gene. To determine whether these mutations were common to Korean GSD-1b patients, mutation screening of more patients should be undertaken. In summary, we identified a novel missence mutations in the *SLC37A4* gene in a Korean boy with the typical phenotype of GSD-1b, which we believe would improve our understanding of the genotype-phenotype correlations of *SLC37A4* gene mutations. The DNA-based diagnosis of GSD-1b will enable us to make an accurate determination of carrier status and to perform prenatal diagnosis of this disease. To our knowledge, this is the first report of genetically confirmed case of GSD-1b in Koreans. This work was supported by National Research Laboratory Grants from the Korea Institute of Science & Technolgy Evaluation and Planning, Korea. {#F1} | High | [
0.65648854961832,
32.25,
16.875
] |
#!/usr/bin/python # # Copyright 2018-2020 Polyaxon, Inc. # # 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. import polyaxon_sdk from marshmallow import fields, validate from polyaxon.polyflow.run.kinds import V1RunKind from polyaxon.schemas.base import BaseCamelSchema, BaseConfig from polyaxon.schemas.fields.ref_or_obj import RefOrObject class RaySchema(BaseCamelSchema): kind = fields.Str(allow_none=True, validate=validate.Equal(V1RunKind.RAY)) spec = RefOrObject(fields.Raw(required=True)) @staticmethod def schema_config(): return V1Ray class V1Ray(BaseConfig, polyaxon_sdk.V1Ray): SCHEMA = RaySchema IDENTIFIER = V1RunKind.FLINK | Mid | [
0.562653562653562,
28.625,
22.25
] |
I love this dish and the ease of cooking it. You can freeze the rolled meatballs after rolling and defrost overnight the day before cooking. They are also lovely the next day if cooked in advance. This all makes the dish so easy to add to a tapas feast or prepare in advance for a dinner party. It is questionable with meatballs whether the bacon and onion are best cooked before rolling into the mix, yet this is why I have enjoyed this recipe I believe – it is not only easier to skip this step, I also find the flavour more subtle and at the same time fuller and more rounded. My favourite meatball recipe – thankyou Richard Huddleston! Pictured: Meatballs baked in Passata Meatball Ingredients -500g pork or beef mince3 rashers bacon, finely diced (uncooked)1 red onion, finely diced1 lemon, zest onlyParmesan cheese, a good small handful1 eggBreadcrumbs - a good handful, more if necessary to bind - you can use dried or day old bread.Parsley, a small handful, or to tasteOptional - 2 red chillis, finely diced Combine mince, bacon, red onion, lemon zest, parmesan, egg, breadcrumbs, parsley, and chilli if using. Roll into large balls the size of golf balls. If mixture feels delicate you can firm up in the fridge for half an hour. Shallow fry in a pan to brown - as you will be baking these as well, they do not need to be cooked through, you are adding flavour at this stage with the browning, and sealing the meatballs into shape. Set aside and preheat oven to 180°C. Heat the tomato passata with the garlic and basil to infuse the flavour. When warm pour over meatballs and place in oven for 45 minutes until cooked through and bubbling. Serve over pasta, or rice, or as I did - part of a Spanish tapas feast. | High | [
0.677494199535962,
36.5,
17.375
] |
PKD: a new protein kinase C-dependent pathway in platelets. Protein kinase D (PKD, also known as PKCmu) is closely related to the protein kinase C superfamily but is differentially regulated and has a distinct catalytic domain that shares homology with Ca(2+)-dependent protein kinases. PKD is highly expressed in hematopoietic cells and undergoes rapid and sustained activation upon stimulation of immune receptors. PKD is regulated through phosphorylation by protein kinase C (PKC). In the present study, we show that PKD is expressed in human platelets and that it is rapidly activated by receptors coupled to heterotrimeric G-proteins or tyrosine kinases. Activation of PKD is mediated downstream of PKC. Strong agonists such as convulxin, which acts on GPVI, and thrombin cause sustained activation of PKC and PKD, whereas the thromboxane mimetic U46619 gives rise to transient activation of PKC and PKD. Activation of PKD by submaximal concentrations of phospholipase C-coupled receptor agonists is potentiated by G(i)-coupled receptors (eg, adenosine diphosphate and epinephrine). This study shows that PKD is rapidly activated by a wide variety of platelet agonists through a PKC-dependent pathway. Activation of PKD enables phosphorylation of a distinct set of substrates to those targeted by PKC in platelets. | High | [
0.6976744186046511,
31.875,
13.8125
] |
I. N-linked Oligosaccharide Side Chains The function of N-linked oligosaccharide side chains that are covalently attached to the majority of eukaryotic secretory and membrane proteins is not yet fully understood. It has been suggested that the N-linked oligosaccharide side chains play a variety of roles including (i) maintenance of the structure and stability of the glycoproteins: (ii) directing the transport of glycoproteins to various subcellular compartments both after biosynthesis and for degradation: and (iii) recognition functions leading to specific adhesion of cells and tissue organization during development or neoplasia (Gibson, R. et al, Trends Biol. Sci., 5:290-293 (1980); Hughes, R. C. et al. Trends Biochem. Sci., 6:228-230 (1981); Pollack, L. et al, J. Cell. Biol., 97:293-300 (1983); Elbein. A. D., Trends Biochem. Sci., 6:219-221 (1981); and Elbein, A. D., Annu. Rev. Biochem., 56:497-534 (1987)). Studies using drugs that are specific inhibitors of the addition or modification of N-linked oligosaccharide side chains have been performed in attempts to define the functional roles of these carbohydrate moieties (Elbein. A. D., Annu. Rev. Biochem., 56:497-534 (1987)). Further, the advent of recombinant DNA technology has facilitated studies involving the removal of individual glycosylation sites using oligonucleotide mutagenesis (Machamer, C. E. et al, Mol. Cell Biol., 5:3074-3083 (1985); Miyazaki, J. et al, J. Exp. Med., 163:856-871 (1986); Santos-Aguado, J. et al, Molec. and Cell Biol., 7:982-990 (1987); Guan. J. et al, J. Biol. Chem., 263:5306-5313 (1988); Matzuk, M. M. et al, J. Cell Biol., 106:1049-1059 (1988)). The majority of these investigations have indicated that N-linked oligosaccharide side chains play a role in glycoprotein structure and stability, with the structure and stability of different glycoproteins being more or less dependent on the presence of their carbohydrate moieties (Elbein, A. D., Annu. Rev. Biochem., 56:497-534 (1987)). In experiments aimed at determining whether oligosaccharides play a direct role in promoting protein transport to the cell surface, oligonucleotide-directed mutagenesis has been used to introduce glycosylation sites at novel positions on nascent polypeptides. In some of these cases, the extra oligosaccharides promoted the intracellular transport of mutant proteins that were previously blocked in transport along the secretory pathway (Guan, J. et al, Cell, 42:489-496 (1985); Machamer, C. E. et al, J. Biol. Chem., 263:5948-5954 (1988); and Machamer, C. E. et al, J. Biol. Chem., 263:5955-5960 (1988)). Because the three-dimensional structures of these proteins were not known, it was not possible to predict whether the novel oligosaccharide side chains were attached at positions normally located on the surface or within the interior of the wild-type protein. | Mid | [
0.6405405405405401,
29.625,
16.625
] |
‘White substance’ is sent to Barack Obama’s DC office Police are investigating a white substance that was sent to former President Obama’s office in DC. Information on whether Barack Obama was present when the substance was found has not been released. The suspicious package was reported at approximately 12:30 pm and was delivered in a letter marked as having come from Hong Kong. At this time, Fire and EMS Battalion Chief Edward Smith believes the white substance is baby powder. Obama has been leasing the office space since the time he left the White House in January 2017 and it is used to conduct business while he is in the city. The non-profit World Wildlife Fund owns the building and also has its headquarters there. The surrounding area has been closed to traffic and will remain so until the investigation wraps up. Similar incident happened to the Trumps The situation comes one day after a white substance, along with a threatening note, was sent to Donald Trump Jr.’s wife in New York City. On Monday morning at around 10:00 a.m., Vanessa Trump opened the package, which had been sent to Trump Jr.’s Manhattan apartment. When firefighter and police arrived along with emergency medical responders, Vanessa Trump and two other people were decontaminated and taken to the New York-Presbyterian Weill Cornell Medical Center as a precaution. “The substance was deemed to be non-hazardous and is being transported to a lab in New York City for further analysis,” said NYPD spokesman J. Peter Donald, according to ABC News. The NYPD also said that the Secret Service would also be a part of the investigation. The letter accompanied with the powder read, “You’re an awful person and now you get what you deserve.” The white substance turned out to be cornstarch. These incidents are reminiscent of letters containing lethal anthrax spores that were sent following the 9/11 terrorist attacks. The letters were sent to the offices of several politicians and media outlets and resulted in five deaths. | Low | [
0.534615384615384,
34.75,
30.25
] |
Embattled D.C. Mayor Concedes In Primary Last night, Muriel Bowser, Democratic mayoral candidate in Washington, D.C., won the primary election positioning her to be the next mayor of the nation’s capital. The election took a dramatic twist three weeks ago when federal prosecutors alleged that the current Mayor Vincent Gray was aware of an illegal $680,000 slush fund that aided his 2010 mayoral campaign. And Washington, D.C. has a new mayor-elect, sort of. Last night, Muriel Bowser won the Democratic primary election, which is usually, for all intents and purposes, the general election in D.C. She beat Mayor Vincent Gray, who was elected in 2010 in a campaign that was plagued with corruption, which Bowser alluded to in her victory speech. MURIEL BOWSER: We believe that corruption at city hall in unacceptable. We believe that our mayor must break new ground and command the moral authority to lead. HOBSON: Now, the race is a local race, but it is the nation's capital in a city that has seen an economic boom in recent years. Patrick Madden is city hall reporter with WAMU in Washington. He's with us now. Patrick, welcome. PATRICK MADDEN, BYLINE: Thank you, Jeremy. HOBSON: Well, what are people saying this morning? Is this an upset? MADDEN: This was an interesting race because on one hand, as you mentioned, D.C.'s economy is booming, test scores are up, violent crime is down. This, for all intents and purposes, should've been a cakewalk for the mayor, Mayor Gray, who's the incumbent facing re-election. But there was a big campaign finance scandal. And about three weeks before the primary, federal prosecutors basically alleged that the mayor knew about this illegal, off-the-books shadow campaign that helped his previous race in 2010, and that changed the total dynamics of the race. And one of his challengers, who's a local city councilmember, really capitalized on it and surged to victory. HOBSON: But D.C. is certainly well versed in the world of campaign political scandals, right? Marion Barry comes to mind. MADDEN: Right. D.C. is no stranger to scandal, especially at the local level. We've had several councilmembers who have been sent to jail for various crimes. And, of course, we have Marion Barry who is now on the council as we speak, and he actually played a role in this race. He endorsed the mayor in the final days of the race. And actually on Twitter, Marion Barry last night, after the results came in, said that this race was decided by the U.S. attorney, Ron Machen, sort of pointing out, which many of the supporters of the mayor have said is that the timing of this in court really hurt the mayor's chances. HOBSON: Now, there was a lot of distress four years ago when the city's former mayor, Adrian Fenty, was ousted by Vincent Gray after just one term, because he was seen as a real reformer whereas Gray was seen as more of a status quo politician who would protect, for example, people who had jobs working for the city. Is Bowser more like Gray or Fenty or something different? MADDEN: Bowser is essentially a Fenty protege. She became a councilmember with the support of Adrian Fenty. A lot of her campaign staff were Fenty campaign staff. They have the same campaign colors - this bright green - so she really is part of the Fenty camp. And what's also interesting, if you look back, similar dynamics with Fenty. People thought the city was going - heading in the right direction. They just essentially didn't like him. With Gray, people think the city was going in the right direction. They just couldn't see past the ethics scandal. HOBSON: Now, we mentioned in the introduction, Patrick, that D.C. has had a real economic boom over the last several years. How did that play into the race? Because the issues that come along with that include gentrification, which I know many D.C. residents who have lived in neighborhoods for a long time are very upset that they're being priced out. MADDEN: Well, I think you nailed it right there. This race - a lot of the issues besides the ethic scandal came down to just how expensive D.C. is. I mean one of the real flashpoints in the race was the explosion of homeless families. And it's become a real sort of symbol for what's happened in the District in terms of families being placed out of the city because of how expensive it is and gentrification. HOBSON: Patrick Madden is the city hall reporter for WAMU in Washington. Patrick, thanks so much for joining us. MADDEN: Thanks a lot. HOBSON: This is HERE AND NOW. Transcript provided by NPR, Copyright NPR. | Mid | [
0.5647058823529411,
36,
27.75
] |
Vaccination has reduced the occurrence and burden of many diseases, making us forget how truly awful some of them were. This video by geobeats explores the 10 deadliest diseases throughout all of human history. | High | [
0.698499317871759,
32,
13.8125
] |
Intensive insulin regimens: evidence for benefit. It is now well established that the risk of experiencing diabetic complications is dependent on the degree of glycaemic control in patients with diabetes. Clinical trials such as the Diabetes Control and Complications Trial (DCCT) and Kumamoto study have demonstrated that tight glycaemic control achieved with intensive insulin regimens can reduce the risk of developing or progressing retinopathy, nephropathy or neuropathy in patients with type I or II diabetes. The EDIC trial, a follow-up to the DCCT, has shown that the previous degree and duration of glycaemic exposure are also important determinants of risk of developing microvascular diabetic complications. It appears that beneficial outcomes with regard to microvascular risk can be achieved with the improved metabolic control associated with intensive insulin regimens; however, data examining the effect of intensive insulin regimens on macrovascular risk is inconclusive. Epidemiological data highlight the role of postprandial blood glucose in cardiovascular disease and mortality, especially in patients with type II diabetes. Consequently, it is logical to suppose that insulin regimens that control both fasting plasma glucose and postprandial glucose excursions should also achieve the best macrovascular risk outcomes and there are some data that suggest this. Intensive insulin treatment can also improve prognosis in acute clinical situations such as myocardial infarction in patients with or without diabetes. In summary, intensive insulin regimens achieve strict metabolic control in patients with diabetes and could offer the best possible outcomes with regard to microvascular and macrovascular complications. | High | [
0.678217821782178,
34.25,
16.25
] |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.