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[ "Ta•o Taido\n\nis a 1993 fighting arcade game developed and published by Video System. ", "It was Video System's only attempt in the fighting game genre, and it was created during the fighting game trend of the 1990s that was popularized by Capcom's 1991 arcade hit Street Fighter II.", "\n\nGameplay\nThe game takes place on Earth, where eight martial artists from around the planet compete against each other to fight and defeat the legendary master and reveal the secrets of Ta•o Taido. ", "The game appears to be similar to other 2D versus fighting games during its release, but has different gameplay. ", "The player's character fights against his or her opponent in single round matches in a single player tournament mode with the computer or against another human player, while using very simplistic commands that summon charging attacks. ", "Players press and hold two out of three buttons down to charge up, then move the joystick toward a direction to perform an attack. ", " The longer the players hold two buttons down, the more powerful and longer the attack gets and lasts; however, there are three levels of energy, and after the third and highest charge, it returns to the first and lowest charge. ", "Short charges create weak moves, medium charges create moderate moves, and long charges create strong attacks. ", "Both players have 3 levels of health in each round, instead of one like in most other fighting games. ", " Ta•o Taido also has a cooperative 2-player feature similar to the ones in SNK's Street Smart and Fatal Fury: King of Fighters. ", " The controls can be switched to what most other fighting games have.", "\n\nCharacters\nPlayers have a character roster of eight fighters to choose from, and one unplayable boss. ", "Each with their own unique fighting style and special techniques.", "\n - The protagonist of the game.", "\n\n - Later appeared in the 1995 Neo Geo title Aero Fighters 3.", "\n\nBoss\n - Teacher Chung's older twin.", "\n\nExternal links\nTa•o Taido at The Large Cult Fighting Game March \n\nTa•o Taido at arcade-history\n\nCategory:1993 video games\nCategory:Arcade games\nCategory:Arcade-only games\nCategory:Cooperative games\nCategory:Video System games\nCategory:Multiplayer video games\nCategory:Versus fighting games\nCategory:Video games developed in Japan" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "Curtis-Wright Flow Control Wins 25k Grant for Energy Management Program\n\nCurtiss-Wright Flow Control Company''s EMD business unit, located in Cheswick, PA, was awarded a $25,000 grant from the Pennsylvania Technical Assistance Program, sponsored by the U.S. Department of Energy (DOE),\n\nCurtiss-Wright Flow Control Company”s EMD business unit, located in Cheswick, PA, was awarded a $25,000 grant from the Pennsylvania Technical Assistance Program, sponsored by the U.S. Department of Energy (DOE), to support its efforts to become ISO 50001 certified for excellence in energy management.", "\n\nEMD applied for a grant through a new DOE-sponsored program called the Pennsylvania Technical Assistance Program, which is administered through Pennsylvania State University. ", "In May, EMD was selected to participate in the Pennsylvania Superior Energy Performance Demonstration project.", "\n\nAs a participant, EMD will receive training and other support to implement an energy management program that conforms to ISO 50001. ", "Certification and assessment to the ISO standard will take approximately 18 months to achieve. ", "To date, only 35 companies in the nation have been selected to participate in the certification program.", "\n\n“We are honored to be selected as a member of this elite group and look forward to applying energy management best practices throughout all of our businesses,” said Greg Hempfling, senior VP & GM of the Electro-Mechanical Systems Division of Curtiss-Wright Flow Control Company." ]

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[ "Introduction {#sec1_1}\n============\n\nTumor markers may be defined as molecules which indicate the presence of cancer or provide information about the likely future behavior of a cancer (i.e., likelihood of progression or response to therapy) \\[[@B1],[@B2]\\]. ", "In asymptomatic subjects, tumor markers are potentially used in screening for early malignancy. ", "In symptomatic patients, markers may help in the differential diagnosis of benign and malignant disease. ", "Following diagnosis and surgical removal of a malignancy, markers may be used for assessing prognosis, postoperative surveillance, therapy prediction and monitoring response to systemic therapy \\[[@B1],[@B2]\\].", "\n\nIrrespective of its application, an ideal tumor marker should exhibit the following characteristics: possess a high positive and negative predictive value;have an inexpensive, simple, standardized and automated assay with clearly defined reference limits;be acceptable to subjects undergoing the test; andhave its clinical value validated in a large prospective trial.", "\n\nSuffice it to state, the ideal tumor marker does not currently exist. ", "Despite this, several markers are now indispensable in the management of patients with cancer. ", "The aims of this article are to review the most widely measured markers in clinical practice and summarize published guidelines for their use.", "\n\nUse of Markers in Screening for Cancer {#sec1_2}\n======================================\n\nScreening involves the detection of early disease or a preclinical state in subjects without signs or symptoms of disease. ", "Unlike disease diagnosis, screening is performed on individuals without any clinical sign of disease. ", "Compared to established screening tests such as mammography for breast cancer, the Papanicolaou test for cervical cancer and colonoscopy for colorectal cancer (CRC), the use of tumor markers might be expected to have practical advantages in cancer screening \\[[@B3]\\]. ", "These advantages include \\[[@B3]\\]: Markers can be measured in fluids such as blood and urine that can be obtained with minimal inconvenience to the individuals undergoing screening.", "For many markers, automated assays are available, allowing the processing of large numbers of samples in a relatively short period of time.", "Tests for markers provide quantitative results with objective endpoints.", "Assays for markers are relatively cheap compared to radiological, histological and endoscopy procedures.", "\n\nDespite these advantages, markers have several limitations as cancer screening tests. ", "In particular, lack of sensitivity for early invasive disease or premalignant lesions and lack of specificity for malignancy limit the use of existing markers in screening asymptomatic subjects for early malignancy \\[[@B1],[@B3]\\]. ", "The dual problem of limited sensitivity and specificity, especially when combined with the low prevalence of most cancers in the community, means that markers, if used alone, have low positive predictive values in screening asymptomatic populations. ", "Indeed, it is the low prevalence of cancer in the general population that prohibits most biomarkers from being used in screening for cancer \\[[@B1],[@B3]\\]. ", "Despite this, a number of markers have either undergone or are presently undergoing evaluation for cancer screening (table [1](#T1){ref-type=\"table\"}). ", "Some of the most widely investigated markers in cancer screening are now discussed.", "\n\nFecal Occult Blood Testing in Screening for CRC {#sec2_1}\n-----------------------------------------------\n\nOne of the best validated screening markers is the use of fecal occult blood testing (FOBT) in screening for CRC. ", "Indeed, 4 large randomized prospective trials carried out in Europe and North America have all shown that screening apparently healthy subjects over 50 years of age using FOBT significantly reduced mortality from CRC \\[[@B4]\\]. ", "Combined results from the 4 trials showed that the screening resulted in a 16% reduction in the relative risk of CRC mortality \\[[@B4]\\]. ", "Following adjustment for those subjects that failed to attend screening, mortality reduction increased to 25%.", "\n\nScreening healthy individuals aged ≥50 years using FOBT is now recommended, especially in Europe \\[[@B5],[@B6]\\]. ", "Although the 4 prospective randomized trials mentioned above all used a guaiac-based FOBT, both the European Group of Tumor Markers (EGTM) and a European Union expert panel currently recommend the use of a fecal immunochemical test in screening for CRC \\[[@B5],[@B6]\\]. ", "As previously reviewed, the use of fecal immunochemical tests have several advantages vis-à-vis FOBTs, including greater analytical sensitivity and specificity, improved clinical performance and potential for automation \\[[@B5]\\].", "\n\nProstate-Specific Antigen in Screening for Prostate Cancer {#sec2_2}\n----------------------------------------------------------\n\nIn contrast to FOBT in screening for CRC, the clinical value of prostate-specific antigen (PSA) in screening for prostate cancer is less clear \\[[@B7]\\]. ", "In 2009, results from 2 large randomized prospective trials evaluating the screening potential of this marker were published. ", "The first of these trials was carried out in the USA and involved 76,693 men that were randomized to either annual screening or regular care \\[[@B8]\\]. ", "Following analysis at 7--10 years of follow-up, death rates were similar in the 2 groups. ", "A limitation of this study was that approximately 50% of men in the control group underwent screening during the study. ", "This trial could thus be regarded as a comparison between a heavily screened group and a less heavily screened group rather than a true randomized trial \\[[@B8]\\]. ", "A further limitation was that approximately 40% of the men participating had a PSA test prior to the start of the trial. ", "These men were thus less likely to be diagnosed with prostate cancer during the trial proper.", "\n\nIn a somewhat similar but larger trial carried out in Europe, 162,243 men were randomly allocated to PSA screening or to a control group not subjected to screening \\[[@B9]\\]. ", "After a median follow-up of 9 years, death rates from prostate cancer were found to be 20% lower in the screened compared to the control group. ", "This apparent benefit, however, resulted in major overdetection and overtreatment. ", "Thus, according to the paper\\'s authors, 1,410 men would have to be screened and 48 additional cases of prostate cancer would have to undergo treatment to prevent 1 death from prostate cancer \\[[@B9]\\].", "\n\nWith these conflicting findings it is not surprising that guidelines published by expert panels vary with respect to PSA screening for prostate cancer, i.e., while some groups recommend screening, others are opposed to the practice \\[[@B7],[@B10]\\]. ", "Although expert panels disagree on whether or not to recommend PSA screening, most recommend that prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early disease detection \\[[@B7]\\]. ", "Only after receiving such information should PSA screening be initiated.", "\n\nCA 125 in Screening for Ovarian Cancer {#sec2_3}\n--------------------------------------\n\nFor the past decade or so, 2 large prospective randomized trials have been evaluating the role of CA 125 and transvaginal ultrasound in screening for ovarian cancer \\[[@B11],[@B12]\\]. ", "One of these trials recently reported its findings \\[[@B13]\\]. ", "In this trial carried out in the USA, 78,216 women aged 55--74 years were randomized to undergo either annual screening with CA 125 for 6 years and transvaginal ultrasound for 4 years or standard care. ", "After 13 years of follow-up, death rates were similar in the screened and control groups. ", "Clearly, in this trial, screening with CA 125 and transvaginal ultrasound did not reduce ovarian cancer mortality \\[[@B13]\\]. ", "According to the EGTM guidelines, CA 125 either alone or in combination with other modalities cannot be recommended in screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial \\[[@B14]\\].", "\n\nα-Fetoprotein in Hepatocellular Cancer {#sec2_4}\n--------------------------------------\n\nSubjects at increased risk of developing hepatocellular cancer (HCC) include those with cirrhosis due to infection with hepatitis B virus or hepatitis C virus, genetic hemochromatosis or biliary cirrhosis. ", "Guidelines published by expert panels differ in their recommendations regarding the use of α-fetoprotein (AFP) in screening for HCC. ", "Thus, the National Academy of Clinical Biochemistry USA (NACB) \\[[@B15]\\] state that, 'AFP should be measured and abdominal ultrasound performed at six-monthly intervals in patients at high risk of HCC, especially in those with hepatitis B and hepatitis C-related liver cirrhosis. ", "AFP concentrations that are \\>20 µg/l and showing consistent increases in concentration should prompt further investigation even if ultrasound is negative.' ", "On the other hand, the American Association for the Study of Liver Disease recommend that surveillance of high-risk subjects should be performed only with ultrasound. ", "According to this organization, AFP should only be used when ultrasound is not available. ", "This latter recommendation is based on the limited use of AFP in detecting early HCC.", "\n\nUse of Markers as Diagnostic Aids for Cancer {#sec1_3}\n============================================\n\nAs discussed above with screening, limited sensitivity for small or early cancers and lack of tumor specificity preclude the use of serum markers for the primary diagnosis of cancer. ", "In a limited number of situations, however, markers may aid in the differential of benign and malignant disease. ", "Thus, CA 125 is used as an adjunct in differentiating between benign and malignant pelvic masses in postmenopausal women \\[[@B14]\\]. ", "The EGTM recommend that CA 125 should be measured in postmenopausal women presenting with such masses. ", "According to this expert panel, patients with elevated levels (e.g. \\>35 U/l) should be considered for referral to a surgeon specialized in gynecological oncology surgery \\[[@B14]\\]. ", "This recommendation was based on studies showing superior outcome in patients with ovarian cancer if treated by a gynecological oncologist rather than by a general surgeon \\[[@B16]\\].", "\n\nAnother marker that may be helpful in cancer diagnosis is AFP in the detection of HCC. ", "According to the American Association for the Study of Liver Disease, finding a hepatic mass of \\>2 cm in diameter in a patient with a cirrhotic liver is highly suspicious of HCC. ", "If AFP is \\>200 µg/l and the radiological appearance is suggestive of HCC, the likelihood is that the lesion is HCC and biopsy is not essential \\[[@B17]\\]. ", "Similar recommendations have been published by the NACB \\[[@B15]\\]. ", "AFP, however, is of limited value in aiding the diagnosis of lesions \\<2 cm in diameter.", "\n\nUse of Markers in Assessing Prognosis {#sec1_4}\n=====================================\n\nPrognostic markers provide information on the likely outcome following diagnosis of a disease. ", "Such markers may help avoid undertreatment of patients with aggressive disease and overtreatment of those with indolent disease. ", "Prognostic markers are most important in cancers that vary widely in their outcome such as prostate and breast cancer. ", "In these cancers, prognostic markers may help identify those patients with aggressive disease that could benefit from additional therapies and simultaneously select those patients who may not require additional therapy.", "\n\nPrognostic markers are most widely used in breast cancer, especially in the subset with lymph node-negative disease. ", "In this subgroup of patients with breast cancer, prognostic markers help identify patients who may be spared the toxicity and side effects of adjuvant chemotherapy. ", "The 2 best validated prognostic markers for breast cancer are the Oncotype DX test and uPA/PAI1. ", "The Oncotype DX test measures the expression of 16 cancer-associated and 5 control genes by RT-PCR on RNA isolated from paraffin-embedded breast cancer tissue \\[[@B18]\\]. ", "This test is currently available from a commercial laboratory in the USA. ", "Although the Oncotype DX test is recommended by several expert panels including the American Society of Clinical Oncology (ASCO), NACB and EGTM \\[[@B10],[@B19],[@B20]\\], the test has not yet been validated in a large prospective randomized trial. ", "Such a study, however, is ongoing as part of the TAILORx trial.", "\n\nuPA and PAI-1 are the best validated prognostic markers in breast cancer, especially for patients with lymph node-negative disease \\[[@B21]\\]. ", "uPA is a protease that mediates invasion and metastasis. ", "Although PAI-1 normally functions as an endogenous inhibitor of uPA activity, at the high concentrations frequently present in tumors it appears, like uPA, to also play a role in cancer spread \\[[@B21]\\]. ", "Unlike any other marker in breast cancer, the prognostic impact of uPA and PAI-1 has been validated in both a multicenter randomized prospective trial and a pooled analysis of raw data from several small retrospective and a prospective study \\[[@B22],[@B23]\\], i.e., in 2 level I evidence studies.", "\n\nAs with Oncotype DX, measurement of uPA/PAI-1 is recommended by a number of expert panels \\[[@B10],[@B19],[@B20]\\]. ", "According to ASCO, 'uPA and PAI-1 may be used for the determination of prognosis in patients with newly diagnosed, node negative breast cancer. ", "Low levels of both markers are associated with a sufficiently low risk of recurrence, especially in hormone receptor-positive women who will receive adjuvant endocrine therapy, that chemotherapy will only contribute minimal additional benefit. ", "Furthermore, CMF-based adjuvant chemotherapy provides substantial benefit, compared with observation alone, in patients with high risk of recurrence as determined by high levels of uPA and PAI-1' \\[[@B19]\\]. ", "Other widely studied cancer prognostic markers are listed in table [2](#T2){ref-type=\"table\"}.", "\n\nTherapy-Predictive Markers in Cancer {#sec1_5}\n====================================\n\nAs mentioned above, therapy-predictive markers are factors that prospectively identify likely response or resistance to a specific treatment. ", "Predictive markers are important in cancer patient management as patients with the same histological type of malignancy respond very differently to a specific drug. ", "Thus, response rates for patients with different types of advanced cancer to currently available systemic treatments vary from about 10 to \\>90% \\[[@B24]\\]. ", "Many of the newer biological therapies, in particular, have efficacy in only a minority of patients. ", "This finding, when combined with the high costs of these drugs \\[[@B25]\\], illustrates the importance of having accurate predictive markers.", "\n\nAs well as assessing efficacy, predictive markers may also be able to identify optimum drug dose and predict toxicity. ", "Thus, measurement of predictive markers can increase drug efficacy and result in decreased toxicity. ", "This, in turn, should reduce overall health care costs and lead to an enhanced quality of life for patients \\[[@B26]\\].", "\n\nAs with prognostic markers, predictive markers are most developed for breast cancer. ", "Thus, in breast cancer, measurement of estrogen receptors and progesterone receptors is universally used to identify patients for treatment with hormone therapy (tamoxifen or aromatase inhibitor), while the assay of human epidermal growth factor receptor 2 is routinely used to select patients for treatment with trastuzumab (Herceptin) or lapatinib \\[[@B27]\\]. ", "Newly introduced predictive markers include mutant KRAS status for identifying responsiveness to anti-epidermal growth factor receptor antibodies (cetuximab and panitumumab) in advanced CRC and epidermal growth factor receptor mutation status for selecting patients with advanced non-small cell lung cancer for treatment with anti-epidermal growth factor receptor kinases (gefitinib and erlotinib) \\[[@B27]\\].", "\n\nUse of Markers in Surveillance following Initial Treatment for Cancer {#sec1_6}\n=====================================================================\n\nOne of the most frequent uses of tumor markers at present is in the postoperative follow-up of patients following a diagnosis of malignancy (table [3](#T3){ref-type=\"table\"}). ", "In several situations, serial levels of cancer markers can predict the presence of early recurrent/metastatic disease, i.e., provide a lead time over clinical or radiological findings. ", "It is assumed that the early detection of recurrent/metastatic disease followed by the initiation of treatment enhances the chance of cure or results in an improved survival \\[[@B2]\\]. ", "For some cancer types, however, the evidence currently available does not support this widely held assumption. ", "Indeed, the value of makers in postoperative surveillance may vary from cancer to cancer. ", "Below, I discuss the usefulness of markers in surveillance following the diagnosis of different cancers.", "\n\nCarcinoembryonic Antigen in CRC {#sec2_5}\n-------------------------------\n\nMultiple studies have shown that following curative surgery for CRC, patients undergoing an intensive surveillance regime that included regular carcinoembryonic antigen (CEA) measurements had a significantly better outcome than those undergoing surveillance without CEA testing \\[[@B28],[@B29]\\]. ", "Most expert panels in Europe and the USA therefore recommend serial measurements of CEA following curative surgery for CRC \\[[@B10],[@B30],[@B31],[@B32]\\]. ", "According to the EGTM, 'CRC patients with stage II and III (Dukes' B and C) CRC that may be candidates for either liver resection or systemic treatment in the event of recurrence in that organ, should have CEA measured every 2 to 3 months for at least 3 years after diagnosis' \\[[@B30],[@B31]\\]. ", "Although serial measurements of CEA are widely recommended as part of a surveillance regime, agreement is lacking as to the extent of concentration change that constitutes a clinically significant increase in marker levels. ", "According to the EGTM group \\[[@B30]\\], 'a significant increase in CEA levels occurs if the elevation is at least 30% over that of the previous concentration'. ", "This organization also states that prior to initiating therapy, any increase must be confirmed by a second sample taken within approximately 1 month. ", "If the second sample is also increased, the patient should undergo further investigations such as imaging \\[[@B30]\\].", "\n\nAFP and Human Chorionic Gonadotrophin in Patients with Germ Cell Tumors {#sec2_6}\n-----------------------------------------------------------------------\n\nTwo main histological types of germ cell tumors exist, seminoma and non-seminoma. ", "The use of AFP and human chorionic gonadotrophin (HCG) in monitoring patients with the non-seminomatous type germ cell tumors of the testis is often regarded as approximating the ideal use of tumor markers \\[[@B2]\\]. ", "This is because these 2 markers are sensitive indicators of germ cell disease status, i.e., whether disease is stable, progressing or regressing. ", "A further reason why these markers are particularly helpful in patients with germ cell tumors is that these malignancies are highly chemosensitive. ", "Indeed, it is now widely accepted that following orchidectomy for non-seminomatous testicular germ cell tumors, increasing AFP or HCG levels in the absence of radiological or clinical evidence of disease suggests active disease and may provide sufficient reassurance to initiate treatment, provided likely causes of false-positive marker levels can be eliminated \\[[@B2]\\].", "\n\nAccording to the ASCO guidelines, AFP and HCG should be assayed during surveillance following definite therapy for non-seminomatous germ cell tumors, regardless of stage \\[[@B33]\\]. ", "These measurements may be carried out every 1--2 months in the first year, every 2--4 months in the second year, every 3--6 months in the third and fourth years, every 6 months in the fifth year and annually thereafter. ", "Surveillance should be continued for at least 10 years after therapy is completed. ", "For monitoring patients with pure seminoma, HCG and/or LDH are generally recommended \\[[@B33]\\].", "\n\nCA 125 in Patients with Ovarian Cancer {#sec2_7}\n--------------------------------------\n\nThe clinical value of serial determination of CA 125 in post-therapy monitoring of patients with a history of ovarian cancer is unclear. ", "Although regular measurement of the marker may detect early recurrences with a median lead time of 4--5 months \\[[@B34]\\], a recently completed prospective randomized trial found no survival benefit from starting early treatment based on a rising serum CA 125 level \\[[@B35]\\]. ", "This trial involved 1,442 women previously diagnosed with ovarian cancer but in clinical remission. ", "CA 125 levels were measured every 3 months, but the results were not made available to patients or their doctors. ", "The women were randomized when their marker concentrations reached twice the upper limit of the normal range, to receive treatment immediately or to continue with blinded CA 125 determinations. ", "In this latter situation, women underwent treatment only when there was clinical evidence of recurrence. ", "Despite the earlier introduction of second-line chemotherapy, no significant difference in overall survival was found in the 2 groups. ", "This negative finding may relate, at least in part, to the lack of effective therapy for recurrent ovarian cancer.", "\n\nUncertainties therefore exist with respect to the value of CA 125 measurement and timing of treatment for relapsed ovarian cancer. ", "Although the NACB panel currently recommends serial measurement of CA 125 following surgery and initial systemic therapy for ovarian cancer \\[[@B10]\\], the EGTM panel is opposed to this practice \\[[@B14]\\]. ", "With such conflicting recommendations, a practical way forward may be to take the patients' wishes into consideration.", "\n\nPSA in Prostate Cancer {#sec2_8}\n----------------------\n\nIrrespective of whether men with diagnosed prostate cancer undergo active treatment (e.g. with radical prostatectomy, radiotherapy or brachytherapy) or active surveillance, regular monitoring with PSA is now commonly carried out \\[[@B36]\\]. ", "Following successful radical prostatectomy, PSA levels should decline to undetectable levels. ", "A subsequent increase to ≥0.2 µg/l is defined as biochemical recurrence \\[[@B37]\\]. ", "Generally, decreases in PSA levels following radiation therapy are less than those following radical prostatectomy. ", "A rise in PSA levels of ≥2 µg/l over and above the nadir value has been proposed as a definition of radiation therapy failure \\[[@B38]\\]. ", "It is still unclear whether the introduction of salvage therapy based on these definitions of PSA recurrence enhances patient outcome or quality of life.", "\n\nCA 15-3 in Breast Cancer {#sec2_9}\n------------------------\n\nThe most widely used marker in surveillance following a diagnosis of breast cancer is CA 15-3 \\[[@B39]\\]. ", "Although widely used in some countries for this purpose, it is unclear whether serial measurement improves patient outcome. ", "Consequently, guidelines vary with respect to their recommendations on the use of CA 15-3 in monitoring asymptomatic women following a diagnosis of breast cancer. ", "While expert panels such as ASCO recommend against routing use of CA 15-3 in surveillance in the surveillance of breast cancer patients \\[[@B19]\\], EGTM endorses its measurement in this setting \\[[@B20]\\]. ", "According to the NACB guidelines \\[[@B10]\\], 'CA 15-3 should not be routinely used for the early detection of recurrences/metastases in patients with diagnosed breast cancer. ", "However, as some patients, as well as some doctors, may wish to have these measurements, the ultimate decision on whether or not to use CA 15-3 must be taken by the doctor in consultation with the patient.'", "\n\nMonitoring Systemic Therapy {#sec1_7}\n===========================\n\nAnother frequent use of tumor markers is in monitoring patients with advanced cancer receiving systemic therapy (table [3](#T3){ref-type=\"table\"}) \\[[@B1],[@B2],[@B10]\\]. ", "The markers used in monitoring therapy in a specific malignancy are the same as those measured in postoperative surveillance (see above). ", "Generally, decreasing levels of markers following the initiation of therapy correlates with tumor regression and increasing levels predict progressive disease. ", "Tumor markers, however, should not be used alone in assessing response to therapy.", "\n\nA caveat in the use of markers in monitoring therapy in patients with advanced malignancy is the possible occurrence of transient increases or spikes within the first few weeks of administering therapy. ", "These transient increases appear to be due to tumor cell necrosis or apoptosis in response to the initial treatment with chemotherapy. ", "Such transient increases have not yet been reported with biological therapies such as therapeutic antibodies (e.g. Herceptin, cetuximab or panitumumab).", "\n\nConclusion {#sec1_8}\n==========\n\nFrom above, it is clear that certain tumor markers are mandatory in the management of patients with certain types of cancer. ", "Indeed, in some situations, markers can be used as the sole criterion for clinical decision making. ", "This applies particularly for therapy-predictive markers such as estrogen receptor and human epidermal growth factor receptor 2 in breast cancer. ", "Another good example is the use of HCG and AFP in therapy decision making in patients with diagnosed non-seminomatous germ cell tumors. ", "In other situations, however, the value of markers is less clear, for example, the role of PSA in screening for prostate cancer, assay of CA 125 following surgery and chemotherapy for ovarian cancer and assay of CA 15-3 in the surveillance of patients following the diagnosis of breast cancer. ", "Hopefully, future studies will provide definite answers on the use of these markers, in the near future. ", "New procedures for measuring tumor markers in the future are likely to focus on gene expression microarray, proteomics and detection of circulating tumor cells.", "\n\nThe authors wish to thank Science Foundation Ireland, Strategic Research Cluster Award (08/SRC/B1410) to Molecular Therapeutics for Cancer Ireland.", "\n\n###### \n\nBiomarkers that have undergone or are currently under-going evaluation in screening asymptomatic subjects for cancer\n\n Marker or test Malignancy\n ---------------- -------------------------------------------------\n FOBT colorectal\n PSA prostate\n CA 125 ovarian\n VMA/HVA neuroblastoma\n AFP hepatocellular[^1^](#T1F1){ref-type=\"table-fn\"}\n Pepsinogen gastric[^1^](#T1F1){ref-type=\"table-fn\"}\n HCG trophoblastic[^2^](#T1F2){ref-type=\"table-fn\"}\n\nVMA = Vanillylmandelic acid; HVA = homovanillic acid.", "\n\nOnly in high-risk areas/high-risk subjects.", "\n\nIn patients who have had a previous hydatidiform mole.", "\n\n###### \n\nMarkers that may be used for determining prognosis in different cancers\n\n Cancer Marker(s)\n ------------ ------------------------\n Breast Oncotype DX, uPA/PAI-1\n Germ cell AFP, HCG, LDH\n Colorectal CEA, MSI\n Prostate PSA\n Ovarian CA 125\n\nLDH = Lactate dehydrogenase; MSI = microsatellite instability.", "\n\n###### \n\nSerum markers that may be used in postoperative surveillance and monitoring therapy in different cancers\n\n Cancer Marker(s)\n -------------------------- -----------------\n Colorectal CEA\n Hepatocellular AFP\n Pancreatic CA 19-9\n Ovarian CA 125\n Breast CA 15-3\n Prostate PSA\n Germ cell AFP, HCG\n Lung (non-small cell) CYFRA 21-1, SCC\n Lung (small cell) NSE, proGRP\n Melanoma S100\n Trophoblastic HCG\n Thyroid (differentiated) thyroglobulin\n\nSCC = Squamous cell carcinoma; NSE = neuron-specific enolase.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Jarl Öhman\n\nJarl (\"Lali\") Öhman (14 November 1891 in Helsinki – 20 January 1936 in Kokkola) was a Finnish amateur football player who competed in the 1912 Summer Olympics.", "\n\nHe was a part of the Finnish football team squad, which finished fourth in the football event. ", "He participated in all four matches in the main tournament and scored two goals.", "\n\nHe was also the first manager of the Finland national football team.", "\n\nCategory:1891 births\nCategory:1936 deaths\nCategory:Association football forwards\nCategory:Finnish footballers\nCategory:Finland international footballers\nCategory:Finland national football team managers\nCategory:Vaasan Palloseura players\nCategory:Footballers at the 1912 Summer Olympics\nCategory:Olympic footballers of Finland\nCategory:Sportspeople from Helsinki\nCategory:Finnish football managers" ]

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[ "India’s Q1 solar power production surges 103%\n\nMay 4 (Renewables Now) - Solar photovoltaic (PV) parks in India generated 8.54 billion kWh of electricity in the first quarter of 2018, registering a 103% year-on-year jump, Mercom Capital Group said on Friday.", "\n\nSolar power production was also 31% higher as compared to the fourth quarter of last year, which saw generation of over 6.5 billion kWh, the consultancy said, citing data from India’s Central Electricity Authority (CEA). ", "The growth was achieved on the back of rising solar capacity additions.", "\n\nAccording to Mercom’s India Solar Project Tracker, the cumulative installed solar power capacity in India at the end of January was 20 GW, while at the end of March it exceeded 22 GW. ", "First-quarter capacity deployments surged due to the commissioning of several large-scale PV parks that could not secure grid-connection last year.", "\n\nFor 2018, Mercom previously projected that India will put on stream 7 GW of fresh PV capacity, expecting the market to be affected by the rising prices of Chinese PV modules, certain infrastructure and power evacuation issues and the renegotiation of power purchase agreements (PPAs) terms in line with the record-low level of solar tariffs." ]

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[ "An experimental geneticist looks at catecholamine metabolism.", "\nThe contributions of genetic variation, including that at unstable and duplicated loci, interactions between alleles at different loci and genotype-environment interaction to observable phenotypic variation in experimental animals are discussed with particular reference to catecholamine metabolism. ", "The possibilities and complexities involved in extrapolating to human populations, and to behavioural consequences of biochemical variation, are outlined." ]

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[ "Q:\n\nargs4j: How to make an argument required if another argument is/isn't given?", "\n\n@Options(name=\"--in-file\")\nString fileName;\n\n@Option(name=\"--table\")\nString table;\n\nI would like to make the --table option be required if and only if no value is given for --in-file. ", "How might I go about doing this? ", "I know that there are some solutions (I think at least) where I can do this with multiple classes, but that seems like overkill for only two arguments in a simple program. ", "\nI know I can also manually check the values after the parsing is completed, but that seems to defeat the purpose of using args4j.", "\n\nA:\n\nI realized I can use the forbids annotation option to most of accomplish this. ", "You only need the tag on one or the other, but I put it on both for completeness.", "\nUsing forbids\n@Options(name=\"--in-file\", forbids{\"--table\"})\nString fileName;\n\n@Option(name=\"--table\", forbids={\"--in-file\"})\nString table;\n\nOne could use the depends annotation for reverse logic.", "\n\nWhy the above is not complete:\nThe above is only partially correct: the solution still fails if you want one of the options to be required if another isn't given. ", "The required part overrules the forbids, so doing\n@Options(name=\"--in-file\", forbids{\"--table\"})\nString fileName;\n\n@Option(name=\"--table\", required=true, forbids={\"--in-file\"})\nString table;\n\ncauses a logic error in that if I give --in-file it tries to forbid --table but it can't because --table is required.", "\nSo, the original solution fails because it allows the user to give neither option, even though I want --table' to be required, if and only if --in-file` is not given. ", "So, basically, my original question.", "\nSo\n\nA:\n\nYou can use forbids as you mentioned. ", "\n@Options(name=\"--in-file\", forbids{\"--table\"})\nString fileName;\n\n@Option(name=\"--table\", forbids={\"--in-file\"})\nString table;\n\nAnd you can add check-condition in your class.", "\nif (fileName == null && table == null) {\n throw new CmdLineException();\n}\n\nYou can set exception message same with message shown when required option set.", "\n\n" ]

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[ "Obsession with the customer drives Amazon success\n\nThis video is probably pretty old now judging by the look of Jeff Bezos, the founder of Amazon.com. ", "However, it does bring to light something that is fast becoming the most important criteria to success in the global economy today.", "\n\nLooking at Amazon’s rise to success seems rapid and overnight, but like any successful venture, there is significant amount of foundation that is unseen to make it happen. ", "My Amazon account dates back to 1995 when I was an undergraduate in the US and it seemed like a novel way to buy books. ", "No more driving twenty miles to Borders bookstore in sub-zero temperatures, snow and all just to get my favorite book. ", "Let the UPS or FedEx driver brave the elements instead! ", "Fast forward 25 years years since Amazon started, and the company is basically selling everything literally A to Z, but more importantly, it is also growing its technology portfolio of cloud, AI, smart assistant and other service offerings.", "\n\nWatch the video attached here. ", "The reporter seems to focus only on whether Amazon.com was a pure Internet play. ", "I suppose, with the hindsight of the dotcom bubble, it’s easy to to laugh at this reporter but at that time, everything internet was the rage. ", "I like how Bezos continuously deflects the questions back to the customer. ", "Whether the company was a pure internet play, or whether the investors are concerned. ", "It is about obsessive attention to the customer experience – end to end. ", "And the last line is the best : There is never any misalignment between customer interest and shareholder interest.", "\n\nSo, let’s start today with an obsessive attention to the customer experience." ]

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[ "Sneak Peek | Inside Out Magazine's Colour (April) Issue!", "\n\nInside Out Mag sent over a bundle of colourful pixels from their new \"Colour Issue\" (April edition) out this Thursday for a sneak peek! ", "The latest issue features a heap of palette-flirting throughout the whole magazine and Managing Editor, Lee Tran Lam gives us the details:\n\n\"The cover story is all about getting playful with colour – and how you don't have to do anything too dramatic (or regret-inducing!) ", "at home, but you can sneak in new tones in a friendly way; for instance, add a band of lilac to wrap around your room, or an ocean-like splash to a white wall – or just drop a bright trim on your kitchen window or colour-match the mood of an artwork in your bedroom, as you can see in these photos styled by Julia Green and photographed by Armelle Habib.\"", "\n\nPhoto styled by Julia Green and photographed by Armelle Habib\n\nPhoto styled by Julia Green and photographed by Armelle Habib\n\nPhoto styled by Julia Green and photographed by Armelle Habib\n\n\"Another fun story in the magazine is our feature on the home of stylist and international pilot (yes, that's right!) ", "LeeAnn Yare. ", "Her Auckland home is as worldly and vibrant as her border-crossing work itinerary. ", "There's not a single dull patch in her house – the kitchen bench is covered in harlequin-patterned colours while her office is a wild patchwork of her favourite wallpapers. \"", "This is where I admit I have really gone crazy with an explosion of colour – it's like working inside a giant moodboard!\" ", "she says. ", "I love how unapologeticaly vivid and over-detailed her place is!\"", "\n\n~Lee Tran Lam\nManaging Editor, Inside Out Magazine\n\nStyling Leeanne Yare | Photo Larnie Nicolson\n\nStyling Leeanne Yare | Photo Larnie Nicolson\n\nStyling Leeanne Yare | Photo Larnie Nicolson\n\nStyling Leeanne Yare | Photo Larnie Nicolson\n\nThank you Lee Tran! ", "The April issue of Inside Out Magazine is out Thursday and is available at newsagents or digitally via Zinio, Google Play, iTunes & Nook." ]

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[ "(1) Field of the Invention\n(2) Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98\nThe disclosure and prior art relates to garden hose's and more particularly pertains to a new garden hose support for supporting a garden hose above a ground surface." ]

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[ "Dutch budget clothing store Zeeman plans to open 100 new outlets this year, most of them outside the Benelux region.", "\n\nThe retailer currently operates 1,236 stores across Europe, 550 of which are in the Netherlands and 279 in Belgium. ", "CEO Bart Karis told Belgian business daily De Tijd his company wants to expand further into other markets, ‘because we’re pretty much done with new stores in Belgium and the Netherlands’.", "\n\n‘Do we want to become a European chain? ", "We already are,’ said Karis, whose company also has outlets in Germany, Luxembourg and France.", "\n\nThe CEO said he saw his main competition coming from other cut-price retailers such as Primark. ‘", "Primark does indeed offer more fashionable clothing for low prices. ", "We sell more timeless clothing. ", "And yes, when a Primark opens up near a Zeeman we feel it.’", "\n\nZeeman scored an internet hit on Tuesday morning when it launched a wedding dress for €30. ", "The first batch of 1,500 garments was sold out within hours of going on sale at 6am." ]

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[ "Psychosocial factors influencing risk-taking in middle age for STIs.", "\nTo increase the knowledge of the psychosocial factors influencing sexual risk-taking for STIs among adults in late middle age. ", "Individual interviews were conducted either face to face or by telephone with 31 heterosexual men and women aged between 45 and 65. ", "They were recruited from NHS sexual health services (n=16) and council run culture and leisure facilities (n=15) in a large Scottish city. ", "A total of 18 women and 13 men were interviewed. ", "All interviews were transcribed in full and thematically analysed. ", "Analysis detailed important psychosocial and sociocultural factors; the prioritisation of intimacy above and beyond concerns about risks for STI in sexual partnerships; the importance of unwanted pregnancy in shaping risk perceptions throughout the life course; vulnerability associated with periods of relationship transition (eg, bereavement, divorce or separation); social norms and cultural expectations relating to age-appropriate sexual and health-seeking behaviours. ", "This is the first qualitative study to examine the factors associated with sexual risk-taking among heterosexual adults in late middle age in the UK. ", "Many factors associated with sexual risk-taking are similar to those reported within other populations. ", "However, we also detail population-specific factors, which should be considered in terms of the development of interventions for 'at risk' older adults, or the tailoring of wider behaviour change interventions to this specific age group." ]

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[ "Germany's 65-year-old former finance minister won 93.45 percent support from the Social Democrats (SPD), officially naming him as the party's man to challenge Angela Merkel in the next federal election, likely to take place in September. ", "Earlier in the week, Merkel won a similar Christian Democrat vote by an even clearer margin, claiming over 98 percent of her party's support.", "\n\nPrior to his election, Steinbrück - who had already been announced as candidate in waiting - delivered a combative 105-minute speech to the party at its conference in Hanover.", "\n\n\"I am running for the office of chancellor of the Federal Republic of Germany,\" Steinbrück said, telling his allies \"we owe it to this country to once again provide a Social Democratic chancellor.\"", "\n\nWatch video 01:06 Social Democrats place hopes in Steinbrück\n\nHe called the ruling Christian Democrats - who are comfortably the most popular single German party in opinion polls - a \"power machine.\"", "\n\n\"But retaining power is not the central target in politics,\" Steinbrück said, saying that Chancellor Merkel would too often speak in \"popcorn sentences\" - phrases that could be interpreted in many ways and offered little concrete substance.", "\n\n\"With Frau Merkel, many things remain vague - and that's not without its dangers,\" Steinbrück said.", "\n\nA Green or a Grand coalition?", "\n\nJudging by public broadcaster ARD's most recent opinion polls, a change in German government is currently likely at the next elections - but what shape that might take is unclear. ", "Merkel's junior coalition partners are in freefall, meaning that the current alliance with the pro-business Free Democrats looks unlikely to survive.", "\n\nSome say the most likely constellation would be a so-called \"grand coalition;\" an alliance between the Christian Democrats and the Social Democrats. ", "Steinbrück served as finance minister in such a government, but said he did not want to see it repeated.", "\n\nCalling for \"a full change in government,\" not half measures, Steinbrück told delegates \"the answer as to how this could work is quite obvious: red-green.\"", "\n\nThe SPD's party color is red, and its closest ally in opposition currently is the ecologist Green Party. ", "Combined, the two parties are six percent shy of the 50-percent level of support they would need to form a government. ", "Even though the SPD trails the Christian Democrats by nine percent, the combined pair are polling one-percent more strongly than the current coalition government.", "\n\nWith neither the natural left or right coalitions currently on course to win a majority, Steinbrück also urged his Social Democrats to stay unified during the election campaign to improve their standings.", "\n\n\"If we march side-by-side, then we will manage it,\" he told the delegates.", "\n\nmsh/pfd (AFP, dpa, Reuters)" ]

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[ "UPDATE (July 27, 2018):\n\nOn Thursday, a judge sentenced Perry Brown, Jr., of Elkton, to ten years in jail, with eight of those years suspended.", "\n\nBrown was accused of breaking into a home on 17th Street in Grottoes and assaulting two people in the house while wielding a handgun, sending Cotey Mitts, a 23-year-old Elkton man, to UVA Medical Center for treatment.", "\n\nIn fall of 2017, he was charged with felony attempted murder, felony malicious wounding, felony shooting into an occupied dwelling, felony assault and battery, and felony use of a firearm in the commission of a felony, in addition to breaking and entering.", "\n\nA school in the area was locked down as investigation happened, and police began a manhunt ending with Brown's arrest hours later.", "\n\nBut, through a plea deal, the only charge he was ultimately found guilty of was malicious discharge of a firearm into an occupied building.", "\n\nHis five additional felony charges were each dropped.", "\n\nThe eight years suspended from his jail time were given to Brown in probation instead.", "\n\nHowever, on July 27, he faced a probation violation hearing, which resulted in a 5-year sentence.", "\n\n________\n\nUPDATE (2:40 p.m. Sept. 14, 2017):\n\nPerry Brown Jr., the suspect in a Grottoes shooting that led to a school lockdown and manhunt last month, now faces additional charges.", "\n\nBrown was previously charged with breaking and entering, assault and battery, and possession of a firearm by a convicted felon.", "\n\nHe is now also charged with felony attempted murder, felony malicious wounding, felony shooting into an occupied dwelling and felony use of a firearm in the commission of a felony.", "\n\nHe is believed to have broken into a home on 17th Street in Grottoes and assaulted two people in the house while wielding a handgun, sending Cotey Mitts, a 23-year-old Elkton man, to UVA Medical Center for treatment.", "\n\n_____\n\nUPDATE (1:31 p.m. Sept. 1, 2017):\n\nThe Rockingham County Sheriff tells WHSV Perry Brown Jr. has been charged with breaking and entering, assault and battery, and possession of a firearm by a convicted felon. ", "Other charges are pending.", "\n\nHe is currently being held at the Rockingham County jail without bond.", "\n\n_____\n\nUPDATE (10:52 p.m. Aug. 31, 2017):\n\nAccording to Rockingham County Sheriff Bryan Hutcheson, the suspect was taken into custody. ", "WHSV has learned Perry Brown Jr. was arrested without incident at the Harris Garden Apartments in Harrisonburg on Thursday night.", "\n\n_____\n\nUPDATE (3:50 p.m. Aug. 31, 2017):\n\nFollowing a reported shooting Thursday morning in Grottoes, police are asking for the public's help to find the suspect involved.", "\n\nAccording to Rockingham County Sheriff Bryan Hutcheson, police are searching for Perry Brown, Jr., a 23-year-old Elkton man.", "\n\nAt about 10:30 a.m., the Rockingham County Sheriff's Office and the Grottoes Police Department responded to a call for a reported shooting in the 200 block of 17th Street, where Brown allegedly broke into a home with a handgun and assaulted a male and female inside at the time.", "\n\nThe incident occurred a few blocks from South River Elementary School, which led the school to be placed on a modified lockdown.", "\n\nAccording to the initial report, a loud noise sounded like a gun being fired in the home, which led police to describe the scene as a shooting investigation.", "\n\nHowever, the female in the home was assaulted without the use of any weapon. ", "The man, though, was airlifted from the scene to UVA Medcal Center with non-life threatening injuries. ", "Police did not confirm if the injuries he received were from a gunshot wound. ", "The woman suffered minor injuries and was not taken from the home.", "\n\nThe male victim has been identified as Cotey Mitts, a 23-year-old also from Elkton.", "\n\nThe sheriff's office says brown may be driving a blue 4-door Hyundai sedan, with license plate VUZ-7019.", "\n\nHe has multiple charges pending against him and has been previously arrested. ", "The mugshot above is from a prior arrest.", "\n\nAnyone with information is encouraged to contact the Crimesolvers hotline at 574-5050 or the Rockingham County Sheriff’s Office at 564-3800.", "\n\nNeighbors were shocked when they heard the first responders outside. ", "They say it is a quiet area to live in and events like this do not usually happen.", "\n\n\"You would expect something like this to happen in the city, or something like that... not a quiet suburban neighborhood,\" said Cynthia Reeves who lives next door to the victims.", "\n\n_____\n\nA shooting investigation is underway in the Town of Grottoes, resulting in the lockdown of two elementary schools.", "\n\nDeputies with the Rockingham County Sheriff's Office were on scene at 208 17th Street, which isn't far off of Dogwood Avenue, after a shooting that allegedly happened in the area around 11 a.m.\n\nNeighbors told WHSV's Marina Barnett they heard a woman screaming \"Get out of here\" before seeing a man speed down the home's driveway and flee.", "\n\nThe person believed to have been shot was taken from the scene in an ambulance to a spot where they could be picked up by AirCare and transported to UVA Medical Center. ", "Police on scene said the individual is expected to be alright.", "\n\nSouth River Elementary School, which is located just a few blocks away, was placed on modified lockdown due to what Rockingham County Public Schools Superintendent Dr. Oskar Scheikl called \"an incident in the area.\" ", "Parents of students at Elkton Elementary School also reported that school was placed on lockdown as well.", "\n\nDeputies were at South River as a precaution, but the superintendent stresses there was no incident at the school.", "\n\nNeighbors in the area said they were shocked by what had happened, because it's always been such a quiet neighborhood.", "\n\nInvestigation continues, and the Grottoes Police Department told WHSV they will be unable to talk for some time.", "\n\nStay with WHSV for updates." ]

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[ "The Korea Baseball Organization announced on Wednesday that Japan's Nippon Professional Baseball has requested a status check on Samsung Lions' closer Oh Seung-hwa n.\n\nThe KBO notified the Japanese that Oh still officially plays for Samsung Lions and that the team is willing to negotiate a transfer deal.", "\n\nThe Hanshin Tigers in the NPB's Central League are believed to be interested in acquiring Oh. ", "Japan's Sports Hochi reported that the two sides are close to hammering out a deal.", "\n\n" ]

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[ "Background\n==========\n\nThe key to effective chemotherapy responses in cancer is the presence of the Fas receptor (CD95, Apo-1), a member of the tumor necrosis factor superfamily of cell death receptors \\[[@B1]\\]. ", "These receptors form trimers in the plasma membrane and, upon the binding of their respective ligands, activate the initiator caspase-8 through the recruitment of adaptor proteins (FADD and/or TRADD) to the receptors' death domains. ", "In type I apoptosis, the activated caspase-8 directly activates executioner caspases. ", "In type II apoptosis, caspase-8 cleaves Bid triggering permeabilization of the mitochondrial outer membrane, cytochrome C release, and propagation of the apoptotic signal downstream of the cascade \\[[@B1]\\].", "\n\nMany studies suggest that drug-induced apoptosis occurs through Fas signaling; thus, defective Fas signaling could be responsible for the resistance to chemotherapy that is frequently observed in cancers \\[[@B2]-[@B5]\\]. ", "Several studies have shown that the Fas-mediated cell-death pathway is altered in malignant hematological cells \\[[@B6],[@B7]\\], which can be viewed as one of the mechanisms of resistance to chemotherapy. ", "The CD44 isoforms v6 and v9, hepatocyte growth factor receptor/Met (HGFR/Met), and HHV-8 oncoprotein K1 have been shown to bind to Fas and regulate its activity \\[[@B8]-[@B11]\\]. ", "Therefore, treatments targeting these Fas regulators in cancer cells could be an effective strategy to increase sensitivity to Fas-mediated apoptosis and to chemotherapy.", "\n\nLymphomas occur frequently in association with infectious agents such as the Epstein-Barr virus, human immunodeficiency virus, or HHV-8 \\[[@B12],[@B13]\\]. ", "We have shown that the HHV-8-derived K1 protein interacts with Fas and blocks apoptosis \\[[@B8],[@B10]\\]. ", "In the current study, we investigated whether peptides derived from the Ig-like domain of the K1 protein could alter K1-Fas interaction and, consequently, apoptosis in lymphoma cells. ", "For this purpose, we treated K1-expressing cells as well as B-cell lymphoma and T-lymphoblastic leukemia cells with peptides corresponding to the Ig-like domain of K1, followed by cell death analysis. ", "Our results show that the K1-derived S20-3 peptide kills lymphoma and leukemia cells *in vitro* and *in vivo* by a mechanism dependent on Fas and/or TNF-α receptors.", "\n\nMethods\n=======\n\nCells\n-----\n\nHuman lymphoblastoma cell lines BJAB, Daudi; HHV-8-positive primary effusion lymphoma-derived B-cell lines BC-3, BCBL-1, KS-1; human T-lymphoblastic cell line Jurkat (all from ATCC, Manassas, VA), a caspase-8-- and FADD--deficient Jurkat cell lines (I9.2 and I2.1) (donated by Dr. J. Chandra, The University of Texas MD Anderson Cancer Center) were grown in RPMI 1640 medium supplemented with 10% FBS (both from Mediatech, Herndon, VA) and maintained in a 5% CO~2~ atmosphere at 37°C. ", "The 293T cells (ATCC) were cultured in Dulbecco's modified Eagle\\'s medium (DMEM) (Mediatech) supplemented with 10% FBS. ", "Collection of blood samples was in accordance with approved MD Anderson Cancer Center protocol. ", "Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated from heparinized venous blood by density gradient centrifugation and used immediately in the experiments. ", "BJAB cells stably expressing K1 (BJABK1) were described previously \\[[@B8],[@B10]\\].", "\n\nPeptide synthesis\n-----------------\n\nPeptides were chemically synthesized by multiple peptide solid-phase synthesis (New England Peptide, Gardner, MA, and Celtek Bioscience, Nashville, TN). ", "All peptides were purified to \\>95% purity by high-performance liquid chromatography. ", "Peptide stocks (10 mM) were prepared in dimethyl sulfoxide (DMSO) (Thermo Fisher, Waltham, MA), and aliquots were stored at −20°C.", "\n\nApoptosis analysis\n------------------\n\nApoptosis analysis was performed using the FITC AnnexinV Apoptosis Detection Kit I, according to the manufacturer's protocol (BD Biosciences, San Jose, CA). ", "Cells were re-suspended in serum-free medium (1 × 10^6^/mL) and treated with either 100 μM peptide alone or combined with 20 μM z-VAD (BD Biosciences) for 1 hour, or pretreated for 15 minutes with the peptide and combined with 200 ng/mL of recombinant soluble Fas ligand (FasL) (Alexis, San Diego, CA) for the indicated times. ", "Subsequently, cells were washed, re-suspended in a binding buffer containing AnnexinV-FITC and propidium iodide (PI), and analyzed by flow cytometry (FACSCalibur; Beckman-Coulter, Brea, CA) after 15 minutes of incubation.", "\n\nCaspase activity assay\n----------------------\n\nThe activities of caspase-8, -9, and -3 were determined by flow cytometry using the CaspGLOW^TM^ Fluorescein Active Caspase Staining Kit (BioVision, Mountain View, CA), according to the specifications of the manufacturer. ", "Briefly, 1 × 10^6^ cells were seeded in serum-free medium and treated with 100 μM S20-3 peptide for 1 hour. ", "Cells were then washed, cultured in medium containing 10% FBS for 3 hours, and, subsequently, incubated with 1 μl of FITC-IETD-FMK (for caspase-8 activity), FITC-LEHD-FMK (for caspase-9 activity), or FITC-DEVD-FMK (for caspase-3 activity) for 60 minutes at 37°C. ", "Cells were washed twice and analyzed by flow cytometry.", "\n\nImmunoblotting\n--------------\n\nThe cells (10 × 10^6^) were resuspended in 1 mL of lysis buffer (Cell Signaling Technology, Beverly, MA) supplemented with protease inhibitors (Roche), and incubated 1 hour on ice. ", "One hundred micrograms of each extract were separated on 10% SDS-polyacrylamide gels (Bio-Rad Laboratories, Hercules, CA) and transferred to nitrocellulose membranes (Whatman Schleicher & Schuell, Keene, NH). ", "Membranes were blocked at room temperature for 1 hour in blocking buffer (5% nonfat dry milk, 0.1% Tween-20 in PBS). ", "Separated proteins were analyzed by Western blot with anti-GAPDH (1:1000, Santa Cruz Biotechnology, Santa Cruz, CA; loading control), anti-TNFRI and anti-TNFRII antibodies (1:1000, both kind gifts from Dr. B. B. Aggarwal, MD Anderson Cancer Center) overnight at 4°C. ", "Blots were washed and then incubated with either anti-mouse (Santa Cruz Biotechnology) or anti-rabbit (Cell Signaling Technology) horseradish peroxidase-conjugated antibody (1:5000). ", "The signal was visualized by chemiluminescence Western blot kit (PerkinElmer, Waltham, MA) and exposure to film (Amersham, Piscataway, NJ).", "\n\nLDH assay\n---------\n\nCells (1 × 10^6^) were pre-incubated for 1 hour with 5 μg/mL of TNFRI or TNFRII blocking antibodies (both from R&D Systems, Minneapolis, MN) at 37°C and then treated with TNF-α (10 ng/mL) (Life Technologies - Gibco, Carlsbad, CA) or the peptide S20-3 (100 μM) for 1 hour. ", "After treatment, the growth medium was removed and stored at −20°C. ", "An LDH assay was performed according to the manufacturer\\'s protocol (BioVision). ", "Standard media were used as blank controls; \"high control\" corresponds to the sample of cells treated with lysis solution. ", "Results were normalized to control cells, and the percentage of necrotic cells was calculated using the following formula: % cytotoxicity = \\[(treated-- control)/(high control-- control)\\] × 100.", "\n\n*In vivo* tumor growth assay\n----------------------------\n\nAll animal studies were conducted according to protocols approved by MD Anderson Cancer Center's Institutional Animal Care and Use Committee. ", "Jurkat cells (5 × 10^6^ per injection) were re-suspended in sterile PBS and subcutaneously injected into the right flank of 5-week-old CB17/SCID mice (Harlan Laboratories, Indianapolis, IN). ", "When xenograft tumors reached 100 mm^3^, the mice were given a single intratumoral injection of peptides (33.9 mg/kg): S20-3, TCR, or vehicle; 4 mice each. ", "The mice were killed 8 days after injection, and the tumor tissue was harvested. ", "Tumor width (W) and length (L) were measured by calipers, and size was calculated using the formula W^2^× L/2. ", "The tumoricidal activity was evaluated by comparison of tumor size among groups.", "\n\nStatistical analysis\n--------------------\n\nThe 2-tailed Student's *t* test was used to estimate the statistical significance of the differences between results from triplicate samples or experiments, and the results are expressed as mean values ± standard deviations or standard errors, respectively. ", "The level of significance was set at *P* \\< 0.05.", "\n\nResults\n=======\n\nS20-3 peptide induces cell death of BJABK1 cells\n------------------------------------------------\n\nOur previous studies demonstrated that wild-type K1, but not a truncated K1 with the Ig-like domain deleted, binds to Fas and prevents Fas activation by FasL or by an agonistic Fas antibody \\[[@B8],[@B10]\\]. ", "To further elucidate K1-mediated regulation of Fas, we designed peptides derived from the Ig-like domain of K1 (Table [1](#T1){ref-type=\"table\"}), targeting the K1 binding site on the Fas receptor.", "\n\n###### \n\nProtein sequence of the Ig-like domain of human herpesvirus 8 K1 protein and derived peptides\n\n      \n ---------------- -------------------------------- ----------------------------------------------\n K1 Ig-domain   HSLWITWYPQPVLQTLCGQPSNTVTCGQYVTLYCSTSGNYVTVW\n K1 peptides    \n 20 amino acids S20-1 HSLWITWYPQPVLQTLCGQP (84--103)\n S20-2 PVLQTLCGQPSNTVTCGQYV (94--113) \n   S20-3 SNTVTCGQYVTLYCSTSGNYV (104--124)\n 10 amino acids S10-1 SNTVTCGQYV (104--113)\n   S10-2 TVTCGQYVTL (106--115)\n 8 amino acids S8-1 TVTCGQYV (106--113)\n   S8-2 VTLYCSTS (113--120)\n\nWe first investigated whether K1 peptides could sensitize the Burkitt's lymphoma cell line BJAB stably expressing K1 (BJABK1) to Fas-mediated apoptosis. ", "Cells were treated with 100 μM peptide in combination with 200 ng/mL of FasL for 24 hours, followed by analysis of apoptosis by flow cytometry. ", "The combination of S20-3 and S10-1 peptides with FasL showed a significant (2.2- and 2.5-fold, respectively) increase in cell death compared with FasL alone (Figure [1](#F1){ref-type=\"fig\"}A). ", "No significant differences in apoptosis rates were seen with FasL in combination with other K1-derived peptides shown in Table [1](#T1){ref-type=\"table\"} (20--1, 20--2, S10-2, S8-1, S8-2).", "\n\n{#F1}\n\nIn the control experiment, BJABK1 cells were treated with 100 μM peptides or buffer for 1 hour, and apoptosis was evaluated 24 hours after treatment by flow cytometry. ", "Surprisingly, two of the longest overlapping peptides (S20-2 and S20-3) individually induced a significant (1.9- and 2.4-fold, respectively) increase in apoptotic cell death in the BJABK1 cells compared with buffer control (Figure [1](#F1){ref-type=\"fig\"}B). ", "None of the other peptides overlapping the 20-amino acid sequence of the peptide S20-3 (Table [1](#T1){ref-type=\"table\"}) showed a significant apoptotic effect.", "\n\nThe S20-3 peptide showed a reproducible, dose-dependent increase in apoptotic cell death (up to 40% at 100 μM) as early as 4 hours after treatment, while the control peptide S8-2 was ineffective at all tested concentrations (Figure [1](#F1){ref-type=\"fig\"}C). ", "Further studies were performed to understand the underlying mechanism for the induction of cell death by the S20-3 peptide.", "\n\nThe proper control for the peptide activity would have been a scrambled S20-3-derived peptide. ", "However, we encountered difficulty obtaining reasonable quantities of any S20-3-derived scrambled peptide of desired purity (\\>95%), suitable for the experiments. ", "One possibility was to use inactive 20-mer peptide S20-1 as a negative control, but this peptide does not share any residues with the active S20-3 peptide. ", "Based on the results in Figure [1](#F1){ref-type=\"fig\"}A and B, the S8-2 peptide, which overlaps part of S20-3 peptide, was included as negative control reagent in subsequent studies.", "\n\nThe S20-3 peptide activates caspases and triggers apoptosis in BJABK1 cells\n---------------------------------------------------------------------------\n\nStimulation of the Fas death receptor results in the recruitment of the adaptor protein, FADD, and activation of caspase-8, which initiates propagation of the death signal down the caspase cascade \\[[@B14],[@B15]\\]. ", "To determine the involvement of caspase-8, -9, and -3 in the cell death induced by the S20-3peptide, we used caspase-specific fluorescently-tagged substrates to monitor caspase activation. ", "In the BJABK1 cells, exposure to S20-3 significantly (*P* \\< 0.01) increased the activity of all caspases tested: caspase-8 (39.6% vs. 3.7%), caspase-9 (78.3% vs. 7.4%) and caspase-3 (75.2% vs. 10.2%) (Figure [1](#F1){ref-type=\"fig\"}D). ", "These findings indicate the role of the caspase-8--initiated apoptotic pathway in S20-3 peptide-induced cell death. ", "The control S8-2 peptide showed no effect on caspases' activity (Figure [1](#F1){ref-type=\"fig\"}D).", "\n\nAnother important feature of apoptosis is a decrease of the mitochondrial membrane potential (Ψm) \\[[@B16]\\]. ", "Changes in the Ψm in cells exposed to peptides S20-3 and S8-2, or the agonistic Fas antibody CH-11 as positive control, were measured by staining with tetramethylrhodamine ethyl ester (TMRE). ", "A decreased TMRE signal corresponding to decreased membrane potential was observed in a significant number of S20-3 peptide-treated (20%) and CH-11--treated (22%) cells as early as 4 hours after treatment, relative to treatment with buffer or the control S8-2 peptide (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S1).", "\n\nThe S20-3 peptide is effective against various hematological cancer cell lines\n------------------------------------------------------------------------------\n\nWe further investigated whether the S20-3 peptide would be effective in inducing cell death in HHV-8--positive cancer cell lines (KS-1, BC-3, BCBL-1), which have been shown to express K1 \\[[@B10]\\]. ", "All HHV-8--infected cell lines tested were sensitive to the S20-3 peptide, which induced death in about 20--35% of cells, whereas no significant effect on cell death was detected with the S8-2 control peptide (Figure [2](#F2){ref-type=\"fig\"}A).", "\n\n{#F2}\n\nTo evaluate whether the peptides were able to modulate the interaction between Fas and K1, 293T cells were transiently transfected with the vector expressing Flag-tagged K1 protein, lysed, and subjected to co-immunoprecipitation analysis used previously to show a direct physical interaction of Fas with K1 \\[[@B8]\\]. ", "We observed that K1-Fas interaction was not disrupted by incubation of cells with the S20-3 or other K1-derived peptides with the exception of the shorter peptide S10-1 (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S2).", "\n\nThe lack of S20-3 peptide's effect on the K1-Fas interaction suggested a possible cell-killing mechanism independent of K1. ", "To confirm this hypothesis, we tested the peptide's ability to kill K1-negative cell lines. ", "The S20-3 peptide was able to induce significant levels of cell death in K1-negative BJAB cells (30%) and in the T-cell leukemia Jurkat cell line (25%) (Figure [2](#F2){ref-type=\"fig\"}B). ", "Quite surprisingly, the S20-3 peptide was equally effective in killing Daudi cells (35%), which express low levels of Fas on the cell surface and are considered Fas-resistant \\[[@B17]\\].", "\n\nIn contrast, human PBMCs from healthy donors, treated with S20-3 peptide, showed no significant amount of cell death (Figure [2](#F2){ref-type=\"fig\"}C). ", "Overall, S20-3 peptide treatment induced a 4.6 ± 1.6% increase in cell death in 3 PBMC control samples from different donors, whereas the same treatment induced a 23.8 ± 5.7% increase in death of Jurkat cells. ", "These results suggest that the S20-3 peptide derived from the HHV-8 K1 protein selectively induces cell death in malignant hematological cells, but is not toxic to normal human cells.", "\n\nThe S20-3 peptide kills cells in the absence of the Fas receptor\n----------------------------------------------------------------\n\nTo investigate whether S20-3--induced apoptosis depends on the signaling of the Fas receptor, we tested the S20-3 peptide in Fas-resistant Jurkat cell lines I2.1 and I9.2, which have defective FADD and caspase-8 functions, respectively \\[[@B18]\\]. ", "The S20-3 peptide induced slightly less cell death in I2.1 cells than in the wild type Jurkat cells (21% vs. 24% above control; Figure [3](#F3){ref-type=\"fig\"}A). ", "The response of caspase-8 function-defective Jurkat cell line I9.2 to the S20-3 peptide was significantly blunted compared with that of wild-type Jurkat cells (14.4% vs. 24% above control; 60% reduction) but not completely eliminated (Figure [3](#F3){ref-type=\"fig\"}A). ", "In line with this result, we found that the pan-caspase inhibitor z-VAD also only partially blocked S20-3-induced death in BJAB cells (8.9% vs. 13.3% above control; 67% reduction) (Figure [3](#F3){ref-type=\"fig\"}B) as well as apoptosis induced by the Fas-agonistic antibody CH-11 (14% vs. 29% above control; 48% reduction) (data not shown).", "\n\n{#F3}\n\nFurther examination of the cell death induced by the S20-3 peptide in Daudi cells revealed that the S20-3 peptide induced necrosis (33.7% PI--positive cells) rather than apoptosis (0.3% AnnexinV--positive/PI--negative cells) in Fas-resistant Daudi cells (Figure [3](#F3){ref-type=\"fig\"}C and Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S3A), and z-VAD further enhanced this effect (41.1% PI--positive cells) (Figure [3](#F3){ref-type=\"fig\"}C). ", "An LDH release assay further confirmed that the S20-3 peptide was causing necrosis as early as 1 hour post treatment (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S3B).", "\n\nCell killing by the S20-3 peptide involves TNF-α receptors\n----------------------------------------------------------\n\nThe fact that the S20-3 peptide induced necrosis of Fas-resistant Daudi cells, together with the observed rapid kinetics of cell killing (significant cell death at 4 hours), pointed to the possibility that the S20-3 peptide is promiscuous and interacts not only with Fas, but it may also engage one of the closely related death receptors sharing a significant structural similarity \\[[@B19]\\]. ", "Such promiscuity is not unprecedented. ", "For example, IFN-α--treated Daudi cells upregulate expression of TNF-α and Fas. ", "Produced TNF-α then activates the closely related Fas receptor \\[[@B20]\\]. ", "Based on these facts, we hypothesized that a peptide designed to bind Fas receptor may also interact with and affect the TNF receptor.", "\n\nWe first evaluated the expression levels of TNFRI and TNFRII in BJAB, Jurkat, and Daudi cells and found that all 3 cell lines expressed TNFRI, but only BJAB and Daudi cells expressed detectable levels of TNFRII (Figure [4](#F4){ref-type=\"fig\"}A). ", "We next evaluated the effect of TNFR-blocking antibodies on necrosis induced by TNF-α or S20-3 peptide by measuring LDH release as early as 1 hour after treatment to evaluate necrosis/necroptosis rather than post-apoptotic secondary necrosis \\[[@B21]\\]. ", "Figure [4](#F4){ref-type=\"fig\"}B clearly shows that pre-incubation of Daudi cells with the TNFRI blocking antibody decreased TNF-α and S20-3 peptide induced necrosis/necroptosis, while the TNFRII-blocking antibody showed a rather enhanced killing. ", "The latter finding is consistent with the inhibition of pro-survival signaling mediated by TNFRII \\[[@B22]\\] by the blocking antibody. ", "These results suggest that, besides Fas, TNFRI is also targeted by S20-3. ", "We then tested the effect of TNFRI-blocking antibody on peptide-induced necroptosis in TNFRI-positive BJABK1 and BJAB cells. ", "In both cell lines, the TNFRI-blocking antibody significantly decreased death induced by TNF-α and S20-3 peptide (Figure [4](#F4){ref-type=\"fig\"}C). ", "However, the TNFRI-blocking antibody-mediated inhibition of cell-killing was more prominent in BJABK1 cells, where the S20-3 peptide binding to Fas is blocked by K1 (a lack of displacement of K1 from Fas by S20-3 peptide; Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S2). ", "Thus, in this case, the peptide acts primarily on TNFRI. ", "On the other hand, TNFRI-blocking antibody affected cytotoxicity of TNF-α and S20-3 peptide to a lesser extent in BJAB cells, consistent with the availability of Fas for peptide S20-3 binding in the absence of K1 and, thus, for primary peptide signaling effects.", "\n\n![**", "The S20-3 peptide--induced cell death involves TNFRI.** (**", "A**) Immunoblot analysis of total cellular levels of TNF receptors I and II in BJAB, Jurkat, and Daudi cells. ", "Numbers represent expression levels relative to GAPDH (loading control). (**", "B**) Daudi cells were pre-incubated for 1 hour with 5 μg/mL of TNFRI- or TNFRII-blocking antibodies, followed by 1 hour of treatment with 5 ng/mL of TNF-α or 100 μM peptide S20-3, and immediately analyzed for necrosis by LDH release assay. (**", "C**) BJABK1 cells (left panel) and BJAB cells (right panel) were pre-incubated for 1 hour with 5 μg/mL of TNFRI-blocking antibody, subsequently treated with 100 μM peptide S20-3 or 5 ng/mL of TNF-α for 1 hour, and analyzed as in (**B**). ", "The relative cytotoxicity values in (**B**) and (**C**) were calculated as LDH release in \\[(treated-control)/(high control-control)\\]x100 and are shown as means ± SD of triplicate wells; \\**P* \\< 0.005, \\*\\**P* \\< 0.02.](1756-9966-31-69-4){#F4}\n\nThe S20-3 peptide corresponds to the Ig-like domain of K1 and shares the conserved residues with other Ig-like domains (Figure [5](#F5){ref-type=\"fig\"}A). ", "To further explore structure-related promiscuity, we tested a 20--amino acid peptide derived from the Ig-like domain of the human T-cell receptor (TCR) (Figure [5](#F5){ref-type=\"fig\"}A), homologous to the peptide S20-3 from K1. ", "Both peptides share 5amino acid residues common to the Ig-like domains and exhibit high hydrophobicity. ", "The TCR peptide showed 60--80% of the cell death-inducing activity of the S20-3 peptide in 3 independent experiments (Figure [5](#F5){ref-type=\"fig\"}C), further underscoring a mechanism involving possible structural promiscuity of peptides and/or receptors.", "\n\n*)*. (**", "C**) Jurkat cells were treated with 100 μM peptides (S20-3, TCR) or buffer for 1 hour and, subsequently, incubated in complete medium for 24 hours. ", "Cell killing was analyzed by flow cytometry, and background death (buffer) was subtracted. ", "Values are presented as the means of the percentage of activity relative to the activity of S20-3 ± SE from 3 independent experiments. (**", "D**) Flanks of SCID mice were injected with 5 × 10^6^ Jurkat cells. ", "Two weeks later, tumors were injected with a single dose of S20-3, TCR peptide, or vehicle (DMSO) in 50 μL of saline (4 mice each). ", "Eight days after treatment, mice were killed and the tumors were harvested and measured. ", "Tumor measurements are reported as means ± SD; \\**P* \\< 0.05.](1756-9966-31-69-5){#F5}\n\nInhibition of tumor growth by the S20-3 peptide in a xenograft model\n--------------------------------------------------------------------\n\nThe SCID mice injected subcutaneously with Jurkat cells developed solid tumors at the inoculation site. ", "Using this model, we tested the ability of the peptide S20-3 to alter growth of xenograft tumors*.* ", "Mice received a single intratumoral injection of vehicle, S20-3, or TCR peptide. ", "Treatment with the S20-3 peptide resulted in a modest but significant (*P* \\< 0.05) suppression of tumor growth 8 days after injection compared with vehicle control (Figure [5](#F5){ref-type=\"fig\"}D). ", "In line with our *in vitro* results, the TCR peptide showed a smaller suppressive effect on tumor growth, without statistical significance. ", "Importantly, the mice treated with the peptides did not exhibit signs of toxicity, such as agitation or impaired movement and posture. ", "These results support intratumoral administration of the S20-3 peptide as a potentially safe approach for inducing significant inhibition of xenograft tumor growth.", "\n\nDiscussion\n==========\n\nIn this report, we present evidence showing that the peptide S20-3, corresponding to the Ig-like domain of the Fas-targeting K1 protein of HHV-8, selectively kills hematological cancer cells, and the mechanism involves the Fas and TNFRI receptors. ", "The cell-killing effect appears to be selective for cancer cells *in vitro. ", "In vivo,* even a single intratumoral dose of peptide was active against the growth of xenograft tumors.", "\n\nFrom the array of K1 Ig-like domain peptides tested (Table [1](#T1){ref-type=\"table\"}), only the S20-3 peptide demonstrated strong and reproducible cell-killing activity (Figure [1](#F1){ref-type=\"fig\"} and Figure [2](#F2){ref-type=\"fig\"}) in all 6 hematological cell lines tested but not in PBMC controls (Figure [2](#F2){ref-type=\"fig\"}). ", "While it is not clear as to why S20-3, and also less reproducibly S20-2, but not other K1 Ig-like domain-derived peptides, possess cell-killing activity, the structural features of the predicted Ig-domain (Figure [5](#F5){ref-type=\"fig\"}B) reveal a unique feature of the S20-3 peptide; a loop (centered at conserved glycine residue) linking 2 beta sheets, which are predicted to be destabilized or absent in the rest of peptides tested (Table [1](#T1){ref-type=\"table\"}). ", "A truncated version of the S20-3 peptide, S10-1, representing the first beta sheet and the loop (Figure [5](#F5){ref-type=\"fig\"}B), as well as S8-2 peptide, representing the second beta sheet (Figure [5](#F5){ref-type=\"fig\"}B), lack cell killing properties (Figure [1](#F1){ref-type=\"fig\"}B). ", "On the other hand, a TCR-derived peptide sharing 5 structure-defining residues with S20-3 (Figure [5](#F5){ref-type=\"fig\"}A) also showed cell-killing effect (Figure [5](#F5){ref-type=\"fig\"}C), suggesting that the biological effect of S20-3 is related to its structure.", "\n\nA seemingly contradictory effect of the whole Ig-like domain in K1 protein and S20-3 peptide on Fas signaling may also be explained by the structure-function relationship. ", "The fact that peptide S10-1, but not S20-3 or any other K1 peptide, was able to disrupt the K1-Fas complex (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S2) suggests that first beta sheet is involved in K1-Fas interaction. ", "This is further supported by the fact that peptide S10-2, lacking 3 residues from the first beta sheet, failed to displace K1 (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S2) and did not show any enhancement of FasL activity (Figure [1](#F1){ref-type=\"fig\"}A). ", "Additionally, peptide S20-2, which also contains S10-1 residues, showed cell-killing properties similar to peptide S20-3, but with reduced reproducibility, suggesting that the second beta sheet in peptide S20-3 increases structural stability of the peptide and the additional residues, preceding (S20-2) or following (S20-3) S10-1 region, affect peptide behavior. ", "Taking all this into account, we hypothesize that the smaller size and possible flexibility of the loop within S10-1peptide as compared to S20-3 peptide (Figure [5](#F5){ref-type=\"fig\"}B) allow access of this peptide to the K1 binding site and, thus, displacement of K1 from Fas (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S2). ", "The second beta sheet in the S20-3 peptide stabilizes the loop, but at the same time, it decreases loop flexibility and increases bulkiness of the peptide, limiting its access to the K1 binding site in the presence of the K1 protein.", "\n\nThis hypothesis also helps explain the differential effects of the K1 Ig-like domain, S10-1, and S20-3 on Fas receptor activation. ", "The S10-1 sequence within the Ig-like domain in the whole K1 protein is flanked by additional domains of K1 protein. ", "Assuming the S10-1 region within K1 is exposed and available to bind Fas, the limitations of the movement imposed by surrounding K1 domains \"lock\" the Fas receptor in the closed conformation, preventing binding of FasL described previously \\[[@B8]\\]. ", "On the other hand, the beta sheet and flexible loop in the S10-1 peptide can also bind the receptor, but without the rigidity of surrounding structures, its binding does not affect receptor conformation. ", "Therefore, the S10-1 peptide has no direct effect on the receptor on its own, but sensitizes K1-positive cells to FasL (Figure [1](#F1){ref-type=\"fig\"}A) by displacing the K1 protein (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S2). ", "The S20-3 peptide, more rigid and bulkier that S10-1peptide, can bind Fas only in the absence of K1. ", "Without the flanking domains of the K1 protein and the whole Ig-like domain, S20-3 (and S20-2) can bind Fas receptor similarly to S10-1, but the presence of additional residues/structures induces conformational change mimicking the active state of the receptor.", "\n\nThe extrinsic apoptotic pathway involves activation of death receptors, recruitment of FADD, cleavage of pro-caspase-8, activation of caspases\\' cascade, and a drop in mitochondrial membrane potential \\[[@B1]\\]. ", "While the precise target for the cell-killing activity of the S20-3 peptide is unclear, data presented here clearly show that the peptide activates caspase-8, -9, and -3 (Figure [1](#F1){ref-type=\"fig\"}D) and decreases mitochondrial membrane potential (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S1), suggesting involvement of a death receptor, such as Fas. ", "However, a conventional dose of the pancaspase inhibitor z-VAD blocked cell killing only incompletely (Figure [3](#F3){ref-type=\"fig\"}B), and Jurkat cells with mutated inactive caspase-8 or dominant-negative FADD also showed only partial blockage of S20-3--induced cell-killing (Figure [3](#F3){ref-type=\"fig\"}A), despite their inability to form the death-inducing signaling complex (DISC) \\[[@B23]\\]. ", "This persistence of the S20-3 peptide to kill mutant Jurkat cells (Figure [3](#F3){ref-type=\"fig\"}A), the killing of Daudi cells that are considered Fas-resistant \\[[@B17],[@B24]\\], the increase of necrotic death in the z-VAD-treated Daudi cells (Figure [3](#F3){ref-type=\"fig\"}C and Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S3A), and their relatively fast killing \\[necrotic cell death in Daudi cells was detectable 1 hour after peptide exposure (Additional file [1](#S1){ref-type=\"supplementary-material\"}: Figure S3)\\] suggested to us that S20-3 also activates a TNF receptor.", "\n\nEven though Fas belongs to the TNF receptor family and shares a significant structural similarity with TNFR \\[[@B19]\\], the outcomes of activating these receptors can be quite different \\[[@B25]\\]. ", "For example, activation of Fas receptor in L929 cells triggers apoptosis, whereas activation of TNFR triggers necrosis \\[[@B26]\\]. ", "Owing to the structural similarity, TNF-α is able to also bind and activate the Fas receptor \\[[@B20]\\]. ", "We, thus, investigated the possibility that, because of the structural promiscuity (further supported by the killing properties of a structurally related TCR peptide), the S20-3 peptide designed to bind the Fas receptor may also bind TNFR and trigger necrosis. ", "We detected TNFRI expression in BJAB, Jurkat, and Daudi cells (Figure [3](#F3){ref-type=\"fig\"}), and the TNFRI-blocking antibody significantly inhibited S20-3-- and TNF-α--induced cell killing in all 3 cell lines (Figure [4](#F4){ref-type=\"fig\"}B and C). ", "On the contrary, the TNFRII-blocking antibody showed no inhibitory effect on the S20-3 cell-killing of TNFRII-positive Daudi cells (Figure [4](#F4){ref-type=\"fig\"}B). ", "This finding is not surprising considering the fact that activation of TNFRII triggers pro-survival signaling in hematological cancer cells \\[[@B22]\\], and activation of TNFRI is required for any death signaling from TNFRII due to the lack of a death domain in TNFRII \\[[@B27]\\].", "\n\nOur results with FADD-- and caspase-8--defective Jurkat cells are in agreement with the reports showing that under apoptosis-deficient conditions (such as non-functional caspase-8 or FADD), stimulation with FasL or TNF-α could induce cell death with morphological features of necrosis/necroptosis \\[[@B21],[@B28],[@B29]\\]. ", "Furthermore, lack of FADD, but not of caspase-8, was shown to sensitize Jurkat cells to TNF-α--induced necrosis \\[[@B30]\\]. ", "Smac mimetic BV6 enhanced TNF-induced cell death in leukemia cells in 2 different ways: necroptosis, when the cells were apoptosis resistant (FADD-- and caspase-8--deficient), and caspase-8--dependent apoptosis in apoptosis-proficient cells \\[[@B31]\\].", "\n\nWe hypothesize that the different death pathways can be activated in response to S20-3 treatment in Jurkat, Daudi, and BJAB cells, depending on the availability of and sensitivity to Fas and TNFRs. ", "Another possibility is a cross talk between signaling events from TNF and Fas receptors, as reported by Takada et al., ", "in which TNFRI is recruited by Fas to induce apoptosis \\[[@B32]\\].", "\n\nAn additional important observation is that the S20-3 peptide activity seemed to be specific to malignant cells; leukemia T cells displayed a much greater sensitivity to S20-3 than nonmalignant cells (Figure [2](#F2){ref-type=\"fig\"}C). ", "While the constitutive expression of TNF receptors was clearly demonstrated in most tumor cells, in normal peripheral lymphocytes, the expression of TNF receptors is subjected to a positive and negative regulation and can be induced by different stimuli \\[[@B33],[@B34]\\]. ", "However, normal unstimulated PBMCs express very low amounts of mRNAs for TNFRII \\> TNFRI \\> Fas \\[[@B35]\\], and normal lymphocytes were shown to be resistant to stimulation with activating antibodies targeting TNFRI, TNFRII, or Fas \\[[@B36]\\]. ", "Thus, our findings of cancer-specific killing by the S20-3 peptide are in agreement with these reports.", "\n\nConclusions\n===========\n\nThis is the first report where a peptide derived from the Ig-like domain of the virus-encoded protein effectively induces cell death, specifically in human lymphoma and leukemia cells with minimal toxicity to normal PBMCs and, thus, may expose a novel alternative to conventional chemotherapy, which may also be applied to other cancer types.", "\n\nCompeting interests\n===================\n\nThe authors declare that they have no competing interests.", "\n\nAuthors' contributions\n======================\n\nUD performed peptide experiments testing responses of Fas and wrote the manuscript; CK performed experiments testing responses of TNF receptors and wrote the manuscript; RHT, JW, XA performed mouse experiments and edited the manuscript; ZB and FS designed the experiments and wrote the manuscript. ", "All authors read and approved the final manuscript.", "\n\nSupplementary Material\n======================\n\n###### Additional file 1\n\nMethods.", "\n\n###### \n\nClick here for file\n\nAcknowledgements\n================\n\nWe thank Dr. Chad C. Bjorklund for assistance with mouse experiments, Dr. Joya Chandra for help with the mitochondrial membrane permeability measurements, Dr. Jagannadha K. Sastry for his peptide expertise and help with preparation of this manuscript, Mrs. Angelique Harkins and Mrs. Frances Dressman for proofreading the manuscript. ", "This work was supported by grants from the American Cancer Society (118447-MRSG-10-052-01-LIB to ZB), the National Institutes of Health (CA1206173, CA153170, CA158692, and DK091490 to F.S.), and the Leukemia & Lymphoma Society (R6132-06 and R6187-09 to F.S.). ", "We also thank the Richard Spencer Lewis Foundation, patients and their families for their support and willingness to join us in our efforts in developing new therapies for lymphoma.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "January 20, 2011\n\nThe Yankees finally found their fourth outfielder today. ", "Andruw Jones, a five-time All-Star and 10-time Gold Glover, agreed to a $2 million deal which includes an additional $1.2 million in performance bonuses.", "\n\nAs a backup the past few seasons with the Dodgers, Rangers and White Sox, Jones isn’t getting many hits but he’s making them count when he does — 50.3 percent of his hits have gone for extra bases.", "\n\nPlus, as he’s done his entire career, he still mashes against southpaws — last season to the tune of .272/.380/.565." ]

{ "pile_set_name": "Pile-CC" }

[ 0.000856917817145586, 0.0006098583107814193, 0.0013033051509410143, 0.0018796998774632812 ]

[ "from abc import ABC, abstractclassmethod\nfrom threading import Thread\nfrom rx.subject import Subject\n\n\nclass WakeButton(ABC, Thread):\n\n def __init__(self):\n super().__init__()\n self.subject = Subject()\n\n @abstractclassmethod\n def run(self):\n pass\n\n def on_detected(self):\n self.subject.on_next(\"Hotword\")\n" ]

{ "pile_set_name": "Github" }

[ 0.0007937116897664964 ]

[ "Q:\n\nMy coding seems inefficient... Any way to speed it up?", "\n\nSo I tried this program which was supposed to find out what position these doors are in. ", "They start out closed, and then you toggle every door. ", "The next time you toggle every second, then every third, fourth, so on. ", "I got the coding right but it seems really inefficient. ", "If I tried this with larger numbers, then the program would take too long. ", "Is there any way to do this more efficiently? ", "Here is my coding:\n public class doors\n {\n public static void main(String [] args)\n {\n int x, y = 1;\n boolean [] doors = new boolean[100];\n for (int a = 0; a < doors.length; a++)\n doors[a] = false; //false means closed\n do\n {\n for (x = 0; x < doors.length - 1; x++)\n {\n if ((x+1) % y == 0)\n {\n if (doors[x] == true)\n doors[x] = false;\n else if (doors[x] == false)\n doors[x] = true;\n } \n }\n y++;\n }while (y <= doors.length);\n for (boolean b : doors)\n System.out.println(b);\n }\n}\n // Thanks!!!", "\n\nA:\n\nLet's simplify the code one step at a time.", "\n\n1) When an array is allocated, all elements are initialized to their default value, which means 0, false, or null. ", "In your case that means false, so no need to loop through and do that.", "\n// before\nboolean [] doors = new boolean[100];\nfor (int a = 0; a < doors.length; a++)\n doors[a] = false; //false means closed\n\n// after\nboolean[] doors = new boolean[100];\n\n2a) Since the array is not a zero-length array, the do-while loop might as well be a normal while loop (it will execute at least once).", "\n2b) As a normal while loop, with an initializer right before the loop, and the increment at the end of the loop, it is the same as a for loop.", "\n2c) Since y is not used after the loop, it can be declared in the loop.", "\n// before\nint x, y = 1;\ndo\n{\n //code\n y++;\n}while (y <= doors.length);\n\n// after\nint x;\nfor (int y = 1; y <= doors.length; y++)\n{\n //code\n}\n\n3a) doors[x] == true is the same as doors[x]. ", "doors[x] == false is the same as ! ", "doors[x].", "\n3b) if (x) {} else if (! ", "x) {} is the same as if (x) {} else {}. ", "The test after else is redundant.", "\n3c) if (x) x = false; else x = true; is the same as x = ! ", "x;.", "\n3d) You can skip the double evaluation by doing ^= true (XOR).", "\n// before\nif (doors[x] == true)\n doors[x] = false;\nelse if (doors[x] == false)\n doors[x] = true;\n\n// after\ndoors[x] = ! ", "doors[x];\n\n// skip double evaluation of index lookup\ndoors[x] ^= true;\n\n4a) (x+1) % y == 0 will only be true for x values of y-1, 2*y-1, 3*y-1, and so on, so make loop start at y-1 and increment by y, eliminating the need for the if statement.", "\n4c) Since x is not used after the loop, it can be declared in the loop.", "\n// before\nint x;\nfor (x = 0; x < doors.length - 1; x++)\n{\n if ((x+1) % y == 0)\n {\n //code\n }\n}\n\n// after\nfor (int x = y - 1; x < doors.length - 1; x += y)\n{\n //code\n}\n\nResult so far (after also removing unnecessary braces)\nboolean[] doors = new boolean[100];\nfor (int y = 1; y <= doors.length; y++)\n for (int x = y - 1; x < doors.length - 1; x += y)\n doors[x] ^= true;\nfor (boolean b : doors)\n System.out.println(b);\n\n5a) Limiting x to < doors.length - 1 means that last value of the array will never be used/updated. ", "Drop the - 1.", "\n// before\nfor (int x = y - 1; x < doors.length - 1; x += y)\n\n// after\nfor (int x = y - 1; x < doors.length; x += y)\n\n6a) Printing the array with one boolean true/false value per lines is not very human readable. ", "Print is as a binary number on one line.", "\n// before\nfor (boolean b : doors)\n System.out.println(b);\n\n// after\nfor (boolean b : doors)\n System.out.print(b ? '", "1' : '0');\nSystem.out.println();\n\n7a) Move the printing inside the outer loop, and you'll see an interesting pattern.", "\nboolean[] doors = new boolean[100];\nfor (int y = 1; y <= doors.length; y++) {\n for (int x = y - 1; x < doors.length; x += y)\n doors[x] ^= true;\n for (boolean b : doors)\n System.out.print(b ? '", "1' : '0');\n System.out.println();\n}\n\n1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111\n1010101010101010101010101010101010101010101010101010101010101010101010101010101010101010101010101010\n1000111000111000111000111000111000111000111000111000111000111000111000111000111000111000111000111000\n1001111100101001111100101001111100101001111100101001111100101001111100101001111100101001111100101001\n1001011101101011111000100001101100001000111110101101110100111001011101101011111000100001101100001000\n1001001101111011101000110001111100011000101110111101100100101001001101111011101000110001111100011000\n1001000101111111101010110000111100111000111110110101100000101011001100111011001000100001110100011100\n1001000001111110101010100000111000111001111110100101100100101010001100101011001100100000110100001100\n1001000011111110111010100010111000101001111100100101110100101000001100111011001110100000100100001110\n1001000010111110111110100010101000101000111100100001110100111000001101111011001010100000110100001111\n1001000010011110111111100010101010101000111000100001111100111000011101111011101010100001110100001101\n1001000010001110111111110010101010111000111000110001111100101000011101101011101010110001110100011101\n1001000010000110111111110110101010111010111000110000111100101000111101101011111010110001111100011101\n1001000010000010111111110111101010111010101000110000111000101000111100101011111010100001111100011001\n1001000010000000111111110111111010111010101010110000111000111000111100101001111010100001101100011001\n1001000010000001111111110111111110111010101010100000111000111001111100101001111110100001101100001001\n1001000010000001011111110111111111111010101010100010111000111001111000101001111110101001101100001001\n1001000010000001001111110111111111101010101010100010101000111001111000111001111110101001111100001001\n1001000010000001000111110111111111101110101010100010101010111001111000111000111110101001111100101001\n1001000010000001000011110111111111101111101010100010101010101001111000111000111010101001111100101000\n1001000010000001000001110111111111101111111010100010101010101011111000111000111010111001111100101000\n1001000010000001000000110111111111101111111110100010101010101011101000111000111010111000111100101000\n1001000010000001000000010111111111101111111111100010101010101011101010111000111010111000111000101000\n1001000010000001000000000111111111101111111111110010101010101011101010101000111010111000111000111000\n1001000010000001000000001111111111101111111111110110101010101011101010101010111010111000111000111001\n1001000010000001000000001011111111101111111111110111101010101011101010101010101010111000111000111001\n1001000010000001000000001001111111101111111111110111111010101011101010101010101000111000111000111001\n1001000010000001000000001000111111101111111111110111111110101011101010101010101000101000111000111001\n1001000010000001000000001000011111101111111111110111111111101011101010101010101000101010111000111001\n1001000010000001000000001000001111101111111111110111111111111011101010101010101000101010101000111001\n1001000010000001000000001000000111101111111111110111111111111111101010101010101000101010101010111001\n1001000010000001000000001000000011101111111111110111111111111110101010101010101000101010101010101001\n1001000010000001000000001000000001101111111111110111111111111110111010101010101000101010101010101011\n1001000010000001000000001000000000101111111111110111111111111110111110101010101000101010101010101011\n1001000010000001000000001000000000001111111111110111111111111110111111101010101000101010101010101011\n1001000010000001000000001000000000011111111111110111111111111110111111111010101000101010101010101011\n1001000010000001000000001000000000010111111111110111111111111110111111111110101000101010101010101011\n1001000010000001000000001000000000010011111111110111111111111110111111111111101000101010101010101011\n1001000010000001000000001000000000010001111111110111111111111110111111111111111000101010101010101011\n1001000010000001000000001000000000010000111111110111111111111110111111111111111100101010101010101011\n1001000010000001000000001000000000010000011111110111111111111110111111111111111101101010101010101011\n1001000010000001000000001000000000010000001111110111111111111110111111111111111101111010101010101011\n1001000010000001000000001000000000010000000111110111111111111110111111111111111101111110101010101011\n1001000010000001000000001000000000010000000011110111111111111110111111111111111101111111101010101011\n1001000010000001000000001000000000010000000001110111111111111110111111111111111101111111111010101011\n1001000010000001000000001000000000010000000000110111111111111110111111111111111101111111111110101011\n1001000010000001000000001000000000010000000000010111111111111110111111111111111101111111111111101011\n1001000010000001000000001000000000010000000000000111111111111110111111111111111101111111111111111011\n1001000010000001000000001000000000010000000000001111111111111110111111111111111101111111111111111111\n1001000010000001000000001000000000010000000000001011111111111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001001111111111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000111111111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000011111111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000001111111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000111111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000011111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000001111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000111110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000011110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000001110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000110111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000010111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000000111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001111111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001011111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001001111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000111111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000011111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000001111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000111111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000011111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000001111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000111111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000011111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000001111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000111101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000011101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000001101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000101111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000001111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000011111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010111111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010011111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010001111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000111111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000011111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000001111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000111111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000011111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000001111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000111111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000011111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000001111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000111110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000011110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000001110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000000110\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000000010\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000000000\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000000001\n\nNow, when you look at the pattern of the result (last line), you'll see that your code could be reduced to (very fast):\nboolean[] doors = new boolean[100];\nfor (int idx = 0, incr = 1; idx < doors.length; idx += (incr += 2))\n doors[idx] = true;\n//print here\n\n1001000010000001000000001000000000010000000000001000000000000001000000000000000010000000000000000001\n\n" ]

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[ "LONDON — These are salutary times for the English. ", "Their clubs have wealthy foreign backers, and their Premier League has just netted the biggest overseas television contract ever written, yet when Chelsea plays Manchester City in London on Sunday, they do so as European failures.", "\n\nChelsea’s Russian owner has responded by firing the coach yet again. ", "City’s Abu Dhabi benefactors have made no public announcement after that team — the English champion — went out in the first round of the Champions League for the second year in a row.", "\n\nLet’s try an experiment and for once not mention the extreme costs involved here. ", "Let’s acknowledge that the Spanish and the Germans, with all seven of their teams headed to the last 16, appear to have a better understanding of what it takes to win Europe’s big league than the British do at the moment.", "\n\nTo be fair, Chelsea could, still, squeak through if the results of the final group games go its way Dec. 5. ", "That will be no succor to Roberto Di Matteo, who was fired Wednesday to allow Rafael BenC-tez to be Chelsea’s ninth new coach since 2004.", "\n\nTo be fair to Manchester City, its group was by far the toughest anyone could draw in the first round. ", "Even so, with five games gone and not a single victory, City’s coach was asked the inevitable question following a 1-1 home tie Wednesday against Real Madrid.", "\n\nGiven what happened at Chelsea, does Mancini fear losing his job?", "\n\n“No,” was the Italian’s reply. “", "Why? ", "I don’t fear this. ", "If we think we can win a Champions League after two years, I think we are crazy.", "\n\n“The Champions League is strange, is difficult. ", "Probably we need to improve our team. ", "There are a lot of teams better than us in the Champions League.”", "\n\nHis side, he pointed out, goes into its game Sunday as leader of the Premier League. ", "But as he tries to rationalize the inexperience of his club in Europe, others point out that City has amassed a core of world-renowned figures.", "\n\nIn the words of Joe Hart, City’s goalie: “This has been a bad campaign for us. ", "We have surprised ourselves in a very, very bad way.”", "\n\nThe goalkeeper made no excuses, and the opposing coach on Wednesday, Jose Mourinho, offered no sympathy. “", "We knew before the start that in this group, a big team would go out,” he said.", "\n\n“And it’s good that it is City, because Roberto can work on without any problem,” Mourinho said, referring to Mancini. “", "If it was me, the press wouldn’t let me back in Madrid.”" ]

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[ "Oogenesis in the leech Glossiphonia heteroclita (Annelida, Hirudinea, Glossiphonidae). ", "I. Ovary structure and previtellogenic growth of oocytes.", "\nGlossiphonia heteroclita has paired ovaries whose shape and dimensions change as oogenesis proceeds: during early previtellogenesis they are small and club-shaped, whereas during vitellogenesis they broaden and elongate considerably. ", "During early oogenesis (previtellogenesis), each ovary is composed of an outer envelope (ovisac) that surrounds the ovary cavity and is filled with hemocoelomic fluid, in which a single and very convoluted ovary cord is bathed. ", "The ovary cord consists of germline cells, including nurse cells and young oocytes surrounded by a layer of elongated follicle cells. ", "Additionally, follicle cells with long cytoplasmic projections occur inside the ovary cord, where they separate germ cells from each other. ", "The ovary cord contains thousands of nurse cells. ", "Each nurse cell has one intercellular bridge, connecting it to a central anucleate cytoplasmic mass, the cytophore (rachis); it in turn is connected by one intercellular bridge with each growing oocyte. ", "Numerous mitochondria, RER cisternae, ribosomes, and Golgi complexes are transported from the nurse cells, via the intercellular bridge and cytophore, to the growing oocytes. ", "Oogenesis in G. heteroclita is synchronous with all oocytes in the ovary in the same stage of oogenesis. ", "The youngest observed oocytes are slightly larger than nurse cells, and usually occupy the periphery of the ovary cord. ", "As previtellogenesis proceeds, the oocytes gather a vast amount of cell organelles and become more voluminous. ", "As a result, in late previtellogenesis the oocytes gradually protrude into the ovary cavity. ", "Simultaneously with oocyte growth, the follicle cells differentiate into two subpopulations. ", "The morphology of the follicle cells surrounding the nurse cells and penetrating the ovary cord does not change, whereas those enveloping the growing oocytes become more voluminous. ", "Their plasma membrane invaginates deeply, forming numerous broad vesicles that eventually seem to form channels or conducts through which the hemocoelomic fluid can easily access the growing oocytes." ]

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[ "Prostate cancer has high incidence in both the United States and Russian Federation. ", "An unresolved problem with a large impact on public health is differential diagnosis of its progressive and metastatic forms. ", "Prostate cancer progression presents a number of fundamental questions that concern the heterogeneity of cell populations within the tumor environment, cell-cell communication, and what defines the invasive phenotype mechanistically. ", "This proposal addresses these issues in an integrative collaboration format within the framework of the U.S.-Russia Bilateral Collaborative Research Partnerships on Cancer. ", "Capitalizing on the complementary expertise of the two collaborating teams, the project aims to improve the differentiation of progressive phenotypes using a recently discovered myosin isoform and to study its mechanistic underpinnings. ", "The unconventional molecular motor myosin IC (isoform A) has been shown to be differentially expressed in samples of progressive prostate cancer. ", "Preliminary results point to its involvement in exosome secretion and an epigenetic transmission of its expression from invasive to noninvasive cells. ", "One aim is to study this process on the electron-microscopic level and its impact on the motility of the recipient cells. ", "We will test the hypothesis of myosin IC involvement in the exosome uptake, which would make its upregulation in the recipient cells adaptive on the cellular level yet contributing to the tissue invasivity via an increased total secretion. ", "This will be tested using shRNA and mutant forms of the isoform. ", "The second aim is to improve differentiation of invasive phenotypes by the isoform A expression. ", "A battery of new samples will be tested and a method developed for cell sorting based on the isoform A expression. ", "If successful, this method will be applied to break down each sample into cell subpopulations in order to increase the differentiation of isoform A-expressing components. ", "The hypothesis is that their relative mass will have a higher correlation with tumor progression, improving the prognostic use of this biomarker. ", "Both aims are fully integrated research plans building on the complementary expertise with the applicant for the linked Russian grant, namely myosin IC molecular biology and biomarker work in the American and electron microscopy and sorting in the Russian laboratory." ]

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[ "1. ", "Field of the Invention\nThis invention relates to in situ doping of polycrystalline silicon with phosphorous trichloride, tertiary butyl phosphine, isobutyl phosphine, trimethyl phosphate and tetramethyl phosphate.", "\n2. ", "Brief Description of the Prior Art\nIn situ doping of polycrystalline silicon (polysilicon) is known in the art, such doping generally using phosphine as the phosphorous containing dopant and diborane as the boron containing dopant. ", "However, special techniques are required when phosphine is the dopant to improve sheet resistance and thickness uniformity and to achieve an acceptable deposition rate. ", "Also, the prior art phosphorous-containing dopants are highly toxic and therefore require a great deal of care in handling. ", "This prior art is set forth in an article by B. S. Meyerson and M. L. Yu, ECS Extended Abstracts 83-1. ", "651(1983), an article by D. L. Flowers in the same publication 84-1. ", "256(1984) and an article of H. Kurokawa, Journal of the Electrochemical Society, 129.26.20(1982).", "\nIn situ doping of polysilicon is attractive because the dopant distribution is uniform throughout the film if the dopant is incorporated during and along with the deposition of the polysilicon. ", "This dopant uniformity is extremely advantageous in the refilling of trenches with polysilicon since doping concentrations will then be the same throughout the entire trench, thereby eliminating the need for complicated implants and anneals currently used to fill trenches.", "\nIn situ doping differs from other prior art doping methods, such as ion implantation and solid solid source diffusion in a furnace tube, wherein the dopant is put down interstitially with the polysilicon and simultaneously therewith. ", "This provides the uniform build-up of the polysilicon film with the dopant uniformly distributed therein. ", "However, as stated above, the dopants utilized in the prior art have been extremely toxic and have led to the requirement that measures be taken to protect against the fumes and other effluent thereof, this requiring a great deal of expense. ", "It is therefore a need of the art to provide a dopant for use in the in situ doping process which does not have the toxic effect of prior art dopants, yet can provide the same results." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Mass Alex: Mass Effect 2 - Part 16\n\nCommander Navarro finds himself dealing with swings ranging from the consequences of headbutting a Krogran to the fallout from a planet-wide sterility campaign.", "\n\nThere are billions of stories in the universe, so why not play the best one?", "\n\nMay. 14 2019\n\nCast: Vinny, Alex\n\nPosted by: Vinny" ]

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[ "Deadbeat Illinois: Highland students pay more as state falters\n\nFREEPORT — Jake Olberding enrolled at Highland Community College thinking it would be an affordable higher education option, but he’ll pay more for tuition this fall because his school is squeezed by Illinois’ $5.8 billion backlog of delinquent bills.", "\n\nBy Nick Crow\n\nJournal Standard\n\nBy Nick Crow\n\nPosted Jun. 4, 2013 at 12:01 AM\nUpdated Jun 4, 2013 at 3:00 AM\n\nBy Nick Crow\n\nPosted Jun. 4, 2013 at 12:01 AM\nUpdated Jun 4, 2013 at 3:00 AM\n\nClick on the graphic to go to\n\nthe series' Facebook page.", "\n\nFREEPORT — Jake Olberding enrolled at Highland Community College thinking it would be an affordable higher education option, but he’ll pay more for tuition this fall because his school is squeezed by Illinois’ $3.3 billion backlog of delinquent bills.", "\n\nHighland trustees approved a 9.5 percent tuition hike in March, which means Olberding will pay $115 per credit hour to take classes this fall, his second year of college. ", "However, the tuition increase hasn’t derailed the Lena student’s college path.", "\n\n“It’d have to be a pretty big (tuition) increase for me not to go,” Olberding said.", "\n\nHighland administrators worry that not all students will share his resolve.", "\n\nRevenue supporting the city’s community college has historically resembled a three-legged stool of property taxes, tuition and state aid. ", "Today, the stool is tipping over because HCC’s state aid is a fraction of what it used to be and those payments typically arrive three months later than they’re supposed to.", "\n\nCommunity colleges and practically any public or private sector agency that does business with Illinois is feeling the pinch of the state’s fiscal crisis.", "\n\nComptroller Judy Barr Topinka warned May 22 that the state’s $3.3 billion backlog of unpaid bills — down from $8.5 billion in early April — may swell back to $7.5 billion by August. ", "Longer payment delays could be in store, too.", "\n\nIllinois is $380,000 in arrears to HCC. ", "State aid once accounted for a third of the college’s revenue, but has fallen by $500,000 a year for the last three years. ", "This year, state aid accounts for about 14 percent of HCC’s budgeted revenue, said HCC Vice President of Administrative Services Jill Janssen.", "\n\n“It’s been the perfect storm where property values have gone down 2 to 3 percent per year for the past four years in addition to losing state money and having a decrease in enrollment,” Janssen said. “", "With all these changes we may have to rethink the paradigm of college education.”", "\n\nTaxes and tuition\n\nBetween 2009 and 2012, property values fell 9 percent within the Highland Community College district, which includes Stephenson and Jo Daviess counties and parts of Ogle and Carroll counties.", "\n\nCollege trustees have held the line on the district’s tax levy, and HCC property tax revenues fell in lockstep from $9 million to $8.2 million during those years.", "\n\nStudents, not taxpayers, are filling the gap created by the college’s declining and delinquent state aid.", "\n\nHighland’s tuition rate has risen between 3 percent and 5 percent each year over the past five years. ", "The most recent increase came in March when trustees approved a 9.5 percent hike, raising the per-credit hour tuition rate from $105 to $115. ", "In 2012, trustees approved a $10-per-credit-hour tuition rate increase.", "\n\nPage 2 of 3 -\nThis trend, college officials say, is unsustainable. ", "Sooner or later, HCC will become unaffordable for students and enrollment will suffer. ", "In fiscal 2012, HCC enrollment fell 5.4 percent to 5,110 full- and part-time students.", "\n\n“We keep looking for new things we can do,” said President Joe Kanosky. “", "We keep looking to try new things. ", "We may have to discontinue some programs to get by. ", "It’s going to be a challenge for everyone for the next few years.”", "\n\n‘Just no payments’\n\nSome state funding to community colleges hasn’t come at all, such as money for the Illinois Veteran Grants program, which subsidizes higher education for vets.", "\n\nThe state is no longer funding the program, forcing Illinois community colleges to waive tuition for eligible veterans to the collective tune of $13 million to $14 million, said Ellen Andres, chief financial officer for the Illinois Community College Board.", "\n\n“Waiving tuition causes problems in the sense that it’s unfunded liability,” Andres said. “", "Community colleges are now having to waive payments that 10 years ago the state would have covered. ", "That’s not late payments by the state, that’s just no payments.”", "\n\nAndres said that the state budget for fiscal year 2014 again leaves out funding for vets. ", "She said that schools can expect most of their state funding, but shouldn’t expect it to come on time.", "\n\n“We’re basically telling them that their fiscal year 2013 funds won’t be received before Dec. 30 this year,” Andres said. “", "We don’t anticipate that they will stop making payments, they will just come late.”", "\n\nFuture uncertain\n\nHighland and other Illinois community colleges face many financial uncertainties in the years ahead, Kanosky said.", "\n\n“The game and model are changing,” Kanosky said. “", "The way we do business will have to be looked at as we move forward. ", "There’s different things we’re having to look at.”", "\n\nOne option Kanosky mentioned: beefing up HCC’s menu of online courses, which don’t cost the college as much to offer as a traditional courses.", "\n\n“Online classes aren’t expensive as far as technology goes, but if there’s no new funding you can’t keep up on technology and there are certain things you can’t do online,” Andres said. “", "It’s not the answer.”", "\n\nThe answer, Andres said, may be hard to swallow.", "\n\n“At colleges with a small tax base, student tuition can only be raised so much or students can’t come,” Andres said. “", "They will have to increase class sizes or not offer as many classes. ", "Student services like tutoring and counseling will go away and you end up with a staff that is a jack-of-all-trades. ", "It’s definitely a disadvantage to the colleges. ", "Most end up with more part-time than full-time faculty. ", "I can tell you that the services already probably aren’t where they were five years ago.”" ]

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[ "Bolsonaro diz que está 90% fechado com o PSL.", "\n\nMudaram-se os planos. ", "Segundo colocado nas pesquisas eleitorais, o deputado Jair Bolsonaro (PSC-RJ) não irá mais disputar a presidência da República pelo Patriota, novo nome do Partido Ecológico Nacional (PEN). ", "A razão é um racha com o presidente do PEN, Adilson Barroso. ", "Bolsonaro está seguindo para o Partido Social Liberal (PSL). ", "Ele afirmou à Gazeta do Povo que está “90%” fechado com essa nova legenda.", "\n\nLEIA MAIS: Presidente do Patriota diz que só aceitaria pedidos de Bolsonaro ‘se fosse débil mental’\n\n“No Patriota, o cara prometeu que eu teria a maioria das ações do partido. ", "Mas não entrega. ", "E agora chegou num limite. ", "Estou namorando o PSL. ", "Tive uma conversa excelente com o presidente [do partido] Luciano Bivar e terei 51% das ações. ", "Conversamos ontem e anteontem”, disse Bolsonaro à Gazeta do Povo, na noite desta quarta-feira (20). “", "E tem mais. ", "O PR também está interessado no meu passe. ", "Converso com todo mundo, menos com aqueles ‘partidecos’ de esquerda.”", "\n\nBolsonaro: de estrela do Patriota a incômodo dentro do partido\n\nBolsonaro já havia anunciado oficialmente sua ida para o Patriota. ", "Foi a estrela de um programa partidário do PEN e chegou até a assinar uma ficha simbólica de filiação, como prova de seu compromisso. ", "Mas a coisa desandou.", "\n\nO racha com Adilson Barroso, o presidente do Patriota, envolve não só cargos de direção no partido mas também o fundo partidário. ", "Bolsonaro criticou o dirigente do PEN e disse que, sem ele como candidato do partido, dificilmente a legenda vai atingir a cláusula mínima de 1,5% dos votos válidos para deputados federais no país. ", "Só assim, com esse desempenho, uma legenda tem direito a tempo na TV e acesso ao fundo partidário.", "\n\nLEIA TAMBÉM: PEN/Patriota chegou a mudar seu estatuto e seus princípios para receber Bolsonaro\n\nBolsonaro afirmou que, no PEN, está tendo problemas de uso do fundo partidário – que, no seu entendimento, deveria pagar as despesas de viagens que ele têm feito país afora. ", "Ele afirmou que o fundo do partido é minúsculo.", "\n\n“Sei que vai entrar muito dinheiro [na minha campanha]. ", "De pessoas mais simples, que vão depositar de R$ 5 a R$ 10, e gente com mais condições financeiras”, disse Bolsonaro. “", "Faço minha campanha, no máximo, com R$ 2 milhões.”", "\n\nPSL vai perder a ala mais liberal para que Bolsonaro possa entrar\n\n“Esse partido [o PSL] é liberal. ", "Vai mudar seu regimento. ", "Além de defender valores familiares, vão defender a questão do armamento. ", "Tem uma ala, o ‘Livres’, que vai deixar de existir e não terá mais espaços no partido”, afirmou Bolsonaro. ", "O PSL, antes de Bolsonaro, inclusive cogitava a ideia de mudar de nome para virar “Livres”, adotando um liberalismo mais radical.", "\n\nFavorável à adesão de Bolsonaro, o presidente do partido, Luciano Bivar é deputado federal (PSL-PE) e comanda há anos o PSL. ", "Bolsonaro afirmou que Bivar é um empresário bem sucedido e que não sobrevive do fundo. ", "O presidente da sigla atua no ramo de previdência privada.", "\n\nEm nota, PSL nega filiação\n\nAinda na noite desta quarta-feira, o PSL divulgou nota no Facebook informando que não fará a filiação de Bolsonaro. ", "Leia a íntegra:\n\n1. ", "Não procedem, de forma alguma, as notícias de que o deputado federal Jair Bolsonaro possa se filiar ao PSL.", "\n\n2. ", "Após solicitação feita por Bolsonaro, o presidente nacional do PSL e também deputado federal, Luciano Bivar, recebeu-o em reunião. ", "Conversaram sobre o Imposto Único, histórica bandeira do PSL.", "\n\n3. ", "Em função das evidentes e conhecidas divergências de pensamento, o projeto político de Jair Bolsonaro é absolutamente incompatível com os ideais do LIVRES e o profundo processo de renovação política com o qual o PSL está inteiramente comprometido.", "\n\n4. ", "Bolsonaro representa o autoritarismo e a intolerância tanto na economia quanto nos costumes, sendo a antítese completa das nossas ideias." ]

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[ "Q:\n\nJquery : To redirect from one page to another page\n\nI have two js pages(Source.js and Target.js) at two different location, now all i want to do is when user clicks on dropdown list of source page , it redirects user to target page and vice-versa. ", "I am providing you the exact coding with all location and everthing, i just want to know how to switch from one page to second page.", "\nSource.js coding\nvar SourceSc = function() {\nvar that = {};\nvar _view = null;\nvar _childPanel = \"#content\";\nvar _sourceDlgMgrC = null;\nvar BEGIN = \"BEGIN\";\nvar STARTING = \"STARTING\";\nvar END = \"END\";\nvar TARGET = \"TARGET\"; \nvar _state = BEGIN;\nthat.create = function(parent, panel) {\n\n _parent = parent;\n _panel = panel;\n _transition(STARTING);\n};\nthat.destroy = function() {\n _transition(END);\n};\nthat.eventTargetLanguageView = function() {\n _transition(TARGET_LANGUAGE_VIEW);\n};\nvar _transition = function(newState) {\n _state = newState;\n switch(_state) { \n case STARTING: _enterStarting(); break;\n case TARGET: _enterTargetDlg(); break;\n case END: _enterEnd(); break;\n }\n};\nvar _enterStarting = function() {\n modelMgr.loadInclude('code/app/sc/LoggedIn/sc/Source/c/SourceDlgMgrC.js', function() {\n modelMgr.getHTML('code/app/sc/LoggedIn/sc/Source/Source.html', function(html) {\n _sourceDlgMgrC = SourceDlgMgrC();\n _sourceDlgMgrC.create(_childPanel);\n var req = {};\n var fnSuccess = function(res) {\n _view = SourceV();\n _view.create(that, _panel, html, res); \n }; \n });\n });\n}; \nvar _enterTargetDlg = function() \n{\n//now what i have to write here, to load target page\n};\nvar _enterEnd = function() {\n //coding of destroy \n}; \nreturn that;};\nvar SourceV = function() {\nvar that = {};\n\nvar _sc = null;\nvar _panel = null;\n\nthat.create = function(sc, panel, html, res) {\n _sc = sc;\n _panel = panel;\n that.layoutUi(html);\n that.bindEvents(); \n}; \nthat.layoutUi = function(html) {\n\n $(_panel).html(html); \n};\nthat.bindEvents = function() {\n\n $('#viewList').change(_sc.eventTargetLanguageView);\n};\nthat.destroy = function() {\n $(_panel).html('');\n _panel = null;\n _sc = null;\n};\nreturn that; };\n\ni can post source.html full coding but i guess that'll be use less so i'll post only the dropdown list coding\n <select id = \"viewList\" class=\"fl width160\">\n <option>Source</option>\n <option>Target</option>\n </select>\n\nnow coding of target page is also exact same but location of Target.js is \"code/app/sc/LoggedIn/sc/Target/Target.js\"\n\nA:\n\ntry this...(just for example)\n codeLoadingMgr.loadInclude( path + '/AdminSc.js', function() {\n _adminSc = AdminSc();\n _adminSc.create(that, path, _childPanel,_selectedAdminTab, _programId); \n });\n\n" ]

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[ "The organization of serotonergic projections to cerebral cortex in primates: retrograde transport studies.", "\nRetrograde axonal transport and immunocytochemical methods were utilized to determine the origin of serotonergic afferents to selected primary projection and association areas of cerebral cortex in macaque monkeys. ", "After injections of Fast Blue or Diamidino Yellow in primary motor, somatosensory, or visual cortex, retrogradely labeled neurons are found in both the dorsal and median raphe nuclei. ", "The sets of dorsal raphe neurons which innervate these cortical areas differ in their spatial distributions along the rostrocaudal axis of the brainstem; a coarse rostrocaudal topographic relationship is found between these groups of dorsal raphe neurons and their cortical targets. ", "In contrast, neurons in the median raphe which innervate these primary projection areas are not differentially distributed along the rostrocaudal axis. ", "However, in both the median and dorsal raphe nuclei, most neurons projecting to primary visual cortex are situated lateral to the cells which project to motor and somatosensory areas; many of these visually projecting neurons lie among the fascicles of the medial longitudinal fasciculus. ", "For comparison with the serotonergic innervation of primary projection areas, the locations of raphe cells projecting to three areas of association cortex were examined: dorsolateral prefrontal cortex, area 5 and area 7b. ", "Neurons projecting to each of these association areas are found throughout the dorsal and median raphe nuclei. ", "Their distributions are similar to one another; however, more cells projecting to dorsolateral prefrontal cortex are in the rostral part of the dorsal raphe. ", "The dorsal and median raphe neurons projecting to these association areas are intermingled with neurons projecting to motor and somatosensory cortex, but are medial to most of those projecting to visual cortex. ", "Thus, separate cortical areas are innervated by different sets of raphe neurons; these sets partially overlap, yet differ in their rostrocaudal and mediolateral distributions. ", "Ascending serotonergic projections to cerebral cortex form a widely distributed system which exhibits a highly intricate anatomic organization. ", "The present observations support the hypothesis that the dorsal raphe nucleus is comprised of distinct sets of neurons whose output is distributed to multiple, interconnected cortical areas; these serotonergic projections may play a role in the coordination of excitability in functionally related areas of cortex. ", "In contrast, the serotonergic projections arising from the median raphe appear to be more divergent and are likely to have a global influence on cortical activity. ", "Since these individual raphe nuclei have different projection patterns, they are likely to have distinct functional roles." ]

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[ "Marine dinoflagellate cysts as indicators of eutrophication and industrial pollution: a discussion.", "\nThe results from an investigation of dinoflagellate cysts as indicators of eutrophication in Tokyo Bay, Japan, by Matsuoka [Sci Total Environ 231 (1999) 17] are discussed with reference to other pertinent literature not discussed in the original article. ", "Both the Japanese study and previous work from Norwegian fjords show that pollution (including cultural eutrophication) may produce changes in the phytoplankton reflected by a shift from more autotrophic--to more heterotrophic--dominance of cyst assemblages. ", "However, this is a proportional change that seems likely to result from reduced autotrophic production rather than the increased heterotrophic production suggested by Matsuoka. ", "This is not unequivocal evidence of eutrophication, since Tokyo Bay is impacted also by heavy industrial pollution, the possible effects of which cannot be distinguished, and the quantitative method used for estimating changes in cyst productivity is flawed." ]

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[ "11/2/2007\n\nThe Japanese American National Museum once again displays its amazing ability to hone in on topics of widespread interest while still staying true to its mission in its new exhibition, “Giant Robot Biennnale”!", "\n\nDeveloped in collaboration with Eric Nakamura of Giant Robot and the Japanese American National Museum\n\nIn celebration of its 50th issue and in collaboration with the Japanese American National Museum, the pop-culture magazine Giant Robot has assembled works by ten cutting-edge artists from around the country in Giant Robot Biennale: 50 Issues. ", "APAK | Gary Baseman | David Choe | Seonna Hong | Sashie Masakatsu | Saelee Oh | Pryor Praczukowski | Souther Salazar | Eishi Takaoka | Adrian Tomine\n\nThe curator of the exhibition and owner/co-editor of Giant Robot is Eric Nakamura, a fascinating character who has been pursuing his passions in the pages of this amazing magazine for the past 13 years. ", "Part of what is exciting about his work in the magazine is that his and other authors’ articles perfectly measure the pulse of Asian and Asian American pop culture as a living, breathing entity rather than as a somewhat stale object of scholarly enquiry. ", "Rather than linking interest in Japanese video games and J-pop stars with the now common stereotype of the urban otaku teenagers locked in their rooms, Giant Robot exposes the likes and dislikes, the artistic and musical travels, and the subtle but omni-present cultural politics of diverse individuals who identify with Japan while not being contained by it.", "\n\nIt’s also worth noting that as Giant Robot has increased its subscription base and attracted more attention and funding, Eric and his partner have become serious patrons of local and international artists, setting up galleries and improving their communities in various ways. ", "I wish more academic institutions approached community relations the way these entrepreneurs do!" ]

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", "Corners will have a targeting program which teaches you where the ball can go. ", "If you aren't a lover with this method, you should use the old method of swinging the baseball in. ", "The targeting system didn't seem all that helpful, especially when you're using somebody locally who can discover exactly what you're performing.", "\n\nA very important factor that's for certain is the fact that we will see lots of 'dabbing' in recreation this season, after the Frenchmanis hallmark party was added to gameplay. ", "The overall game is already available to preorder plus a demo model of FIFA 17 will soon be launched by EA Sports two-weeks prior to the principal discharge. ", "For a while, Germany simply delivered three squads for the Champions League, but they exceeded Italy and, lately, Serie A continues to be the next league with no next rep staff. ", "Previously just the top-three national links received then four Champions League allocations as well as merely three were guaranteed. ", "There is no fun in taking control of Nyc in FIFA 16 and being educated that any (or all) of David Accommodation, Andrea Pirlo and Frank Lampard were quitting by the end of season one, without any way of dissuading them.", "\n\nEurope's soccer governing body UEFA have popped disciplinary proceedings against Celtic after having an area of their support exhibited Palestine flags during Saturday's Champions League play-off first leg against Hapoel Beer-Sheva of Israel. ", "Command, control as well as a determination to large-level performance will be trophy winners' hallmarks - implementing these attributes towards football's organisation is among the principal goals of the course. ", "Uefa has assured the ‘Champions' route for champions of domestic leagues that were smaller will stay. ", "There have been murmurs of the entrant but UEFA established that these programs never got the ground off. ", "http://www.cofifa.com/fifa-17-point.html\n\nUEFA works land and membership competitions like UEFA Super Pot, UEFA Champions League, UEFA Europa League, and the fifa 17 points European Tournament, represents the national football links of Europe, and handles the award cash, rules, and advertising rights to these games. ", "Though this concept is quite similar to the Career function of preceding Winners League activities, and the likes of Become A Pro, this can be almost a cross of both. ", "The diminutive Spaniard is Area's next and ultimate person to characteristic within the all-star listing, shedding in FIFA 16 by way of a simple figure from his 88. ", "With Guardiola in-charge at the Etihad, Silva like Aguero and De Bruyne might have his best season to-date and come back to his past rating next period. ", "Already a lot more than 4 lacs fans have casted their ballots and also have picked their favorite leagues and which leagues they wished to discover in the next FIFA game.", "\n\nOne of many sights of organization football is that a sport that is casual may be played with only equipment that is nominal - a simple sport can be enjoyed with items and only a ball on nearly every open area of affordable measurement to mark the placements of two models of goalposts. ", "This is actually the new FIFA 17 style for 2016 that can come alongside other game modes that are standard as well as Ultimate Team. ", "Every year EA presents new hit of FIFA a number of gamin consoles within the couple of days of its launch, i.e. Xbox 360, PS4, Xbox One and afterall PC. ", "If you are considering FIFA 17 Release-Date then mark this dates on your own gambling calender right now!", "\n\nThe separate UEFA Handle, Honesty and Disciplinary Body (CEDB) met on 24 July in Paris to manage the disciplinary cases opened against the after the situations which happened in the Belgium-Republic of Ireland (3-0) match played on 18 August in Bordeaux. ", "By 2018, the top four leagues will present four teams each for the group periods of the Champions League as a result of the modifications announced by UEFA on Friday. ", "As the final treatment happens in Ny, where players learn about the American type of activity, exceptionally, the very first period occurs at headquarters in Switzerland. ", "Since EA produces these games for the forthcoming season although we are in 2016, we're truly looking forward to the FIFA 17 release-date. ", "This change might come into result from your 2018/19 season - the growing season which immediately Follows the 2018 World Cup.", "\n\nPlease enable 10 business days from vessel of one's purchase before informing us of any delayed deliveries. ", "Chosen players who successfully listed for the Beta may receive a minute mail around July 18 with access signal for ps 4. ", "More are focused by KR Basketball Enjoyment, another headline font to the true soccer than tops or helmets. ", "The winners and runners-up of the fifth and sixth-placed leagues, at present Italy and Paris, may proceed to possess two places as the winners of the seventh to 10th rated leagues, currently Italy, Ukraine, Belgium and Turkey, may also qualify automatically. ", "Somewhat, a leagueis coefficient and so a team will soon be swayed by ancient success” - for example past European wins - as opposed to just their performance in more modern periods. ", "Thus, FIFA 2017 release-date will remain pretty much the same as the prior years. ", "http://www.mmovc.com/fifa-17/fifa-17-comfort-trade\n\nIn its newest quote to stick out from fifa 17 point for sale broadcasting competitor BT, Atmosphere is releasing a brand new sports station that will not be unavailable to clients who do not buy a Sports pack. ", "What's good relating to this predicament for basketball video-editing by displaying a player on the industry or adding arrows is that Apple Activity is very wording focused. ", "After the demonstration version was launched and presently the speculation about person rankings went into overdrive,. ", "Another soccer template can be used as a scrapbook format or an university layout. ", "This kind of event - while beautiful for your relaxed soccer supporter - might have ruined the integrity of not just the Champions Europeis prime domestic leagues but additionally League also.", "\n\nThe Gaelic policies were used by Davin and published inside the Usa Ireland magazine on January 7, 1887. ", "Davin's regulations exhibited the effect of games such as hurling as well as a need to formalise a definitely Irish rule of football. ", "The numberone of System joins Mesut Ozil one of the leagueis better to complete the make. ", "On his rating of 85, Cech has improved at the age of 34 after featuring sparsely for Chelsea while in the build-up to FIFA 16. ", "Operated by Frostbite, how you play, participate, and emotionally relate to the sport is transformed by FIFA 17. ", "The perfect example of the differentiation was having less an offside rule (a feature which, for many years, was provided solely by other Irish activities like hurling, and by Foreign rules football). ", "You play as Finder as he embarks on his prodigious career alongside lifelong friend Walker.", "\n\nAnimation: the most important thing of the sport which in fact makes it appear and feel better is animation and we already have seen some engaging & fascinating animation added to Professional Evolution Soccer 2016, that doesn't really suggest EA had done nothing in regard to FIFA 2017 but it doesn't really feel different than the prior hit. ", "The sophomore quarterback put together as remarkable a performance as has been wished for, leading the Bucs to ratings on the first four offensive possesions and joining with No. ", "1 receiver Mike Evans on several situations. ", "RealScorz Football can be a software that enables consumers participate in a mobile model of Fantasy Football. ", "www.fifasale.com\n\nChildren of all ages enjoy activities, and normally buy fifa 17 coins you'll find games which are not inappropriate for various age brackets. ", "When it comes to 5-yearold boys the games should be participating and fun without seeking too much control because kids haven't yet formulated accurate control capabilities at this era. ", "What's promising is that there are plenty of games that entertained for awhile and will maintain them chaotic.", "\n\nMake wedding cake, wedding cake, a customized birthday cake, and celebration cake. ", "It is as you really are a skilled pastry cook. ", "Create your own personal bakeshop and become like a professional pastry chef and FIFA 17 create efforts that could preserve your online customers coming back for more.", "\n\nNintendo launched the eShop at launch for that Wii-U last year and it is very similar to Xboxlive. ", "You'll be able to 2016 new games, whether it be a retail or indie concept. ", "It will likely be super easy for Developers to release games at the same time on Smartphones along with the Wii-U together With The Wiiu having a controller that resembles a capsule. 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", "Particularly when it comes to exciting games for boys.", "\n\nTramadol is actually a medication that is used-to alleviate moderate to moderately severe pain. ", "Additionally it works extremely well to deal with pain caused by surgery and chronic ailments for example cancer or joint pain and functions reducing response and the mind's understanding to pain. ", "It also lowers scale or the dimension of the pain signal passed to a different FIFA 17 in one nerve. ", "Like a product form to become consumed orally every 4-6 hours as needed tramadol comes. ", "It could be obtained with or without food. ", "Follow the recommendations on your own prescription label cautiously, and ask your doctor or pharmacist to describe any part you don't realize. ", "Take Tramadol directed. ", "Tramadol can be habitforming. 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", "There a number of other activities made particularly for boys, where they are able to struggle with bad people and conserve the princess from your system, but these dinosaur games be cheap FIFA 17 PS4 coins seemingly less crazy and more right for all ages.", "\n\nThis holidays, we keep in mind that it is the thought that matters. ", "If you plan to purchase a reward for your child, why don't you obtain buy fifa 17 coins the money's best offer price. ", "A gift that'll not merely provide delight and grin to your child, but in the same time a toy which will enhance the skills. ", "Below will be the list of the Very Best 10 Christmas Gadgets 7 Yrs Old, and Ladies 5, 6.", "\n\nThe very first thing to accomplish is make a listing. ", "Virtually, you cannot make note of what you don't understand however and the finest point to guide you with all the record may be the web. ", "Browse for colors and types that look best for you personally. ", "Record along or save some images of the spring sneakers that goes well together with your attire. ", "There is variety to decide on in virtually any online merchants, that provides bargains that are warm aswell. ", "It does not matter should you FIFA 17 spring sneakers or a costly one, a lot of people could not even inform the difference. ", "Way too long, everbody knows just how to carry oneself, up until the day last.", "\n\nOpening the lucky solutions truly way to pay an enormous sum for them? ", "Not necessarily . ", "For using the games that you don't need to pay huge dollars. ", "A number are of sites available online which provides the center to download-free games. ", "Nevertheless, you'll also get the sites which impose a moderate amount to 2016 new games and their solutions around you would like . ", "Both varieties of sites might be seen from your web. ", "However , a trusted site to download free games for PSP is difficult to find .", "\n\nGame titles involving Barbie are truly undemanding. ", "You will quickly play with the sport without having looking for secrets and secrets as well as manuals. ", "Clicking and dragging are primarily the duties that you simply do. ", "their convenience as well as dress-Up games for boys is among the reasons why people appreciate them so much.", "\n\nStore a video game match. ", "These could be a lot of enjoyment for you along with your gaming pals. ", "You're able to both do this online, your own house or in a friends area. ", "Offer some fun treats when you can concerned and get as many individuals,. ", "This can be a great way to savor your game playing .", "\n\nCertainly a selection are of techniques on what the seized cars were placed for the government's person. ", "Reason or the most frequent and also the most sensible reason will be that bad people, or those that broke guidelines or breached rules used these vehicles.", "\n\nBoth of these devices that are red are part of the click here number of green gadgets of Device Epoint that has certainly been rocking the world that is system. ", "And women have certainly been drooling to own them.", "\n\nAmong the finest items that could have \"2k17 coins\" occurred towards the videogame sector was the discharge of the Sony PlayStation. ", "There has been many versions of the PS video game system. ", "The newest version being the PlayStation 3, which has been quite effective to date with people. ", "The ps3 was provided for videogame people worldwide in 2006. ", "Since that time, it's managed to develop a significant large user-base for itself.", "\n\nMark: Does Pong count? ", "When the NHL problem did not make me feel outdated, this one surely does. ", "I am truly found myself in enjoying with them rather than not of the gaming technology. ", "It only seemed to me that if you were going to play video-games, it had been kind of foolish to play with things like activities you could do in actual life. ", "I would much rather perform Missile Command or Area Invaders or Asteroids.", "\n\nYou would think that a four player co op game that happens in a scifi universe and includes an immeasurable amount of guns available, could go for a thing that might stress teamwork. ", "I had been imagining something of getting the Borderlands concept on-top having a still shot of the four key figures walking deprived leave over the lines. ", "It'd provide a calm assurance in a badass type of way. ", "What 2K games delivered nevertheless, is just something I didnot anticipate.", "\n\nPrepare a home heating, cocktail or potluck celebration and request people to come over. ", "You can also make tokens that are tiny to give out for your guests at the party's end. ", "This would be your opportunity to be introduced to a lot of people in one single venue.", "\n\nAn Xbox or other nba 2k17 technique is usually a welcome addition to a sailor's possessions. ", "Look like a few of the later -generation PS2s, for anything slimline; sailors don't possess lots of space in their bunking places, and something they own needs to be locked up. ", "In case you ship activities or shows, ship them sans appearance, as only a cardboard-secured DVD, and save for once they get home the situation. ", "Whatever decreases area filled may help.", "\n\nFree visitor MMOGs will be the type you could use your browser while not having to download or deploy something and so are also absolve to play (f2p). ", "These elements practically reduce best games 2016's several troubles. ", "They may be exciting, simple about may be enjoyed on any computer and the budget and not needing to publicity over assembly or compatibility problems .", "\n\nThe model packages in \"BioShock\", \"BioShock 2\" and all the DLC information into one offer for $ 29.99's good purchase end cost. ", "Likewise, the \"Challenge Locations Pack\" that has been only on the PS3 will now be around to the Xbox 360 Console.", "\n\nOkay, let's take a look . ", "It was actually Rashad Evans, who was planned to combat Mauricio \"Shogun\" Rua but instances own it that has to be Jon Jones. ", "We have now Smith against the Shogun, who do you consider will earn? ", "Several MMA fans believe that Johnson can battle to beat the shogun. ", "But you will find those who believe that Jones cando. ", "But I personally think that Shogun is physically \"buy NBA 2K17 PS3 MT coins\" stronger in comparison to Jon Jones. ", "Well, that is only my estimation. ", "But I am persuaded that this struggle will be prevailed within by Shogun.", "\n\nVideo game sure got a place currently with NBA 2k17 coins for sale numerous adults claiming its \"bad\" for children to play with game. ", "Although there sure are some activities which are not conducive to healthy improvement, it is actually just a small percentage of activities which might be not good. ", "Naturally playing games 12 hours aday is bad for you, but playing soccer 12 hours there is a-day just as detrimental to you. ", "Balance could be the key whatever it's for balanced progress. ", "In reality, system games offers kids an incredible range of amusement and also training and create for good gifts.", "\n\nNumerous gamers dream of starting their online video game shop that is personal someday. ", "What could not be inferior than doing work close-to nba 2k17 games and always owning a substantial selection of video game titles you'll be able to perform? ", "If you're currently seeking to open your individual video nba 2k17 retail store listed below are five suggestions to keep up in mind.", "\n\nWhile Steam's year-end income are nearly over (less than a-day remains) several popular brands continue to be available inexpensive. ", "Newer activities like Battleground: Bad Business 2, Borderlands and also the Adults of Light can be found for 50%-66% off their original charges. ", "Steam offers recreation packages (with numerous games) aswell, from your likes of 2K games, THQ, and Square Enix. ", "The packs are usually while in the number of thousands range, but are actually readily available for less than one-hundred, purchasing Computer players that are so happy!", "\n\nThe final action ought to be to hardship the outfit to get a difficult impact. ", "Very well, these guidelines are of building the costume on the initial stage,! ", "Nevertheless it might be predicted that the look that was completed will likely be a genuine return of Assassin's Creed Altair.", "\n\nIt's 50mm speakers and also the audio delivers clean heights and lows that are heavy. ", "The in-line amplifier allows to quantity controls for the game and conversations for easy access. ", "The distinct contacts for your line sign makes the X12 an excellent headset for enjoying with best games 2016.", "\n\nThe Xbox 360 Console game that I own could be dealt in for $9.00. ", "The Playstation 2 game I discovered was the Gamecube game as well as $5.50 I came across was $6.50. ", "Entirely that is $21.00 or $ 7.00 per game. ", "That is a decent amount. ", "You're never going to reunite a sizable fraction of what you originally paid. ", "If you get $5 - $10 you're doing pretty good and it was definitely better than my first experience with trading in games.", "\n\nYou will find plenty of additional factors you could update for greater Computer effectiveness such as your Disc/ other peripherals, Monitor, sound cards, along with DVD Writers. ", "As well as a large amount of them are usually to enhance your experience using your Computer. ", "In upgrading, generally consider your budget and everything you must have. ", "In my opinion, go for that midstream components (prices at midrange) since opting for the top class pieces could really set you back a whole lot unless you are doing have a lot of extra cash to shell out. ", "Their charges could decline in several weeks. ", "But you will have times when you actually have to enhance you Laptop so do not hesitate look for the least expensive upgrade you may get with the maximum amount of performance and to mmovc.com/nba-2k17-mt ask questions when you can attain on your computer." ]

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[ "1. ", "Field of the Invention.", "\nThe present invention relates to a compensation circuit used for providing a selected output impedance and which is mounted on a board having breakaway tabs so that selected tabs can be removed for quickly and accurately selecting circuit connections for adjusting an output value of the impedance.", "\n2. ", "Description of the Prior Art.", "\nIn the prior art, after testing communication loops for obtaining the proper loop loss, compensating for such loss has required making individual connections to the selected impedance. ", "Manual connections are needed to obtain the correct output compensation impedance from a circuit board containing a variable impedance, such a multi-tap resistor." ]

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[ "March 15th is a national holiday in Hungary. ", "It stands for democracy and freedom and it commemorates the Hungarian Revolution of 1848, which grew into a war for independence from Habsburg rule.", "\nEvery year before that day students of SKAID KODALY ZOLTAN PRIMARY SCHOOL decorate their classrooms with symbols of the holiday. ", "On Friday (14 March) they held a ceremony (commemoration) in the school gym with participation of 6th graders\n\nNATIONAL HOLIDAY IN HUNGARY\n\nHigh School of KORINOS, Greece\n\nThis is an article written by the student Dimitris Prothromidis which has come first in the writing competition of articles on the value of reading books. ", "The article in question will be published shortly, in «PEN», the school newspaper as well as in local newspapers.", "\n\nTHE BOOKS AND THE READING VALUE\n\nThe book, a timeless medium of knowledge, hides in its pages an entire treasure. ", "It reveals the past, it judges the present, and it prepares for the future. ", "What is then, its value for man?", "\n\nFrom the early historic times, man has felt the need to record his knowledge and experiences, so that they will remain intact through time ensuring that the future generations would learn some information with certainty. ", "After all, with oral speech, some important pieces of historical facts get lost, as they pass on, by word of mouth .It is for this reason that man has created books. ", "With books, man could also make guesses about the future. ", "Writers such as Julius Vern, painted with their writings a picture about the future that has been verified today, to a certain point. ", "Therefore the book has a priceless value for man.", "\n\nUnfortunately though, young people aren’t interested in reading books today. ", "They aren’t fond of coming in contact with something which is considered old and obsolete. ", "They prefer to spend their time on new technological inventions such as the television and the Internet. ", "This way however, not only do they not read books but also they become isolated from the world around them. ", "The computer screen is their entire world, without the least bit of paper.", "\n\nHowever it is never too late for something to change. ", "The same stands in this case too. ", "The disengagement from the television screen or from the computer screen and the immediate contact with reality can contribute to the return of young people to the book. ", "The publication of books, which will attract the interest of the contemporary reading audience, can also help. ", "After all there are books of electronic nature as well.", "\n\nTake a look at a library for a while, either your home library or a public one. ", "You will see thousands of books waiting for you there. ", "They are always there. ", "It is just enough, to search for them.", "\n\nMIHAI EMINESCU NATIONAL COLLEGE\n\n\"Carnival of literary person\" is an activity that reminds us of the beautiful days of Winter and its celebrations. ", "Held within the Comenius project, \"Learn to Read and Read to Learn\", it was organised by Maths teacher Adriana Luca, Romanian teacher Monica Dumitras, followed as judges by Maria Hulber and Laura Costa. ", "Deputy director Eniko Hochhauser honoured the participants with her presence.", "\n\nVery enthusiastmatic and very cheerful, the young actors of classes 6 A and 6 B, encouraged by their parents, presented their role in a theatre play, with talent. ", "The play's end was spoken in English, because that's the international language of the project. ", "The students received 14 diplomas, and the most beautiful outfits will be featured in a calendar made by the Comenius project. ", "The most talented kids will play in a theatre play in Romanian, but also in English, when the partners of the National College \"Mihai Eminescu\" will visit.", "\n\nMIHAI EMINESCU NATIONAL COLLEGE: Reading Contest\n\nIn January 2014 we celebrated two years since the first meeting of Reading Club in foreign languages. ", "The partnership with the Faculty of Letters from Oradea and with ”Gheorghe Șincai” County Library involves organizing a reading club in different languages for primary school pupils.", "The languages in wich we read are: Romanian, English, French, German and Hungarian.", "\nThe activity is held on the last Wednesday of each month.", "\nIf in the beginning adults were those who read to the children, the novelty is that now highschoolers and students are addressing to the children.", "\nTwo meetings - one in December and one in June - are dedicated to reading competitions.", "\nThe project team wants to bring the little readers closer to the idea of book and to that of library. ", "The central objective is to train students to come to the library both accompanied and on their own, to borrow books and, as they advance in age, to study in the reading room.", "\nOn December 16th, 2013 the second edition of the reading contest in Romanian, Hungarian, English and German was held.", "\nThe team coordinated by Laura-Teodora Ardelean was responsible for the Romanian language section of the competition and was composed of: Emilia Ciordaş, student at the Faculty of Letters, University of Oradea, Andrada Belenyesi, Beatrice Bungo and Denik Jurcsik, students in twelfth grade at ”Mihai Eminescu” National College; Paul Zoț, librarian and spokesman for ”Gheorghe Șincai” County Library.", "\nThe fragments were chosen from a book written by Florian Cristescu. ", "The title is Familia Roademult. ", "The text was divided into sequences on which a question was formulated.", "\nTwenty primary school students enrolled in the competition for this particular section.", "\nThe jury paid attention to the following aspects: reading accuracy, expressiveness, fluency, adapting to the situation of communication, the understanding of the text.", "\nThe winner of the first prize received a book from Gutenberg bookstore which was the sponsor of the competition.", "\nAll participants were given the opportunity to make free pass to County Library .", "\nLaura-Teodora Ardelean\n\nNews\n\nLEARNING ENGLISH IS FUN\nLiterary and Musical Spectacle of the students from the after-school-care groups – 3rd A and 3rd B classes\nThird graders from the after school care groups (3rd A and 3rd B classes) showed wonderful knowledge in English language at the celebration LEARNING ELNGLISH IS FUN....\n\n\"Biographies. ", "The Romanian writers, as they (really) were\"\nby Maria Hulber (translated by Ioana Pantor)\nThe national curriculum for Romanian Language and Literature for the 10th grade, brings to the students’ attention a series of great writers who influenced the evolution of the epic discourse and...\n\nReading session dedicated to the World Book and Copyright Day - 23rd April\nThe magical world of books\nThe celebration is dedicated to the World Book and Copyright Day – 23rd April\nReading session in Bulgarian, English and French languages with the participation...\n\nThe “Historical Tales” Competition\nby Sorina Duică (translated by Ioana Pantor)\nAs part of the multilateral Comenius Learn to Read and Read to Learn, on Friday February 20th, 2015, at “Mihai Eminescu” National College, took place the reading competition entitled Historical Tales.", "\nAiming at...\n\n\"Word Images\"\nby Maria Hulber (translated by Ioana Pantor)\nIn November 2014, throughout a period of four weeks, the students from class 7th B, coordinated by their teacher, Mrs. Maria Hulber, explored the poems for children written by the Romanian writer Tudor Arghezi, poems inspired by the...\n\nThe youngest students from the High School \"Mihai Eminescu\" are celebrating \"100 Days of School\". ", "The activity was part of Comenius Project \"Learn to Read and Read to Learn\" through the meeting with the actors from the local Theater \"Regina Maria\". ", "They performed and draw parts of Romanian...\n\nThe 1st March – Baba Marta (4th D class, V. Petkova, class teacher)\nA very loved and respected Bulgarian tradition – Baba Marta – was celebrated by the students from 4th D class and their class teacher.", "\nChildren had started their preparation...\n\n27. ", "11 .2014г. ", "In the magical world of the fairy tales\n“Snow-white and the seven dwarfs”\n( in English)\nClass: 4th V, teacher – Desislava Stoyanova\nThe date of 27th November 2015 was a real fairy-tales holiday for the fourth graders from Vazrazhdane Secondary School, working on the Learn to...\n\n27. ", "11 .2014г. – ", "In the magical world of the fairy tales\n‘Who will have taste of the rod’ folk tale\n4th G grade, Teacher: Stefka Kolarova\nHow can a tale become more interesting to children? ", "How can it provoke students’ imagination and make them read..." ]

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[ "Looking towards the skies, for our redemption draws nigh!", "\n\nTrans-Whatism? ", "A State of Confusion…\n\nGreetings and thanks for stopping by The Countdown to see what’s new on the menu.", "\n\nThis morning we have a simple coffee and ‘doughnuts’ breakfast.", "\n\nWe have a video here about Trans-humanism – sorry about not embedding, but with a simple point and click you can watch this 75 minute presentation from Tom Horn.", "\n\nSomething to keep you awake (coffee) and something that has a hole in the center but keeps going around (doughnuts). ", "There truly isn’t anything new under the sun as the scriptures tells us. ", "The fallen angels are still up to no good – operating behind the scenes through deceived humans. ", "Here take a look:" ]

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[ "Q:\n\nShould I use CTE, Subquery, Temp Table, or a different method?", "\n\nI've been working with SQL for a few months and I'm having trouble determining a couple of things for this specific task:\n\nCan SQL output the data the way I need it?", "\nWhich method should I use to make it happen if so?", "\n\nThe table I have has each school broken down by grade level, and the second column has the total enrollment per grade level. ", "I'm trying to sum all enrolled students per grade level for all schools with the following desired output:\nGrade Total Enrolled\nK 7,871\n1 8,321\n2 8,087\n3 8,164\n4 8,237\n5 8,055\n\nThank you for your help!", "\nI tried this using subqueries, but it showed the totals repeating down each row for all records in the table, instead of just one row of totals.", "\nSubquery:\nSELECT (SELECT SUM(Totalenrollment) FROM Dbo.['2013Cycle_1_Data']\n WHERE Grade LIKE '%6%' AND Level = 'MS' ) AS Grade6\n\nCTE Code:\nWITH \n TK AS ( SELECT SUM(Totalenrollment) AS Kindergarten FROM Dbo.['2013Cycle_1_Data'] WHERE Grade LIKE '%KIND%' AND Level = 'ES' )\n, T1 AS ( SELECT SUM(Totalenrollment) AS Grade1 FROM Dbo.['2013Cycle_1_Data'] WHERE Grade LIKE '%1%' AND Level = 'ES' )\n, T2 AS ( SELECT SUM(Totalenrollment) AS Grade2 FROM Dbo.['2013Cycle_1_Data'] WHERE Grade LIKE '%2%' AND Level = 'ES' )\n, T3 AS ( SELECT SUM(Totalenrollment) AS Grade3 FROM Dbo.['2013Cycle_1_Data'] WHERE Grade LIKE '%3%' AND Level = 'ES' )\n, T4 AS ( SELECT SUM(Totalenrollment) AS Grade4 FROM Dbo.['2013Cycle_1_Data'] WHERE Grade LIKE '%4%' AND Level = 'ES' )\n, T5 AS ( SELECT SUM(Totalenrollment) AS Grade5 FROM Dbo.['2013Cycle_1_Data'] WHERE Grade LIKE '%5%' AND Level = 'ES' ) \n\nSELECT * FROM TK \nUNION ALL\nSELECT * FROM T1 \nUNION ALL\nSELECT * FROM T2 \nUNION ALL \nSELECT * FROM T3\nUNION ALL\nSELECT * FROM T4 \nUNION ALL\nSELECT * FROM T5 \n\nA:\n\nJust use a CASE statement to determine the grade level and then group by the grade level:\nselect \n case \n when Grade LIKE '%KIND%' AND Level = 'ES' then 'K'\n when Grade LIKE '%1%' AND Level = 'ES' then '1'\n else 'Other Grades' \n end as GradeLevel,\n sum(TotalEnrollment) as Enrolled\nfrom\n Dbo.['2013Cycle_1_Data']\n group by\n case \n when Grade LIKE '%KIND%' AND Level = 'ES' then 'K'\n when Grade LIKE '%1%' AND Level = 'ES' then '1'\n else 'Other Grades' \n end\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Q:\n\nHow/When to design an interface?", "\n\nI'm trying to get in the habit of designing the interfaces to my websites at the very beginning before I do any actual coding. ", "I've read \"Getting Real\" by 37 signals and they recommend doing the interface first, before any actual code is produced.", "\nWhat exactly is meant by that? ", "Does that mean use pure HTML and CSS to design the site and add php, js logic to page afterwards, or is it okay to sprinkle in the php, js from the beginning? ", "\nWhat if your using a framework, should I set up empty controllers that simply call the views, or should the early stages be solely html, css?", "\nAlso, what do you guys think about design first vs later?", "\nEDIT I'm talking about AFTER I have sketched everything with pen and paper.. I'm taslking solely about the html mockups. ", "And I'm not too sure about using extra tools that I would need to learn to do this\n\nA:\n\nI think that the majority of the benefit of designing the interface first has been achieved after you are done your paper sketches. ", " Basically, you are just ensuring that you have a design in your head and that your coding process is somewhat end-user driven. ", " You are also trying not to waste time on needless documentation.", "\nGetting the HTML in place (or the skeletons of the Views in an MVC app) makes some sense and this is the main thrust of what 37signals says. ", " I would certainly not do anything beyond this that is just going to be thrown away.", "\nI think if you have a proper design, it is immaterial if you next move on to writing the back-end code after the HTML or if you do the CSS and JavaScript. ", "The CSS and the code should not even need to be aware of each other.", "\nDo whatever gets you excited and motivated. ", " Do whatever gets you thinking more deeply about how the app will actually work so you can catch any flaws in your original thinking. ", " I like to code before CSS but that is just me. ", " You might find it important to get the CSS further along before the app takes shape in your head.", "\nJoel Spolsky likes Balsamiq as a mocking tool. ", " I think that 37signals uses Draft (an iPhone app). ", " I use a Sharpie. ", " The key is not getting too detailed though.", "\nOpinions vary, but I believe that JavaScript should come last. ", " I believe most sites should be designed so that they work 100% without JavaScript and then have JavaScript added for polish.", "\nLearn more about Unobtrusive JavaScript\nSo (for me):\n\nQuick and dirty sketches of views\nGet some HTML in place\nMaybe some basic CSS for layout (or more if I need to impress somebody early)\nWrite the core logic\nAdd support for web services and AJAx calls\nPretty it all up with snazzy CSS\nWrite some JavaScript to add the sizzle\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Five-year survivors among children with acute leukemia in Japan.", "\nThis Japanese nation-wide survey was carried out on long-term survivors among children with leukemia, i.e. those who had survived more than 5 years by October of 1974. ", "Eighty-three children were surveyed. ", "This was about 2.5 times as many as the 31 children surveyed in the first Japanese nation-wide survey in 1971. ", "Clinical and laboratory data were also analyzed statistically and compared to that of the first survey. ", "Most of the children had received inductive therapy according to the old protocol, but 10 children were treated with a combination of VCR and steroids. ", "Nine of these 10 were still in a state of remission. ", "CNS involvement occurred in 15.3% of the cases and a late onset of this complication implied a prognostic significance: among the 9 children whose complication had occurred 3.5 years after onset of the disease, 6 died. ", "The relapse rate decreased between the 4th and 5th year after initiation of maintenance therapy. ", "The percentage of the risk of death became zero after the 9th year." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "For many years, it was “fashionable” in the world of international commerce to be considered a proponent of free trade. ", "In principle, free trade means that market forces – not artificial trade restraints, such as tariffs and quotas – are the best means for nations to ensure vibrant domestic and international economies.", "\n\nJust ask Japan, which trade analysts in the early 1980s were forecasting would soon crush American economic interests. ", "Thanks to Japanese protectionism, which walled off both its domestic and international markets over the next two decades, the island empire’s economy remained frozen in concrete, unable to adjust to market forces. ", "While the U.S. economy went through its ups and downs, it remained flexible and was able to adapt better to changing conditions. ", "But Japan, with its rigid and corrupt system, stalled in what now is nearly a 20-year-old recession.", "\n\nSo why, then, even if America has fared better than Japan, is it no longer fashionable to for Americans to worship at the alter of free trade? ", "The answer is simple: Many of our trading partners, such as China, Brazil, Canada and Mexico, have not ceased using government-applied price controls, quotas, tariffs, onerous regulation and the failure to protect intellectual property rights as a means to distort trade and commerce. ", "While we Americans, in our infinite naivete, talk of open markets, trading partners such as these have other ideas.", "\n\nTheir trade negotiators – perhaps more skilled in the “art of the deal” than our own – have won trade concessions from American diplomats, without having their own countries’ sufficiently reciprocate by opening their markets. ", "As a result, trade treaties such as NAFTA, GATT and the U.S.-Chile Free Trade Agreement – which in theory should equally aid all signatories – have been skewed against American interests, increasing foreign imports into our country without sufficiently promoting our exports. ", "And, American trade negotiators have failed in other respects as well.", "\n\nPerhaps the best example of America’s weak trade diplomacy is found in the reasons behind the recently enacted and fiscally irresponsible Medicare legislation. ", "In their infinite “wisdom,” U.S. Senate and House leaders enacted legislation which amounts to a $534 billion tax on American consumers to help pay for and, in effect, subsidize the high price of pharmaceutical drugs sold domestically.", "\n\nThe reason that Congress opted to bust the budget with handouts to the needy, rather than force competition in the drug industry, which would have lowered the price of drugs without taxing the people, stems not only from powerful drug-industry lobbyists having lined the pockets of senators and representatives with campaign contributions and other forms of legalized “bribery,” but from the failure of U.S. trade negotiators to demand that foreign countries remove controls on the maximum price of drugs sold overseas.", "\n\nOver the years, American drug manufacturers moved about 70 percent of their production facilities overseas, where products could be manufactured more cheaply. ", "However, while American drug companies were “off sourcing,” the foreign host governments, which installed socialized systems of medicine, were preventing U.S. pharmaceutical interests from allowing the market to set prices. ", "As a result, in most countries, American drug companies are forced to sell the same product for half the price U.S. consumers can buy it.", "\n\nIn effect, the reason American drug companies are charging U.S. consumers double is because they cannot get a reasonable price for their product overseas. ", "Rather than demand, under threat of sanctions, that the foreign governments remove the price ceilings on drugs – and allow the market to set prices domestically and internationally – our trade negotiators have “rolled over.”", "\n\nGiven that our Senate and House leaders have spent the country into bankruptcy, a strong trade policy is all the more important. ", "Not only should American companies be encouraged not to send production facilities and jobs overseas by “outsourcing” through various incentives to retain production facilities in the United States, but our trade negotiators must be “set free” to drive a hard bargain to ensure that trade relations are fair, not simply free.", "\n\nWhat is free is rarely worth anything – and this can be said of not only our congressional leaders, who hand out hard-earned taxpayer money like drunken sailors, but our trade negotiators, who have given away the store to foreigners.", "\nAs a former international trade lawyer, Reagan Justice Department prosecutor, chairman of Judicial Watch and, God willing, Florida’s next U.S. senator, I will not allow either Congress or our trade negotiators to sell out American interests, particularly without getting equal value in exchange from foreign countries. ", "What counts is fair trade. ", "Free trade is out! ", "The well-being of our economy and our citizens is at stake.", "\n\nA vibrant economy, with jobs for all Americans, and a return to Judeo-Christian values and ethics, along with a strong national and homeland defense, are the keys to preserving liberty." ]

{ "pile_set_name": "Pile-CC" }

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[ "Main Navigation\n\nKidz Motion is a nurturing, child friendly physical therapy facility specializing in the treatment of children and adolescents from birth to age 18.", "\n\nMichele Wallace, P.T., founder and executive director, is dedicated to providing quality pediatric physical therapy to children with diverse backgrounds and needs.", "\n\nTreatment is designed and delivered utilizing a child-centered approach based on their diagnosis and specific needs. ", "Therapy is sensitive to the child’s tolerance, behavioral and emotional needs, and previous exposure to treatment. ", "Often helping the child means working with other disciplines and professionals to comprehensively assist in understanding and best treating the child.", "\n\nHere at kidz motion, we realize that each child is unique and deserves the chance to reach their fullest potential.", "Call today to learn how we can help you help your child!" ]

{ "pile_set_name": "Pile-CC" }

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[ "Network participation indices: characterizing component roles for information processing in neural networks.", "\nWe propose a set of indices that characterize-on the basis of connectivity data-how a network node participates in a larger network and what roles it may take given the specific sub-network of interest. ", "These Network Participation Indices are derived from simple graph theoretic measures and have the interesting property of linking local features of individual network components to distributed properties that arise within the network as a whole. ", "We use connectivity data on large-scale cortical networks to demonstrate the virtues of this approach and highlight some interesting features that had not been brought up in previously published material. ", "Some implications of our approach for defining network characteristics relevant to functional segregation and functional integration, for example, from functional imaging studies are discussed." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Section 108 Study Group Report\n\nby: Michael Jimenez - April 2nd, 2008\n\nThe Section 108 study group has released its report to the Librarian of Congress recommending changes to section 108 of the Copyright Act.", "\n\nSection 108 “permits libraries and archives to make certain uses of copyrighted materials in order to serve the public and ensure the availability of works over time.” ", "The Section 108 study group was “convened under the auspices of the Library of Congress to look at specific changes that might be needed in the copyright law to balance the positions of rights holders and cultural memory organizations such as libraries and archives in the digital world.” ", "See the report, executive summary and press release for more information." ]

{ "pile_set_name": "Pile-CC" }

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[ "So as an American Red Cross Volunteer, I got word of the collaborative project between H.O.T., ARC, and Uganda Red Cross. ", "I've known about H.O.T. for sometime and figured it was a sign that I should pitch in. ", "This project is another amazing example of their work and I'm glad to see the Red Cross helping out. ", "I also learned to be very appreciative of the imagery in the U.S.\n\nGreat work H.O.T. I signed up for the mailing list and will try to pitch in more often." ]

{ "pile_set_name": "Pile-CC" }

[ 0.0005613404209725559, 0.0005773967714048922, 0.000599791354034096, 0.0005497662932612002 ]

[ "INTRODUCTION\n============\n\nMore than 170 million people worldwide are currently infected with the hepatitis C virus (HCV). ", "HCV infection represents a major cause of chronic liver disease and hepatocellular carcinoma ([@B1]). ", "HCV is an enveloped virus belonging to the *Flaviviridae* family and is the unique member of the *hepacivirus* genus. ", "The HCV genome is a single-stranded positive RNA of about 9.6 kb. ", "The 5′ untranslated region (UTR) forms an internal ribosome entry site (IRES) that directs the translation of a precursor polyprotein of about 3000 amino acids. ", "This polyprotein is cleaved co- and post-translationally by cellular and viral proteases, resulting in the synthesis of both structural and non-structural (NS) proteins. ", "The structural proteins core, E1 and E2 are processed by host signal peptidases. ", "The core protein presumably forms the viral nucleocapsid ([@B2]), whereas E1 and E2 are glycoproteins anchored in the viral envelope ([@B3]). ", "The NS proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B are essential for replication of the viral genome ([@B4]). ", "The 3′ UTR is a highly conserved and structured region playing a key role in the initiation and regulation of viral replication.", "\n\nBesides the polyprotein open reading frame, sequence analyses have shown the existence of an alternate reading frame (ARF) overlapping with the core protein encoding sequence in the +1 frame ([@B5]). ", "Xu *et al*. ([", "@B6]) have suggested that this overlapping reading frame encodes a 17 kDa protein. ", "This protein is named 'F' (for frameshift) or 'ARFP' \\[for Alternate Reading Frame Protein ([@B7])\\]. ", "Previous studies have suggested that ARFP\\'s synthesis results from a +1 ribosomal frameshifting event near codon 11. ", "This event occurs after initiation at the AUG initiator codon of the polyprotein ([@B6]). ", "ARFP\\'s existence is supported by a high conservation of its open reading frame (ORF) in all genotypes. ", "Furthermore, peptides corresponding to this +1 reading frame react with antiviral antibodies present in the sera from HCV-infected patients. ", "These findings suggest that ARFP is synthesized *in vivo* and its synthesis results in the induction of anti-ARFP immune responses ([@B8],[@B9]). ", "The function of the ARFP is currently unknown. ", "Following translation, the protein is localized to the endoplasmic reticulum ([@B10],[@B11]).", "\n\nProgrammed ribosomal frameshifting is relatively frequent in viral translation ([@B12],[@B13]), and is used in particular by viruses to express a maximum of information through a limited genome. ", "Several studies \\[reviewed by Giedroc *et al*. ([", "@B14])\\], have mapped the optimal context required to direct a −1 ribosomal frameshifting event. ", "These include a sequence formed by redundant runs of bases, coupled with a stem-loop often folded in a pseudoknot conformation. ", "In this context, the presence of strong RNA structures most likely results in the induction of a ribosomal pause during translation and induces a ribosomal shift from its initial reading frame to the overlapping frame.", "\n\nIn contrast, mechanisms responsible for +1 ribosomal frameshifting can depend on the stability of the ribosome--RNA interaction and on specific RNA structures ([@B15],[@B16]). ", "The bacterial RF2 gene ([@B17]), the yeast TY1 and TY3 retrotransposones ([@B18],[@B19]) and the eukaryotic antizyme ([@B20]) are well-characterized examples of the proteins synthesized by +1 ribosomal frameshifting.", "\n\nThe occurrence of a ribosomal frameshifting event during HCV translation, first described by Xu *et al*. ([", "@B6]), is controversial, since the sequence used to demonstrate the +1 ribosomal frameshift contains a unique 10 adenine stretch at the beginning of the core protein sequence. ", "As suggested by Xu *et al*. ([", "@B6]), this adenine stretch could account for ribosomal pausing. ", "On the other hand, sequences composed of consecutive adenines have been shown to support transcriptional slippage by inducing RNA polymerase stuttering. ", "Stuttering may lead to modification of the final protein amino acid sequence through the insertion of non-template nucleotides during RNA synthesis ([@B21],[@B22]). ", "Moreover, alternative translation mechanisms of the overlapping reading frame have been proposed. ", "These include initiation of translation at different sites resulting in the synthesis of shorter forms of the ARFP. ", "Baril and Brakier-Gingras ([@B23]) have proposed that codon 26 is recognized by ribosomes as a site of non-AUG translation initiation in HCV genotype 1a isolates. ", "On the other hand, Vassilaki and Mavromara ([@B24]) have shown that translation of the +1 frame can initiate on an AUG codon at position 86 or 88 of the polyprotein. ", "The relevance of these mechanisms in translation of functional infectious HCV isolates in target cells of HCV infection is unknown. ", "The ARFP products, presumably resulting from these translation mechanisms, have been named fARFP, ~26~ARFP and, ~86/88~ARFP for ribosomal frameshifting, initiation at codon 26, and initiation at codon 86/88, respectively. ", "Furthermore, mechanisms of regulation of ARFP expression are not understood.", "\n\nTo define the molecular mechanisms of ARFP expression, we transfected chimeric HCV-H77-luciferase constructs into Huh-7 cells. ", "We demonstrate that initiation of ARFP translation occurs mainly at position 86/88 and is regulated by HCV core protein expression. ", "Furthermore, we show that ARFP translation is down-regulated by HCV core protein. ", "Thus, ARFP expression is inversely linked to the level of viral replication which may explain the low-level expression of ARFP during viral infection.", "\n\nMATERIALS AND METHODS\n=====================\n\nCell culture and transfection\n-----------------------------\n\nThe human hepatoma cell line Huh-7 was kindly provided by R. Bartenschlager (University of Heidelberg, Germany). ", "Embryonic kidney cells (HEK 293) were obtained from American Type Culture Collection (ATCC). ", "The cells were grown and transfected as previously described ([@B25]). ", "Medium, fetal calf serum and cell culture additives were purchased from Gibco-BRL.", "\n\nHCV H77 luciferase reporter constructs\n--------------------------------------\n\nA schematic outline of the plasmids is shown in [Figure 1](#F1){ref-type=\"fig\"}. ", "Nucleotide numbering refers to the HCV H77 genome sequence (genotype 1a) encoded by p90/HCV FL-long pU ([@B26]). ", "This plasmid was used as a template for DNA amplifications. ", "Plasmid pIV1066 was obtained by inserting the luciferase gene of pBI-L (Clontech) into the EcoRI-XbaI sites of a pCIneo plasmid vector (Promega). ", "The first nine nucleotides (including the ATG) of the luciferase gene were deleted by PCR, and the resulting fragment was cloned into the EcoRI-XbaI sites of pCIneo. ", "The resulting plasmid was named pIV1115. ", "For plasmids pIV1143 to 1147, and pIV1157, fragments of the HCV core protein encoding sequence (with or without 5′ UTR) were amplified by PCR using p90/HCV FL-long pU as a template. ", "The amplified fragments obtained were then ligated into the EcoRI site of pIV1115. ", "Plasmids pIV1143, pIV1144 and pIV1157 include the 5′ UTR and nucleotides (nts) 342--822 of the core protein sequence. ", "This sequence was fused in the 0, +1 or −1 frame with the luciferase gene. ", "pIV1145, pIV1146 and pIV1147 are the corresponding plasmids without 5′ UTR. ", "Plasmids pIV1204 and pIV1206 contain a single nucleotide substitution at nt 399 of the HCV H77 sequence introduced by the QuickChange® Site-directed Mutagenesis Kit (Stratagene) into plasmids pIV1144 and pIV1146. ", "This substitution leads to a stop codon in the core protein sequence (0 frame) (Q~20~ → TAG) without affecting the ARFP amino acid sequence. ", "Plasmids pIV1203 and pIV1240 contain a single nucleotide substitution at nt 407 of the HCV H77 sequence introduced by the QuickChange® Site-directed Mutagenesis Kit (Stratagene) into plasmids pIV1143 and pIV1144. ", "This substitution leads to a stop codon in the ARFP protein sequence (+1 frame) (S~22~ → TGA) without affecting the core amino acid sequence. ", "For plasmids pIV1242 to pIV1247, an XbaI - SalI restriction fragment encoding the 3′ UTR of HCV (nts 9204--9651) was amplified by PCR. ", "This PCR product was added to the 3′ end of the luciferase gene sequence in all previous plasmid sequences. ", "Figure 1.Design of core-luciferase and ARFP-luciferase expression constructs. (**", "A**) Schematic outline of the HCV genome. ", "HCV (core/ARFP) potential translation initiation sites are indicated. ", "Numbers correspond to respective codons. (**", "B**) Schematic outline of the plasmid constructs. ", "Plasmid constructs contain the core/ARFP sequence fused with the luciferase sequence in the presence or absence of the IRES and the 3′ UTR. ", "The names, the genomic organization of the plasmids and the nucleotide limits are indicated on the panels. ", "Black arrows indicate the position of the primers (Forward 1 and 2, Reverse 1) used for RT-PCR of HCV-luc transcripts. (**", "C**) Potential proteins resulting from each type of plasmid translation in the 0 and +1 frames (core in black, ARFP in grey, and luciferase in white).", "\n\nRT--PCR analysis of transcripts derived from HCV-luc constructs\n---------------------------------------------------------------\n\nHuh-7 cells were transfected with chimeric HCV-luc expression constructs as described earlier. ", "Total RNA was isolated using the RNeasy kit (Qiagen). ", "Reverse transcription was performed using 5 µg of purified total cellular RNA, SuperScript III reverse transcriptase (Invitrogen), and random primers (Invitrogen), following the manufacturer\\'s recommendations. ", "Subsequent PCR was performed on the reverse transcribed cDNA using Taq DNA Polymerase (Invitrogen), a reverse primer corresponding to the 3′ region of the luciferase gene (Reverse 1, 5′CCTCTAGAACTAGTGGATCCCCCC3′) and a forward primer corresponding to the HCV 5′UTR (nts 1--15) for IRES-containing constructs (Forward 1, 5′GGAATTCGCAGCCCCCTGATG3′) or to the 5′ region of the core protein encoding sequence (nts 342--362) for constructs lacking IRES (Forward 2, 5′GGAATTCATGAGCACGAATCCTAAACCT3′). ", "PCR products were then separated on a 1% agarose gel.", "\n\nRecombinant adenovirus vectors\n------------------------------\n\nRecombinant adenoviral genomes were generated as infectious plasmids by homologous recombination in *E. coli* as previously described ([@B27]). ", "Briefly, a DNA fragment encoding the full-length core protein (nts 342--914) was obtained by PCR using p90/HCV FL-long pU as a template, and was inserted into the EcoRI-XbaI sites of the adenoviral shuttle plasmid pTG13337. ", "The resulting vector, pIV1210, was used for homologous recombination with adenoviral sequences of the backbone vector pTG6624 ([@B27]), resulting in Ad core. ", "Recombinant adenoviruses were synthesized as recently described ([@B4]).", "\n\nLuciferase assay\n----------------\n\nAt 48 h post-transfection, cells were washed twice in PBS and lysed in 250 µl Reporter Lysis Buffer (Promega). ", "Luciferase expression was determined using a TD-20/20 Luminometer (Turner Design). ", "Briefly, 5 µl of cell lysate were mixed with 25 µl of Luciferase Reagent (Promega), and luciferase activity was assessed as described by the manufacturer. ", "Each transfection or infection was performed in triplicate and repeated at least three times. ", "Each set of experiments was normalized to the luciferase activity in cells transfected by a control plasmid encoding the luciferase gene in the absence of the HCV sequence (pIV1066).", "\n\nWestern blot analysis\n---------------------\n\nHuh-7 cells were lysed in Reporter Lysis Buffer (Promega). ", "The lysates were subjected to low-speed centrifugation (500 × *g*; 15 s) to remove nuclei and debris. ", "Proteins were then resolved by SDS--PAGE, transblotted onto Hybond-P membranes (GE Healthcare), and probed with anti-luciferase Mab (Sigma, dilution 1/500 in PBS, 0.1% Tween; 1% skimmed milk) for 1 h at room temperature. ", "After extensive washing, an anti-mouse IgG conjugated to horseradish peroxidase (Sigma, diluted to 1/5000 in PBS, 0.1% Tween, 1% skimmed milk) was added to the blots for 1 h at room temperature. ", "Following an additional wash step, the bound antibodies were detected by chemiluminescence (GE Healthcare).", "\n\nRESULTS\n=======\n\nMapping of HCV genetic elements required for ARFP synthesis\n-----------------------------------------------------------\n\nSince ribosomal frameshifting efficiency can be optimized by specific RNA structures, we evaluated the impact of the RNA context on core/ARFP translation efficiency. ", "To address this question, we fused nts 342--822 of the core protein coding sequence to a luciferase reporter gene cDNA. ", "We assessed translation efficiency in the three frames (0, +1, −1) by adding zero, one or two nucleotides, respectively, between the core protein and luciferase sequences. ", "To study the impact of HCV IRES on ARFP translation a second set of similar plasmids lacking the IRES element was constructed ([Figure 1](#F1){ref-type=\"fig\"}). ", "The chimeric HCV-luciferase reporter plasmids were transfected into Huh-7 cells. ", "To exclude translation initiation at the luciferase AUG, the first nine nucleotides, including the ATG, were deleted in all HCV chimeric luciferase constructs. ", "Thus, for each plasmid, luciferase activity represented translation of the respective frame. ", "The normalization of luciferase values, for each experiment and between different experiments, was performed using transfections with pIV1066 control plasmid lacking HCV sequences.", "\n\nTranslation of the core protein-encoding sequence corresponding to the full-length ARF sequence (nts 342--822) was analyzed by transfection of the HCV-Luc chimeric constructs into Huh-7 hepatoma cells. ", "Compared to translation in the 0 frame (core-luc), a significant level of translation in the +1 frame (ARFP-luc) was observed as shown in [Figure 2](#F2){ref-type=\"fig\"}. ", "The translation ratio ARFP-luc/core-luc was higher when the IRES was absent (compare 45/251 RLU in [Figure 2](#F2){ref-type=\"fig\"}A and 62/94 RLU in [Figure 2](#F2){ref-type=\"fig\"}B). ", "These results clearly show that ARFP translation is not dependent on the presence of the IRES. ", "Luciferase activity was absent in cells transfected with the −1 fusion constructs. ", "These data confirm that translation in the +1 frame, although occurring at low levels, was present ([Figure 2](#F2){ref-type=\"fig\"}). ", "Addition of the proteasome inhibitor MG132 did not modify translation efficiency (data not shown), suggesting that differences in protein expression levels were not due to differences in proteaosomal degradation of HCV-luc fusion proteins. ", "Figure 2.Translation of chimeric HCV core-luciferase sequences in frames 0, +1 and −1 in hepatoma cells. ", "Plasmids containing nts 342--822 of the core coding sequence fused to a luciferase gene reporter cDNA were transfected into Huh-7 cells. ", "The translation of HCV 5′ sequences was studied in the three frames \\[0 (core frame) in black, +1 (ARFP frame) in gray and −1 frame in white\\] and in the presence (**A**) or absence (**B**) of the IRES sequence, using luciferase activity quantification. ", "The integrity of the RNA transcripts was investigated in Huh-7 cells transfected with HCV-luc plasmids containing the IRES (**C**) or lacking the IRES (**D**). ", "RT-PCR of HCV-luc transcripts. ", "Total RNA was purified from Huh-7 cells transfected with the indicated plasmids and reverse transcribed as described earlier. ", "The resulting cDNAs were amplified by PCR using HCV (Forward 1 and 2) and Luc-specific primers (Reverse 1, see [Figure 1](#F1){ref-type=\"fig\"}A for primer position). ", "Plasmid pIV1066 encoding luciferase and Huh-7 cells transfected with an irrelevant plasmid were used as controls.", "\n\nWe next investigated the impact of the HCV 3′ UTR on ARFP translation. ", "Viral 3′ regions have been shown to enhance translation and replication. ", "Furthermore, this region has been shown to play a potential role in HCV genome stabilization and/or encapsidation ([@B28]). ", "The HCV 3′ UTR consists of three regions: a variable sequence, an internal poly (U/UC) stretch and the conserved X region. ", "The poly (U/UC) tail and the highly structured and conserved X region are essential for replication in the chimpanzee ([@B29],[@B30]). ", "Furthermore, the requirement of the HCV 3′ UTR for core protein translation has been recently demonstrated ([@B31],[@B32]). ", "To study whether the 3′ UTR has an impact on core/ARFP translation, we added the HCV 3′ UTR sequence downstream of the luciferase gene coding sequence in plasmids containing the full-length ARF sequence (nts 342--822) ([Figure 1](#F1){ref-type=\"fig\"}). ", "Prior to transfection into Huh-7 cells, plasmids were linearized following the 3′ UTR sequence to generate blunt-ended extremities similar to the authentic HCV RNA. ", "As shown in [Figure 2](#F2){ref-type=\"fig\"}, the addition of the 3′ UTR had no effect on IRES-mediated core-luc synthesis ([Figure 2](#F2){ref-type=\"fig\"}A, compare pIV1143, 251 RLU and pIV1243, 276 RLU). ", "Taken together, these results show that the 3′ UTR has no effect on IRES-mediated core-luc translation as previously shown ([@B25]). ", "The addition of the HCV 3′ UTR induced only a minor decrease in the +1 frame translation, suggesting that this HCV genetic element is not required for ARFP translation ([Figure 2](#F2){ref-type=\"fig\"}B).", "\n\nFinally, we investigated the integrity of the RNA transcripts by performing a RT-PCR of transcripts derived from the luciferase reporter constructs in Huh-7 transfected cells. ", "The reverse transcriptase product was amplified using a forward primer corresponding to the HCV 5′ UTR for IRES-containing plasmids (Forward 1, [Figure 1](#F1){ref-type=\"fig\"}A) or to the 5′ region of the core protein encoding gene for plasmids without IRES (Forward 2, [Figure 1](#F1){ref-type=\"fig\"}A), and a reverse primer corresponding to the 3′ part of the luciferase gene (Reverse 1, [Figure 1](#F1){ref-type=\"fig\"}A). ", "The expected size of the corresponding RT-PCR products was 2.2 kb in constructs containing the HCV IRES and 1.8 kb in constructs without IRES. ", "As shown in [Figure 2](#F2){ref-type=\"fig\"}C and D, analysis of the corresponding amplified RT-PCR products demonstrates the perfect integrity of all transcript templates. ", "No signal was detected in cells transfected with a control plasmid (pIV1066) or mock transfected cells. ", "These data clearly rule out the possibility of cryptic promoters, splicing or other events.", "\n\nTaken together, these data demonstrate that ARFP translation is not dependent on the presence of HCV IRES and 3′UTR.", "\n\nTranslation of ARFP in the +1 frame occurs by alternative initiation\n--------------------------------------------------------------------\n\nIn our model, translation in the +1 frame can account for different fusion proteins: ~26~ARFP-luc and ~86/88~ARFP-luc as well as fARFP-luc. ", "Indeed, since the translation machinery can recognize the core AUG (0 frame) even in the absence of the IRES sequence (compare pIV1143 [Figure 2](#F2){ref-type=\"fig\"}A with pIV1145 [Figure 2](#F2){ref-type=\"fig\"}B), the possibility of a ribosomal frameshifting or a transcriptional slippage event cannot be excluded.", "\n\nTo distinguish ribosomal frameshifting or transcriptional slippage from alternative initiation of translation, we suppressed fARFP synthesis. ", "Using site-directed mutagenesis, a stop codon in the ARF-coding sequence at position 22 (\\*S~22~) was introduced ([Figure 3](#F3){ref-type=\"fig\"}A). ", "The mutation of the ARFP codon 22 into \\*S~22~ stop codon does not modify the core protein amino acid sequence but terminates fARFP-luc protein synthesis at codon 22 ([Figure 3](#F3){ref-type=\"fig\"}B). ", "To demonstrate that the \\*S~22~ (ARFP) stop mutation had no impact at the core-luc protein translation level, we measured the core-luc (0 frame) translation rates of transfected \\*S~22~ '0' frame fusion plasmids and compared those rates to those of regular 0 frame transfected plasmids. ", "As expected, core-luc protein translation (frame 0) was not affected by the \\*S~22~ stop mutation ([Figure 3](#F3){ref-type=\"fig\"}C). ", "Figure 3.Alternative initiation of ARFP translation in the +1 frame. (**", "A**) Plasmid constructs containing the \\*S~22~ stop codon mutation in the +1 frame resulting in knock-out of fARFP expression. ", "Plasmid numbers are indicated. (**", "B**) Potential proteins resulting from translation in the 0 and +1 frames. (**", "C**) Huh-7 cells were transfected with the constructs shown in (A) and luciferase activity was assessed as described above. ", "Black and grey bars correspond to HCV translation in the 0 and +1 frame, respectively.", "\n\nTo determine the fraction of +1 frame translation that results from alternative initiation of translation, we transfected \\*S~22~ +1 frame fusion plasmids into Huh-7 cells ([Figure 3](#F3){ref-type=\"fig\"}A). ", "Using these reporter constructs, we detected significant translation in the +1 frame ([Figure 3](#F3){ref-type=\"fig\"}C). ", "The luciferase expression measured in these constructs, accounts for alternative initiation of translation on codon 26 (~26~ARFP) and/or codon 86/88 (~86/88~ARFP) in the +1 frame, but not for fARFP. ", "The alternative initiation of translation measured corresponded to 50% of the regular non mutated +1 frame translation. ", "Therefore, our experiments demonstrate that translation occurring in the +1 frame is mediated at least in a large part by alternative initiation of translation occurring downstream of the \\*S~22~ stop codon introduced in the ARFP coding-sequence.", "\n\nTo further address the mechanism of ARFP translation in prototype isolate HCV H77 (frameshifting or transcriptional slippage versus alternative internal initiation), we characterized translation products synthesized in the +1 frame in Huh-7 cells transfected with recombinant plasmids containing the HCV H77 ARFP coding sequence (nts 342--822). ", "Since monoclonal anti-ARFP antibodies directed against epitopes of the ARFP N-terminal domain are unavailable, ARFP-luc fusion proteins were analyzed using an anti-luc monoclonal antibody. ", "Expected fusion protein sizes were 60 kDa for luciferase, 78 kDa for the core/fARFP-luc fusion proteins and 75 and 68 kDa for fusion proteins synthesized by alternative initiation at positions 26 (~26~ARFP-luc) and 86/88 (~86/88~ARFP-luc), respectively. ", "Background translation of luciferase in the fusion constructs was minimal, compared to expression of the fusion proteins ([Figure 4](#F4){ref-type=\"fig\"}, lanes 4 and 5). ", "The two forms detected for ARFP synthesis corresponded to products derived from alternative initiation sites: the major band corresponded to ~86/88~ARFP, whereas ~26~ARFP was synthesized at a lower level ([Figure 4](#F4){ref-type=\"fig\"}). ", "In our experimental system, fARFP was not detected. ", "Since the addition of proteasome inhibitor MG-132 did not modify protein expression (data not shown), it is likely that the absence of fARFP detection was not due to a problem with protein stability. ", "Figure 4.Identification of luciferase fusion proteins. ", "Lysates of Huh-7 cells transfected with the luciferase encoding plasmid (pIV1066, lane 1), the empty pCI-neo vector (mock, lane 2), plasmids containing sequences encoding core-luc (pIV1143, lane 3), ARF-luc (pIV1144, lane 4) or ARF-luc containing the \\*Q~20~ core mutation (pIV1204, lane 5) were analyzed by Western blotting using an anti-luciferase monoclonal antibody as described in 'Material and methods' section. ", "Identified translation products are indicated on the right of the panel.", "\n\nThus, we conclude that the observed +1 frame (ARFP-luc) translation occurs from alternative initiation of translation. ", "The decrease in ARFP-luc translation observed in the \\*S~22~-mutated constructs ([Figure 3](#F3){ref-type=\"fig\"}C) is likely the result of a decrease in alternative initiation of translation at position 26, due to the \\*S~22~ mutation itself, rather than a suppression of a putative ribosomal frameshifting event.", "\n\nRegulation of ARFP alternative initiation by HCV core protein expression\n------------------------------------------------------------------------\n\nCore protein is known to play a role in HCV polyprotein translation. ", "It has been shown to decrease the translation activity of the IRES through interactions involving 5′ regions ([@B33]). ", "Whether this inhibition depends on RNA--RNA ([@B34],[@B35]) or core-RNA interactions ([@B36],[@B37]) remains unclear. ", "Thus, we aimed to study whether core protein plays a role in the regulation of ARFP translation.", "\n\nFirst, we investigated the impact of core protein on the +1 frame translation in *cis*. ", "To address this question, we constructed plasmids containing a stop codon (\\*Q~20~) in the core-encoding sequence fused in the +1 frame to the luc gene ([Figure 5](#F5){ref-type=\"fig\"}A). ", "In these plasmids, core protein is not synthesized, whereas ARFP translation is maintained. ", "Interestingly, in the absence of the core protein, we observed a marked, 4-fold enhancement of ARFP-luc fusion protein expression in the +1 frame ([Figure 5](#F5){ref-type=\"fig\"}C, compare black and white bars). ", "Thus, the premature stop of core protein translation at codon 20 in the 0 frame resulted in a marked increase of ARFP synthesis. ", "This observation suggested a negative regulation of core protein on ARFP synthesis. ", "Moreover, the core protein inhibitory effect was corroborated by Western blot analysis of the expressed proteins. ", "As shown in [Figure 4](#F4){ref-type=\"fig\"}, the expression of ~86/88~ARFP-luc fusion protein (pIV1204, lane 5) was markedly increased in Huh-7 cells transfected with plasmids containing the \\*Q~20~ core stop mutation, compared to plasmids allowing core protein expression in *cis* (pIV1144, lane 4). ", "Thus, when core protein translation was absent (pIV1204, lane 5), ~86/88~ARFP represented the major ARFP translation product. ", "Figure 5.Regulation of ARFP translation by HCV core protein. (**", "A**) Plasmids containing a stop codon in the 0 frame (\\*Q~20~). ", "Names of the plasmids are indicated on the panel. (**", "B**) Proteins resulting from plasmid expression in the 0 and +1 frames of constructs lacking the core ORF. (**", "C**) To study the effect of core in *cis*, we transfected cells with +1 frame constructs with or without the \\*Q~20~ mutation. ", "Luciferase activity corresponds to the translation in the +1 frame without mutation (black bars) and with the \\*Q~20~ stop mutation (white bars). (**", "D**) To study the effect of core in *trans*, cells were transfected with +1 frame constructs containing the \\*Q~20~ mutation and transduced with a control adenovirus (Ad control, white bars) or a HCV core-encoding adenovirus (Ad core, hatched bars). ", "Luciferase activity was analyzed in the presence or absence of the HCV IRES as described earlier.", "\n\nTo confirm the negative regulation of ARFP translation by core protein, we studied the impact of core protein expressed in *trans* on ARFP synthesis. ", "To ensure that core protein was expressed in the entire transfected cell population, we constructed a recombinant adenovirus encoding the full-length core protein (Ad core). ", "As a control, we used an adenovirus encoding the green fluorescent protein (Ad control).", "\n\nTo test the hypothesis of a direct effect of core protein expression on ARFP translation, we infected Huh-7 cells transfected with the plasmids containing the \\*Q~20~ stop mutation with the core-encoding recombinant adenovirus (Ad core). ", "The impact of the adenovirus on translation of these plasmids was first evaluated by using the GFP-encoding adenovirus as a control. ", "The control adenovirus induced a global enhancement of translation ([Figure 5](#F5){ref-type=\"fig\"}C and D). ", "However, expression of core in *trans* by the recombinant adenovirus (Ad core) decreased the +1 frame (ARFP-luc) translation to levels similar to those obtained with non-mutated core-encoding plasmids ([Figure 5](#F5){ref-type=\"fig\"}C and D). ", "Since translation in the +1 frame was enhanced in the absence of core protein and was markedly reduced when core protein is added in *trans*, we conclude that core protein expression has an inhibitory effect on ARFP synthesis.", "\n\nDISCUSSION\n==========\n\nIt has been suggested that the core protein encoding sequence directs the synthesis of three different products: (i) the core protein in the 0 frame, (ii) the ARFP in the +1 frame and (iii) a 13 amino-acid peptide in the −1 frame ([@B5]). ", "The ARFP itself can result from a +1 ribosomal frameshifting event ([@B6]) (fARFP) and/or alternative initiation in the +1 frame at codon 26 ([@B23]) (~26~ARFP) and 86/88 ([@B24]) (~86/88~ARFP). ", "In addition, a transcriptional slippage event cannot be excluded. ", "To compare the translation levels of these proteins, we designed plasmids containing the HCV core/ARFP sequence fused in the 0, +1 or −1 frame to a luciferase reporter gene cDNA. ", "Using hepatoma cells transfected with chimeric HCV-luciferase reporter constructs as a model system, we demonstrate that the predominant form of ARFP is a 70 amino acid protein initiated at codon 86/88. ", "Finally, we show that core protein regulates ARFP synthesis by inhibiting ~86/88~ARFP translation.", "\n\nEvidence for a +1 ribosomal frameshifting event was demonstrated *in vitro* by Xu *et al*. ([", "@B6]) using a unique sequence of genotype 1a containing a 10-adenine stretch in the first 50 nt of the core protein coding sequence ([@B6]). ", "However, the incidence of this A stretch appears to be very rare since only a single HCV sequence of this type is found in the European HCV database (<http://euhcvdb.ibcp.fr/>) ([@B38]). ", "Thus, conclusions derived from translation studies using this unique sequence may not generally apply for other, more prevalent HCV strains. ", "To study mechanisms of ARFP translation in well characterized infectious and functional HCV strains, we used prototype infectious clone HCV H77 ([@B39]). ", "Analysis of the translation products of HCV H77 luc plasmids ([Figure 4](#F4){ref-type=\"fig\"}) clearly demonstrates that ARFP synthesis in the HCV H77 strain occurs by alternative internal initiation of translation.", "\n\nThe IRES-independence of the ARFP translation could be related to the nature of codon GUG at position 26 in the HCV genotype 1a sequence that we used. ", "Indeed, in a recent report, Baril and Brakier-Gingras ([@B23]) showed that the ARFP translation is IRES independent when a GUG codon is present at position 26, which is the case in the 1a genotype ([@B23]). ", "Besides IRES-independence, the mechanism responsible for initiation at codon 26 and/or 86/88 remains to be determined. ", "Although our results cannot exclude a linear scanning event, such a mechanism seems to be highly unlikely in the presence of the IRES because of the stability of its structure. ", "At least two other alternative mechanisms could explain the recruitment of ribosomal subunits far upstream of the initiation codon: first, internal initiation could occur through an internal ribosome entry site present in the viral sequence downstream of the HCV IRES; second, specific ribosomal shunting or ribosomal tethering and clustering ([@B40]) could be involved in initiation of ARFP translation. ", "The latter model is highly interesting because it explains how translation can initiate on AUG codons located either downstream or upstream of an IRES. ", "According to this hypothesis, ARFP translation would be dependent on an IRES located downstream of codon 86/88.", "\n\nThe addition of the HCV 3′ UTR induced only a minimal decrease in translation in the 0 or +1 frame, suggesting that this HCV genetic element is not required for ARFP translation. ", "Nevertheless, the HCV-luc model system is limited to the ARFP and core protein coding sequences. ", "Thus, we cannot exclude that results might be different using a full-length infectious clone as a model system. ", "However, the difficulty studying translation of the short +1 frame protein in the full-length clone currently precludes the use of this system to address this question.", "\n\nMost importantly, we demonstrate that HCV core protein plays a key role in the regulation of ~86/88~ARFP translation in HCV target cells. ", "Using a stop mutation preventing core protein expression, we demonstrate that core protein inhibits ~86/88~ARFP synthesis. ", "Furthermore, inhibition of ARFP synthesis can be restored by expression of core protein in *trans*. ", "Since the two proteins partially share the same RNA sequence, a switch between ARFP and core protein translation can be imagined during the viral cycle. ", "Core protein is the capsid protein. ", "Its level may vary during the viral life cycle (i.e. during encapsidation), allowing a modification of ARFP translation efficiency. ", "ARFP could also be synthesized when core protein is expressed at a lower rate, i.e. during the very early or the late phase of chronic infection, when levels of viral replication can be low. ", "Suppression of ARFP translation by HCV core protein suggests that ARFP expression is inversely linked to viral replication. ", "Furthermore, these findings may explain the apparent low-level expression of ARFP during viral infection, precluding its easy detection during HCV infection *in vivo* or *in vitro*.", "\n\nCore-mediated regulation of ARFP translation may have important implications for the role of ARFP in the viral cycle. ", "The interaction of core protein with its RNA coding sequence has been described ([@B33]). ", "Thus, ARFP translation may be silenced in the presence of core protein bound to RNA, and this inhibition is reversed when core protein is expressed at low levels or is channeled into nucleocapsid assembly.", "\n\nIt is conceivable that the observed inhibition of ARFP expression by core protein may also play an important role in suppressing the putative ARFP function. ", "Such a mechanism could result in the establishment of a stoichiometric balance between ARFP and core protein, reminiscent of translation regulation in HIV, where Env protein expression is high and related to a weak Vpu protein synthesis ([@B41]).", "\n\nThe impact of the ARFP role in the viral cycle is still unknown. ", "Since the existence of an additional protein in an alternate reading frame has not yet been described for other members of the *Flaviviridae* family, we looked for the presence of similar proteins in other virus families. ", "Similar to HCV, the translation of picornaviruses is IRES-dependent, resulting in the synthesis of a polyprotein cleaved into structural and non-structural proteins. ", "For encephalomyocarditis virus (EMCV), foot and mouth disease virus (FMDV), hepatitis A virus and Theiler\\'s murine encephalomyelitis virus (TMEV), additional initiation sites exist in the same frame and have been documented *in vitro* (EMCV, hepatitis A and FMDV) ([@B42; @B43; @B44]) and *in vivo* (FMDV) ([@B44]). ", "Initiation sites for L\\* protein in the +1 frame both *in vitro* and *in vivo* have been identified for TMEV ([@B45]). ", "The TMEV L\\* out-of-frame protein was first thought to be an artifact of *in vitro* translation. ", "However, more recent studies indicate that this protein indeed has an anti-apoptotic activity and is involved in viral pathogenesis and persistence ([@B46]). ", "Thus, it is conceivable that ARFP may also play a functional role in the HCV viral life cycle. ", "Although a recent study has demonstrated that ARFP may not be required for viral replication ([@B47]), the constructs used in the latter study ([@B47]) did not prevent expression of ~86/88~ARFP. ", "Thus, a functional role for ~86/88~ARFP in viral replication is still conceivable. ", "Interestingly, HCV-infected patients mount an easily detectable, humoral immune response against ARFP, suggesting that this protein is expressed *in vivo*. ", "The short protein half-life of about 10 min ([@B10],[@B11]) could point to a punctual action during the viral cycle.", "\n\nIn conclusion, suppression of ARFP expression by core protein suggests that ARFP expression is inversely linked to viral replication. ", "The identification of negative regulation by HCV core protein expression may set the stage for further studies addressing the function of ~86/88~ARFP within the viral life cycle and the pathogenesis of HCV infection.", "\n\nWe gratefully acknowledge Charles M. Rice (The Rockefeller University, NY, USA) for providing the p90/HCV FL-Long pU clone, TRANSGENE S. A. (Strasbourg, France) for generously supplying shuttle plasmids pTG13387 and pTG6624, Glaucia Paranhos-Baccala (BioMérieux, Lyon, France) for the kind gift of monoclonal anti-ARFP antibodies, and Marie Parnot for excellent technical assistance with sequencing. ", "We thank Joseph Puglisi (Stanford University School of Medicine, CA, USA) and Pascale Romby (Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France) for helpful discussions and critical reading of the manuscript. ", "M.W. was supported in part by the French Ministry of Research grant (MRT) and a grant from the Association pour la Recherche sur le Cancer. ", "The study was funded by the foundation FRM-BNP Paribas (C.S.), the chair of excellence program of the Agence Nationale de la Recherche (ANR-05-CEXC-008; T.F.B.), France, the Agence Nationale de la Recherche sur le SIDA et les Hépatites Virales (ANRS Grant \\#2005/002 C.S.; ANRS Grant \\#06221; T.F.B.), the 6th framework program of the European Union (LSHM-CT-2004-503359, NoE 'VIRGIL', T.F.B.), Inserm, and the Louis Pasteur University, Strasbourg France. ", "Funding to pay the Open Access publication charges for this article was provided by FRM-BNP Paribas.", "\n\n*Conflict of interest statement*. ", "None declared.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nWarning: Expression Result Unused in RenderScript\n\nI don't get it. ", "Unless I'm missing something, I use it on the next line.", "\nblockAverage >> blockSize; //Warning:expression result unused\nreturn rsPackColorTo8888(blockAverage);\n\nA:\n\nYou meant:\nblockAverage >>= blockSize;\n\nYour code doesn't change blockAverage; you just compute the value of blockAverage shifted right by blockSize bits, then throw the result away.", "\nYou must use assignment to change the value of a variable (the above is, of course, short for blockAverage = blockAverage >> blockSize; i.e. it clearly assigns a new value to blockAverage).", "\n\n" ]

{ "pile_set_name": "StackExchange" }

[ 0.0007058073533698916, 0.0007168937590904534, 0.006720591802150011, 0.0007480033091269433, 0.001995587022975087 ]

[ "---\nabstract: 'We perform a model-independent study for top-antitop and top-top resonances in the dilepton channel at the Large Hadtron Collider. ", "In this channel, we can solve the kinematic system to obtain the momenta of all particles including the two neutrinos, and hence the resonance mass and spin. ", "For discovering top-antitop resonances, the dilepton channel is competitive to the semileptonic channel because of the good resolution of lepton momentum measurement and small standard model backgrounds. ", "Moreover, the charges of the two leptons can be identified, which makes the dilepton channel advantageous for discovering top-top resonances and for distinguishing resonance spins. ", "We discuss and provide resolutions for difficulties associated with heavy resonances and highly boosted top quarks.'", "\nauthor:\n- |\n **Yang Bai$^a$** and **Zhenyu Han$^{b}$**\\\n \\\n $^a$*Fermi National Accelerator Laboratory, P.O. Box 500, Batavia, IL 60510, USA*\\\n $^b$*Department of Physics, University of California, Davis, CA 95616, USA*\ntitle: '**Top-antitop and Top-top Resonances in the Dilepton Channel at the CERN LHC**'\n---\n\nIntroduction\n============\n\nBeing the unique standard model (SM) fermion with a mass of the electroweak symmetry breaking scale, the top quark may be closely related to the TeV scale new physics. ", "In particular, many of the new physics candidates predict a $t\\,\\bar t$ ($t\\,t$) resonance, i.e., a heavy particle that decays to $t\\,\\bar t$ ($t\\,t$). ", "The $t\\,\\bar{t}$ resonance occurs, for example, in Technicolor [@Hill:2002ap], Topcolor [@topcolor], Little Higgs [@lh], and Randall-Sundrum (RS) models [@Randall:1999ee], while the $t\\,t$ resonance exists in the grand unified theory in the warped extra-dimension [@WarpedGUT]. ", "Therefore, it is crucial to study $t\\,\\bar t$ ($t\\,t$) invariant mass distributions and look for possible resonances at the ongoing Large Hadron Collider (LHC), which may provide us the opportunity for revealing the new physics beyond the SM .", "\n\nThe top quark almost only decays to a $b$ quark and a $W$ boson. ", "Depending on how the $W$ boson decays, events with a pair of tops can be divided to the all-hadronic, the semileptonic and the dilepton channels. ", "The all-hadronic channel, in which both $W$’s decay hadronically, has the largest branching ratio of 36/81, but suffers from the largest background since that all observed objects are jets. ", "The semileptonic channel, in which one $W$ decays hadronically and the other one decays leptonically, has a significant branching ratio of 24/81 and also smaller background. ", "Although there is one neutrino in the event, only its longitudinal momentum is unknown, which can be easily extracted using the $W$ mass constraint. ", "Therefore, this has been thought to be the best channel for discovering $t\\,\\bar t$ resonance and most of existing studies have been concentrating on this channel [@Semileptonic; @Baur:2007ck; @Baur:2008uv]. ", "The dilepton channel, in which both $W$’s decay leptonically, has been thought to be a very challenging and not promising channel. ", "The reason is twofold: first, not counting $\\tau$’s, the branching ratio for this channel is only 4/81; second, due to the fact that there are two neutrinos in the final states, the event reconstruction is much more difficult than the semileptonic channel.", "\n\nNevertheless, the dilepton channel also has its own merits, making it more than a complementary to the other two channels. ", "An obvious advantage is that it has much smaller SM backgrounds. ", "More importantly, the two leptons in the decay products carry information that is unavailable in the other channels. ", "First, it is well-known that the charged lepton is the most powerful analyzer of the top spin [@Jezabek:1988ja; @Willenbrock:2002ta], because its angular distribution is $100\\%$ correlated with the top polarization in the top rest frame. ", "The down-type quark from hadronic decay of the $W$ boson has an equal power, but it is indistinguishable from the up-type quark in a collider detector. ", "If the $b$ jet from the top decay is not tagged, the ambiguity is even worse. ", "Only the dilepton channel is free from this ambiguity.", "\n\nSecondly, the charges of the two leptons are both measurable, which makes the same-sign dilepton channel ideal for studying $t\\,t$ or $\\bar t\\,\\bar t$ production, since it has very small SM backgrounds. ", "Note that although we are discussing resonances, the analysis applies equally for any events with two same-sign top quarks, as long as there are not missing particles other than the two neutrinos. ", "For example, it can be used to study the excess of $t\\,t$ or $\\bar t\\,\\bar t$ production in flavor violating processes [@Mohapatra:2007af; @MFV; @Gao:2008vv]. ", "On the contrary, the charge information in the other two channels is unavailable[^1], and hence a more significant event rate is needed to see an excess over the SM $t\\,\\bar\nt$ background.", "\n\nMotivated by the above observations, we perform a model independent study on $t\\,\\bar t$ ($t\\,t$) resonances in the dilepton channel. ", "The crucial step of this analysis is the event reconstruction, which we describe in the next section. ", "We will focus on the most challenging case when the resonance is heavy ($\\ge 2 ~{\\mbox{TeV}}$) and discuss a few related difficulties and their solutions. ", "As an illustration, the method is applied to a KK gluon in the RS model with a mass of 3 TeV. In Section \\[sec:discovery\\], we estimate the discovery limits of representative resonances with different spins. ", "It is shown that despite the smaller branching ratio, the discovery limits from this channel compete with those from the semileptonic channel. ", "In Section \\[sec:spin\\], we present the method for spin measurements and estimate the minimal number of events needed to distinguish the spin of the resonance. ", "Section \\[sec:discussion\\] contains a few discussions and the conclusion.", "\n\nEvent Reconstruction {#sec:reconstruction}\n====================\n\nThe Method\n----------\n\nIn this section, we discuss the method for reconstructing the $t\\,\\bar t$ system in the dilepton channel at the LHC. ", "The process we consider is $pp\\rightarrow \\Pi\\rightarrow t\\bar t\\rightarrow b\\bar b W^{+}\nW^{-}\\rightarrow b\\bar b \\ell^+\\ell^- \\nu_{\\ell}\\bar{\\nu}_{\\ell}$, with $\\Pi$ a $t\\,\\bar{t}$ resonance and $\\ell=e\\,,\\mu$. There can be other particles associated with the $\\Pi$ production such as the initial state radiation, but in our analysis it is crucial that the missing momentum is only from the two neutrinos. ", "The method described in this section can also be applied to $t\\,t$ resonances.", "\n\nAssuming tops and $W$’s are on-shell and their masses are known, the 4-momenta of the neutrinos can be solved from the mass shell and the measured missing transverse momentum constraints [@ATLAS_ttbar]: $$\\begin{aligned}\n&&p_\\nu^2\\,=\\,p_{\\bar\\nu}^2\\,=\\,0\\,,\\nonumber\\\\\n&&(p_\\nu+p_{l^+})^2\\,=\\,(p_{\\bar\\nu}+p_{l^-})^2\\,=\\,m_W^2\\,,\\nonumber\\\\\n&&(p_\\nu+p_{l^+}+p_b)^2\\,=\\,(p_{\\bar\\nu}+p_{l^-}+p_{\\bar b})^2\\,=\\,m_t^2\\,,\\nonumber\\\\\n&&p_\\nu^x+p_{\\bar\\nu}^x\\,=\\,\\slashchar{p}^x,\\; \\; \\quad\n p_\\nu^y+p_{\\bar\\nu}^y\\,=\\,\\slashchar{p}^y \\,, \n\\label{eq:system}\\end{aligned}$$ where $p_{i}$ is the four-momentum of the particle $i$. We have $8$ unknowns from the two neutrinos’ four-momenta and $8$ equations. ", "Therefore, Eqs.", " (\\[eq:system\\]) can be [*solved*]{} for discrete solutions. ", "This system can be reduced to two quadratic equations plus 6 linear equations [@Sonnenschein:2006ud; @Cheng:2007xv]. ", "In general, the system has 4 complex solutions, which introduces an ambiguity when more than one solutions are real and physical. ", "After solving for $p_\\nu$ and $p_{\\bar\\nu}$, it is straightforward to obtain $p_t$ and $p_{\\bar t}$ and calculate the $t\\,\\bar t$ invariant mass $M_{\\Pi}^{2}=(p_{t}+p_{\\bar t})^{2}$.\n\nThe system in Eqs.", " (\\[eq:system\\]) has been applied to measure the top mass [@ATLAS_ttbar; @CMS_ttbar] and to study the spin correlations in $t\\,\\bar t$ decays [@CMS_ttbar; @Beneke:2000hk]. ", "These studies focus on low center of mass energies below 1 TeV and involve only the SM $t\\,\\bar t$ production. ", "We will concentrate on the heavy-resonance case when $t$, $\\bar t$ and their decay products are highly boosted. ", "There are a few complications in disentangling new physics contributions from the SM, as discussed below.", "\n\nThe first complication comes from the fact that for a highly boosted top, its decay products are collimated and therefore are difficult to be identified as isolated objects. ", "In other words, all decay products of the top, in either the hardronic or the leptonic decay channels, form a fat “top jet”. ", "This interesting fact has triggered recent studies for developing new methods to distinguish top jets from ordinary QCD jets [@Boostedtop1; @Boostedtop2]. ", "For the dilepton channel, in order to keep as many signal events as possible, we include both isolated leptons and non-isolated muons. ", "Non-isolated muons can be measured in the muon chamber, while non-isolated electrons are difficult to be distinguished from the rest of the jet and therefore not included in our analysis. ", "This is very different from the low center-of-mass energy case where two isolated leptons can often be identified.", "\n\nOnce non-isolated muons are included, we have to consider the SM non-$t\\,\\bar t$ backgrounds such as $b\\,t$ and $b\\,b$ productions with one or two muons coming from $b$ or $c$ hadron decays. ", "Since muons from hadronic decays are relatively softer, we will use a high $p_T>100~{\\mbox{GeV}}$ cut for the non-isolated muons to reduce the background. ", "This is similar to using the jet energy fraction carried by the muon as a cut [@Boostedtop1]. ", "Similarly, it is unnecessary to require one or two $b$-jet taggings, which may have a small efficiency at high energies [@btag]. ", "Instead, we consider all signal and background events with two high-$p_{T}$ jets. ", "Besides high-$p_{T}$ cuts, the mass-shell constraints in Eqs.", " (\\[eq:system\\]) are also efficient for reducing the background/signal ratio.", "\n\nThe second complication is caused by wrong but physical solutions. ", "Part of the wrong solutions come from wrong combinatorics–either one or more irrelevant jets or leptons from sources other than $t\\,\\bar{t}$ are included in the reconstruction equations, or the relevant jets and leptons are identified but combined in a wrong way. ", "Even when we have identified the correct objects and combinatorics, there can be wrong solutions due to the non-linear nature of the equation system. ", "As mentioned before, there could be up to three wrong solutions in addition to the correct one. ", "The wrong solutions will change the $t\\,\\bar t$ invariant mass distribution. ", "This is not a severe problem for a light ($<1$ TeV) resonance because both signals and backgrounds can be large. ", "The wrong solutions will smear but not destroy the signal peak. ", "For heavy resonances in the multi-TeV range, the signal cross section is necessarily small due to the rapid decreasing of the parton distribution functions (PDF’s). ", "This would not be a problem if we only obtained the correct solution since the decreasing would happen for both the signals and the backgrounds. ", "However, when a wrong solution is present, it will shift the $t\\,\\bar t$ invariant mass to a different value from the correct one, either lower or higher. ", "Due to the large cross section of the SM $t\\,\\bar t$ production in the low invariant mass region, even if a small fraction of masses are shifted to the higher region, the signal will be swamped.", "\n\nWrong solutions exist because the momenta of the neutrinos are unknown except the sums of their transverse momenta. ", "Clearly, for a $t\\,\\bar t$ invariant mass shifted to be higher than the correct value, the solved neutrino momenta are larger than their right values statistically. ", "Therefore, we can reduce the fraction of wrong solutions by cutting off solutions with unnaturally large neutrino momenta. ", "This is achieved by two different cuts. ", "First, we can cut off “soft” events before reconstruction. ", "That is, we apply a cut on the cluster transverse mass $m_{T_{cl}}$ defined from the measured momenta [@Baur:2007ck]: $$m_{T_{cl}}^2\\,=\\,\\left(\\sqrt{p_T^2(l^+\\,l^-\\,b\\,\\bar\n b)+m^2(l^+\\,l^-\\,b\\,\\bar b)}+\\slashchar{p}_T\\right)^2- \n \\left(\\vec{p}_T(l^+\\,l^-\\,b\\,\\bar b)+\\vec{\\slashchar{p}}_T\\right)^2,$$ where $\\vec{p}_T(l^+l^-b\\bar b)$ and $m^2(l^+l^-b\\bar b)$ are the transverse momentum and the invariant mass of the $l^+l^-b\\bar b$ system, and $\\slashchar{p}_T=|\\vec{\\slashchar{p}}_T|$. Second, after reconstruction, we define a cut on the fraction of the transverse momentum carried by the neutrinoes, $$r_{\\nu b}\\,=\\,\\frac{p_T^\\nu+p_T^{\\bar\\nu}}{p_T^b+p_T^{\\bar b}}<2\\,. ", "\\label{eq:rcut}$$ As we will see in Section \\[sec:kkgluon\\], the $r_{\\nu b}$ cut is useful for increasing signal/background ratio. ", "The value in Eq.", " (\\[eq:rcut\\]) is approximately optimized for the examples we consider and taken to be fixed in the rest of the article. ", "On the other hand, we choose to explicitly vary the $m_{T_{cl}}$ cut to optimize the discovery significance because it is what the significance is most sensitive to. ", "In practice, one could as well optimize all other cuts and obtain better results.", "\n\nThe third issue is with regard to the experimental resolutions. ", "The smearing of the measured momenta modifies the coefficients in Eqs.", " (\\[eq:system\\]). ", "When the modification is small, the correct solutions of the neutrino momenta are shifted, but we still obtain real solutions.[^2] However, when the modification is large, it is possible to render the solutions to be complex. ", "Again, this effect is more significant when the top is more energetic. ", "The absolute smearings are larger (although the fractional resolution is better), which make it harder to have real solutions . ", "For comparison, $38\\%$ signal events from a 1 TeV resonance have real solutions. ", "The percentage decreases to $26\\%$ for a 3 TeV resonance. ", "This is based on a semi-realistic analysis detailed in the next subsection.", "\n\nThe best treatment of this problem is perhaps to find the real solutions by varying the visible momenta, and then weight the solutions according to the experimental errors. ", "In this article, we adopt a much simpler solution, namely, we keep those solutions with a small imaginary part. ", "More precisely, we first solve Eqs.", " (\\[eq:system\\]) for $p_\\nu$ and $p_{\\bar\\nu}$. Then we keep all four complex solutions and add them to the corresponding lepton and $b$-jet momenta to obtain $p_t$ and $p_{\\bar t}$. We demand $$|{\\rm Im}(E_t)|<0.4\\,|{\\rm Re}(E_t)|\\,,\\ \\ |{\\rm Im}(E_{\\bar\n t})|<0.4\\,|{\\rm Re}(E_{\\bar t})|\\,.\\label{eq:realcut}$$ where $E_t$ and $E_{\\bar t}$ are respectively the energies of $t$ and $\\bar t$. Similar to the $r_{\\nu b}$ cut, the values we choose in Eq.", " (\\[eq:realcut\\]) are approximately optimized and taken to be fixed through the rest of the article. ", "For events passing the above cuts, we make the 4-momenta of $t$ and $\\bar t$ real by taking the norm of each component, but keep the sign of the original real part. ", "Note that complex solutions always appear in pairs, giving the same real solution after taking the norm. ", "We only count it once.", "\n\nEvent Generation {#sec:eventgeneration}\n----------------\n\nThe hard process of $pp\\rightarrow \\Pi\\rightarrow t\\bar t\\rightarrow\nb\\bar b \\ell^+\\ell^- \\nu_{\\ell}\\bar{\\nu}_{\\ell}$ is simulated with TopBSM [@Frederix:2007gi] in MadGraph/MadEvent [@Alwall:2007st], where $\\Pi$ denotes the $t\\,\\bar t$ resonance. ", "In this article, we will consider a spin-0 color-singlet scalar, a spin-0 color-singlet pseudo-scalar, a spin-1 color octet and a spin-2 color-singlet. ", "The major SM background processes, including $t\\,\\bar t$, $b\\,\\bar b$, $c\\,\\bar c$, $bb\\ell\\nu$ and $jj\\ell\\ell$, are also simulated with MadGraph/MadEvent using CTEQ6L1 PDF’s [@Pumplin:2002vw]. ", "We choose the renormalization and factorization scales as the square root of the quadratic sum of the maximum mass among final state particles, and $p_{T}$’s of jets and massless visible particles, as described in MadGraph/MadEvent. ", "Showering and hadronization are added to the events by Pythia 6.4 [@Sjostrand:2006za]. ", "Finally, the events are processed with the detector simulation package, PGS4 [@pgs4]. ", "We have not included theoretical uncertainties in the cross-section calculations, which mainly comes from PDF uncertainties at high invariant mass [@Frederix:2007gi]. ", "In Ref.", " [@Frederix:2007gi] (Fig.", " 3), it is estimated using the CTEQ6 PDF set that the SM $t\\bar\nt$ cross-section has a theoretical uncertainty around 20%$\\sim$ 30% at 2 TeV, increasing to about 80% at 4 TeV, which may significantly affect some of the results in our analysis. ", "Nevertheless, we note that the PDFs can be improved with the Tevatron data [@Diaconu:2009jj] at large $x$, and our focus here is event reconstruction. ", "Therefore, we ignore systematic errors in the following discussions.", "\n\nThe cuts used to reduce the background/signal ratio are summarized below, some of which have been discussed in the previous section:\n\n1. ", " Before reconstruction\n\n - At least two leptons satisfying: $p_T>20~{\\mbox{GeV}}$ for isolated leptons or $p_T>100~{\\mbox{GeV}}$ for non-isolated muons. ", "The two highest $p_T$ leptons are taken to be the leptons in Eqs.", " (\\[eq:system\\]);\n\n - $m_{\\ell\\ell}>100~{\\mbox{GeV}}$ where $m_{\\ell\\ell}$ is the invariant mass of the two highest $p_{T}$ leptons.", "\n\n - At least two jets satisfying: $p_T>50~{\\mbox{GeV}}$ for $b$-tagged, $p_T>150~{\\mbox{GeV}}$ for not-b-tagged. ", "The two highest $p_T$ jets are taken to be the b jets in Eqs.", " (\\[eq:system\\]);\n\n - $\\slashchar{p}_T>50~{\\mbox{GeV}}$;\n\n - Varying $m_{T_{cl}}$ cut.", "\n\n2. ", " After reconstruction\n\n - $|{\\rm Im}(E_t)|<0.4\\,|{\\rm Re}(E_t)|\\,,\\ \\ |{\\rm Im}(E_{\\bar\n t})|<0.4\\, |{\\rm Re}(E_{\\bar t})|$;\n\n - $r_{\\nu b}<2$.\n\nThe complex solutions are made real using the method discussed in the previous section. ", "There can be 0-4 solutions after the above cuts. ", "We discard events with zero solution. ", "For a solvable event with $n\\ge 1$ solutions, we weight the solutions by $1/n$.\n\nKK gluon as an example {#sec:kkgluon}\n----------------------\n\nWe illustrate the efficiency of the reconstruction procedure by considering the KK gluon in the basic RS model with fermions propagating in the bulk. ", "The KK gluon is denoted by $\\Pi^{1}_{o}$, which has the following couplings to the SM quarks, $$g_{L,R}^q=0.2\\,g_s\\,,\\ \\ g_L^{t}=g_L^{b}=g_s\\,,\\ \\ g_R^{t}=4\\,g_s\\,,\\ \\ g_R^{b}=-0.2\\,\ng_s\\,, \n\\label{eq:KKgluon}$$ where $g_s$ is the strong coupling constant and $q$ represents quarks in the light two generations. ", "With this set of couplings, the KK gluon has a width $\\Gamma_{\\Pi^{1}_{o}}=0.153\\,M_{\\Pi^{1}_{o}}$, and the branching ratio $Br(\\Pi^{1}_{o}\\rightarrow t\\,\\bar{t})=92.6\\%$. For a KK gluon of mass 3 TeV, the total leading-order cross section in the dilepton channel is approximately 10 fb. ", "The parton level $m_{t\\bar t}$ distribution is shown in Fig.", " \\[fig:parton\\], together with the SM $t\\,\\bar t$ background, also in the dilepton channel. ", "The interference between the KK gluon and the SM is small and ignored in Fig.", " \\[fig:parton\\]. ", "Within the mass window $(M_{G}-\\Gamma_{G}, M_{G}+\\Gamma_{G}) \\approx\n(2500, 3500)$ GeV, the total number of events is around 770 for the signal and 610 for the background, for 100 $\\mbox{fb}^{-1}$.\n\nAlthough the SM $t\\,\\bar t$ production in the dilepton channel comprises the largest background, we have to consider backgrounds from other sources since we are utilizing not-b-tagged jets and non-isolated leptons, which can come from heavy flavor hadron decays. ", "The major additional backgrounds are:\n\n1. ", " $t\\,\\bar t$ processes in other decay channels, which include the semi-leptonic channel, the all-hadronic channel and channels involving $\\tau$’s;\n\n2. ", " Heavy flavor di-jets, including $b\\bar b$ and $c\\bar c$ with $b\\bar b$ dominating.", "\n\n3. ", " Other processes that contain one or more isolated leptons including $jj\\ell\\ell$, $bb\\ell v$ productions.", "\n\nThe above backgrounds are included in our particle level analysis. ", "In Table \\[table:breakdown\\], we show the number of events of the signal and backgrounds before and after the reconstruction procedure. ", "The cuts discussed in the previous subsection are applied, with a moderate $m_{T_{cl}}>1500$ GeV cut. ", "Note that these numbers are without any mass window cut, while the kinematic cuts in the previous subsection have been applied. ", "Also note that the number of signal events is much smaller after detector simulation and applying the kinematic cuts: this is because most of the leptons are non-isolated when the $t\\bar t$ resonance mass is as high as 3 TeV, and we have only included non-isolated muons in the analysis. ", "The probability for both leptons from $W$ decays to be muons is only 1/4. ", "This fact, together with the kinematic cuts, drastically reduces the number of signal events. ", "This reduction also occurs for the SM $t\\,\\bar t$ dilepton events with a high center of mass energy.", "\n\n ------------------------------------------------------------------------------------------------------------------\n 3 TeV KK gluon $t\\bar t$ dilep $t\\bar t$ others $b\\bar b$, $c\\bar $jj\\ell\\ell, bb\\ell v$\n c$ \n --------------- ---------------- ----------------- ------------------ ------------------- ------------------------\n Before Recon. ", " 167 317 96 68 63\n\n After Recon. ", " 82 159 37 33 13\n\n $r_{vb}<2$ 73 146 31 7 11\n ------------------------------------------------------------------------------------------------------------------\n\n : \\[table:breakdown\\]Number of signal and background events for 100 ${\\mbox{fb}}^{-1}$ before and after reconstruction.", "\n\nFrom Table \\[table:breakdown\\], we can see the effects of the event reconstruction. ", "Before applying the $r_{\\nu b}$ cut, the reconstruction efficiencies for the signal events and the SM $t\\,\\bar t$ dilepton events are approximately equal and around 50%. ", "The efficiencies for the other backgrounds are substantially smaller. ", "Moreover, the cut on the variable $r_{\\nu b}$, which is only available [*after*]{} the event reconstruction, also favors the signal and the SM $t\\,\\bar t$ dilepton events. ", "Therefore, we obtain a larger $S/B$ at the cost of slightly decreasing significance $S/\\sqrt{B}$. In the following, we will define the significance after the event reconstruction.", "\n\nOf course, the effects of event reconstruction are beyond simple event counting. ", "More importantly, we obtain the 4-momenta of the top quarks, which are necessary for determining the spin of the $t\\,\\bar t$ resonance. ", "We will discuss the spin measurement in Section \\[sec:spin\\]. ", "We also obtain the mass peak on top of the background after reconstruction, as can be seen from Fig.", " \\[fig:mtcl\\], where we show the $m_{t\\bar t}$ distributions of both background and signal+background for a few different $m_{T_{cl}}$ cuts. ", "For the left plot with $m_{T_{cl}}>1500$ GeV, there is a clear excess of events, although the mass peak is not obvious. ", "By comparing with Fig.", " \\[fig:parton\\], we see that $S/B$ is smaller than the parton level distribution in the mass window (2500, 3500) GeV $\\approx\n(M_{G}-\\Gamma_{G}, M_{G}+\\Gamma_{G})$. This indicates that wrong solutions from the lower $m_{t\\bar t}$ background events have contaminated the higher $m_{t\\bar t}$ distribution. ", "As we increase the $m_{T_{cl}}$ cut, the numbers of both signal events and background events decrease, but $S/B$ is increasing, showing that the contamination is reduced. ", "The contamination reduction is also confirmed by tracing back the reconstructed $m_{t\\bar t}$ to its Monte Carlo origin. ", "For the $m_{T_{cl}}$ cut of 1500 GeV, the reconstructed background $m_{t\\bar\n t}$ in the mass window of (2500, 3500) GeV is decomposed as: 44% from the SM $t\\,\\bar{t}$ events with original $m_{t\\bar t}$ smaller than 2500 GeV; 25% from the SM $t\\,\\bar{t}$ events with original $m_{t\\bar t}$ larger than 2500 GeV; the other 21% come from other SM backgrounds. ", "The decomposition becomes (in the same order as above) {23%, 43%, 34%} for the $m_{T_{cl}}$ cut of 2000 GeV, and {13%, 60%, 27%} for the $m_{T_{cl}}$ cut of 2500 GeV. Nevertheless we cannot choose too high a $m_{T_{cl}}$ cut since it can reduce $S/\\sqrt{B}$. For the KK gluon example, the significance is maximized when the $m_{T_{cl}}$ cut is around 2000 GeV. More precisely, in the mass window (2500, 3500) GeV for $M_{G}$, we have $S/B=0.69, 1.3, 1.8$ and $S/\\sqrt{B}=4.9, 6.1, 4.5$ for $m_{T_{cl}}\\ge 1500, 2000, 2500$ GeV, respectively.", "\n\nDiscovery Limits {#sec:discovery}\n================\n\nHaving discussed our strategy of selecting cuts to optimize the discovery limit, we now consider the needed signal cross section for different $t\\,\\bar{t}$ and $t\\,t$ resonances at $5\\,\\sigma$ confidence level (CL) at the LHC.", "\n\nStatistics {#sec:statistics}\n----------\n\nWe are interested in heavy resonances with masses from $2$ to $4$ TeV. In order to cover most of the signal events, we examine reconstructed masses in the range of $1.5-5.1$ TeV. We ignore uncertainties from the overall normalization of the signal and background cross sections, which can be determined from the low $m_{t\\bar t}$ mass events, where the statistics is much better. ", "To utilize the shape differences, we equally divide the mass range to $N_{\\rm bin}=18$ bins, which amounts to having a $200$ GeV bin width. ", "In each bin, we define the number of the background events as $b_{i}$, while the number of the signal events as $s_{i}$. When the number of events is small, the distribution is Poisson. ", "Following [@PDG], we first calculate the Pearson’s $\\chi^{2}$ statistic \\^[2]{}=\\_[i]{}\\^[N\\_[ bin]{}]{}=\\_[i]{}\\^[N\\_[ bin]{}]{}, where $n_{i}=b_{i}+s_{i}$ is the measured value and $v_{i}=b_{i}$ is the expected value. ", "Assuming that the goodness-of-fit statistic follows a $\\chi^{2}$ probability density function, we then calculate the $p$-value for the “background only” hypothesis p=\\^\\_[\\^[2]{}]{}z\\^[N\\_[ bin]{}/2-1]{}e\\^[-z/2]{}dz, where $N_{\\rm bin}$ counts the number of degrees of freedom. ", "For a $5\\,\\sigma$ discovery, we need to have $p=2.85\\times 10^{-7}$ and therefore $\\chi^{2}\\approx 65$ for $N_{\\rm bin}=18$.\n\nFor a particular resonance, we define a reference model with a known cross section. ", "We then vary the $m_{T_{cl}}$ cut from $1.5$ TeV to $3.5$ TeV in $100$ GeV steps to generate different sets of $b_{i}$ and $s_{i}$. We find the optimized $m_{T_{cl}}$ cut that maximizes the $\\chi^{2}$. After optimizing the $m_{T_{cl}}$ cut, we multiply the number of signal events by a factor of $Z$ to achieve $\\chi^{2}=65$ or $5\\,\\sigma$ discovery. ", "This is equivalent to requiring the production cross section of the signal to be $Z$ times the reference cross section.", "\n\nDiscovery limits {#discovery-limits}\n----------------\n\nFor $t\\,\\bar{t}$ resonances, we choose a representative set of $t\\,\\bar{t}$ resonances with different spins and quantum numbers under $SU(3)$ color gauge group. ", "We label spin-0 color-singlet scalar, spin-0 color-singlet pseudo-scalar, spin-1 color octet and spin-2 color-singlet particles as $\\Pi^{0}$, $\\Pi^{0}_{p}$, $\\Pi^{1}_{o}$ and $\\Pi^{2}$ respectively. ", "For the spin-0 particles, $\\Pi^{0}$ and $\\Pi^{0}_{p}$, we assume that they only couple to top quarks with couplings equal to the top Yukawa coupling in the standard model, and hence they are mainly produced through the one-loop gluon fusion process at the LHC. ", "Their decay widths are around $3/(16\\,\\pi)$ times their masses and calculated automatically in the Madgraph. ", "For the spin-one particle, $\\Pi^{1}_{o}$, we still use the KK gluon described in Section [\\[sec:kkgluon\\]]{} as the reference particle, and use the same couplings defined in Eq.", " (\\[eq:KKgluon\\]). ", "The decay width of the KK gluon is fixed to $0.153$ times its mass. ", "For the spin-two particle, $\\Pi^{2}$, we choose the first KK graviton in the RS model as the reference particle, and choose the model parameter, $\\kappa/M_{pl}$ = 0.1, where $M_{pl}$ is the Planck scale and $\\kappa$ is defined in [@Randall:1999ee]. ", "Its decay width is calculated in Madgraph.", "\n\nFor $t\\,t$ resonances, we study the spin-one particle, which is suggested to exist at the TeV scale in grand unified models in a warped extra-dimension [@WarpedGUT]. ", "Under the SM gauge symmetries, the $X$ gauge boson is the up part of the gauge bosons with the quantum numbers $(\\bar{3}, 2, 5/6)$. It has the electric charge $4/3$ and couples to up-type quarks with a form $g_{i}\\,\\epsilon_{abc}\\,\\bar{u}_{i\\,L}^{{\\cal\n C}\\,a}\\,\\overline{X}^{\\,b}_{\\mu}\\,\\gamma^{\\mu}\\,u^{c}_{i\\,L}\\,+\\,h.c.$ ($i$ is the family index; $a,b,c$ are color indices; ${\\cal C}$ denotes charge conjugate). ", "In general, the gauge couplings $g_{i}$ depend on the fermion localizations in the fifth warped extra-dimension. ", "However, we do not specify any details of model buildings including how to suppress the proton decay, and only focus on the discovery feasibility at the LHC. ", "For simplicity, we model the $t\\,t$ resonance the same way as the KK gluon, but flip the sign of one lepton at the parton level. ", "We also choose the reference $t\\,t$ production cross section through $X$ as the cross section of $t\\,\\bar{t}$ production through the KK gluon described in Eq.", " (\\[eq:KKgluon\\]). ", "We fix the decay width of $X$ to be $10\\%$ of its mass. ", "In our analysis, we use the same set of background events as in the $t\\,\\bar{t}$ case. ", "There are two main sources of the SM backgrounds for same-sign dileptons. ", "The lepton charges from $b$-jets can have either sign. ", "Another source is lepton charge misidentifications. ", "There are other intrinsic SM backgrounds from processes like $u\\,\\bar{d}\\rightarrow W^{+}W^{+}d\\,\\bar{u}$. However, this is a pure electroweak process and hard to pass the reconstruction cuts. ", "We neglect such processes in our analysis.", "\n\nIn Fig.", " \\[fig:discoverylimit\\], we show values of the multiplying factor $Z$ for the $t\\,\\bar{t}\\,(t\\,t)$ production cross sections to have $5\\,\\sigma$ discovery at the LHC for $100~{\\rm\n fb}^{-1}$ integrated luminosity. ", "Note that we do not change the widths of the resonances according to the models described above when multiplying the factor $Z$. Those models serve as reference points only. ", "In obtaining the discovery limits, we have ignored all interferences between the resonances and the SM $t\\,\\bar t$ productions. ", "As shown in Ref.", " [@Frederix:2007gi], the interference between a KK gluon or a KK graviton and the SM $t\\,\\bar t$ productions is negligible. ", "For a spin-0 resonance (scalar or pseudo-scalar), a peak-dip structure in the $m_{t\\bar t}$ distribution is generally visible at the parton level if the resonance is produced through gluon fusion similar to the SM Higgs. ", "We do not anticipate that the interference will change our results significantly.", "\n\nThe discovery limits for the KK gluon are $3.2$ TeV and $3.7$ TeV for $100~{\\rm fb}^{-1}$ and $300~{\\rm fb}^{-1}$ integrated luminosity. ", "For comparison, the discovery limit for the KK gluon in the semileptonic channel is $3.8$ TeV for $100~{\\rm fb}^{-1}$ and $4.3$ TeV for $300~{\\rm fb}^{-1}$ given in [@Baur:2008uv]. ", "There they combine the invariant mass and top $p_{T}$ distributions. ", "If only the invariant mass distribution were used, the discovery limit would be reduced by a few hundred GeV. Therefore, the discovery limit in the dilepton channel is competitive to the semileptonic channel. ", "Comparing the black (solid) line and the orange (thick dashed) line, we have a better discovery limit for the $t\\,t$ resonance than the $t\\,\\bar{t}$ resonance when they have the same production cross section. ", "This is because the SM background for $t\\,t$ is much smaller than the background for $t\\,\\bar{t}$. The $X$ gauge boson can be discovered with a mass up to $4.0$ TeV and $4.4$ TeV, respectively, for $100~{\\rm fb}^{-1}$ and $300~{\\rm fb}^{-1}$.\n\nIf a $t\\,\\bar t$ resonance is discovered, it is important to measure the mass. ", "The peak position of the $m_{t\\bar t}$ distribution in general does not coincide with the true resonance mass, and also shifts according to the $m_{T_{cl}}$ cut applied, as can be seen in Fig.", " \\[fig:mtcl\\]. ", "We can eliminate this systematic error, as well as minimize the statistical error by using the usual “template” method. ", "That is, we can generate the $m_{t\\bar t}$ distributions for different input masses, and then compare them with the measured distribution to obtain the true mass. ", "A detailed study of mass measurement is beyond the scope of this article.", "\n\nSpin Measurements {#sec:spin}\n=================\n\nThe momenta of all particles are known after event reconstruction, which allows us to determine the spins of the $t\\,\\bar t$ resonances. ", "We first consider the angular distributions of the top quark in the $t\\,\\bar t$ resonance rest frame. ", "To minimize the effect of initial state radiation, we use the Collins-Soper angle [@Collins:1977iv] defined as the angle between the top momentum and the axis bisecting the angle between the two incoming protons, all in the $t\\,\\bar t$ rest frame. ", "In the case that the initial state radiation vanishes, this angle becomes the angle between the top momentum and the beam direction. ", "Using the lab frame momenta, the Collins-Soper angle is conveniently given by $$\\cos\\theta=\\frac{2}{m_{t\\bar t} \\sqrt{m_{t\\bar t}^2+p_T^2}}(p^+_t\\,p^-_{\\bar t}-p^-_t\\,p^+_{\\bar t}),$$ where $m_{t\\bar t}$ and $p_T$ are the invariant mass and the transverse momentum of the $t\\,\\bar t$ system and $p^{\\pm}_{t}$, $p^{\\pm}_{\\bar t}$ are defined by $$p^{\\pm}_t=\\frac{1}{\\sqrt{2}}(p_t^0\\pm p_t^z)\\,,\\quad \\ p^{\\pm}_{\\bar\n t}=\\frac{1}{\\sqrt{2}}(p_{\\bar t}^0\\pm p_{\\bar t}^z)\\,.$$\n\nOne can also consider angular correlations among the decay products of top quarks. ", "As mentioned in the introduction, the best analyzer for the top polarization is the charged lepton. ", "Therefore, we examine the opening angle $\\phi$ between the $\\ell^+$ direction in the $t$ rest frame and the $\\ell^{-}$ direction in the $\\bar t$ rest frame. ", "The parton level distribution for the opening angle has a form $$\\frac1\\sigma\\frac{d\\sigma}{d\\cos\\phi}=\\frac12(1-D\\cos\\phi)\\,,$$ where $D$ is a constant depending on the $t\\,\\bar t$ polarizations, and hence model details. ", "At particle level, the distribution is affected by the experimental resolutions and wrong solutions from event reconstruction.", "\n\nIn Fig.", " \\[fig:spin\\], we show the particle level distributions of $\\cos\\theta$ and $\\cos\\phi$ for 4 different $t\\,\\bar t$ resonances: a scalar, a pseudo-scalar, a vector boson that couples to left- and right-handed quarks equally, and a KK graviton in the RS model. ", "The cuts described in Sec.", " \\[sec:eventgeneration\\] are applied with $m_{T_{cl}}>1500{\\mbox{GeV}}$. A mass window cut of $(1600\\,{\\mbox{GeV}}, 2400\\,{\\mbox{GeV}})$ is also applied on the solutions to increase $S/B$. From the left panel of Fig.", " \\[fig:spin\\], we see significant suppressions in the forward and backward regions of $\\cos\\theta$, due to the kinematic cuts. ", "Except that, both the scalar and the pseudo-scalar have a flat distribution in $\\cos\\theta$ and are hard to be distinguished from each other. ", "The $\\cos\\theta$ distributions for the vector boson and the graviton show the biggest difference with respect to each other. ", "As shown in the right panel of Fig.", " \\[fig:spin\\], the slope of the pseudo-scalar distribution in $\\cos \\phi$ has an opposite sign to all others, which can be used to identify a pseudo-scalar resonance. ", "Therefore one has to use both distributions to distinguish the four particles.", "\n\nGiven the distributions, we can estimate how many events are needed to determine the spin of a $t\\,\\bar t$ resonance. ", "We first reform the question in a more specific way: given experimentally observed distributions in $\\cos\n\\theta$ and $\\cos \\phi$ generated by a particle of spin $s_a$, we ask how many events are needed to decide, at $95\\%$ CL, that they are not from a particle of spin $s_b$. This is being done by comparing the observed distributions with Monte Carlo distributions of different spins. ", "If the observed distributions are inconsistent with all but one spin, we claim that we have identified the spin. ", "Of course, without real data, the “observed” distribution in this article is also from Monte Carlo. ", "We quantify the deviation of two distributions from different spins $s_{a}$ and $s_{b}$ as \\^[2]{}\\_[s\\_[a]{}:s\\_[b]{}]{}=\\_[i]{}\\^[N\\_[bin]{}]{}, where $N_{\\rm bin}$ is the total number of bins and is equal to 20 by choosing a $0.1$ bin size for both $\\cos \\theta$ and $\\cos \\phi$; $n_{s_{a},\\,i}$ and $n_{s_{b},\\,i}$ are the number of events in the $i$’th bin, which satisfy $\\sum n_{s_{a},\\,i}=\\sum\nn_{s_{b},\\,i}$. When $\\chi^{2}=33$, we claim that we can distinguish the spin $s_{a}$ particle from the spin $s_{b}$ particle at $95\\%$ CL, corresponding to the $p$-value of $2.5\\times 10^{-2}$, for $19$ degrees of freedom (here we keep the total number of events fixed, and hence we have one degree of freedom less). ", "The number of signal events (after reconstruction) needed to distinguish each pair of spins are listed in Table \\[table:spin\\]. ", "The same cuts as for obtaining Fig.", " \\[fig:spin\\] are applied.", "\n\n $s_a$$\\backslash$ $s_b$ Vector Scalar Pseudo-scalar Graviton\n ------------------------- ----------- ----------- --------------- -----------\n Vector - 661 (501) 262 (140) 316 (122)\n Scalar 705 (577) - 199 (94) 771 (455)\n Pseudo-scalar 275 (182) 200 (116) - 240 (128)\n Graviton 356 (243) 878 (694) 239 (123) -\n\n : \\[table:spin\\]Number of [*signal*]{} events after reconstruction needed to distinguish a particle of spin $s_a$ from spin $s_b$ at 95% CL. ", "The number of background events is fixed to 136, corresponding to $100\\, {\\rm fb}^{-1}$ data. ", "All resonance masses are $2$ TeV. For reference, the needed numbers of signal events without background are given in the parentheses.", "\n\nIn Table \\[table:spin\\], we have shown two sets of numbers. ", "The numbers of events outside the parentheses are the minimum numbers of signal events needed to distinguish the spin for $100\\, {\\rm fb}^{-1}$ data. ", "We use the same cuts as for Fig.", " \\[fig:spin\\]. ", "The number of background events is 136 with the $t\\bar t$ dilepton events dominating (109). ", "For reference, we also list in the parentheses the numbers of needed events assuming no background. ", "The background distributions are canceled when comparing the observed distributions and the Monte Carlo distributions. ", "However, they do introduce uncertainties that can significantly increase the number of needed signal events.", "\n\nThe numbers listed in Table \\[table:spin\\] are large but achievable in some models. ", "For example, a KK gluon of 2 TeV in the basic RS model yields 230 events for $100\\, {\\rm fb}^{-1}$ in the mass window $(1600\\,{\\mbox{GeV}}, 2400\\,{\\mbox{GeV}})$, which is not enough to distinguish it from other spins at 95% CL. ", "With $300\\, {\\rm fb}^{-1}$ data, we can distinguish it from a pseudo-scalar or a KK-graviton using the dilepton channel alone, but will need to combine other channels to distinguish it from a scalar.", "\n\nDiscussions and Conclusions {#sec:discussion}\n===========================\n\nAn important assumption leading to the fully solvable system is that the only missing transverse momentum comes from the two neutrinos from the top decays. ", "There are also other sources of missing momenta such as neutrinos from heavy flavor hadron decays. ", "But they are usually soft and their effects have already been included in the simulation. ", "More challengingly, the assumption is invalid when there are other missing particles in the event, for example, in supersymmetric theories with R-parity. ", "Consider the process $pp\\rightarrow \\tilde t\\,\\tilde{t}^* \n\\rightarrow t\\,\\bar t\\,\\tilde\\chi_1^0\\,\\tilde\\chi_1^0$ in the minimal supersymmetric standard model, which has the same visible final state particles as a $t\\,\\bar t$ resonance. ", "We have to be able to distinguish the two cases before claiming a $t\\,\\bar t$ resonance. ", "Distributions in various kinematic observables are certainly different for the two cases. ", "Nevertheless, we find that the most efficient way to separate them is still by using the event reconstruction.", "\n\nAs an example, we have generated 10,000 events in the above MSSM decay chain and let both $t$ and $\\bar t$ decay leptonically, for $m_{\\tilde t}=1500~{\\mbox{GeV}}$ and $m_{\\tilde\\chi_1^0}=97~{\\mbox{GeV}}$. There are 705 events which pass the kinematic cuts described in Section \\[sec:reconstruction\\] with a $m_{T_{cl}}$ cut of 1500 GeV. Out of those 705 events, only 30 pass the reconstruction procedure, that is, satisfy Eq.", " (\\[eq:realcut\\]). ", "This is to the vast contrast of a $t\\,\\bar t$ resonance of 3 TeV, where a half of the events after cuts survive the reconstruction procedure. ", "The difference between the two cases is not difficult to understand: for a $t\\,\\bar t$ resonance, ignoring initial state radiations, we have $t$ and $\\bar t$ back-to-back in the transverse plane and their decay products nearly collinear. ", "On the other hand, the directions of the two neutralinos in the MSSM case are unrelated and therefore the direction of the missing $p_T$ is separated from both of the $b\\,\\ell$ systems. ", "It is then very unlikely to satisfy the mass shell constraints simultaneously for both $t$ and $\\bar t$.\n\nIn conclusion, by reconstructing $t\\,\\bar t$ and $t\\,t$ events in the dilepton channel, we studied the $t\\,\\bar t$ and $t\\,t$ resonances at the LHC in a model-independent way. ", "The kinematic system is fully solvable from the $W$ boson and top quark mass-shell constraints, as well as the constraints from the measured missing transverse momentum. ", "After solving this system for the momenta of the two neutrinos, we obtained the $t$, $\\bar t$ momenta and therefore the $t\\,\\bar t$ invariant mass distribution. ", "The same procedure can also be applied to the $t\\,t$ system. ", "We showed that this method can be utilized to discover and measure the spins of $t\\,\\bar t$ and $t\\,t$ resonances at the LHC.", "\n\nThe event reconstruction is the most challenging when the $t\\,\\bar t$ resonance is heavy. ", "This is not only because of the suppression of parton distribution functions at high energies. ", "More importantly, in this case the top quarks are highly boosted and the lepton and the $b$-jet from the same top decay are highly collimated. ", "Therefore, the lepton is often not isolated from the $b$-jet. ", "To solve this problem, we included non-isolated muons, which can be identified in a detector. ", "The $b$-tagging efficiency may also degrade at high energies, which drove us to consider events without $b$-tagged jets. ", "In summary, we included all events with two high $p_T$ (isolated or non-isolated) leptons and two high $p_T$ ($b$-tagged or not-tagged) jets passing the kinematic cuts described in Section \\[sec:eventgeneration\\]. ", "Accordingly, we have to consider all SM backgrounds containing the same final state particles. ", "We simulated and analyzed all major backgrounds and found that they can be efficiently reduced by imposing the kinematic cuts and the mass-shell constraints.", "\n\nThe reconstruction procedure was applied to four $t\\,\\bar t$ resonances with different spins. ", "We found that despite a smaller branching ratio, the dilepton channel is competitive to the semileptonic channel in discovering the $t\\,\\bar t$ resonance. ", "This is due to the better experimental resolution of the lepton momentum measurement and smaller SM backgrounds. ", "For example, the first KK gluon in the basic RS model with fermions propagating in the bulk can be discovered at $5\\,\\sigma$ level or better, up to a mass of $3.7$ TeV for $300~\\rm{fb}^{-1}$ integrated luminosity. ", "We also considered the possibility of finding a $t\\,t$ resonance, for which the dilepton channel is the best because it is the only channel in which the charges of both tops can be identified. ", "Due to the smallness of the SM same-sign dilepton backgrounds, the $t\\,t$ resonance has a better discovery limit than the $t\\,\\bar t$ resonance. ", "Assuming the same production cross section as the KK gluon, the $t\\,t$ resonance can be discovered up to a mass of $4.4$ TeV.\n\nThe dilepton channel is also advantageous for identifying the spin of the resonance. 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", "J. Conway, PGS 4, pretty good simulation of high energy collisions, http://www.physics.ucdavis.edu/ conway/research/software/pgs/pgs4-general.htm.", "\n\nSee, for example, C. Diaconu, arXiv:0901.0046 \\[hep-ex\\]. ", "C. Amsler et al., ", "Phys. ", " Lett. ", " B [**667**]{}, 1 (2008)\n\nJ. C. Collins and D. E. Soper, Phys.", " Rev.  D [**16**]{}, 2219 (1977).", "\n\n[^1]: It is possible to identify the charges of the $b$-jets but only at a few percent level.", "\n\n[^2]: Note that the finite widths of the top quark and the $W$ boson have similar effect, although their $1-2$ GeV widths are negligible compared with the detector resolutions.", "\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Q:\n\nTrying to select columns in R but it only assumes rows\n\nI am trying to select 41 variables from 827 existing ones. ", "I am using the code:\n`myvars <- c('newid', # CU id\n 'region', # region\n 'state', # state\n 'cutenure', # housing tenure \n 'fam_size', # family size\n 'no_earnr', # number of earners\n 'num_auto', # number of vehicles owned\n 'popsize', # population size (see codes)\n 'inclass', # income class\n 'age_ref', # age reference person \n 'educ_ref', # education reference person (see codes)\n 'ref_race', # race reference person (1=white, 2=black, 3= nat-am, 4=asian, 5=pac-isl, 6=multi-race)\n 'inc_hrs1', # hours x week by ref person\n 'inc_hrs2', # hours x week by spouse\n 'incweek1', # number weeks worked ref person\n 'incweek2', # number weeks worked spouse\n 'fincbtax', # income before tax past 12 month\n 'fincatax', # income after tax past 12 month\n 'fsalaryx', # wage and salary income before ded.", "\n 'totexppq', # tot exp prev quarter\n 'totexpcq', # tot exp curr quarter\n 'majapppq', # major appliances prev quarter\n 'majappcq', # major appliances curr quarter\n 'FOODHOME', # Expenditures food at home\n 'FOODAWAY', # Food away from home\n 'ALCBEV', # Alcholic Beverages\n 'OWNDWECQ', # Owned Dwellings\n 'ZRENTDWL', # Rented Dwellings\n 'OTHLODCQ', # Other Lodging\n 'UTILCQ', # Utilities\n 'MISCEQPQ', # Household Equipment\n 'HOUSOPCQ', # Household Operations\n 'APPARCQ', # Apparel and Services\n 'VEHICLCQ', # Vehicle Expenditures\n 'OTHVEHCQ', # Other Vehicle Expenditures\n 'GASMOCQ', # Gasoline\n 'TRNOTHCQ', # Public Transportation\n 'HEALTHCQ', # Health Care\n 'ENTERTCQ', # Entertainment\n 'PERSCACQ', # Personal Care\n 'READCQ', # Reading\n 'EDUCACQ', # Education\n 'TOBACCCQ' # Tobacco\n )\n\nnewdataQ1 = dataQ1[,myvars]`\n\nAfter this I received the error:\nError in [.data.frame(dataQ1, , myvars): undefined columns selected\nTraceback:\n\ndataQ1[, myvars]\n[.data.frame(dataQ1, , myvars)\nstop(\"undefined columns selected\")\n\nIf I change the comma and put\nnewdataQ1 = dataQ1[myvars,]\nIt allows me to procede, but keeps 41 rows instead of 41 columns, keeping the original number of columns.", "\nHow can I fix this?", "\nThank you.", "\n\nA:\n\nMaybe dplyr would be a good way for you to partition your data.", "\nIt's a great package that makes your request very easy and well readable\n(I'm using pipe operators, they also make life much easier and the code more readable)\nnewdataQ1 <- dataQ1 %>% select(myvars)\n\nIt's worth checking out the tutorials of dplyr (e.g. on datacamp) to get familiar with the syntax.", "\nIf you want to use basic R only you need to specify that you want to select colnames:\nnewdataQ1 <- dataQ1[, colnames(dataQ1) %in% myvars]\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "The Dent County Commissioners met for their regular meeting at the Dent County Courthouse Thursday morning. ", "In the road report, District 1 Commissioner Dennis Purcell reported that grading would be done on Dent County Roads 5690, 6520, 6540 and 6590; and material would be hauled and ditch work would be done on Dent County Road 4180. ", "Purcell also attended a Homeland Security Oversight Committee yesterday afternoon in St. James. ", "District 2 Commissioner Gary Larson reported that grading would be done on Dent County Roads 4030 and 4400, and rock would be hauled to Dent County Roads 4290 and 4300. ", "Larson also said that one brush cutter is being repaired, but the other brush cutter would be used on Dent County Road 2330. ", "Presiding Commissioner Darrell Skiles reported that he along with other members of emergency response entities met with Dent County Emergency Management Director Brad Nash to discuss the 2010 Interoperable Communications proposal that was received from Interoperable Solutions, which was the only company to submit a proposal. ", "The proposal was for $35,000 with a five-year annual fee of $3,500, and that would also include licensing fees. ", "The Commission would like to go ahead and acquire the equipment, but is waiting to see which other emergency response entities are willing to share in the cost before a definite decision is made. ", "Skiles also talked with a representative from Verkamp and Malone about the proposal they presented concerning the year required 2010 audit that they would be conducting due to the county receiving over $500,000 in federal money. ", "Their initial proposal was for an indefinite amount of $10,000 to $12,000, however the state conducted their audit of the county for the years 2008 and 2009, and that paperwork was submitted to Verkamp and Malone, therefore relieving the company of some work and knocking their initial proposal down to $7,500. ", "After a short discussion the commission agreed to go ahead and accept their proposal. ", "The commissioners also discussed moving forward with Great River Associates Engineering Firm on the Swiney Bridge project in Bunker. ", "The cost will be $25,000 for the design of the bridge and for them to oversee the project. ", "Since the county will be receiving financial assistance from the Missouri Department of Conservation and the National Forest Service on this project, an amended budget hearing will be held on August 8th at 10:00 in the morning. ", "The projected amended budget will be made available to the public on Tuesday, July 26th. ", "Matt Lloyd with Fabick and Company also stopped in to touch base with the Commissioners on the backhoe proposal. ", "The Commission decided to go ahead and accept Fabick and Company’s bid and they will be looking into local financing options for the lease purchase. ", "The next meeting of the Dent County Commissioners will be Monday morning at 9:00 at the courthouse, and is open to the public.", "\n\nThe Salem R-80 Board of Education held their regular meeting Thursday evening at the district administrative offices. ", "Superintendent Cindy Rumpf was not present so Assistant Superintendent John McCulloch ran the meeting. ", "The board set the Open House dates and times. ", "They are 6:00 to 7:00 on August 15th for the William Lynch Elementary School and from 6:30 to 7:30 the same night at the Upper Elementary School. ", "The Senior High and Junior High will hold their Open House from 6:30 to 8:00 Tuesday night, August 16th. ", "The board will also take their tours of the buildings at that time. ", "He reported that in the annual bus inspection, 11 of the 12 busses were approved and one needed a new tie rod end which has been repaired. ", "Because Salem exceeded the 90% approval rating, they received the Total Fleet Excellence Award. ", "This is the 7th year in a row that Salem has received that award. ", "Stan Podorski from KSMO Radio and Gabe Mankin from Fidelity Communications discussed the new Fidelity Local Channel 6 and that there are ten fall Salem Tiger Sporting events scheduled to be televised by Salem students on a delayed basis including all five home football games. ", "Mankin stated that this is just the beginning of bringing local events to TV to the Salem area and that the events will also be available live on the web on a subscription service or on demand. ", "In the future, Fidelity hopes to expand the service to other school and local events on their public access channel which is now Channel 95 as well as on Channel 6. ", "The board approved the bids on school surplus property and the amount the school will receive will be $320. ", "The board approved the bid on food items from US Foodservice, the bid on Bread from IBC Sales Corporation, the bids on milk and juice from Hiland Dairy, and the bid from pest control from Advanced Pest Control. ", "The board approved reprimanding Board Member Carol Jordan for the dissemination of unfounded rumors by a vote of 4-1-1. ", "The board accepted the resignation of Elementary School Para-Professional Julie Hatridge, and the board approved a Professional Development Contract with Dr. Wesley Byrd for $27,000 to share in classroom strategies with math teachers from kindergarten through the 6th grade four times a month with a review at the end of the year to see what strategies worked best. ", "The board then went into closed session.", "\n\nThe Salem Football Tigers will host a “mini jamboree” tonight starting at 6:30 at the Salem High School Football Field. ", "Teams involved in the “mini jamboree” will include Rolla, West Plains and Blair Oaks. ", "The “mini jamboree” is open to all.", "\n\nAlbert Pujols clubbed a two-run homer and Jake Westbrook tossed eight solid innings, as the St. Louis Cardinals avoided a three-game sweep with a 6-2 victory over the New York Mets at Citi Field. ", "Westbrook (8-4) allowed two runs on four hits with one walk for the Cardinals, who snapped their losing streak at three games. ", "Skip Schumacher and John Jay also had RBI’s for the Cardinals who start a three game set with Pittsburgh tonight starting at 5:30 on KSMO.", "\n\nThe Kansas City Royals had the day off yesterday and will host the Tamp Bay Rays starting tonight at Kaufmann Stadium.", "\n\nFuneral services for Carl R. Baker of Salem will be held today at 11:00 at the James 7 Gahr Mortuary in Salem. ", "Interment will be in the Empire Cemetery. ", "Memorials are suggested to the Empire Cemetery in Gladden.", "\n\nFuneral services for Ruth Louise Mullnack of Salem, age 88, will be held today at 2:00 at the Wilson Mortuary Chapel in Salem. ", "Interment will be in the North Lawn Cemetery.", "\n\nFuneral services for Delbert D. “Tod” Counts, Salem, will be held Sunday at 2:00 at the James & Gahr Mortuary in Salem. ", "Visitation will be Saturday from 5:00 to 7:00. ", "Interment will be in the New Hope Cemetery. ", "Memorials are suggested to the New Hope Cemetery.", "\n\nFuneral services for Lillian Faye Beasley of Rolla, age 74, are incomplete and under the direction of the James & Gahr Mortuary in Rolla.", "\n\nToday..Mostly sunny, hot and humid, high of 96 with a heat index of 106.", "\nTonight..Mostly clear, low of 78.", "\nSaturday..Partly cloudy, hot and humid, with a 20% chance for thunderstorms, high of 95 with a heat index of 102.", "\nSaturday night..Partly cloudy, low of 74.", "\nSunday..Partly sunny, with a 40% chance for thunderstorms, high of 93." ]

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[ "Q:\n\nA Semi-infinite right circular cylinder problem\n\nA semi-infinite right circular cylinder whose axis lie along the $z$ axis, has its base on the $x$-$y$ plane.", "The base is maintained at a constant potential $V_0$ and the side of the cylinder is maintained at zero potential. ", "Write down the Laplace equation to determine the potential inside the cylinder. ", "Separate the PDE into a set of ODEs and write down the boundary conditions.", "\nPlease help....\n\nA:\n\nClearly, there is no angular dependence, so the potential will be a function of $r$ and $z$. We may separate variables by letting the potential $V(r,z)= R(r)Z(z)$ The equation for the potential is then\n$$\\frac{1}{rR} \\frac{dR}{dr} + \\frac{1}{R} \\frac{d^2 R}{d r^2} + \\frac{1}{Z} \\frac{d^2 Z}{d z^2} = 0$$\nWe deal with the $R$ equation first:\n$$\\frac{1}{rR} \\frac{dR}{dr} + \\frac{1}{R} \\frac{d^2 R}{d r^2} = -\\lambda^2$$\nwhere $\\lambda$ is some separation constant. ", " Then \n$$r R'' + R' + \\lambda^2 r R = 0$$\nwhere, for $z>0$, $R(a) = 0$. The solution to this equation is a Bessel function of the first kind, of order zero: $R(r) = A \\, J_0(\\lambda r)$. By requiring that the potential be zero at $r=a$ leads to $\\lambda = j_{0,n}/a$, where $j_{0,n}$ is the $n$th zero of the Bessel function. ", " \nBecause we have a semi-infinite cylinder with a boundary condition at $z=0$, then the solution for $Z(z)$ must take the form\n$$Z(z) = B_n \\, e^{- j_{0,n} z/a}$$\nThe general solution is\n$$V(r,z) = \\sum_{n=1}^{\\infty} B_n \\, J_0\\left ( j_{0,n} \\frac{r}{a} \\right ) \\, e^{- j_{0,n} z/a}$$\nBecause $V(r,0) = V_0$, and the fact that the $J_0\\left ( j_{0,n} \\frac{r}{a} \\right )$ form an orthogonal basis set over $L^2[0,a]$, we may determine the $B_n$ from\n$$B_n = \\frac{\\displaystyle V_0 \\int_0^a dr \\, r \\, J_0\\left ( j_{0,n} \\frac{r}{a} \\right )}{\\displaystyle\\int_0^a dr \\, r \\, J_0\\left ( j_{0,n} \\frac{r}{a} \\right )^2} = \\frac{2 V_0}{j_{0,n} J_1(j_{0,n})} $$\n\n" ]

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[ "Beim ersten Auftritt an der Anfield Road darf Jürgen Klopp sein erstes Tor als Trainer des FC Liverpool bejubeln. ", "Gegen Rubin Kasan reicht es trotzdem wieder nur zu einem Unentschieden. ", "Ein anderer Deutscher trifft zudem in der Türkei.", "\n\nWieder „nur“ ein Unentschieden: Zumindest bejubelt Jürgen Klopp sein erstes Tor an der Anfield Road Bild: Reuters\n\nJürgen Klopp ist bei seinem Heimdebüt als Trainer des FC Liverpool nicht über ein Unentschieden hinausgekommen. ", "Seine Mannschaft trennte sich am Donnerstagabend in der Fußball-Europa-League 1:1 (1:1) vom früheren russischen Meister Rubin Kasan. ", "Marko Devic (15.) ", "hatte die Gäste an der Anfield Road in Führung gebracht, Nationalspieler Emre Can (37.) ", "glich nach einem Platzverweis für Kasans Oleg Kuzmin aus.", "\n\nAuf den Rängen feierten Liverpools Fans den neuen Trainer mit Klopp-Schals und -Bannern. ", "Auch Klubbesitzer John W. Henry verfolgte die Partie im Stadion. ", "Für Liverpool war es das dritte Remis im dritten Europa-League-Spiel. ", "Klopp veränderte seine Startelf im Vergleich zur Premiere am Samstag bei Tottenham Hotspur (0:0) auf nur einer Position.", "\n\nMehr zum Thema 1/\n\nVon Beginn an spielten die Reds bissig und schnell nach vorne, ließen sich in der Defensive aber früh überrumpeln: Nach einer Flanke aus dem Halbfeld griffen Kasans Verteidiger Devic nicht entschlossen genug an. ", "Durch Kuzmins Platzverweis wegen wiederholten Foulspiels schwächten sich die Gäste dann aber elbst (36.) - ", "die folgende Freistoßflanke verlängerte Divock Origi auf Can, der aus kurzer Distanz einschob.", "\n\nDer eingewechselte Christian Benteke vergab in der 80. ", "Minute mit einem Pfostenschuss Liverpools beste Chance auf den Sieg. ", "Die Reds festigten mit dem Remis den zweiten Platz in der Gruppe B der Europa League hinter dem FC Sion. ", "Auch Liverpools Duelle mit Bordeaux und Sion hatten jeweils mit einem Remis geendet. ", "In der Liga empfängt Klopps Mannschaft am Sonntag den FC Southampton.", "\n\nUnterdessen hat ein Tor des 60-maligen Nationalstürmers Mario Gomez Besiktas Istanbul noch ein Remis gesichert. ", "Gomez traf am Donnerstag in der 64. ", "Minute zum 1:1-Endstand gegen Lokomotive Moskau. ", "Besiktas verteidigte damit den zweiten Rang der Gruppe H vor Sporting Lissabon und blieb auch im dritten Spiel ungeschlagen.", "\n\nFür Gomez war es das erste Europapokal-Tor für seinen neuen Verein. ", "In der türkischen Liga erzielte der 30-Jährige in acht Spielen bereits sechs Tore. ", "Bundestrainer Joachim Löw hatte zuletzt betont, Gomez sei auch weiterhin eine Option für die Nationalelf. ", "Gomez bestritt sein bislang letztes Länderspiel im September 2014." ]

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[ "Le mouvement de grève annoncé à l’hôpital public pour le 7 mars vise la loi de santé de Marisol Touraine et ses Groupements hospitaliers de territoire. ", "Si ces rapprochements entre établissements, officialisés l’été dernier, continuent à susciter des protestations, je crois que la colère des praticiens hospitaliers, et du corps médical dans son ensemble, trouve aussi sa source, dans ce qui ressemble de plus en plus à du « médecin-bashing ».", "\n\nEn effet depuis quelque temps, les critiques pleuvent sur la tête des médecins. ", "On leur reproche, pêle-mêle, leur manque de disponibilité et d’empathie, voire la maltraitance vis-à-vis des patients, leur sentiment de supériorité, leur situation de nantis prompts aux dépassements d’honoraires. ", "On leur fait porter la responsabilité des « déserts médicaux » en France. ", "Et la liste des récriminations n’est pas exhaustive.", "\n\nCommençons par Les Brutes en blanc, le dernier livre de Martin Winckler, nom de plume d’un médecin généraliste devenu écrivain à succès (Flammarion). ", "Cet essai dépeint une profession majoritairement hautaine, autoritaire et paternaliste. ", "Il s’est vendu en cinq mois à 24 000 exemplaires, selon Edistat. ", "Ce tableau caricatural m’a heurté, en tant que médecin, et poussé à donner un autre point de vue.", "\n\nDes comportements archaïques de mandarins subsistent\n\nCertes il existe, comme partout, des attitudes déviantes dans le corps médical. ", "Au sein des CHU, des comportements archaïques de « mandarins » subsistent. ", "Les plus jeunes médecins en font les frais, des attitudes sexistes perdurent, et les étudiants comme les patients en pâtissent. ", "Le modèle paternaliste a encore de beaux restes, même si les médecins ont compris depuis longtemps que les patients doivent être de plus en plus impliqués dans les soins.", "\n\nMais les médecins sont aussi confrontés, désormais, à des patients consuméristes dont la conduite est désarçonnante. ", "Ils n’appliquent pas les conseils d’hygiène et d’alimentation prodigués par leur médecin traitant… mais se précipitent chez un coach cher payé, pour entendre exactement le même discours. ", "Ou bien ils préfèrent télécharger une application sur leur téléphone, qui va leur dire quoi manger et quand faire de l’exercice.", "\n\nDans mon exercice de radiologue hospitalier, dans celle de mes collègues généralistes en cabinet, l’empathie se pratique au quotidien. ", "En tant que spécialiste en échographie de grossesse, j’annonce chaque semaine à des couples que leur fœtus est porteur de malformations, parfois graves. ", "Je suis amené, souvent, à partager leur décision d’interruption de grossesse. ", "Supporter – au sens propre – la souffrance d’autrui n’a rien d’anodin. ", "C’est une vocation.", "\n\nUn taux de suicide supérieur à la moyenne\n\nOn oublie trop souvent, voire on ignore, que la profession de médecin connaît un taux de suicide supérieur à la moyenne. ", "Dans un rapport au Conseil national de l’ordre des médecins datant de 2003, le Dr Yves Léopold indique que 14 % des décès de médecins entre 30 et 65 ans ont pour cause le suicide ; dans la population générale, cette proportion n’est que de 5,4 %. ", "Sans parler d’un risque supérieur de conduites addictives, de divorces et de maladies, physiques ou mentales. ", "En cause, aussi, les rapports plus tendus avec les patients. ", "C’est aujourd’hui le lot des médecins, que d’être agressés – verbalement ou physiquement – dans les lieux mêmes où ils soignent.", "\n\nLe dénigrement des médecins est pratiqué avec une intensité croissante par des autorités de tutelle tout sauf empathiques. ", "Elles leur reprochent de ne pas vouloir repeupler des « déserts médicaux » qui sont en fait des déserts tout court. ", "L’État s’y est désengagé depuis des années, personne ne veut plus s’y installer car on y manque de tout, pas seulement de médecins. ", "L’exercice médical isolé que pratiquait mon grand-père, par exemple, n’est plus possible au XXIᵉ siècle. ", "Un généraliste a besoin de trouver, à proximité de son cabinet, des laboratoires d’analyses médicales, de l’imagerie, des soins infirmiers et de kinésithérapie.", "\n\nUn autre reproche, encore… Les médecins rechignent à appliquer la généralisation du tiers payant, mesure phare de la loi de santé. ", "Mais ils ont, tout simplement, de bonnes raisons de résister. ", "Cette mesure va réduire un peu plus, dans l’esprit des patients, la valeur de l’acte médical. ", "J’en veux pour preuve cette anecdote, qui m’a été racontée par un ami généraliste. ", "Un patient, ne pouvant pas se déplacer au cabinet disait-il, lui avait demandé de venir à son domicile. ", "Mon collègue sonne, ne reçoit aucune réponse, s’inquiète et s’apprête à appeler les pompiers, quand il voit le patient arriver en voiture et se garer. « ", "J’étais chez le coiffeur », déclare-t-il posément au médecin. ", "Son attitude s’explique aisément. ", "Chez le coiffeur, l’acte a de la valeur : il faut payer. ", "Pas chez le médecin.", "\n\nUn précédent ministre de la Santé, Bernard Kouchner, parlait d’un « droit à la santé » pour les patients. ", "Comme si les médecins appliquaient des procédés, avec une obligation de résultats. ", "Le malade serait ainsi fondé, quand il franchit le seuil du cabinet, à exiger des soins qui lui rendent la santé à coup sûr… Marisol Touraine, elle, n’emploie plus qu'exceptionnellement le mot « médecin ». ", "Elle lui préfère celui de « professionnel de santé » ou de « prescripteur », qui le réduit à un technicien de la médecine. ", "Or on sait que la façon de donner un médicament compte autant que l’action du médicament en lui-même. ", "La base de ce métier est une relation unique avec le patient, un « colloque singulier » pour reprendre une expression parlante, propre à la médecine française. ", "Je ne me sens pas « professionnel de santé ». ", "Je me sens médecin.", "\n\nL’acte médical engage la responsabilité du praticien, juridique mais surtout morale. ", "Un généraliste de ma connaissance m’a rapporté la surprise de certains patients, auxquels il demande de se déshabiller et d’effectuer des séries de pompes alors qu’ils viennent, disent-ils, « juste pour un certificat médical pour le sport ». ", "Il doit leur rappeler la responsabilité qu’il prend en signant le certificat, et les années d’études et d’expérience qui l’y autorisent.", "\n\nJ’ai 40 ans et je suis médecin spécialiste hospitalo-universitaire. ", "Mon épouse est médecin généraliste en libéral. ", "Mes deux grands-pères étaient médecins. ", "Mes parents sont médecins à la retraite. ", "Dans un tel contexte familial, vous comprendrez mieux, je l’espère, le sens que je donne au mot « vocation » employé plus haut. ", "Je prends un plaisir immense, au quotidien, à soigner les patients et à transmettre mon savoir aux étudiants en médecine. ", "Le « médecin-bashing » me heurte, car il met en doute ce qui me constitue, mes convictions, une forme d’altruisme – j’ose à peine écrire ce mot qui, aujourd’hui, pourrait passer pour de la provocation.", "\n\nSi je pouvais faire des propositions, je mettrais l’empathie au cœur de la formation initiale des médecins, dès les bancs de la faculté. ", "J’aimerais, aussi, promouvoir la bienveillance au cours de leurs études, pour en finir avec les suicides d’internes et leur maltraitance en général. ", "Une centaine d’élèves infirmiers, aides-soignants ou internes en médecine témoignent d’ailleurs des « violences gratuites » infligées par leur hiérarchie dans un livre tout juste paru, Omerta à l’hôpital (éditions Michalon). ", "J’appelle, aussi, à un management humaniste des carrières hospitalières et universitaires. ", "Car les médecins titulaires sont tout autant en situation de risque « psychique », pour employer un euphémisme.", "\n\nJ’ai trois enfants qui seront bientôt en âge de choisir un métier. ", "Je pense aujourd’hui leur déconseiller vivement d’embrasser la vocation familiale. ", "Autour de moi, d’autres parents orientent leurs enfants vers la médecine, « pour la sécurité de l’emploi ». ", "Cela m’attriste profondément. ", "Si la situation perdure, nous aurons bientôt réduit l’engagement dans ce métier à un choix pragmatique destiné à minimiser le risque de chômage. ", "Pour les patients, c’est là que les vrais ennuis vont commencer.", "\n\nParce que soigner l’Autre ne doit jamais devenir anodin." ]

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[ "Accuracy of magnetic resonance imaging in diagnosing thyroid cartilage and thyroid gland invasion by squamous cell carcinoma in laryngectomy patients.", "\nWe examined the accuracy of magnetic resonance imaging in assessing thyroid cartilage and thyroid gland invasion in patients undergoing total laryngectomy for squamous cell carcinoma, by comparing histopathology results with imaging findings. ", "A retrospective study reviewed histology and magnetic resonance scan results for all total laryngectomies performed between 1998-2008 at University Hospital Aintree, Liverpool. ", "Pre-operative magnetic resonance images were reviewed independently by two consultant head and neck radiologists masked to the histology; their opinions were then compared with histology findings. ", "Eighty-one magnetic resonance scans were reviewed. ", "There were 22 laryngectomy patients with histologically verified thyroid cartilage invasion and one patient with thyroid gland invasion. ", "There were 31 patients with apparent radiological thyroid cartilage invasion pre-operatively (with 17 false positives), giving sensitivity, specificity, and positive and negative predictive values of 64, 71, 45 and 84 per cent, respectively. ", "On assessing thyroid gland invasion, there were nine false positive scans and no false negative scans, giving sensitivity, specificity, and positive and negative predictive values of 100, 89, 10 and 100 per cent, respectively. ", "Magnetic resonance scanning over-predicts thyroid cartilage and gland invasion in patients undergoing total laryngectomy. ", "Magnetic resonance scans have limited effectiveness in predicting thyroid cartilage invasion by squamous cell carcinoma in laryngectomy patients." ]

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[ "News Story\n\nLead writer Mac Walter has said the next Mass Effect from BioWare won't be using any of Commander Shephard's 'events' from the first three games as anchor points in the next instalment.", "\n\nOne of the team's key goals is that it can't \"just feel like a spin-off,\" that it must be a Mass Effect adventure \"at its heart, at its core.\" ", "No Shepard or \"Shepard specific companions.\"", "\n\nBioWare had already made it quite clear they wanted a clean break from the Shephard saga, but now we know they also intend to avoid the subject in narrative too.", "\n\n\"Well, I can’t get into details, but the idea is that we have agreed to tell a story that doesn’t relate necessarily to any of the Shepard events at all, whatsoever. ", "Beyond that, that’s what we’ve been deciding for awhile,\" said Mac Walter.", "\n\n\"But throughout it all, one of the key things is that it has to be Mass Effect. ", "It can’t just feel like a spin-off. ", "It has to feel like a Mass Effect game at its heart, at its core. ", "Just without the Shepard character or the Shepard specific companions.\"", "\n\nThe BioWare lead writer also touched on Mass Effect 3's ending.", "\n\n\"It’s been 18-19 months since it came out and my thoughts on it are that we addressed it the best we could in the extended cut. ", "We’re obviously not going to be changing anything now. ", "We’re only going forward.\"", "\n\nWalter touches on the player's hand being forced after having so much freedom throughout was what likely caused the backlash to BioWare's choice of endings for Shephard. \"", "You know, you’ve been given free choice to make all these decisions with this character, with the fates of millions of people, and then, you don’t get to choose your own fate.\"", "\n\n\"And I’m not saying that our decision was wrong or right. ", "I think we just underestimated the impact that would have on certain players. ", "To be fair, I get people, especially at the Cons, who will say, “I loved it. ", "It was heart-wrenching, but I felt it was right for my Shepard.” ", "And to me, that’s why it was the right path,\" Walter told Complex Gaming.", "\n\n\"But because there was no choice, it was going to be right for some people, and for others, in the middle, and other people were obviously very upset about it. ", "In hindsight, I don’t think there was anything we would have changed about that, but it is a really good lesson learned.\"", "\n\nThe next Mass Effect is being developed using DICE's Frostbite 3 engine, as is Dragon Age: Inquisition." ]

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[ "THE APOCALYPSE WAS on its way, and it would begin in Mexico. ", "Where else? ", "When archaeologists dug up Mayan calendars that ominously seemed to run out in the final days of 2012, some doomsayers predicted the end of the world. ", "To many Mexicans it seemed like just another example of their country’s unending run of bad luck. ", "The steepest recession on the American mainland, a plague of H1N1 swine flu and a deepening war against organised crime had made the preceding few years fairly grim. ", "In 2009 the Pentagon had given warning that Mexico could become a “failed state”. ", "Armageddon would be the icing on the cake.", "\n\nBut it turns out that the Mayan glyphs were misunderstood. ", "The men with magnifying glasses now say that the world is not about to end—in fact, it seems that the Mayans were predicting something more like a renewal or a fresh start. ", "Could the same be true of Mexico?", "\n\nThis special report will argue that there is a good chance of it. ", "Some awful years are giving way to what, if managed properly, could be a prosperous period for Latin America’s second-largest economy. ", "Big, irreversible trends, from a falling birth rate at home to rising wages in China, are starting to move in Mexico’s favour. ", "At the same time the country’s leaders are at last starting to tackle some of the home-grown problems that have held it back.", "\n\nMany of the things that the world thinks it knows about Mexico are no longer true. ", "A serially underachieving economy, repeatedly trumped by dynamic Brazil? ", "Mexico outpaced Brazil last year and will grow twice as fast this year. ", "Out-of-control population growth and an endless exodus to the north? ", "Net emigration is down to zero, if not negative, and the fertility rate will soon be lower than that of the United States. ", "Grinding poverty? ", "Yes, but alleviated by services such as universal free health care. ", "A raging drug war? ", "The failure of rich countries’ anti-drugs policies means that organised crime will not go away. ", "But Mexico’s murder rate is now falling, albeit slowly, for the first time in five years.", "\n\nA vast country with deeply ingrained problems and unreformed corners, Mexico could yet squander the opportunities that are coming its way. ", "But there are signs that it is beginning to realise its potential. ", "With luck, the dire predictions made by the Pentagon and others may turn out to be as reliable as a misread Mayan calendar.", "\n\nPreparing to lead Mexico into this brightening future is the party most associated with its past. ", "The Institutional Revolutionary Party (PRI) ran Mexico without interruption for most of the 20th century, silencing opposition through a mixture of co-option, corruption and occasional violence. ", "Only in 2000 did it give up its grip on power to the conservative National Action Party (PAN), which fielded two presidents in succession: Vicente Fox, a former executive at Coca-Cola, and Felipe Calderón, a lawyer whose father was a founding member of the party. ", "On December 1st Mr Calderón will hand over the presidency to the PRI’s Enrique Peña Nieto, who won a clear election victory on July 1st. ", "A handsome 46-year-old with a gift for communication, Mr Peña claims to be the opposite of the crooked party men who ran the country in its pre-democratic days. ", "But will the change be more than superficial?", "\n\nMr Peña says his priority is to make the economy grow faster in order to reduce poverty. ", "Nearly half the population are poor, many of them in the south (see map). ", "To achieve more rapid growth he will need to introduce a series of big economic reforms, some of which Mr Calderón attempted during his presidency, only to see them get stuck in Mexico’s cantankerous Congress. ", "The PRI had hoped to win a majority in the summer’s elections, but it fell short by 11 in the 500-member Chamber of Deputies and by four in the 128-member Senate. ", "In any case, some of the most important reforms will need changes to the constitution, which require a two-thirds majority in Congress. ", "However, Mr Peña has reason to be optimistic. ", "The opposition PAN shares much of Mr Peña’s agenda, and together the two parties have a two-thirds majority in both houses of Congress. ", "A new power to fast-track two bills per congressional session will help. ", "A lot will depend on who ends up leading the PAN, which is restive and rudderless after finishing third in the presidential election. ", "The handover period between July’s election and December’s inauguration has been a model of presidential co-operation. ", "Mr Calderón’s crackdown on Mexico’s vindictive criminals has given him a personal reason to stay on good terms with the new government, to make sure of the protection he and his family will need when he leaves office. ", "Fighting on two fronts Mr Peña’s main problem in Congress may well be his own party. ", "As this special report went to press Congress was about to pass a labour-law reform, which among other things would make hiring and firing easier. ", "But linked measures to make Mexico’s over-mighty unions more transparent and democratic were voted down by congressmen from Mr Peña’s own PRI, which has strong ties to unions. ", "If the unions cannot be tamed, Mr Peña’s other reforms—to open up the monopolised energy sector and overhaul the tax system—may be similarly diluted.", "\n\nThe runner-up in the election was the left-winger Andrés Manuel López Obrador, known as AMLO, who came a very close second to Mr Calderón in 2006 but lost to Mr Peña by 6.8%. ", "After both defeats he claimed fraud. ", "The evidence is thin. ", "The left has about a quarter of the seats in Congress, but many of its congressmen have little patience with AMLO, whose magnetic personality repels as many voters as it attracts.", "\n\nThe government may also face opposition outside Congress. ", "Though a majority of the political class now seems to be convinced of the need for economic reforms along the lines that Mr Peña proposes, the same may not yet be true on the street, in the public universities or in much of the press. “", "Mexico is a country where doctrine and principle matter more than practical considerations and results,” says Enrique Krauze, a historian. ", "The state-run oil monopoly is the sort of sacred cow that could emit a deafening, destabilising moo if Mr Peña tried to tether it. ", "Mexico City already sees an average of 14 protests a day.", "\n\nThe internet is making politics more unpredictable. ", "During the election campaign Mr Peña paid a disastrous visit to a university and fled after being heckled. ", "This gave rise to an anti-Peña student movement calling itself YoSoy132, or “I am the 132nd” (the initial protest was led by 131 students). ", "It is now capable of summoning large crowds via Twitter and Facebook to march against Mr Peña (and often, it seems, for AMLO). ", "During Mexico’s independence celebrations on September 16th anonymous hackers took down several government websites.", "\n\nSo it will not be an easy ride. ", "Mr Krauze remembers that the optimism when the North American Free-Trade Agreement (NAFTA) came into force in 1994 was quickly punctured by the Zapatista uprising in Mexico’s south on New Year’s Day. “", "We thought we were there in the first world, on the final lap of our historic marathon. ", "Then on January 1st we woke up to the astonishing news of a rebellion in Chiapas,” he says.", "\n\nCompare the murder rate and body count of each Mexican state against entire countries with our interactive equivalents map\n\nMexico has form in turning triumph to disaster, and could yet do so again. ", "Its economy remains dependent on the fortunes of the United States, and financial crises in Europe make investors jittery. ", "Promised reforms will depend on persuading entrenched interests to accept them. ", "Corruption and bad government, especially at the local level, may cause good initiatives to fall at the last hurdle. ", "And the drug war is by no means over. ", "But Mexico deserves a fresh look—not least because its economy is revving up, as the next article explains." ]

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[ "Untangling the Trump administration’s lawsuit over an HIV prevention drug\n\nThe U.S. government routinely sues pharmaceutical companies for making false claims, bilking Medicare, illegal kickbacks, and sloppy manufacturing practices. ", "But on 6 November, the U.S. Department of Justice (DOJ) filed suit against Gilead Sciences Inc. of Foster City, California, for reasons that cannot easily fit on a bumper sticker. ", "At the center of the dispute are monkey studies done by researchers at the U.S. Centers for Disease Control and Prevention (CDC) with a Gilead drug called Truvada, and the drug’s use as part of a highly effective HIV prevention strategy called pre-exposure prophylaxis (PrEP).", "\n\nTruvada for PrEP has earned Gilead billions of dollars, and the government contends it deserves some of those earnings because it helped develop the intervention. ", "Specifically, the government alleges Gilead failed to obtain licenses to use four patents that CDC obtained on research results related to PrEP. “", "Gilead has repeatedly refused to obtain a license from CDC to use the patented regimens,” the federal lawsuit states. “", "Meanwhile, Gilead has profited from research funded by hundreds of millions of taxpayer dollars … but has not paid any royalties to CDC.” ", "The lawsuit contends that “Gilead’s conduct was malicious, wanton, deliberate, consciously wrongful, flagrant, and in bad faith.”", "\n\nGilead has rejected the allegations, arguing that each of the four government patents at issue is invalid. ", "The work conducted by CDC researchers was obvious and proposed by others before they even published their experiment, the company argued in petitions sent to the U.S. Patent and Trademark Office (USPTO) earlier this year. ", "It has asked the agency to cancel the patents.", "\n\nResearchers familiar with the field say CDC researchers did not invent the concept underpinning PrEP —that the same antiretroviral drugs (ARVs) used to treat HIV could, like malarial pills given to travelers, works as preventives. ", "In essence, the key CDC study, which was reported in 2006, suggested a refinement to the PrEP strategy that other researchers had already shown had great promise. ", "But that does not necessarily mean the federal patents are invalid; that is one of the key questions a judge will have to decide.", "\n\nIf the government wins the case, which could take years to wind through the courts, it’s unclear what would happen to any monetary damages collected from the company—but the litigation itself might pressure Gilead to cut the price of the drug. ", "Reducing drug prices in general has become a high priority for both the Trump administration and Democrats in Congress. ", "And Gilead has drawn widespread criticism from HIV/AIDS advocacy groups for its steep pricing of Truvada, which, using list pricing, has an annual cost of $21,388 per patient in the United States. ", "In May, members of Congress grilled Gilead CEO Daniel O’Day about the pricing issue at a hearing with the unsubtle title “HIV Prevention Drug: Billions in Corporate Profits after Millions in Taxpayer Investments.”", "\n\nScience reviewed the litigation filed by both sides in the dispute and spoke with leading researchers and HIV/AIDS advocates to try to clarify the arguments in this messy and long-running battle. ", "Neither Gilead nor Department of Health and Human Services representatives would speak with Science about the details.", "\n\nWhy is this issue coming to the fore now?", "\n\nEven though several studies have shown that PrEP stops HIV by various routes of transmission and can play a critical role in bringing epidemics to a halt, it isn’t widely used. ", "According to the AIDS Vaccine Advocacy Coalition (AVAC), a New York City–based nonprofit that tracks PrEP usage, as of October, fewer than 400,000 people in the world were using PrEP. ", "So, one possibility is that the lawsuit is “a negotiating ploy that’s meant to decrease the price of PrEP and improve access,” suggests Mitchell Warren, head of AVAC.", "\n\nAlthough the annual cost of Truvada made by generic drugmakers in several countries outside the United States is $54 a year, Gilead controls the U.S. market—and some contend the high U.S. price is a barrier to access. ", "The PrEP4All Collaboration, an HIV/AIDS activist–led group, launched a #BreakThePatent campaign that has received high-profile media attention. ", "The collaboration has had support from the Global Health Justice Partnership at Yale Law School, which provided an extensive legal analysis in March that concluded “the U.S. government could possibly be entitled to collect money damages.” ", "Representative Alexandria Ocasio-Cortez (D–NY) introduced this analysis at the May congressional hearing. ", "Proving once again that politics make for strange bedfellows, DOJ noted when it filed suit against Gilead that the issue also meshes with President Donald Trump’s “Ending the AIDS Epidemic: A Plan for America,” which he announced at this year’s State of the Union address.", "\n\nWho invented PrEP?", "\n\nThe idea for PrEP grew out of attempts to prevent transmission of the AIDS virus from a pregnant, infected mother to her baby.", "\n\nIn 1992, monkey researchers from the University of California (UC), Davis, led by Koen Van Rompay published a study in Antimicrobial Agents and Chemotherapy that gave infant animals AZT, the first marketed anti-HIV drug, 2 hours before they intentionally attempted to infect them with the simian immunodeficiency virus (SIV), a simian version of the AIDS virus. ", "The study, which only protected two monkeys, received little attention.", "\n\nTwo years later, a landmark human study established that if given both to the infected mother during pregnancy and the infant at birth, AZT could prevent mother-to-child transmission. ", "Then in 1995, Science (17 November, pp. ", "1121 and 1197) published a monkey study that turned many heads: A group led by researchers at the University of Washington in Seattle gave 25 animals an antiretroviral called PMPA both shortly before and after injecting them with SIV. ", "The drug protected all animals.", "\n\nPMPA is also known as tenofovir, and is one of two drugs in Truvada. ", "The closing line of the paper noted that, as was becoming clear with ARV treatment, the drug might work even better if combined with other ARVs.", "\n\nVan Rompay, who published several more PMPA monkey PrEP experiments over the subsequent decade, says he was surprised that CDC won patents for its later Truvada studies. “", "I don’t think they have enough evidence to argue they discovered something novel,” van Rompay says. “", "They just added a second drug.”", "\n\nWhat led USPTO to issue the patents based on the CDC work?", "\n\nIn 2005, the CDC group reported that daily tenofovir alone protected animals when “challenged” with a rectal dose of SHIV (an SIV/HIV hybrid) once a week, but this only worked for 5 weeks and was deemed “partial protection.” ", "The researchers the next year reported that if they repeated the experiment but added a second Gilead drug called FTC—the second ingredient in Truvada—monkeys were still protected after 14 challenges. “", "As a result of CDC’s breakthrough, two human PrEP trials already underway changed their drug regimens to match CDC’s new PrEP regimens,” the U.S. government lawsuit notes. ", "The complaint also contends that “no one in the field” expected that tenofovir combined with FTC or any other drug would have such “superior effectiveness.”", "\n\nWhat’s Gilead’s main argument against these patents?", "\n\nIn patent-speak, if something is “obvious” to a “person of ordinary skill in the art” then it doesn’t deserve a patent. ", "Gilead has two main arguments that Truvada for PrEP was an obvious invention. ", "One is that after Truvada received approval from the U.S. Food and Drug Administration (FDA) in 2004 as a treatment for HIV infection, CDC guidelines endorsed it for PrEP’s close cousin, postexposure prophylaxis (PEP). (", "PEP, which must be used within 3 days, is primarily advocated in emergency situations such as sexual assault, or when a health care worker has an accidental needlestick at work.) ", "Gilead’s second argument is that two California HIV/AIDS organizations, jointly known as Cal-PrEP, published a report in 2004 that advocated using Truvada for PrEP. ", "One of the co-founders of Cal-PrEP, psychologist Thomas Coates, who heads the Global Health Institute at UC Los Angeles, provided a declaration to Gilead’s lawyers that left no doubt on this point. “", "At the time Cal-PrEP was published in November 2004, I had every expectation that both Truvada and [tenofovir] would be effective for use as PrEP,” stated Coates, who told Science he was not compensated by Gilead for providing his declaration. “", "I expected that Truvada would have somewhat better efficacy.”", "\n\nHow much better is Truvada than tenofovir alone?", "\n\nThe U.S. government’s patents revolve around the assertion that Truvada is better than tenofovir alone, but the data on this point are unclear. ", "The researchers who conducted the first CDC monkey study noted that the partial protection may have been linked to variable levels of the drug in the animals (which was fed to them in their food). ", "Van Rompay, who was a reviewer of the published paper that described the work, says he questioned whether infections occurred in animals who did not eat all the drug. “", "I often did similar studies and the taste was really bad,” van Rompay says. ", "CDC’s Truvada study better accounted for drug levels in the monkeys. ", "No monkey experiment ever did a convincing head-to-head comparison of tenofovir and Truvada, he notes. ", "And he points to a large human study in Kenya and Uganda that did do such a comparison in heterosexual couples (one partner was infected at the outset), which found that both preparations offered significant and statistically indistinguishable levels of protection. ", "A separate study of tenofovir PrEP in people who inject drugs in Thailand also showed that it significantly reduced the risk of HIV infection.", "\n\nWhat do official PrEP guidelines say?", "\n\nThe CDC guidelines recommend Truvada for PrEP and a newer formulation of the combo drug. ", "World Health Organization recommendations suggest PrEP regimens need only contain tenofovir.", "\n\nWhat did Gilead contribute to the development of PrEP?", "\n\nO’Day told Congress that Gilead had invested $1.1 billion in the R&D for Truvada, but said it did not make sense to separate out how much of that went to treatment versus PrEP, as there was so much overlap in everything from preclinical work to human trials. ", "The U.S. government suit contends that Gilead had a hands-off approach to clinical trials of PrEP and only provided drugs for the CDC studies. ", "Science reported in 2005 (12 August, p. 1002) that Gilead said it had “no interest in pursuing PrEP because of fears that uninfected people who take tenofovir and still become infected might sue the company.”", "\n\nIf the lawsuit does ultimately drive down Truvada’s price, how much impact will that likely have on usage in the United States?", "\n\nAn estimated 1.1 million Americans are at high risk of becoming infected with HIV and qualify for PrEP, but AVAC estimates only about 135,000 at most now use it. ", "It’s difficult to assess how much pricing has affected usage to date—and will affect it in the future.", "\n\nA few days before the congressional hearing in May, Gilead announced that it would donate to CDC enough Truvada to treat up to 200,000 Americans for 11 years. ", "In 2020, it also will allow one generic manufacturer to sell the drug in the United States—1 year earlier than required by patent law. ", "Although some HIV/AIDS advocates suspect that change won’t have a major impact on pricing and want Gilead to allow as much generic competition as possible, they say Truvada PrEP’s price tag undoubtedly will drop.", "\n\nFurther complicating the picture, FDA last month approved a new Gilead drug for PrEP, Descovy, that putatively has an improved version of tenofovir. ", "The company has not announced plans to give away Descovy or allow its generic manufacture in the United States. ", "The U.S. government lawsuit claims that the sale of Descovy for PrEP also infringes its patents.", "\n\nWarren says in the end, price matters, but PrEP usage faces larger obstacles such as health systems scaling up programs to encourage its proper use. “", "If price was out of the equation,” he says, “it would take one of many barriers away, but it wouldn’t magically increase uptake.”" ]

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[ "One of the designers who made it happen\n\nCarla has been amazing to work with. ", "Positive and efficient, very kind and hardworking. ", "Job well done! ", "I will work with Carla again.", "\nYulia\n\n- Yulia Biryulina\n\nHow cheryljulia started their logo design journey\n\nCompany name\n\nCheryl Julia Photography\n\nOverview\n\nI am a photographer in Charleston, SC who has been building a portfolio for less than two years. ", "I am really looking to start marketing my business and feel that I am on the cusp of getting it to take off.", "\n\nTell us a bit about who you are and the people you reach\n\nI want to target folks who are not afraid to trust my vision. ", "I am tired of cookie-cutter images of people in matching outfits on the beach. ", "I want to rebuild my portfolio with candid, fresh, fun and lively photos. ", "Like most, I am looking for clients that don't mind paying for creativity and artistic talent.", "\n\nRequirements\n\nI want my logo to be sophisticated. ", "Stated otherwise, I am looking for elegance with style. ", "I tend to love the designs that involve very clever use of letters/initials. ", "I am not opposed to lively design elements, but I don't want it to be overwhelming. ", "I need my logo for website (perhaps to place on a textured background), stationery, business card and watermark." ]

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[ "An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart.", "\nThe expression of the sodium/calcium exchanger NCX1 increases during cardiac hypertrophy and heart failure, playing an important role in Ca(2+) extrusion. ", "This increase is presumed to result from stress signalling induced changes in the interplay between transcriptional and post-transcriptional regulations. ", "We aimed to determine the impact of the SRF transcription factor known to regulate the NCX1 promoter and microRNA genes, on the expression of NCX1 mRNA and protein and annexin A5 (AnxA5), a Ca(2+)-binding protein interacting with NCX1 and increased during HF. ", "NCX1 mRNA was decreased while the protein was increased in the failing heart of the cardiomyocyte-restricted SRF knock-out mice (SRF(HKO)). ", "The induction of NCX1 mRNA by the pro-hypertrophic drug phenylephrine observed in control mice was abolished in the SRF(HKO) though the protein was strongly increased. ", "AnxA5 protein expression profile paralleled the expression of NCX1 protein in the SRF(HKO). ", "MiR-1, a microRNA regulated by SRF, was decreased in the SRF(HKO) and repressed by phenylephrine. ", "In vitro and in vivo manipulation of miR-1 levels and site-directed mutagenesis showed that NCX1 and AnxA5 mRNAs are targets of miR-1. ", "AnxA5 overexpression slowed down Ca(2+) extrusion during caffeine application in adult rat cardiomyocytes. ", "Our study reveals the existence of a complex regulatory loop where SRF regulates the transcription of NCX1 and miR-1, which in turn functions as a rheostat limiting the translation of NCX1 and AnxA5 proteins. ", "The decrease of miR-1 and increase of AnxA5 appear as important modulators of NCX1 expression and activity during heart failure." ]

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[ " Opinions of the United\n2008 Decisions States Court of Appeals\n for the Third Circuit\n\n\n1-9-2008\n\nGartner v. USA\nPrecedential or Non-Precedential: Non-Precedential\n\nDocket No. ", "07-2344\n\n\n\n\nFollow this and additional works at: http://digitalcommons.law.villanova.edu/thirdcircuit_2008\n\nRecommended Citation\n\"Gartner v. USA\" (2008). ", "2008 Decisions. ", "Paper 1775.", "\nhttp://digitalcommons.law.villanova.edu/thirdcircuit_2008/1775\n\n\nThis decision is brought to you for free and open access by the Opinions of the United States Court of Appeals for the Third Circuit at Villanova\nUniversity School of Law Digital Repository. ", "It has been accepted for inclusion in 2008 Decisions by an authorized administrator of Villanova\nUniversity School of Law Digital Repository. ", "For more information, please contact Benjamin.Carlson@law.villanova.edu.", "\n\f NOT PRECEDENTIAL\n\n UNITED STATES COURT OF APPEALS\n FOR THE THIRD CIRCUIT\n ___________\n\n No. ", "07-2344\n ___________\n\n JOHN B. GARTNER,\n Appellant\n\n v.\n\n UNITED STATES OF AMERICA\n\n ____________________________________\n\n On Appeal from the United States District Court\n for the Eastern District of Pennsylvania\n (D.C. Civil Action No. ", "07-mc-00052)\n District Judge: Honorable Juan R. Sanchez\n ____________________________________\n\n Submitted Pursuant to Third Circuit LAR 34.1(a)\n December 20, 2007\n\n Before: SLOVITER, BARRY and WEIS, Circuit Judges\n\n (Opinion filed: January 9, 2008)\n ___________\n\n OPINION\n ___________\n\nPER CURIAM\n\n Appellant John B. Gartner appeals pro se the district court’s denial of his petition\n\nto quash two Internal Revenue Service (IRS) third-party recordkeeper summonses. ", "We\n\nhave jurisdiction over this appeal under 28 U.S.C. § 1291. ", "Moutevelis v. United States,\n\f727 F.2d 313, 314 (3d Cir. ", "1984) (citing 26 U.S.C. § 7609(h)(1)).", "\n\n Under 26 U.S.C. § 7601, the Secretary of the Treasury is directed to make\n\ninquiries of every person who may be liable to pay tax. ", "Further, under 26 U.S.C. § 7602,\n\nthe Secretary is vested with the authority to issue summonses in order to fulfill the\n\nSecretary’s investigatory obligation. ", "These summonses include third-party recordkeeper\n\nsummonses which may be issued to banks and credit unions, among other entities. ", "See 26\n\nU.S.C. § 7609.", "\n\n Upon review of the record and the parties’ briefs, we find no reversible error in the\n\ndistrict court’s denial of Gartner’s petition to quash.", "\n\n Accordingly, we will affirm the District Court’s order entered April 20, 2007.", "\n\f" ]

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[ "Berlin (AFP) – Injury-prone Germany winger Marco Reus returned for Borussia Dortmund on Saturday against Bundesliga strugglers Hamburg having been sidelined for the last 259 days by a torn cruciate knee ligament.", "\n\nReus, 28, has been out since suffering the injury in last May’s German Cup final, when Dortmund beat Eintracht Frankfurt in the Berlin showcase.", "\n\nBerlin (AFP) – Injury-prone Germany winger Marco Reus returned for Borussia Dortmund on Saturday against Bundesliga strugglers Hamburg having been sidelined for the last 259 days by a torn cruciate knee ligament.", "\n\nReus, 28, has been out since suffering the injury in last May’s German Cup final, when Dortmund beat Eintracht Frankfurt in the Berlin showcase.", "\n\nBerlin (AFP) – Injury-prone German international winger Marco Reus could make his return after torn cruciate knee ligaments for Borussia Dortmund on Saturday against strugglers Hamburg, just four months out from the World Cup.", "\n\nReus, 28, has been sidelined since last May’s German Cup final, when Dortmund beat Eintracht Frankfurt in Berlin, and has been working his way back to fitness in recent weeks.", "\n\nBerlin (AFP) – Injury-prone German international winger Marco Reus could make his return after torn cruciate knee ligaments for Borussia Dortmund on Saturday against strugglers Hamburg, just four months out from the World Cup.", "\n\nReus, 28, has been sidelined since last May’s German Cup final, when Dortmund beat Eintracht Frankfurt in Berlin, and has been working his way back to fitness in recent weeks.", "\n\nBerlin (AFP) – Marco Reus’ injury misery continued Monday when Borussia Dortmund confirmed the winger partially tore his cruciate ligament in Saturday’s German Cup final – a set-back which could sideline him for months.", "\n\n“In the coming days, there will be further tests and a decision will be made on the necessary treatment,” said Dortmund in a statement.", "\n\nBerlin (AFP) – Marco Reus’ injury misery continued Monday when Borussia Dortmund confirmed the winger partially tore his cruciate ligament in Saturday’s German Cup final – a set-back which could sideline him for months.", "\n\n“In the coming days, there will be further tests and a decision will be made on the necessary treatment,” said Dortmund in a statement.", "\n\nBig results for USMNT players in Mexico and Germany. ", "CONCACAF crowned Pachuca champions in an all-Liga MX finale to the 2016-17 CONCACAF Champions League and there will be USMNT players in both teams for the 2016-17 DFB Pokal final.", "\n\nThis season's CONCACAF Champions League concluded with Pachuca lifting the trophy at Estadio Hidalgo.", "\n\nMonaco (AFP) – Teenage sensation Kylian Mbappe scored again to set Monaco on their way to a 3-1 second-leg victory over Borussia Dortmund on Wednesday that allowed them to win their Champions League quarter-final 6-3 on aggregate.", "\n\nRadamel Falcao also netted for the home side in a whirlwind start at the Stade Louis II, and Dortmund were left with too much to do to save the tie.", "\n\nMonaco (AFP) – Teenage sensation Kylian Mbappe scored again to set Monaco on their way to a 3-1 second-leg victory over Borussia Dortmund on Wednesday that allowed them to win their Champions League quarter-final 6-3 on aggregate.", "\n\nRadamel Falcao also netted for the home side in a whirlwind start at the Stade Louis II, and Dortmund were left with too much to do to save the tie.", "\n\nMonaco (AFP) – Borussia Dortmund coach Thomas Tuchel has left both Marcel Schmelzer and Ousmane Dembele out of his starting line-up for Wednesday’s Champions League quarter-final second leg in Monaco.", "\n\nThe duo start on the bench along with Sven Bender as Erik Durm, Raphael Guerreiro and Matthias Ginter all start for the German club, who are looking to overturn a 3-2 first-leg deficit at the Stade Louis II.", "\n\nMonaco (AFP) – Borussia Dortmund coach Thomas Tuchel has left both Marcel Schmelzer and Ousmane Dembele out of his starting line-up for Wednesday’s Champions League quarter-final second leg in Monaco.", "\n\nThe duo start on the bench along with Sven Bender as Erik Durm, Raphael Guerreiro and Matthias Ginter all start for the German club, who are looking to overturn a 3-2 first-leg deficit at the Stade Louis II.", "\n\nBerlin (AFP) – Borussia Dortmund players and fans paid tribute to defender Marc Bartra as they beat Eintracht Frankfurt 3-1 on Saturday in their first Bundesliga match since the midweek bomb attack on their team bus.", "\n\nGermany winger Marco Reus scored on his return after six weeks out and Sokratis Papastathopoulos and leading scorer Pierre-Emerick Aubameyang were also on target in a home victory which allowed Thomas Tuchel’s side to all but wrap up a top-four finish and boost morale at the end of a traumatic week.", "\n\nBerlin (AFP) – Borussia Dortmund players and fans paid tribute to defender Marc Bartra as they beat Eintracht Frankfurt 3-1 on Saturday in their first Bundesliga match since the midweek bomb attack on their team bus.", "\n\nGermany winger Marco Reus scored on his return after six weeks out and Sokratis Papastathopoulos and leading scorer Pierre-Emerick Aubameyang were also on target in a home victory which allowed Thomas Tuchel’s side to all but wrap up a top-four finish and boost morale at the end of a traumatic week.", "\n\nBerlin (AFP) – Germany winger Marco Reus scored on his return after six weeks out as Borussia Dortmund beat Eintracht Frankfurt 3-1 on Saturday in their first Bundesliga match since the midweek bomb attack on their team bus.", "\n\nSokratis Papastathopoulos and leading scorer Pierre-Emerick Aubameyang were also on target in a victory which allowed Thomas Tuchel’s side to all but wrap up a top-four finish and boost morale after a shocking last week.", "\n\nBerlin (AFP) – Germany winger Marco Reus scored on his return after six weeks out as Borussia Dortmund beat Eintracht Frankfurt 3-1 on Saturday in their first Bundesliga match since the midweek bomb attack on their team bus.", "\n\nSokratis Papastathopoulos and leading scorer Pierre-Emerick Aubameyang were also on target in a victory which allowed Thomas Tuchel’s side to all but wrap up a top-four finish and boost morale after a shocking last week.", "\n\nDortmund (Germany) (AFP) – Spain international Marc Bartra, who was hurt in Tuesday’s bomb attack on the Borussia Dortmund team bus, was replaced by Sven Bender for Wednesday’s rescheduled Champions League quarter-final first leg against Monaco.", "\n\nCentre-back Bartra underwent surgery on a broken wrist after he was hit by flying glass as three explosions shattered windows on the Dortmund coach as it made its way to Signal Iduna Park on Tuesday.", "\n\nDortmund (Germany) (AFP) – Spain international Marc Bartra, who was hurt in Tuesday’s bomb attack on the Borussia Dortmund team bus, was replaced by Sven Bender for Wednesday’s rescheduled Champions League quarter-final first leg against Monaco.", "\n\nCentre-back Bartra underwent surgery on a broken wrist after he was hit by flying glass as three explosions shattered windows on the Dortmund coach as it made its way to Signal Iduna Park on Tuesday.", "\n\nBerlin (AFP) – Defender Sokratis Papastathopoulos says Borussia Dortmund must improve ‘300 percent’ in Wednesday’s Champions League showdown in their bid to reach the quarter-finals and add to Benfica’s miserable record in Germany.", "\n\nBenfica arrive in Dortmund for the last 16, second-leg, clash holding a precious 1-0 lead after Konstantinos Mitroglou’s winning goal in the first-leg win in Lisbon.", "\n\nDortmund (Germany) (AFP) – With Germany winger Marco Reus injured, French ‘wunderkind’ Ousmane Dembele will look to shine as Borussia Dortmund bid to overturn a first leg deficit against Benfica in the Champions League.", "\n\nDortmund host Benfica at their Westfalenstadion home in the last 16 second-leg on Wednesday looking to overturn a 1-0 defeat in Portugal three weeks ago.", "\n\nDortmund (Germany) (AFP) – With Germany winger Marco Reus injured, French ‘wunderkind’ Ousmane Dembele will look to shine as Borussia Dortmund bid to overturn a first leg deficit against Benfica in the Champions League.", "\n\nDortmund host Benfica at their Westfalenstadion home in the last 16 second-leg on Wednesday looking to overturn a 1-0 defeat in Portugal three weeks ago.", "\n\nAfter entering as a 44th minute substitute for Marco Reus, the U.S. Men's National Team winger scored a second half goal, pushing the Borussia Dortmund lead to 4-2 in Saturday's clash with Bayer Leverkusen.", "\n\nDortmund (Germany) (AFP) – Marc Bartra gave blood, other Borussia Dortmund players have nightmares about the bomb attack on their bus and now the German team may need the sweat of Marco Reus to pull off a fairy tale place in the Champions League last four.", "\n\nThe scars left by three bombs that scorched the side of the bus and fired metal shards inside before the quarter-final against Monaco have gone much further than Bartra’s fractured wrist." ]

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[ "LaMarcus Aldridge gave a few teams their fair shot, but in the end, it was the San Antonio Spurs who won the prized free agent. ", "Aldridge has chosen to team up with Tim Duncan, Tony Parker, and Kawhi Leonard, signing a four-year, $80 million dollar deal with the Spurs.", "\n\nThe frenzy of fun that is NBA free agency is officially underway, with Aldridge the player who has made the first splash out of the gate. ", "The former Portland Trail Blazer had a tough decision to make, but as USA Today reported, Aldridge didn’t even give former teammate Damian Lillard a shot at a face-to-face meeting to hopefully lure him back to town.", "\n\n“Lillard, upon return from a promotional trip in Paris, was hoping to pull off some fourth-quarter heroics on Thursday. ", "He started planning a trip via charter plane to Los Angeles to meet with Aldridge and try to work it out. ", "But the trip never happened because, well, it was already too late.”", "\n\nDon’t worry though, Portland, because it wasn’t just you who got turned down by Aldridge, as the Los Angeles Lakers were also rejected. ", "As the Los Angeles Times reported, the Lakers made their pitch to Aldridge, but came up short on the high-profile free agent.", "\n\nNext up for the offseason rumor mill? ", "Well, it’s time to talk about how the impressive lineup below which features Aldridge is one that will immediately make life tough on the Golden State Warriors.", "\n\nG Tony Parker G Danny Green F Kawhi Leonard F Lamarcus Aldridge C Tim Duncan I will take that lineup hands down. ", "https://t.co/QDFdBGX4zO — JayDee (@sportstlk365) July 5, 2015\n\nWith all due respect to LeBron James (and more than likely the Cleveland Cavaliers), that group is the most dangerous starting five in the NBA, thanks to Aldridge. ", "The Spurs had firepower before, but adding Aldridge inside just makes this team scary all-around.", "\n\nThe Warriors deserve heaps of respect after their 67-15 regular season record and an NBA Championship, but they may be in for a matchup nightmare against both Duncan and Aldridge inside. ", "Obviously, we’re still a ways away from even talking about a 2016 Western Conference Finals series between these two, but finding a way to slow down Aldridge (and of course Duncan) on the inside? ", "It seems like a pretty daunting task.", "\n\nOne vital move for the Spurs moving forward will be attempting to get Manu Ginobili to come back for one more season. ", "His depth would be key to helping the Spurs make another championship push, and it’s safe to say that he’s probably a bit intrigued by the potential to play with LaMarcus Aldridge.", "\n\nAldridge will carry in impressive numbers of 23.4 points, 10.2 rebounds, and one block per game last season. ", "Those numbers were the best of Aldridge’s nine-year career, showing that he very well may be peaking at the perfect time for his new team.", "\n\nWith the Aldridge signing, the Spurs look like the early front-runner for the best signing of the 2015 offseason. ", "Best of all, Aldridge in town means this team is once again a serious contender.", "\n\n[Image via Streeter Lecka]" ]

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[ "Features: Fiberglass fuse and balsa built -up wing. ", "Wing Covering Material: Covering, painted, decals applied and clear coated. ", "The aircraft has a beautiful flat, non-glossy finish. ", "This is superior to glossy covering materials. ", "It is scratch, tear and wrinkle resistant. ", "The covering material is a brand name covering which has a special paint adherant layer. ", "The covering goes on clear, and is then primed and painted, then clearcoated.", "\n\nThough the Hellcat bore a superficial resemblance to its earlier cousin, the F4F Wildcat, the Hellcat was a completely different aircraft. ", "Its Pratt and Whitney R-2800 put out 2000 hp (the Wildcat's engine put out 1200 hp), and the result was one of the most successful military aircraft of all time, scoring 5200 kills, most of which occurred in the pacific theatre (though 8 kills were recorded during the invasion of southern France).", "\n\nThe Hellcat was already in development by the time of the attack on PearlHarbour, but subsequent air battles revealed that the need for a replacement for the Wildcat was urgent. ", "The A6M Zero could out turn and out climb the Wildcat. ", "The only advantages the Wildcat had were the ability to absorb more damage, heavier armament and the ability to dive faster. ", "Building on these existing advantages, the engineers at Grumman sought to build an aircraft which would outclass the Zero in every category. ", "Besides the combat capabilities, the Hellcat was also easy to produce and maintain, making it a perfect wartime aircraft.", "\n\nThe first production versions were activated for combat duty in February 1943, and began to see combat in September. ", "The first major engagement was over Rabaul on 11 November 1943, they ed with F4U Corsairs in a day long dogfight with Zeros, scoring nearly 50 kills. ", "Over Tarawa atoll on 23 November 1943, they scored 30 kills for one loss. ", "From that point on, the Hellcat saw combat in virtually every action in the Pacific theatre, including the Battle of the Phillipine sea, which the pilots nicknamed the 'Great Marianas Turkey Shoot'. ", "The F6F aced for 75% of aerial kills in the pacific theatre. ", "By the end of the war there were 350 Hellcat aces, though this can be attributed as much to the inexperience of Japanese pilots as to the skill of Hellcat pilots, or the capability of the airframe.", "\n\nThe Hellcat also saw service with the Royal Navy, who recieved over 1200 as part of the lend lease act. ", "The aircraft saw duty against Messerscht's and FW-190's in this context and proved itself very capable in that role. ", "After the war the Hellcat saw use by the French Navy who used it in the French-IndoChina war, and the Uruguayan navy used the Hellcat into the 1960's. ", "In the US Navy the Hellcat was replaced by the F8F Bearcat.", "\n\nThis model is based on an aircraft from VF-27, operating from the USS Princeton in October 1944 during the Great Marianas Turkey Shoot. ", "It was flown by Rid Stambook, who claimed 10 kills in his F6F-3 Hellcat." ]

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[ "Current treatments for tuberculosis (TB) are very effective in controlling TB infection caused by Mycobacterium tuberculosis (Mtb). ", "They don't, however, always prevent reinfection. ", "Why this happens is one of the long-standing questions in TB research.", "\n\nSo why are our bodies unable to generate permanent immunity to TB, -- the leading infectious disease killer worldwide? ", "A team of scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) and McGill University may have found the answer... in the gut. ", "In a study published recently in Mucosal Immunology, they showed that anti-TB drugs caused changes to gut microbiota -- the diverse community of microbes living our intestines -- and increased susceptibility to Mtb infection.", "\n\nGut microbiota are critical to keeping us healthy; they help to digest food, combat pathogenic microbes and reinforce our immune system. ", "Recent research has shown that chronic use of antibiotic leads to disruption of this community, which can in turn lead to dysregulation of the immune system. ", "It remains unclear, however, whether changes in the composition of the microbes living in our gut have an influence on TB infection.", "\n\nImpact of anti-TB drugs on microbiome\n\nTo find out, Drs. ", "Irah King and Maziar Divangahi from the Meakins-Christie Laboratories at the RI-MUHC, with colleagues from McGill's Macdonald Campus, treated mice with the most commonly used anti-TB drugs -- isoniazid, rifampicin and pyrazinamide -- for a period of eight weeks. ", "They found that while all three drugs significantly altered the composition of the mice's gut microbiome, only mice treated with isoniazid combined with pyrazinamide showed an increase in susceptibility to Mtb infection.", "\n\nTo make sure the vulnerability of the host to Mtb infection was due to a compromised gut microbiota, the researchers looked at... feces. ", "By transplanting feces from mice that had been treated with anti-TB drugs (specifically isoniazid and pyrazinamide) into untreated mice prior to infection, they were able to show for the first time that fecal transplant was sufficient to compromise immunity to Mtb.", "\n\nRelationship between the gut microbiome and the lungs\n\nKing and his colleagues also wanted to better understand the gut-lung axis -- a bidirectional communication system between microorganisms residing in the gastrointestinal tract and the lungs -- in order to how this might be involved in Mtb infection and immunity.", "\n\nTo do so, they evaluated a number of lung cell types known to be important for resistance to Mtb infection. ", "Following anti-TB treatment, alveolar macrophages, a type of immune cell located in the airways of mice and humans and the first cell to encounter Mtb upon infection, were compromised in their ability to kill Mtb.", "\n\n\"We need to do more research in order to understand how the microbiome affects alveolar macrophages because these cells are critical for controlling early TB infection. ", "We also need to identify the molecular pathways involved in the gut-lung axis,'' explains King.", "\n\n\"Anti-TB therapies have been incredibly efficient in controlling the TB epidemic by decreasing morbidity and mortality associated with Mtb,'' says King. \"", "Now, this work provides a basis for novel therapeutic strategies exploiting the gut-lung axis in Mtb infection.''", "\n\nResearchers are already thinking of monitoring patients who are being treated with these drugs to see how their gut microbiota changes over time and once treatment has stopped. ", "The idea will be to control changes to the microbiome in combination with drugs that are effective at killing Mtb." ]

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[ "Q:\n\nlife cycle callbacks of fragments are not called accordingly\n\nI have a main activity with view pager and three action tabs \"fragment\". ", "and i implemented the life cycle callbacks for each of the main activity and the\nthree fragments. ", "and in each of the life cycle call back i placed a log statements indicates which life cycle callback being called to know how\nthe action bars with view pager behaves. ", "at run time i perceived a strange behaviour which i cant understand or attribute it to any reason.", "\nfirst behaviour\nwhen the App fisrt starts I receive:\n\n02-08 15:16:14.771 32243-32243/com.example.com.vpager_00 W/MainActivity: onCreate()\n02-08 15:16:14.901 32243-32243/com.example.com.vpager_00 W/MainActivity: onStart()\n02-08 15:16:14.901 32243-32243/com.example.com.vpager_00 W/MainActivity: onResume()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_1: onAttach()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_1: onCreate()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_1: onCreateView()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_1: onStart()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_1: onResume()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_2: onAttach()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_2: onCreate()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_2: onCreateView()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_2: onStart()\n02-08 15:16:14.941 32243-32243/com.example.com.vpager_00 W/Frag_2: onResume()\n\nand i cant find any reason why only the life cycle callbacks of the mainactivty, frag_1 and frag_2 were called BUT NOT frag_3? ", "any explaination?", "\n2nd behaviour\noccured when i touched tab3 \"frag_3\", i received:\n\n02-08 15:16:36.031 32243-32243/com.example.com.vpager_00 D/ViewRootImpl: ViewPostImeInputStage ACTION_DOWN\n02-08 15:16:36.121 32243-32243/com.example.com.vpager_00 W/Frag_3: onAttach()\n02-08 15:16:36.121 32243-32243/com.example.com.vpager_00 W/Frag_3: onCreate()\n02-08 15:16:36.121 32243-32243/com.example.com.vpager_00 W/Frag_3: onCreateView()\n02-08 15:16:36.121 32243-32243/com.example.com.vpager_00 W/Frag_3: onStart()\n02-08 15:16:36.121 32243-32243/com.example.com.vpager_00 W/Frag_3: onResume()\n02-08 15:16:36.461 32243-32243/com.example.com.vpager_00 W/Frag_1: onPause()\n02-08 15:16:36.461 32243-32243/com.example.com.vpager_00 W/Frag_1: onStop()\n02-08 15:16:36.471 32243-32243/com.example.com.vpager_00 W/Frag_1: onDestroy()\n\ni think being the life cycle callbackes were called this is understandable, but why ONLY the life cycle callbacks of frag_1 also called, i think,\nbeside the callbacks of frag_3 and frag_1, aslo frag_2 callbacks must have been called because frag_2 was in its onResume() state lately.", "\nany explaination?", "\nmainactivity\npublic class MainActivity extends AppCompatActivity {\n\nprivate final String TAG = this.getClass().getSimpleName();\n\nprivate Toolbar mTB = null;\nprivate TabLayout mTL = null;\nprivate ViewPager mVP = null;\nprivate VPagerAdapter mVPAdapter = null;\n\n@Override\nprotected void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n Log.w(TAG, \"onCreate()\");\n\n this.initViews(R.layout.act_main);\n this.initObjs();\n}\n\nprivate void initObjs() {\n this.mVPAdapter = new VPagerAdapter(getSupportFragmentManager(), this.mTL.getTabCount());\n this.mVP.setAdapter(this.mVPAdapter);\n\n this.mVP.addOnPageChangeListener(new TabLayout.", "TabLayoutOnPageChangeListener(this.mTL));\n this.mTL.setOnTabSelectedListener(new TabLayout.", "OnTabSelectedListener() {\n @Override\n public void onTabSelected(TabLayout.", "Tab tab) {\n mVP.setCurrentItem(tab.getPosition());\n }\n\n @Override\n public void onTabUnselected(TabLayout.", "Tab tab) {\n\n }\n\n @Override\n public void onTabReselected(TabLayout.", "Tab tab) {\n\n }\n });\n}\n\nprivate void initViews(int rootView) {\n setContentView(rootView);\n\n this.mTB = (Toolbar) findViewById(R.id.toolbar);\n this.mTL = (TabLayout) findViewById(R.id.tab_layout);\n this.mVP = (ViewPager) findViewById(R.id.pager);\n\n setSupportActionBar(this.mTB);\n this.mTL.addTab(this.mTL.newTab().setText(\"Tab 1\"));\n this.mTL.addTab(this.mTL.newTab().setText(\"Tab 2\"));\n this.mTL.addTab(this.mTL.newTab().setText(\"Tab 3\"));\n this.mTL.setTabGravity(TabLayout.", "GRAVITY_FILL);\n}\n\n@Override\nprotected void onStart() {\n super.onStart();\n Log.w(TAG, \"onStart()\");\n}\n\n@Override\nprotected void onResume() {\n super.onResume();\n Log.w(TAG, \"onResume()\");\n}\n\n@Override\nprotected void onPause() {\n super.onPause();\n Log.w(TAG, \"onPause()\");\n}\n\n@Override\nprotected void onStop() {\n super.onStop();\n Log.w(TAG, \"onStop()\");\n}\n\n@Override\nprotected void onDestroy() {\n super.onDestroy();\n Log.w(TAG, \"onDestroy()\");\n}\n\n}\nfrag_1\npublic class Frag_1 extends Fragment {\n\nprivate final String TAG = this.getClass().getSimpleName();\n\n@Override\npublic void onAttach(Context context) {\n super.onAttach(context);\n Log.w(TAG, \"onAttach()\");\n}\n\n@Override\npublic void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n Log.w(TAG, \"onCreate()\");\n}\n\n@Nullable\n@Override\npublic View onCreateView(LayoutInflater inflater, ViewGroup container, Bundle savedInstanceState) {\n Log.w(TAG, \"onCreateView()\");\n\n return inflater.inflate(R.layout.frag_1, container, false);\n}\n\n@Override\npublic void onStart() {\n super.onStart();\n Log.w(TAG, \"onStart()\");\n}\n\n@Override\npublic void onResume() {\n super.onResume();\n Log.w(TAG, \"onResume()\");\n}\n\n@Override\npublic void onPause() {\n super.onPause();\n Log.w(TAG, \"onPause()\");\n}\n\n@Override\npublic void onStop() {\n super.onStop();\n Log.w(TAG, \"onStop()\");\n}\n\n@Override\npublic void onDestroy() {\n super.onDestroy();\n Log.w(TAG, \"onDestroy()\");\n}\n\n}\nfrag_2:\npublic class Frag_2 extends Fragment {\n\nprivate final String TAG = this.getClass().getSimpleName();\n\n@Override\npublic void onAttach(Context context) {\n super.onAttach(context);\n Log.w(TAG, \"onAttach()\");\n}\n\n@Override\npublic void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n Log.w(TAG, \"onCreate()\");\n}\n\n@Nullable\n@Override\npublic View onCreateView(LayoutInflater inflater, ViewGroup container, Bundle savedInstanceState) {\n Log.w(TAG, \"onCreateView()\");\n\n return inflater.inflate(R.layout.frag_2, container, false);\n}\n\n@Override\npublic void onStart() {\n super.onStart();\n Log.w(TAG, \"onStart()\");\n}\n\n@Override\npublic void onResume() {\n super.onResume();\n Log.w(TAG, \"onResume()\");\n}\n\n@Override\npublic void onPause() {\n super.onPause();\n Log.w(TAG, \"onPause()\");\n}\n\n@Override\npublic void onStop() {\n super.onStop();\n Log.w(TAG, \"onStop()\");\n}\n\n@Override\npublic void onDestroy() {\n super.onDestroy();\n Log.w(TAG, \"onDestroy()\");\n}\n\n}\nfrag_3:\npublic class Frag_3 extends Fragment {\n\nprivate final String TAG = this.getClass().getSimpleName();\n\n@Override\npublic void onAttach(Context context) {\n super.onAttach(context);\n Log.w(TAG, \"onAttach()\");\n}\n\n@Override\npublic void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n Log.w(TAG, \"onCreate()\");\n}\n\n@Nullable\n@Override\npublic View onCreateView(LayoutInflater inflater, ViewGroup container, Bundle savedInstanceState) {\n Log.w(TAG, \"onCreateView()\");\n\n return inflater.inflate(R.layout.frag_3, container, false);\n}\n\n@Override\npublic void onStart() {\n super.onStart();\n Log.w(TAG, \"onStart()\");\n}\n\n@Override\npublic void onResume() {\n super.onResume();\n Log.w(TAG, \"onResume()\");\n}\n\n@Override\npublic void onPause() {\n super.onPause();\n Log.w(TAG, \"onPause()\");\n}\n\n@Override\npublic void onStop() {\n super.onStop();\n Log.w(TAG, \"onStop()\");\n}\n\n@Override\npublic void onDestroy() {\n super.onDestroy();\n Log.w(TAG, \"onDestroy()\");\n}\n\n}\n\nA:\n\nIn the ViewPager, fragments are being created ahead of time.", "\nThat means, that your Frag_2 is not visible yet (because Frag_1 covers the entire screen), but it still creates the view beforehand, so scrolling to Frag_2 will be smooth.", "\nBy default, the ViewPager preloads one fragment on each side. ", "So if you would set the start position of the ViewPager to Frag_2, it would load Frag_1 and Frag_2 as well, because they are the neighbors.", "\nYou'll notice that Frag_3 will be created when you swipe to Frag_2\nYou can increase the number of preloaded fragments by calling ViewPager.setOffscreenPageLimit(int limit).", "\nNote that the min. ", "number is 1, so this can not be disabled.", "\n\n" ]

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[ "Expats Mark Swain and his son, Sam, have become the first father and son duo to cycle the 15,685 kilometers between Ireland and Tokyo, Japan.", "\n\nThe inspiring story began in west Ireland, went through Europe, Turkey, India, Southeast Asia and China before reaching its destination. ", "All in all, it took them 10 months from beginning to end. ", "And the journey was originally inspired by Sam when he was just 10 years old (now 19).", "\n\nAs Mark, 51, explained: “He knew that his mother and I first met when we worked in Japan and there was a kind of mystique about the country. ", "He didn’t know how far it was and at the time I thought he was crazy.”", "\n\nIn other words, it was his parents’ previous expatriation which planted the seed of curiosity in the young child’s mind about other places. ", "Furthermore, the journey has done much to forge a father and son bond between the adventurous duo.", "\n\nOn the journey, they averaged about 135 km a day, and would normally use local hostels for accommodation.", "\n\nWhile being an expat is certainly not a necessary element in beckoning such a journey, we like to think that it’s the traveling, adventure-seeking, risk-taking spirit of expatriation that played a part in inspiring such a heroing escapade.", "\n\nComments" ]

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[ "**What was known?**", "\n\nCutaneous T cell pseudolymphoma is a rare, but well known complication of phenytoin therapy.", "\n\nIntroduction {#sec1-1}\n============\n\nCutaneous pseudolymphomas are a group of benign reactive T-cell or B-cell lymphoproliferative processes of varying etiologies that can mimic lymphoma.\\[[@ref1][@ref2]\\] One of the precipitating factors for pseudolymphoma is drugs like anticonvulsants, antidepressants, angiotensin-converting enzyme inhibitors and antihistamines.\\[[@ref2]\\] We report an 80-year-old male patient on phenytoin who presented with skin lesions resembling cutaneous lymphoma which showed complete resolution on withdrawal of the drug.", "\n\nCase Report {#sec1-2}\n===========\n\nAn 80-year-old male patient presented with pruritic rash of 1 month duration without any constitutional symptoms. ", "He received treatment with antihistamines and systemic steroids (prednisolone 30 mg for 5 days) from a nearby hospital; there was temporary relief during steroid therapy, but the symptoms reappeared on its withdrawal. ", "He was receiving phenytoin sodium 100 mg three times daily since 2 years for late onset seizures. ", "A neurology work up at that time identified ischemic infarct to be underlying cause for seizures. ", "He was not on any other drugs.", "\n\nAt the time of admission, his vitals were stable and there were multiple, firm, mobile, non-tender and enlarged axillary nodes. ", "He also had diffuse erythematous rash with infiltrated papules and plaques on the face \\[[Figure 1a](#F1){ref-type=\"fig\"}\\], trunk and limbs with relative sparing of distal extremities. ", "Systemic examination revealed no abnormality.", "\n\n{#F1}\n\nComplete hemogram was normal except for an elevated erythrocyte sedimentation rate (ESR) at 60 mm/hour. ", "Urine microscopy, random blood sugar, liver and renal function tests, lactate dehydrogenase level, chest radiography and ultrasonography of abdomen and pelvis were within normal limits. ", "Peripheral smear showed no atypical cells or blast forms.", "\n\nA biopsy from an infiltrated plaque on the chest showed normal epidermis with pronounced perivascular and periappendageal lymphocytic infiltrate \\[[Figure 1c](#F1){ref-type=\"fig\"}\\] composed of moderate to large sized (two to three times the normal size) lymphocytes \\[[Figure 1c](#F1){ref-type=\"fig\"}\\] having fine chromatin. ", "Many cells showed small nucleoli. ", "Occasional mitotic figures were seen. ", "Many normal looking lymphocytes were also seen. ", "Immunohistochemistry revealed most of the large cells to be CD 20 positive \\[[Figure 2a](#F2){ref-type=\"fig\"}\\] and CD 10 and bcl2 negative. ", "A significant portion of normal sized, CD 3 \\[[Figure 2b](#F2){ref-type=\"fig\"}\\] and CD 5 positive cells \\[[Figure 2c](#F2){ref-type=\"fig\"}\\] were also noted. ", "Contrast-enhanced tomogram of thorax and abdomen did not detect any abnormality. ", "Biopsy and immunohistochemistry of axillary lymph node revealed paracortical widening and retention of follicles \\[Figures [3a](#F3){ref-type=\"fig\"} and [b](#F3){ref-type=\"fig\"}\\] with CD 20 positive follicular cells \\[[Figure 3c](#F3){ref-type=\"fig\"}\\] and CD3 positive paracortical cells \\[[Figure 3d](#F3){ref-type=\"fig\"}\\]. ", "Bone marrow study, though offered, was refused by the patient.", "\n\n{#F2}\n\n{#F3}\n\nConsidering the differential diagnoses of cutaneous B-cell lymphoma and phenytoin-induced cutaneous B-cell pseudolymphoma, phenytoin was substituted with levetiracetam and the patient was managed with antihistamines and emollients. ", "Complete resolution of the rash was attained in 2 weeks \\[[Figure 1b](#F1){ref-type=\"fig\"}\\] and the ESR value came down to 20 mm/hour. ", "He was reviewed once in every 2 weeks and was carefully assessed for any reappearance of the rash, progression of lymphadenopathy and organomegaly. ", "Complete hemogram and peripheral smear analysis were repeated at each visit. ", "At the end of 2 months, the patient remained asymptomatic with normal blood parameters with complete regression of axillary Lymphadenopathy.", "\n\nConsidering the prompt, complete and sustained improvement observed after withdrawing phenytoin and the normal histology and immunohistochemistry of a lymph node specimen, we made a final diagnosis of phenytoin-induced B-cell cutaneous pseudolymphoma. ", "He is kept under regular follow up for early detection of any malignant transformation.", "\n\nDiscussion {#sec1-3}\n==========\n\nPhenytoin-induced cutaneous lymphoproliferative disorders include benign lymphoid hyperplasia, pseudolymphoma, pseudo-pseudolymphoma and malignant lymphoma.\\[[@ref2][@ref3]\\] Drug-induced pseudolymphoma manifest with predominant or exclusive skin involvement without any constitutional symptoms or systemic involvement.\\[[@ref2][@ref4][@ref5]\\] An interval of up to 7 years (between the onset of drug intake and the appearance of symptoms) has been reported in drug-induced pseudolymphoma as in our case.\\[[@ref2]\\]\n\nPresence of medium- to large-sized lymphocytes, that may appear atypical, with many ordinary small lymphocytes (as observed by us) is cited as the histology feature that distinguishes pseudolymphoma from other benign cutaneous inflammatory cell infiltrates.\\[[@ref6]\\] Distinguishing pseudolymphomas from true lymphomas is difficult as both may show atypical cells and mitotic figures. ", "Immunoglobulin and T-cell gene rearrangement studies may aid in distinguishing between the two, but polyclonal cutaneous lymphomas and monoclonal pseudolymphomas are rarely encountered.\\[[@ref2]\\] Hence, response to drug withdrawal (occasionally systemic steroids may be required to achieve control of the disease process)\\[[@ref2]\\] is taken as the reliable indicator to determine the benign or malignant nature of the disease. ", "A long-term follow up is recommended following reports of malignant lymphoma after an initial resolution in few of these patients, who are categorized as having pseudo-pseudolymphoma.", "\n\nDepending on the predominant cell, pseudolymphomas are classified into T-cell and B-cell types. ", "Drugs well known to induce cutaneous B-cell pseudolymphomas are antidepressants, whereas phenytoin-induced cutaneous pseudolymphomas are mostly T-cell predominant.\\[[@ref7]\\] We believe ours to be B-cell pseudolymphoma as majority of the atypical cells were CD20 positive. ", "Usually B-cell pseudolymphomas appear as solitary lesions, but rarely can occur with multiple papules and plaques as observed by us.\\[[@ref2][@ref6]\\]\n\nIt is proposed that pseudolymphomas are induced by drugs that facilitate blast transformation and disrupt T-cell suppressor function eliciting an exaggerated lymphocyte response to exogenous antigens which could be the drug itself or a nonpharmacological agent.\\[[@ref2]\\]\n\nPhenytoin-induced cutaneous T-cell pseudolymphomas are well reported. ", "Though lymph node biopsy specimen from patients with phenytoin-induced lymphadenopathy has revealed features of B-cell pseudolymphoma, to the best of our knowledge cutaneous B-cell pseudolymphoma induced by phenytoin is hitherto unreported.\\[[@ref8]\\]\n\nWe report this case to highlight the significance of a thorough drug history in patients who develop atypical cutaneous infiltrates and the importance of a long-term follow up even in patients who show complete clinical resolution.", "\n\n**What is new?**", "\n\nTo the best of our knowledge, cutaneous B-cell pseudolymphoma induced by phenytoin is hitherto unreported.", "\n\n**Source of support:** Nil\n\n**Conflict of Interest:** Nil.", "\n" ]

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[ "Much has been made both during and after Jim Buss and Mitch Kupchak’s departures about the various final straws that might have pushed Jeanie Buss over the line. ", "One such issue was how hard the Los Angeles Lakers pursued then Sacramento King DeMarcus Cousins.", "\n\nIn a podcast with Zach Lowe, Ramona Shelburne (both of ESPN) provided detail as to why trade discussions didn’t get very far, as well as who might’ve preferred a certain direction for the Lakers at that time.", "\n\nGiven what the Kings wound up taking for Cousins after all was said and done, the haul they expected from the Lakers seems pretty daunting. ", "Kupchak and Buss were probably right to pass on this, and the raised asking price probably cost the Kings a better prospect than the one they got (Buddy Hield).", "\n\nHere’s how the exchange went between Lowe and Shelburne, who is as plugged into the Lakers as anyone.", "\n\nShelburne: (The trade) was supposed to be Ingram and D'Angelo. ", "That was what the Kings wanted. ", "Lowe: Do you think when push comes to shove, the Lakers do that? ", "Shelburne: No. ", "Actually, I think Jim would've. ", "At that moment, I heard he was very in favor of doing the trade for Cousins. (", "Cousins) is a great player and the Lakers feel like they need a great player and every organization at some level has to have that confidence to say well it didn't work over there but we can make it work here.", "\n\nMy first question here would be: If Jim was so intent on making this trade and Kupchak was willing to remain loyal to the long-term rebuild even while knowing such a strategy could cost him his job, why fire him along with Jim?", "\n\nTo take that question a step further, after firing him, why not show gratitude for either (or both) the service spanning decades or for the aforementioned loyalty the what was better for the organization?", "\n\nThere’s still plenty about that situation that will have to come forth and it most assuredly will over the next few months, if not years. ", "For now, we should remain pretty glad the Lakers passed on the Kings’ ransom." ]

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[ "You hear about these sorts of things happening. ", "Just never to you.", "\n\nA person sees a painting at a garage sale, decides to buy it for $5 only to later discover it was painted by someone incredibly famous and worth more than they could have possibly imagined.", "\n\nSame thing here — only with an egg. ", "A scrap metal dealer in the Midwest stumbled upon an incredibly rare Faberge egg at a sale, the Daily Telegraph reports. ", "The unidentified man, sensing the golden egg was worth considerably more than the $13,000 being asked, plunked down the cash.", "\n\nIt isn't often wise to pay $13,000 for an egg, but in this case, the man's risk was well rewarded. ", "Turns out the piece of art is worth a whopping $33.3 million, according to the Daily Telegraph. ", "Why? ", "The egg was once owned by Russia's Tsar Alexander III and was seized during the Russian Revolution. ", "It is one of only a few original Faberge eggs still known to exist.", "\n\nKieran McCarthy, the Faberge expert who verified the man's discovery, compared the find to \"Indiana Jones finding the Lost Ark,\" according to the Daily Mail.", "\n\nAfter the man bought the treasure, he did some online research and found a 2011 article seeking the whereabouts of the exact egg in his possession.", "\n\nHe sought out an expert opinion and — voila — instant retirement fund, and then some.", "\n\nThe last time the egg had been seen in public was in March 1902, according to Press Association's report.", "\n\nFollow Mike Krumboltz on Twitter (@mikekrumboltz)." ]

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[ "AIDS in pregnancy, part II: Treatment in the era of highly active antiretroviral therapy and management of obstetric, anesthetic, and pediatric issues.", "\nInternational guidelines recommend resistance testing of maternal virus for all human immunodeficiency virus (HIV)-infected pregnant women. ", "The use of highly active antiretroviral therapy leads to maximal virologic suppression, thus minimizing the risk of drug resistance, but it is available only in developed countries. ", "In developing countries, the use of short-course regimens is becoming more widespread. ", "Women infected with HIV may be at greater risk for complications during pregnancy, including ectopic pregnancy, early abortions, bacterial pneumonia, urinary tract infection, oral and recurrent vaginal thrush, malaria, and tuberculosis. ", "Regional anesthesia is often the treatment of choice when administering anesthesia in an HIV-infected pregnant woman. ", "Infected children present decreased survival rates, while uninfected children born to infected mothers present a higher incidence of poor weight gain, short stature, and wasting than would be expected for the general population. ", "Transmission of HIV-1 can occur via breast-feeding." ]

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[ "Geography of New Brunswick\n\nNew Brunswick () is one of Canada's three Maritime provinces. ", "While New Brunswick is one of Canada's Maritime Provinces, it differs from its neighbours both ethnoculturally and physiographically. ", "Both Nova Scotia and Prince Edward Island are either wholly or nearly surrounded by water and the ocean therefore tends to define their climate, economy and culture. ", "New Brunswick, on the other hand, although having a significant seacoast, is sheltered from the Atlantic Ocean proper and has a large interior which is removed from oceanic effects. ", "New Brunswick therefore tends to be defined by its rivers rather than its seacoast.", "\n\nPhysical geography\n\nBoundaries\nNew Brunswick is bounded on the north by Quebec's Gaspé Peninsula and Bay of Chaleur and on the east by the Gulf of Saint Lawrence and Northumberland Strait. ", "In the southeast, the Isthmus of Chignecto connects it to Nova Scotia. ", "On its west, the province borders the American state of Maine.", "\n\nThe total land and water area of the province is 72,908 square kilometres.", "\n\nThe major river systems in the province include the Saint John River, Petitcodiac River, Miramichi River, St. Croix River and the Restigouche River. ", "The Saint John River is thought to be the second longest river on the North American eastern seaboard between the St. Lawrence River and the Mississippi River.", "\n\nThe northern seacoast, along Miramichi Bay, the Gulf of St. Lawrence and the Bay of Chaleur is called the North Shore, a region predominately Francophone, but with sizable English-speaking communities\n\nTopography\nNew Brunswick lies entirely within the Appalachian Mountain range, a chain of ancient, eroded mountains which have created river valleys and low, gently rolling hills throughout large parts of the province. ", "Zones of the province include:\n The Chaleur Uplands, extending from Maine to the north of the province and drained by the Saint John and Restigouche rivers.", "\n The Notre Dame Mountains in the northwest corner, where elevation varies from 150 to 610m, there are many small lakes and steep slopes.", "\n The New Brunswick Highlands, which includes the Caledonia, St. Croix, and Miramichi Highlands.", "\n The Lowlands in the central and eastern parts. ", "This low-lying area is mostly under 100m above sea level, and altitudes rarely exceed 180m.\n\nHydrology\n\nThe majority of western New Brunswick is drained by the Saint John River system. ", "The river, which rises in northern Maine, empties into the Bay of Fundy in Saint John. ", "Notable tributaries within the province include the Madawaska River, Tobique River, Meduxnekeag River, Nashwaak River, Oromocto River, Nerepis River and Kennebecasis River. ", "Other water bodies within the Saint John River system are Grand Lake (which itself is fed by the Salmon River), Washademoak Lake (fed by the Canaan River), and Belleisle Bay. ", "The high tides of the Bay of Fundy often cause the Saint John River to flow upstream, an effect most pronounced at the Reversing Falls in Saint John.", "\n\nThe Petitcodiac River, Shepody River, Tantramar River, and Memramcook River empty into Chignecto Bay at the head of the Bay of Fundy. ", "Like the Saint John River, the Bay of Fundy tides cause another upstream phenomenon, known as a tidal bore. ", "The construction of a causeway on the river at Moncton, approximately 50 kilometres upstream, has lessened the tidal bore's effect and changed the river's ecosystem.", "\n\nOther rivers which empty into the Bay of Fundy include the St. Croix River, Digdeguash River, Magaguadavic River, Lepreau River, Musquash River, and Big Salmon River.", "\n\nThe system of the Miramichi River, which flows into Miramichi Bay at the city of Miramichi, drains a large portion of central New Brunswick. ", "There are two main branches, the Southwest Miramichi River and Northwest Miramichi River, with several smaller tributaries such as the Dungarvon River, Renous River, Bartholomew River and Cains River. ", "The Miramichi River system is noted for its salmon pools and parks.", "\n\nThe Restigouche River system drains a large portion of northwestern and north-central New Brunswick. ", "The river flows into the Bay of Chaleur at its head near Dalhousie, and like the Miramichi, is renowned for its salmon fishing. ", "Notable tributaries are the Kedgwick River, Patapedia River, and Upsalquitch River.", "\n\nThe Nepisiguit River is another notable river feeding the Bay of Chaleur. ", "Smaller rivers into the bay include the Caraquet River, Tetagouche River and Jacquet River.", "\n\nThe Northumberland Strait is fed by the Kouchibouguac, Kouchibouguacis, Richibucto, Bouctouche, Cocagne and Shediac Rivers; while the Gulf of St. Lawrence is fed by the Tabusintac, Big Tracadie and Pokemouche Rivers.", "\n\nClimate\n\nNew Brunswick has a humid continental climate all over the province, with slightly milder winters on the Gulf of St. Lawrence coastline. ", "The far north of the province is just above subarctic with very cold winters. ", "Winters are colder than those being found in Nova Scotia all over the province due to the greater continental influence. ", "Summers are often warm, sometimes hot.", "\n\nSettlement\nAbout 80% of the province is forested, with the other 20% consisting of agricultural land and urban areas. ", "The major urban centres lie in the south of the province. ", "The bulk of the arable land is found in the Upper Saint John River Valley, with lesser amounts of farmland found in the southeast of the province.", "\n\nNearly half of the Province's residents live in rural areas (as defined by type of services available and boundaries of local government units). ", "However, as population growth occurs around the periphery of major cities, these \"urban adjacent\" areas begin to be more urban in character, describing a departure from a rural community population base.", "\n\nMany communities owe their existence to a relationship with or dependence on navigable water because of the access to land and resources it provides.", "\n\nSee also \n\n Communities in New Brunswick\n Counties in New Brunswick\n Schools in New Brunswick\n List of protected areas of New Brunswick\n List of historic places in New Brunswick\n\nReferences\n\nExternal links\n Official site of the Government of New Brunswick" ]

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[ "we know how to make your business stand out\n\nLocal Area Marketing Expertise\n\n\n\nBluetooth & Wifi Marketing\n\n" ]

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[ "T.S. Isaac His Cuba as a “Very Weak” Storm, May Strengthen On Way to Florida\n\nCuba got its first battering Saturday from Tropical Storm Isaac and expects to see a cross-country buildup of the wind and rain whirled in by the storm, whose center crossed the extreme eastern part of the country.", "\n\nIsaac made landfall near Imias, a town in the easternmost province of Guantanamo, around noon with maximum sustained winds of 95 kilometers (60 miles) per hour, and was moving north-northwest headed for Florida.", "\n\nCuban meteorologists said the eye of the storm was almost imperceptible when it hit the country, and forecast its leaving during the early afternoon Saturday at some point on the northern coast between the provinces of Las Tunas and Guantanamo as it enters the Florida Straits.", "\n\nWith that movement the storm is likely to cover Cuba with its clouds and heavy rains that up to noon Saturday continued lashing the Dominican Republic and Haiti, where Isaac caused at least four deaths.", "\n\nCuban meteorologist Jose Rubiera said on state television that the heaviest rains will affect eastern Cuba starting Saturday afternoon and will gradually march across the rest of the country as the storm advances toward the Florida Keys.", "\n\nAccording to Rubiera, Isaac hit Cuba as a “disorganized” and “very weak” storm, though the warm waters of the Florida Straits could whip it into a Category 1 hurricane.", "\n\nThe first reports of people being evacuated this Saturday came from Baracoa, a town in Guantanamo, where some 1,000 locals had to leave their houses due to the advancing sea waters and seek shelter in the homes of friends and family.", "\n\nOfficial media also said that a number of tourist attractions and seaside resorts in the provinces of Holguin, Camaguey and Ciego de Avila were evacuated, in most cases putting an early end to tourists’ summer vacations.", "\n\nDespite being located some 1,000 kilometers (620 miles) west of the eastern tip of the country, winds have strengthened in Havana over the last few hours and some rain has fallen.", "\n\nIn his report, Rubiera said that this weekend “winds will be pretty strong across almost all of the country,” with speeds of 30 to 45 kph (20 to 30 mph) in the western and central areas, from 30 to 55 kph (20 to 35 mph) a little farther east in Camaguey province, and from 70 to 95 kph (40 to 60 mph) on the easternmost tip of the country.", "\n\nAuthorities are keeping a close watch on technical conditions and water volumes in national reservoirs, which on average are currently at 66 percent of capacity.", "\n\nIn provinces like Ciego de Avila, Sancti Spiritus, Villa Clara and Camaguey, however, reservoirs are above 80 percent of capacity and some are completely full, so that a sudden increase in volume is cause for concern.", "\n\nOn the other hand, eastern provinces like Granma have a serious problem with reservoir levels down to around 35 percent of capacity, which prompted the Hydraulic Resources Institute to speculate that Isaac’s rains will be “beneficial” for some of the reservoirs in the region." ]

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[ "[What underlies NYHA class in elderly patients with heart failure? ", "Role of diastolic dysfunction, functional mitral regurgitation and abnormal ventilation during exercise].", "\nColor-Doppler ecocardiography and cardiopulmonary stress test are pivotal in the evaluation of patients with heart failure. ", "Besides determining systolic function through left ventricular ejection fraction (EF), color-Doppler ecocardiography evaluates the presence and degree of functional mitral regurgitation and the severity of diastolic dysfunction. ", "Moreover, in addition to the aerobic capacity indicated by peak O2 consumption, other parameters of cardiopulmonary stress have proven useful for diagnostic purposes, such as the peak VE/VCO2 ratio or ventilatory efficiency. ", "Since in elderly patients with heart failure the functional impairment often is a combination of the effects of aging with those of disease, the relationship between symptoms, i.e. the NYHA class, ventricular pump function and aerobic performance is sometimes difficult to estabilish. ", "In 60 elderly with systolic heart failure (75 +/- 3 years, EF 30 +/- 6%), we correlated symptoms (i.e. NYHA class) with [1] degree of functional mitral regurgitation (FMR) determined by color-Doppler echocardiography; [2] degree of left ventricular diastolic dysfunction, measured by Doppler analysis of transmitralic and pulmonary veins flow; [3] VO2 and VE/VCO2 at peak exercise at cardiopulmonary test. ", "In all patients, NYHA class was only weakly related with EF and peak VO2, with wide overlap of individual values among patients with different NYHA class. ", "Instead, we observed a tight relationship between NYHA class, FMR degree, and severity of diastolic dysfunction and VE/VCO2 ratio at peak exercise (p<0.001), with a more evident partition among patients in different NYHA classes. ", "In elderly heart failure patients, the reduced effort tolerance expressed by the NYHA classification is only weakly associated with reduced aerobic capacity and pump function, but rather is related with the presence of mitral regurgitation, left ventricular diastolic dysfunction, and a poor ventilatory efficiency during exercise." ]

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[ "The Tailor of Panama\n\nThe Tailor of Panama is a 1996 novel by John le Carré. ", "A 2001 film was released based on the novel.", "\n\nPlot \nHarry Pendel is a British expatriate living in Panama City and running his own successful bespoke tailoring business, Pendel and Braithwaite. ", "His wife and children are unaware that almost every detail of his life is fabricated, including his former partner, Mr Braithwaite. ", "In reality, Harry Pendel is an ex-convict who learnt tailoring in prison.", "\n\nAndy Osnard is a young British MI6 agent sent to Panama to recruit agents to gather intelligence and protect British trade interests through the canal. ", "However, Andy has his own agenda and, after he discovers Harry's past, sees the perfect opportunity to recruit a new agent and embezzle money from the British government.", "\n\nConcocting a fictitious network of revolutionaries, known as the silent opposition, Harry, through Andy, manages to attract the interest of the British secret services, U.K and even US governments. ", "However, Harry has used his own friends as the basis for his fantasies, and as the plots are taken more seriously they become known to the Panamanian authorities and Harry struggles to cope with the guilt of setting them up.", "\n\nHarry's wife, Louisa, becomes suspicious of the amount of time he spends with Andy and suspects that Harry is having an affair. ", "She breaks into his office and discovers all his fantastic lies.", "\n\nHarry's friend, Mickie, kills himself rather than face the risk of going back to jail, and Harry helps dispose of the body, making it look like he was executed. ", "As Mickie is the supposed leader of the silent opposition, the UK and US governments use this as an excuse to topple the current Panamanian government.", "\n\nAt the end of the book the US military has begun another invasion of Panama, based largely on Harry's fabrications, and Harry watches the destruction from the window of his house.", "\n\nInspiration\nTo research the novel le Carré visited Panama on five occasions. ", "The book was in part inspired by Graham Greene's Our Man in Havana. ", "Le Carré likens the tale to a \"Casablanca without heroes\", stating that he, \"was drawn by the obvious corruption of Panama and the wonderful collection of characters you meet there.\"", "\n\nIn response to observations that the novel was a more light-hearted affair than his previous books, le Carré replied that, \"I think I'm in the same mood as ever, but in some ways more mature. ", "I guess you could say that, at sixty-five, when you've seen the world shape up as I have, there are only two things you can do: laugh or kill yourself. ", "I think my character does both. ", "In some ways it's a very personal book. ", "I was exploring the relationship between myself and my own fabricator. ", "Anybody in the creative business, as you might call it, has some sense of guilt about fooling around with fact, that you're committing larceny, that all of life is material for your fabulations. ", "That was certainly Harry Pendel's position. ", "So I found some kind of buzz running between me and the main character, which I had not really felt since A Perfect Spy.\"", "\n\nReception\nUpon publication, The Tailor of Panama received generally glowing reviews.", "\n\nThe New York Times stated that, \"What he has done is to venture fiercely into satire, producing a tour de force in which almost every convention of the classic spy novel is violated.\"", "\n\nRushdie Feud\nA long-running literary feud between Le Carre and Salman Rushdie began in 1997 after Le Carre penned a letter to the Guardian, complaining that politically correct forces in the US had labelled him anti-Semitic for his portrayal of one of the novel's characters. ", "Rushdie responded that he wished Le Carre had expressed similar feelings after Rushdie was subject to a fatwa for The Satanic Verses, viewed as anti-Islamic by some Muslims.", "\n\nRushdie opined that Le Carre was an \"illiterate, pompous ass,\" while Le Carre replied that Rushdie was a \"self-canonizing, arrogant colonialist.\"", "\n\nGuardian columnist Mark Lawson claimed the two authors appeared to be 'settling old scores', stating that: \"The Collected Guardian Correspondence of Salman Rushdie and John Le Carre is in the great tradition of literary poison pen letters: both in their inventive viciousness and in the low personal revenges which may lie behind the high rhetoric.\"", "\n\nRushdie and Le Carre appeared to end their dispute in late 2012.", "\n\nReferences\n\nCategory:1996 British novels\nCategory:British novels adapted into films\nCategory:Hodder & Stoughton books\nCategory:Novels by John le Carré\nCategory:British spy novels\nCategory:Fictional tailors" ]

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[ "This is a place for stories. ", "Inspiring stories, challenging stories, and personal stories.", "This is a place to hear from others — and to be heard. ", "What is your story?", "\n\nFighting for Donovan\n\nMy son Donovan was 8 years old in 2010 when he had his first seizure. ", "He suffered thousands of seizures due to febrile infection related epilepsy syndrome.", "\n\nHe was left severely disabled due to this. ", "He was a warrior. ", "He fought for 3 and a half years after that first seizure. ", "He was my world. ", "Sadly on June 10, 2014 his disease reared its ugly head again and my baby passed away. ", "I will continue to fight for him and let people know that epilepsy is a major disorder.", "\n\nhi Melissa! ", "I feel for you and I definitely understand as we lost our son also to epilepsy in 2011! ", "The only advice I can give you is to cherish your memories and make the most of whatever lies ahead! ", "Karen" ]

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[ "They thought their daring hotel robbery scheme was airtight, but three men are about to learn that nothing is that simple at the Hotel Reina.", "\n\nTo rob the finest resort in fascist Spain, three Americans need to blend in among the Mediterranean elite. ", "And to do so, they will each need a gorgeous girl as cover. ", "They find a depraved millionaire, a drug-addled nymphomaniac, and an assistant hotel manager who enjoys mingling with her handsome guests after hours.", "\n\nThe would-be thieves have used an IBM supercomputer to plan the perfect heist. ", "Their crime has been calculated to the last detail, with every possible contingency planned for, save one: the women. ", "The Hotel Reina is crawling with femmes fatales, and these crooks will be lucky to escape with the shirts on their backs.", "\n\nMistaken for a secret agent, a hapless lawyer scrambles to stay alive.", "\n\nAn arms dealer in Copenhagen dies after sipping a poisoned martini. ", "An American diplomat in Lisbon is shot in the back of the head. ", "A Frenchman survives being pushed in front of a train, only to be murdered in his hospital bed. ", "Though seemingly unconnected, these events are part of an international conspiracy that could spell death for Roger Carr.", "\n\nCarr is a lawyer, but he has no love for Lady Justice. ", "A dilettante playboy sent to France on a cushy assignment, he lands himself right in the middle of an international arms deal. ", "Both sides of the conflict have mistaken him for an agent, and the secret service interventions of a dozen countries will do anything to secure him—dead or alive.", "\n\nWhen he finds clues to an ancient treasure, an Egyptologist plans a very modern heist.", "\n\nBrilliant Egyptologist Harold Barnaby has discovered a message hidden inside a particularly difficult set of hieroglyphics. ", "It just may lead him to a secret tomb holding the greatest riches of the ancient world. ", "Barnaby could put his name to the most fantastic archaeological find of the century. ", "But he doesn’t just want to dig it up. ", "He wants to steal it.", "\n\nWith the help of a smuggler, a thief, and an English lord, he plans his heist. ", "They find that tomb raiding is trickier than they thought, and those who steal from dead Egyptians face dangers worse than a mummy’s ancient curse.", "\n\nA smuggler takes a job protecting London’s most despicable businessman.", "\n\nCharles Raynaud feels at home in the jungle. ", "A snake trapper, he makes a tidy profit selling poisonous creatures to the zoos of Europe, but it isn’t just the snake trade that pays his bills. ", "Raynaud is the finest artifact smuggler the world has ever known, and his particular talents are about to be put to the test.", "\n\nBetween jobs in Paris, Raynaud meets an old drinking buddy. ", "One of London’s wealthiest, nastiest men, Richard Pierce has eyes on his late father’s fortune and wants Raynaud to act as his bodyguard until he acquires it. ", "But after the first attempts on Pierce’s life, Raynaud begins to smell a rat. ", "Has he been hired as a bodyguard, or a target?", "\n\nWhile vacationing in Spain, a young doctor finds himself embroiled in a deadly conflict between rival gangs.", "\n\nPeter Ross just wanted a vacation. ", "After years toiling in the radiology department of a large American hospital, he dreams of lying on a Spanish beach with a beautiful girl. ", "The beach proves just as lovely as he hoped. ", "But the girl turns out to be trouble.", "\n\nAngela Locke is on the run from a pair of gangs waging war over a missing artifact, and she sucks Ross straight into the crossfire. ", "From sunny Spain to rain-swept Paris, Ross’s trip will take him into Europe’s darkest corners. ", "An ordinary man on the run for his life, he must uncover a centuries-old secret, or risk becoming its next victim.", "\n\nTo uncover the secrets of a superdrug, a doctor must go undercover and risk it all.", "\n\nWhen a Hell’s Angel is thrown from his bike at 110 miles per hour, he should probably end up in the morgue. ", "But this Angel survives his crash without a scratch, and ends up sleeping peacefully in the hospital. ", "When Dr. Roger Clark inspects him, he finds only one defect: blue urine. ", "Similar reports start to trickle in from hospitals upstate. ", "It seems that a strange new drug is sending people into comas, and only Clark can unravel its mystery.", "\n\nHis search for answers takes him on the strangest trip of his life, into a place called “Eden,” which looks like paradise, but feels like hell.", "\n\nTo recover a sunken yacht, a diver must enter the world’s most dangerous waters.", "\n\nThe Grave Descend lies under more than sixty feet of clear blue Caribbean water, guarded by a coral reef and schools of hungry hammerhead sharks. ", "Raising it would be a near-impossible task, but James McGregor is suited to the impossible. ", "An expert diver, he makes his living exploring sunken ships. ", "But there’s something strange about the wreck of the Grave Descend.", "\n\nHow did she sink? ", "Why do none of the survivors tell the same story? ", "And what was the cargo inside her hull? ", "To answer these questions, McGregor will have to contend with the deadliest sharks around—both underwater and on land.", "\n\nWhen a nerve gas shipment goes missing, the nation’s fate hangs in the balance.", "\n\nJohn Graves is a State Department intelligence agent who made his name on the front lines of the Cold War. ", "Since then, he’s been transferred to domestic work, and his love for the job has withered away. ", "All that sustains him is the hunt for John Wright—a crazed millionaire who is about to unleash the greatest domestic threat Graves’s agency has ever faced.", "\n\nWhen seven mobsters rob a U.S. Army train in the middle of the Utah desert and make off with half a ton of the deadliest nerve gas known to man, Graves believes that Wright is involved. ", "His plan: to detonate the weapon in San Diego during the Republican National Convention—an attack that would kill more than one million Americans, including the president. ", "Stopping Wright will take more than police work. ", "It is a chess match between agent and madman, and for Graves, checkmate is not an option.", "\n\nIn His Own Words\n\nI began writing as a medical student, and felt that I would continue as a doctor and ought to protect my patients from the fear that they might pop up in the pages of a thriller. ", "The best protection would not be to disguise them, but to disguise me. ", "Once I decided not to practice medicine, I dropped the pseudonyms expect for convenience. ", "I wrote too much, so I decided to publish some books under false names, and in that way, could publish more books.", "\n\nThe Med School Years Collection Audio Books\n\nIn Stores Now\n\nThe Med School Years Collection by: Michael Crichton\n\nPerformed by: Christopher Lane\n\nMedia Options: CD, Download, MP3-CD\n\nOrder Today:\n\nFrom the Official Archives\n\n“The Crichton Strain” – BinaryReviewTime magazine, May 8, 1972\n\nIn His Own Words\n\nMy feeling about the Lange books is that my competition is in-flight movies. ", "One can read the books in an hour and a half and be more satisfactorily amused than watching Doris Day. ", "I write them fast and the reader reads them fast and I get things off my back.", "\n\nBehind the Scenes of Pursuit\n\nMichael wrote an article for TV Guide magazine called: “What happened when an author became a director and found himself dealing with two old pros”. ", "Here is an excerpt:\n\n“At one point, E.G. had to make a maniacal political speech. ", "Before we shot, he said, “I do a lot of speaking around the country for health-care legislation. ", "I’ll just do this the way I normally do.” ", "I was horrified: he’s so reasonable, so persuasive. ", "He put his hand on my arm. “", "I’m just kidding,” he said. ", "I relaxed enough to suggest he do it as if he were a well-known rabid political figure. ", "He said fine.", "\n\nThe cameras rolled and E.G. Marshall turned into a madman. ", "His eyes glowed, he pounded the podium; he was unquestionably insane, and very disturbing to watch. ", "When the shot was finished, he stood back and chuckled. “", "How was that?” ", "he said.", "\n\nThe next day, when I saw the film, I realized that he had in fact used all the mannerisms, the gestures and movements, of the political figure I’d mentioned.", "\n\nBen was equally astounding. ", "He wore glasses, placing a terrible technical burden on him. ", "Often he couldn’t move his head at all, or his glasses would catch the lights. ", "It never impaired his performance.", "\n\nAt one point we were shooting in the airport. ", "Ben was among a crowd of passengers arriving from a flight. ", "I wanted the camera to single him out in this crowd, and follow him. ", "We tried it, but the camera operator couldn’t find Gazzara. ", "Afterward, I said, “Ben, the camera can’t find you.”", "\n\n“Okay, I’ll take care of it.”", "\n\n“Yeah, but don’t you want …”\n\n“Don’t worry. ", "I’ll take care of it.”", "\n\nAnd he did. ", "Don’t ask me how.", "\n\n“What happened when an author became a director and found himself dealing with two old pros” by Michael CrichtonTV Guide magazine, November 25, 1972\n\nIn His Own Words\n\nEleven months after Barry Diller at ABC gave the go-ahead, Pursuit was finished. ", "It was planned, shot, looped, edited, scored and dubbed; it was all over. ", "I had made a lot of mistakes and the picture showed most of them (at least to me, having seen it more than a hundred times). ", "But I remain enthusiastic about it, grateful to the actors and crew who kept me out of trouble and eager to do it again.", "\n\nOrson Wells once said that movies were the best set of electric trains a boy ever had. ", "He was right.", "\n\nIn His Own Words\n\nI had never directed anything before Pursuit, a movie for television based on a book (Binary) I had written. ", "Like all new directors, I wanted to do something a little bit different. ", "The story was unusual enough: a race against the clock between a madman who wants to nerve-gas a political convention and the government agent who has to stop him. ", "The film takes place over a single day, with lots of action and a certain amount of violence.", "\n\nI was very nervous and fully aware of my incompetence to do what I was telling everybody I could do. ", "On the first day of shooting, the insurance doctor took my blood pressure. ", "It was 160/115, which is high enough to whisk you straight to a hospital bed. ", "E.G. Marshall (playing the madman) and Ben Gazzara (playing the government agent) found this very amusing. ", "I found nothing amusing at all. ", "I had admired these men for years. ", "Inside me was a tiny screaming voice: You’re going to tell these guys what to do? ", "Are you out of your mind?", "\n\nBook Covers\n\nBinary by John Lange, 1972\n\nBinary by John Lange, 1972\n\nDrug of Choice by John Lange, 1969\n\nDrug of Choice by John Lange, 1969\n\nEasy Go by John Lange, 1972\n\nEasy Go by John Lange, 1968\n\nGrave Descend by John Lange, 1972\n\nGrave Descend by John Lange, 1970\n\nOdds On by John Lange, 1966\n\nOdds On by John Lange, 1966\n\nScratch One by John Lange, 1974\n\nScratch One by John Lange, 1967\n\nThe Venom Business by John Lange, 1971\n\nThe Venom Business by John Lange, 1969\n\nZero Cool by John Lange, 1972\n\nZero Cool by John Lange, 1969\n\nThanks for visiting The Official Site of Michael Crichton where we celebrate the life and works of writer and filmmaker Michael Crichton.", "\n\nNewsletter\n\nStay up to date on the latest from the Official Site of Michael Crichton\n\nEmail Address:\n\nStay Connected!", "\n\nThanks for visiting!", "\n\nTo stay up to date on all the latest information on Michael Crichton and to be the first to know about new website additions from The Official Michael Crichton Archives, please enter your email address here!" ]

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[ "Breaking News\n\nWatch: Van Splashes Pedestrians On Purpose\n\nHere's why this van driver was FIRED!", "\n\nSomebody in Canada posted dashcam video from the back of their car that showed a commercial van going out of its way to hit three different puddles that splashed people who were walking on the sidewalk." ]

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[ "GeoTip - Simple program for your cell phone that will calculate the tip for you at restaurants.", "\n\n· Enter meal amount, tax percent, tip percent, how many people to split the bill with, and an optional extra amount to add on the bill (such as liquor tax).", "\n· Shows the breakdown of tax and tip amounts, total bill, and how much each person owes.", "\n· Option allows you to save the tax and tip percent to use next time." ]

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[ "Number and Operations in Base Ten Leveled Problems: Fractions and Number Lines\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "This lesson requires students to solve problems related to fractions and number lines. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nYou might also like\n\nClothesline Math: The Master Number Sense Maker\n\nGrade: K-12\n\nISBN: 9781493885145\n\nPrice: $45.99\n\nImplement Clothesline Math and teach number sense in K-12 classrooms! ", "This essential resource includes the materials that teachers need to conduct Clothesline Math lessons, and techniques for effectively facilitating the ensuing mathematical discourse.", "\n\nThe How-to Guide for Integrating the Common Core in Mathematics in Grades K-5\n\nGrade: K-5\n\nISBN: 9781425895730\n\nPrice: $34.99\n\nDiscover what it takes to integrate the Common Core in mathematics with this easy-to-use guide. ", "Focusing on elementary mathematics, this resource will leave teachers feeling empowered to construct their own lessons with helpful ideas and suggestions.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nOperations and Algebraic Thinking Leveled Problems: Multiplying and Area Models\n\nGrade: 3\n\nISBN: 9781480785731\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nOperations and Algebraic Thinking Leveled Problems: Array Models\n\nGrade: 3\n\nISBN: 9781480785755\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nOperations and Algebraic Thinking Leveled Problems: Missing Factors\n\nGrade: 3\n\nISBN: 9781480785779\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nOperations and Algebraic Thinking Leveled Problems: Write Equations\n\nGrade: 3\n\nISBN: 9781480785786\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nOperations and Algebraic Thinking Leveled Problems: Using Shapes as Symbols\n\nGrade: 3\n\nISBN: 9781480785823\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nOperations and Algebraic Thinking Leveled Problems: Complete the Math Story\n\nGrade: 3\n\nISBN: 9781480785830\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Base-Ten Blocks and Rounding\n\nGrade: 3\n\nISBN: 9781480785861\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Place Value Word Problems\n\nGrade: 3\n\nISBN: 9781480785878\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Estimate to Solve Equations\n\nGrade: 3\n\nISBN: 9781480785892\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Complete the Math Story\n\nGrade: 3\n\nISBN: 9781480785908\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Distance in Miles\n\nGrade: 3\n\nISBN: 9781480785915\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Multi-step Estimation\n\nGrade: 3\n\nISBN: 9781480785922\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Multiples of Ten\n\nGrade: 3\n\nISBN: 9781480785939\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Fractions Less Than One\n\nGrade: 3\n\nISBN: 9781480785953\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Compare Fractions\n\nGrade: 3\n\nISBN: 9781480785960\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Word Problems\n\nGrade: 3\n\nISBN: 9781480785977\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Ordering Fractions\n\nGrade: 3\n\nISBN: 9781480785984\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: How Much Money?", "\n\nGrade: 3\n\nISBN: 9781480785991\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nNumber and Operations in Base Ten Leveled Problems: Compare Fractions\n\nGrade: 3\n\nISBN: 9781480786004\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels.", "\n\nMeasurement and Data Leveled Problems: Write the Question\n\nGrade: 3\n\nISBN: 9781480786028\n\nPrice: $1.29\n\nDifferentiate problem solving in your classroom using effective, research-based strategies. ", "The problem-solving mini-lesson guides teachers in how to teach differentiated lessons. ", "The student activity sheet features a problem tiered at three levels." ]

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[ "A seven-year-old girl who talked to Donald Trump on Christmas Eve still left out milk and cookies for Father Christmas despite the president telling her it was \"marginal\" for a child of her age to still believe in the jolly old man.", "\n\nThen again, Collman Lloyd of Lexington, South Carolina, said she had never heard the word \"marginal\" before.", "\n\nCollman had called the NORAD Tracks Santa programme on Monday night to check on the journey of Father Christmas delivering toys. ", "In an interview with the Post and Courier of Charleston, she said the scientist who answered the NORAD phone asked her if she would like to speak to the president.", "\n\nSix minutes later, Mr Trump was on the line. \"", "Are you still a believer in Santa?\" ", "he asked. ", "When she responded, \"Yes, sir,\" the president added, \"Because at seven, that’s marginal, right?\"", "\n\nCollman didn’t know what \"marginal\" meant and simply answered, \"Yes, sir.\" ", "Mr Trump closed by saying, \"Well, you just enjoy yourself.\"", "\n\nMr Trump’s chat with Collman was initially reported as being with a boy named Coleman. ", "Only Mr Trump’s end of the conversation could be heard by reporters, but Collman’s family later posted video of the call on YouTube." ]

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[ "A new £8 million funding competition will enable virtual, augmented and mixed reality experiences – also known as immersive content – to be created faster and more efficiently by UK content creators.", "\n\nThe competition is part of the Industrial Strategy Challenge Fund’s audience of the future programme. ", "Up to £33 million is available to develop new products and services that exploit immersive technologies." ]

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[ "I previously wrote about how to build a task app with Laravel and Vue.js. ", "Laravel is a PHP framework for building scalable web applications and APIs. ", "Vue.js is a Javascript framework and alternative to jQuery or React.", "\n\n🌟 Get Started\n\nIn this tutorial we’re going to add functionality to the application we built in the previous tutorial. ", "Clone the github repo, run composer install, npm install and connect to you’re database.", "\n\n$ mysql -uroot -p\n\nmysql> create database laravelTaskApp;\n\nIf you’re stuck at this point check out other articles I’ve written about installing MySQL and initial Laravel setup. ", "At localhost:8000 you can see an app that asynchronously adds and deletes tasks. ", "That means it does the operations and displays the up to date data without refreshing the webpage.", "\n\nThe task app we built in the previous tutorial.", "\n\n🏁 The Repository Design Pattern\n\nIn the previous tutorial we wrote all of our application logic in the controller. ", "There’s an alternative approach to development that abstracts some calls into PHP classes called Repositories. ", "The idea is that we can decouple models from controllers and assign readable names to complicated queries.", "\n\nWe’re going to refactor our app to use the Repository Pattern. ", "The first step is to create a file for app/Repositories/Repository.php.", "\n\n<?", "php namespace App\\Repositories;\n\n\n\nuse Illuminate\\Database\\Eloquent\\Model;\n\n\n\nclass Repository implements RepositoryInterface\n\n{\n\n// model property on class instances\n\nprotected $model;\n\n\n\n// Constructor to bind model to repo\n\npublic function __construct(Model $model)\n\n{\n\n$this->model = $model;\n\n}\n\n\n\n// Get all instances of model\n\npublic function all()\n\n{\n\nreturn $this->model->all();\n\n}\n\n\n\n// create a new record in the database\n\npublic function create(array $data)\n\n{\n\nreturn $this->model->create($data);\n\n}\n\n\n\n// update record in the database\n\npublic function update(array $data, $id)\n\n{\n\n$record = $this->find($id);\n\nreturn $record->update($data);\n\n}\n\n\n\n// remove record from the database\n\npublic function delete($id)\n\n{\n\nreturn $this->model->destroy($id);\n\n}\n\n\n\n// show the record with the given id\n\npublic function show($id)\n\n{\n\nreturn $this->model-findOrFail($id);\n\n}\n\n\n\n// Get the associated model\n\npublic function getModel()\n\n{\n\nreturn $this->model;\n\n}\n\n\n\n// Set the associated model\n\npublic function setModel($model)\n\n{\n\n$this->model = $model;\n\nreturn $this;\n\n}\n\n\n\n// Eager load database relationships\n\npublic function with($relations)\n\n{\n\nreturn $this->model->with($relations);\n\n}\n\n}\n\nThis file defines our Repository class. ", "Instances of this class have a model property that we tie to an Eloquent model. ", "Once this is bound in the constructor we can call Eloquent methods like findOrFail , update or all from the class methods.", "\n\nThe implements RepositoryInterface section isn’t strictly necessary but it adds an extra layer of structure to our code. ", "An interface is a contract that defines the methods a class MUST have defined. ", "In our case the interface looks like this:\n\n<?", "php namespace App\\Repositories;\n\n\n\ninterface RepositoryInterface\n\n{\n\npublic function all();\n\n\n\npublic function create(array $data);\n\n\n\npublic function update(array $data, $id);\n\n\n\npublic function delete($id);\n\n\n\npublic function show($id);\n\n}\n\nIf we make new Repositories that implement this interface we’ll always know these methods are defined. ", "Interfaces provide structure so we know what our code needs to do.", "\n\nBack in our TaskController.php file we instantiate a repository and pass in the Task model to it.", "\n\n<?", "php\n\n\n\nnamespace App\\Http\\Controllers;\n\n\n\nuse App\\Task;\n\nuse App\\Repositories\\Repository;\n\nuse Illuminate\\Http\\Request;\n\n\n\nclass TaskController extends Controller\n\n{\n\n// space that we can use the repository from\n\nprotected $model;\n\n\n\npublic function __construct(Task $task)\n\n{\n\n// set the model\n\n$this->model = new Repository($task);\n\n}\n\n\n\npublic function index()\n\n{\n\nreturn $this->model->all();\n\n}\n\n\n\npublic function store(Request $request)\n\n{\n\n$this->validate($request, [\n\n'body' => 'required|max:500'\n\n]);\n\n\n\n// create record and pass in only fields that are fillable\n\nreturn $this->model->create($request->only($this->model->getModel()->fillable));\n\n}\n\n\n\npublic function show($id)\n\n{\n\nreturn $this->model->show($id);\n\n}\n\n\n\npublic function update(Request $request, $id)\n\n{\n\n// update model and only pass in the fillable fields\n\n$this->model->update($request->only($this->model->getModel()->fillable), $id);\n\n\n\nreturn $this->model->find($id);\n\n}\n\n\n\npublic function destroy($id)\n\n{\n\nreturn $this->model->delete($id);\n\n}\n\n}\n\nThe Laravel service container will automatically resolve our dependencies and inject them into the controller instance (docs).", "\n\nAt this point our application works exactly the same but our code has been refactored to use repositories and we’ve added a couple more API endpoints.", "\n\nSource code available on Github" ]

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[ "\"[ Children shouting in native language ]\" \"[ Man chanting in native language ]\" \"[ Conversations in native language ]\" \"Get in there!\" \"", "Spyglass, this is cobra one.\" \"", "Open bravo South.\" \"", "Over.\" \"", "You bitches!\" \"", "You bad man!\" \"", "You got to shoot them in the head!\" \"", "You torture me...\" \"I torture you!\" \"", "12-hour rotations.\" \"", "Suicide watch every 3 minutes.\" \"", "Do not let that repetition lower your guard.\" \"", "That's exactly what these guys are looking for.\" \"", "You got to remember... some of these dudes have been locked up in here for eight years.\" \"", "They've been in here before some of you were even in high school.\" \"", "They know the procedure better than you do.\" \"", "They will test you, and they will best you.\" \"", "And make no mistake about it...\" \"this is a war zone.\" \"", "Now, they ain't using roadside bombs, and we're not using F-16s.\" \"", "This is still a war zone.\" \"", "Now...\" \"Some of you might think you're here to prevent them from leaving.\" \"", "You're not.\" \"", "The walls do that for us.\" \"", "You are here to prevent them from dying.\" \"", "Yes?\" \"", "Uh, how often do we move the prisoners?\" \" ", "Detainees.\" \" ", "What?\" \"", "You will refer to them as \"detainees.\" ", "You will not call them \"prisoners.\"\" \"", "You all got that?\" \"", "No exceptions.\" \"", "De-tai-nees.\" \"", "Why can't we call them prisoners?\" \"", "Prisoners are subject to the Geneva convention... detainees are not.\" \"", "Rec yard is right down there.\" \"", "Showers are right beside 'em.\" \"", "Unless they're going to medical, being transferred... that's it.\" \"", "That's their world.\" \"", "Is that door shut?\" \"", "Good.\" \"", "This... this is your world.\" \"", "No detainees back here.\" \"", "On your right, gun Sally.\" \"", "Remember, on the walk, the only weapon you have is your radio.\" \"", "Don't be afraid to use it.\" \"", "Over here, this is our security command or observation... our eyes and ears on the whole block.\" \"", "So if you find yourself going up against an uncooperative detainee, remember you're being watched.\" \"", "Last but not least, the mess hall.\" \"", "Like most places on earth, the chicken fingers are the only thing worth eating.\" \"", "Hard to fuck those up.\" \"", "And don't bother telling me the coke's flat 'cause I already fucking know.\" \"", "Echo one, cobra one, Charlie Bronson.\" \"", "I'll say again.\" \" ", "Hold on... the natives is getting restless.\" \" ", "Over.\" \"", "Roger, echo one.\" \"", "Charlie Bronson, echo one.\" \"", "Oscar Mike, over.\" \"\"", "Charlie Bronson's\" our brevity code for an Irf... that's initial reaction force.\" \"", "It's a four-man team called in when shit hits the fan on the walk.\" \"", "Anybody feel like getting their feet wet?\" \"", "Listen.\" \"", "All you need to worry about is his right hand, okay?\" \"", "Each of us takes one.\" \"", "Leg, leg, arm, head.\" \"", "Don't worry about nothing else.\" \"", "You just keep your eye on his right hand, and you gain control of it... got it?\" \"", "Roger.\" \"", "And stay behind me.\" \"", "Let us get the rest of him under control.\" \"", "Hold up.\" \"", "Hold up.\" \" ", "No names on the block.\" \" ", "Yeah.\" \" ", "Okay?\" \" ", "Yeah.\" \"", "You can talk to 'em, but do not let these guys know anything about you.\" \"", "Do not let them get inside your head.\" \"", "You got it?\" \"", "Yeah.\" \"", "All right, grab our shields.\" \"", "Let's go.\" \"", "Spyglass, pop 1-9.\" \"", "Stay tight.\" \" ", "Stay tight, all right?\" \" ", "We got this.\" \"", "Detainee, get back!\" \"", "Get back, detainee!\" \"", "Get back!\" \"", "Get him pinned up.\" \"", "Let's go.\" \"", "Go!\" \"", "Come on.\" \"", "Private, give me those cuffs!\" \"", "Shit!\" \"", "Get your ass down!\" \"", "Ohh!\" \"", "You piece of shit!\" \"", "Get his arm back!\" \"", "Get him on...\" \"Get down, you piece of shit!\" \"", "Get his other hand.\" \"", "Get the fuck up.\" \"", "Out of here... get him out of here.\" \"", "That's it... get down.\" \"", "All right, pull that strap down.\" \"", "You want his hand all the way secure.\" \"", "Make it as tight as you can.\" \"", "Check his waist.\" \"", "Check the belt around his waist.\" \"", "Check that side.\" \"", "We don't want this guy going anywhere on us.\" \"", "Let's roll him out.\" \"", "Welcome to gitmo.\" \"", "Oh, Jackson, did you copy those DVDs for me?\" \"", "And when exactly was I supposed to do that?\" \"", "I mean, I had C.O. standing over my shoulder all day.\" \"", "Dude, what the fuck?\" \"", "Johnson is, like, up my ass about getting it back.\" \"", "Copy that shit for me.\" \"", "Wait.\" \"", "Don't you got kids, anyway?\" \"", "Why don't you...\" \" Yeah.\" \" ", "You ass.\" \"", "So, what...\" \"I can't watch porn?\" \"", "Are you telling me your dad didn't have a stack of nudie mags?\" \"", "He'd to have something to put over your mom's face.\" \"", "Oh!\" \"", "Oh, you're so...\" \"That's cold.\" \"", "That's cold as ice.\" \"", "You all right?\" \"", "Yeah.\" \"", "I'm good.\" \"", "Thanks.\" \"", "Yo, what was that Irf like?\" \"", "Loud.\" \"", "Shit.\" \"", "You didn't think I could handle it?\" \"", "No, that's not what I'm trying to say.\" \"", "You know, I just didn't think you'd want to.\" \"", "I got to say, of all the companies I've rotated through here,\" \"I never had someone get their ticket punched on the first day.\" \"", "Just be glad it wasn't a shit cocktail.\" \"", "What's a shit cocktail?\" \"", "What the fuck do you think that is, Rico?\" \"", "Hey, Cole, what happened?\" \"", "Uh.\" \"", "We... we followed two other guys in, and, um, I was on the left arm.\" \"", "It was my only thing, and I went...\" \"Pop!\" \"", "She got an elbow right to the lip...\" \"knocked her mask clean off.\" \"", "Ohh, does it hurt?\" \"", "Yeah, it fucking hurts.\" \"", "It looks pretty bad.\" \"", "Did medical check it out?\" \"", "It's fine.\" \"", "You know what it looks like?\" \"", "It looks like you got herpes.\" \"", "Hey, no.\" \"", "Oh, shit!\" \"", "It kind of does.\" \" ", "You guys.\" \" ", "No.\" \"", "You're not gonna get any on the island now, Cole.\" \"", "Fuck that...\" \"I'd hit it, anyway.\" \"", "What do you say, Cole?\" \" ", "Well, then, I really would get herpes.\" \" ", "Ohh!\" \"", "Thank you!\" \"", "She got you...\" \"Oh, damn.\" \"", "Whoo!\" \" ", "Mom?\" \" ", "Oh!\" \"", "Honey, how are you?\" \"", "Well, things are fine.\" \"", "Um, the base is real nice.\" \"", "There's a subway.\" \"", "A subway?\" \"", "A subway restaurant, mom.\" \"", "Oh!\" \"", "Yeah.\" \"", "And is that your room?\" \" ", "Yeah.\" \" ", "Can I see it?\" \"", "How is everything back home, mom?\" \"", "Oh.\" \"", "Nothing much ever happens back here... nothing as exciting as what you're doing, I'm sure.\" \"", "It is what it is.\" \"", "I don't know.\" \"", "I, um...\" \"Honey, you can't just leave him hanging and expect him to be there when you get back.\" \"", "I'm not leaving him hanging, and I told you I'm not coming back.\" \"", "I'm going on another deployment, remember?\" \"", "All right.\" \"", "So, how about on the base?\" \"", "Have you met anyone down there?\" \"", "Mom, seriously, stop.\" \"", "I'm not dating an army guy, and I did not join the military to find a husband.\" \"", "Oh, yeah.\" \"", "Oh!\" \"", "Look who wants to say hello.\" \"", "Say hi, scribbles.\" \"", "Look who it is!\" \"", "Look who it is!\" \"", "Say hi, scribbles.\" \"", "The weather today... bright and sunny.\" \"", "High of 85...\" \"Tomorrow, there is a chance of rain...\" \"Thank you, private.\" \"", "Last week...\" \"Come down here.\" \"", "Make sure you...\" \"Uh...\" \"You want a book?\" \"", "Do you want a book?\" \"", "Hey, calm down.\" \"", "Calm down.\" \"", "Take a step back.\" \"", "Take one step back from the glass.\" \" ", "I can't understand what...\" \" Yo, Haji!\" \"", "Chill the fuck out.\" \" ", "I'll take that book, but you give it to me.\" \" ", "All right, all right.\" \"", "Chill out.\" \"", "I got this.\" \"", "Did I do something wrong?\" \"", "No.\" \"", "These guys just don't like girls.\" \"", "It's an arab thing.\" \"", "You want me to take over?\" \"", "No.\" \"", "It's okay.\" \"", "I can handle it.\" \"", "All right.\" \"", "Suit yourself.\" \"", "Do you know those books?\" \"", "What about them?\" \"", "Do you like them?\" \"", "You were watching the books.\" \"", "I'm asking you a question.\" \"", "What do you want from the cart?\" \"", "Do you have the new Harry Potter book?\" \"", "No.\" \"", "This is not the new Harry Potter book.\" \"", "This is the old one.\" \"", "I already read this one.\" \"", "I want the last book.\" \"", "Which one's that?\" \"", "The last book?\" \"", "It's, you know...\" \"You... you see that book there?\" \"", "It has no cover on it, huh?\" \"", "Uh-huh, yes.\" \"", "That book... it used to have a cover.\" \"", "I remember I read this cover, you know, when it has a cover on it.\" \"", "It was saying that Harry Potter, it has seven book, you know?\" \"", "You guys only have six book.\" \"", "Huh?\" \"", "I don't know what to tell you...\" \"I...\" \" You know how long I'm asking for this book?\" \"", "No, you don't.\" \"", "You're new.\" \"", "Two years.\" \"", "Imagine, two years I'm asking you guys to give me this last book.\" \"", "You know what happens at the end of book six?\" \" ", "No.\" \" ", "No.\" \" ", "I...\" \" You know, me, always, always thinking that Snape is a bad guy, okay?\" \"", "Then I was thinking, no, actually, he is not a bad guy... he is the good guy.\" \"", "Then after I read the book six,\" \" I don't know what to think now.\" \" ", "Do you want this book or not?\" \"", "You're not listening, huh?\" \" ", "I read this book...\" \" No, no.\" \"", "You are not listening to me.\" \"...", "10 times.\" \"", "I read this book.\" \" ", "I want the new book.\" \" ", "I'm telling you we don't have it.\" \"", "It ain't here.\" \"", "What we have is on the cart.\" \"", "What do you want?\" \"", "Give me the \"Azkaban\" instead.\" \"", "Is that one of these arab books?\" \"\"", "Prisoner of Azkaban,\" book number three.\" \"", "Yeah.\" \"", "Here you go.\" \"", "Hey.\" \"", "What... what...\" \"what else do you got?\" \"", "I got books, and I got newspapers.\" \"", "Use your eyes.\" \"", "I'm using my eyes.\" \"", "That newspaper is two months old.\" \"", "Now, why do I have to know the news for two months old?\" \"", "So, you're good then?\" \"", "Hold on your horses, huh?\" \"", "No one is going nowhere here... at least, I'm not.\" \"", "What is that picture?\" \"", "That book.\" \"", "No, no, go.\" \"", "Go, go.\" \"", "Go.\" \"", "Too much.\" \"", "Go back.\" \"", "Uh-huh.\" \"", "What is it?\" \"\"", "My Antonia.\"\" \"", "Is it a good book or...\" \"I don't know.\" \"", "I haven't read it.\" \"", "Okay.\" \"", "Just tell me what the cover says, on the back.\" \"\"", "In 19th century Nebraska, the spirited daughter of an immigrant...\"\" \"Nebraska?\" \"", "You said... what was it?\" \"", "It... it's a place in America.\" \"", "Okay.\" \"", "Uh-huh.\" \"", "That... what kind of place is this?\" \"", "Nebraska?\" \"", "Flat.\" \"", "Flat.\" \"", "Time's up.\" \" ", "Hey.\" \" ", "Keep it moving.\" \"", "Hey, I... moptop?\" \"", "Bad timing, okay?\" \"", "Me and blondie... we were having a very beautiful conversation.\" \"", "Uh-huh.\" \"", "And you come here always trying to be a big fucking asshole.\" \"", "You know what?\" \"", "I think you guys don't have the lastHarry Potter on purpose.\" \"", "You like to drive us crazy.\" \"", "But I'm not going crazy.\" \"", "Huh?\" \"", "Happy me.\" \"", "I'm not going crazy... not me!\" \"", "At 2100, detainees on Charlie block complained of a foul-smelling odor coming from ventilation.\" \"", "Maintenance was called.\" \"", "At 2200, detainee 9-1-2 was found with seven strings of different colors.\" \"", "He appeared to be weaving them together, possibly to form a weapon.\" \"", "At 0500, detainee 4-9 was transferred to medical for pain in the abdomen.\" \"", "Diagnosis was constipation.\" \"", "We have 3-6 moves scheduled, 3-8 moves completed.\" \"", "All detainees accounted for.\" \"", "Atten-hut!\" \"", "Honor bound.\" \"", "To defend freedom.\" \"", "Hey, blondie, tell me...\" \"how do you like it here so far?\" \"", "Huh?\" \"", "Blondie.\" \"", "Where are you from?\" \"", "Okay, tell me your name.\" \"", "No?\" \"", "My name is Ali...\" \"Ali Amir.\" \"", "Here, they call me 4-7-1.\" \"", "You don't like to talk?\" \"", "Always, it's like that.\" \"", "Why?\" \"", "I don't know why you guys... you don't like to talk with us.\" \"", "You and us... we are both stuck here.\" \"", "It is boring for both of us.\" \"", "And you and me got nothing to say to each other.\" \"", "Okay.\" \"", "You don't like to read Harry Potter book?\" \"", "You don't like to read that book about...\" \"what was that place, the flat place?\" \"", "Uh, Nebraska?\" \"", "Tell me what you like to read, huh?\" \"", "Oh!\" \"", "You are a soldier.\" \"", "And soldiers... they don't like books.\" \"", "I thought you only read the Qur'an.\" \"", "The Qur'an, yes.\" \"", "We...\" \"I-I've read it one million times.\" \"", "You know what?\" \"", "Ehan, there in 108... he has memorized it, the whole book.\" \"", "Hey, Ehan!\" \"", "Tell something to blondie from the Qur'an.\" \"", "I think he's trying to tell you to leave me alone.\" \"", "Ehan!\" \"", "Hey, blondie.\" \"", "You know, I read your Bible, too.\" \"", "My opinion about Bible is the first half of the book... it is very good.\" \"", "It has armies, plenty of magic, which I like very much... things like that.\" \"", "But, you know, the second half...\" \"it has some magic, but not too much.\" \"", "It is boring.\" \"", "Well, you don't diss my holy book...\" \"I won't diss yours.\" \"", "So you're Christian?\" \"", "Tell me something...\" \"how did you pick your Christianity?\" \"", "It was your parents, hmm?\" \"", "And cut the Hannibal Lecter shit.\" \"", "Just keep it down.\" \"", "What?\" \"", "What is Hannibal Lecter?\" \"", "I said, keep it down.\" \"", "Yeah.\" \"", "I'm...\" \"I'm trying to understand what you are telling me.\" \"", "You were saying that stop Hannibal Lecter, so I have to know what Hannibal Lecter is, then I stop doing that.\" \"", "He's a guy in a movie that talks too much.\" \"", "I haven't heard about this movie.\" \"", "Well, it's probably banned where you're from, anyway.\" \"", "You mean in Germany?\" \"", "Huh?\" \"", "I'm... hey.\" \"", "I'm... hey!\" \"", "I'm talking with you, blondie!\" \"", "Okay.\" \"", "I-I-it's... it's no more talking, huh?\" \"", "Huh?\" \"", "You are always trying to be all of you assholes.\" \"", "I don't know how I cannot get one soldier here who likes to talk about books.\" \"", "Okay.\" \"", "You don't like to talk.\" \"", "Bring me some water, please.\" \"", "Blondie.\" \"", "I'm thirsty.\" \"", "Where's your Qur'an?\" \"", "Are you giving me some water, please, or not?\" \"", "Okay, you bring me the water...\" \"I stop talking, I promise.\" \"", "You wouldn't need this if you didn't talk so damn much.\" \"", "Ah!\" \"", "Shit.\" \"", "Shit.\" \"", "Are you all right?\" \" ", "Oh, man, let me help you.\" \" ", "Motherfucker.\" \"", "Clean yourself up.\" \"", "We'll take care of this.\" \"", "Hey, back the fuck up and shut the bean hole.\" \"", "He's probably got another cocktail.\" \"", "Oh, fuck.\" \"", "Quiet down.\" \"", "4-7-1, take the towel down now.\" \" ", "Fuck you!\" \" ", "Take it down now!\" \"", "No, no.\" \"", "We need to call an Irf.\" \"", "Hold on.\" \"", "Open that thing.\" \"", "No, no.\" \"", "No.\" \" ", "We need to call an Irf.\" \" ", "Calm down.\" \"", "I'm already covered in his shit!\" \"", "Open it up!\" \"", "We are not opening the fucking bean hole.\" \" ", "Now, you need to calm down.\" \" ", "No, we are not opening that up.\" \"", "You stupid fuckers...\" \"Huh?\" \"!\" \"", "I went to university!\" \"", "I know my rights!\" \"", "Hey, back up, fucker!\" \"", "Shit.\" \"", "One more time.\" \"", "Open the fucking thing up.\" \"\"", "F\" you.\" \"", "Do it!\" \"", "Back away from the door.\" \"", "Nice.\" \"", "Nice, nice.\" \"", "Nice, nice.\" \"", "Good, good, good, good, good.\" \"", "Good.\" \"", "Yeah, bitch.\" \" ", "Nice.\" \"", "Shit, he's got a second towel.\" \"", "Seriously?\" \"", "Fuck.\" \"", "Shit, man.\" \"", "Irf him.\" \"", "You Americans treat us like animals?\" \"!\" \"", "Okay, I am an animal!\" \"", "Bravo two, code one, Charlie Bronson.\" \"", "Oh, watch yourselves.\" \"", "If they start covering their Qur'ans, it means they're gonna start throwing shit around!\" \"", "You don't read anything!\" \"", "I read book!\" \"", "I read history!\" \"", "I can't win!\" \"", "Irf!\" \"", "Irf!\" \"", "Irf!\" \"", "Cocktail?\" \"", "Sir, yes, sir.\" \"", "At ease.\" \"", "Did medical check you out yet?\" \"", "Yes, sir.\" \"", "I'm fine.\" \"", "Why don't you, uh, take it easy for the rest of the shift?\" \"", "See if observation needs any help.\" \"", "Thank you, sir.\" \"", "I'm fine.\" \"", "Use the vinegar.\" \"", "It helps with the smell.\" \"", "Hey.\" \"", "Mmm.\" \"", "Cole, you smell amazing.\" \"", "What's that you're wearing... chanel no. ", "2?\" \"", "Mm-hmm.\" \"", "You better watch yourself with those.\" \"", "They drug them to keep them docile.\" \"", "Shit.\" \"", "No, they don't.\" \"", "Hey.\" \"", "What are you doing here?\" \"", "Did medical check you out?\" \"", "I'm fine.\" \"", "We're short a meal, though.\" \"", "Do you mind grabbing one?\" \"", "No, we're not.\" \"", "Your pal 471... he's not coming back today.\" \"", "Why?\" \" ", "I sent him on a flyer.\" \"", "What's that?\" \"", "Our frequent flyer program.\" \"", "We move him from cell to cell every two hours.\" \"", "Night shift won't like it, but fuck 'em.\" \"", "Dude's got to learn somehow.\" \"", "You move him all night long?\" \"", "All night, all day, all week.\" \"", "How does he sleep?\" \"", "He doesn't, dummy... that's the point.\" \"", "Come on, get this shit moving.\" \"", "We're on a schedule.\" \"", "It's brutal.\" \"", "What are you... the red cross?\" \"", "No, I'm just saying.\" \"", "It's...\" \"Brutal.\" \"", "I mean, Jesus, Rico, Cole just got shit flung at her face.\" \"", "Are you cool with that?\" \"", "Of course not.\" \"", "I mean, you don't have to do some big thing over me.\" \"", "I'm...\" \"I'm fine.\" \"", "Yeah, we kind of do.\" \"", "And just so we're clear, I'm down with it.\" \"", "I just think, you know, it's kind of hard-core, right?\" \"", "You want me to call it off?\" \"", "No.\" \"", "Fuck him.\" \"", "Look at you pussies swim!\" \"", "Rico, get the ladder.\" \"", "Pull the ladder up.\" \"", "♪ We bail haters gonna hate, but... ♪\" \"What do you get to be swimming there for?\" \"", "Swim, flounder.\" \"", "To good times, baby.\" \"", "To good times.\" \"", "Yeah, yeah, good times, baby.\" \"", "♪ I love when the... ♪\" \"♪ Got a million, now I'm about to add six more... ♪\" \"Well, I'll be damned...\" \"Cole the fisherman.\" \"", "Be careful there.\" \"", "You want me to bait it for you?\" \"", "No, I think I'm pretty good.\" \"", "Thanks.\" \"", "It's a treble hook.\" \"", "I don't want you to cut your, uh, finger there.\" \"", "You got to make sure you get it on all three.\" \"", "Like that?\" \"", "Not bad.\" \"", "Hey, give me this shit.\" \"", "Hold this.\" \"", "How do you do this thing, anyways?\" \"", "How do you do the pole?\" \"", "Yeah.\" \"", "Yo, I've never done this before, man.\" \"", "Look, the hook's right there.\" \"", "You got to put bait on it.\" \"", "Oh.\" \"", "You cast the fucker out, get a fish, and you reel it back in.\" \"", "Real simple.\" \"", "Shit, be my guest.\" \"...", "pulling your ass out of there.\" \"", "There you go.\" \"", "I like to see the hook.\" \"", "Well, see that?\" \"", "He knows what kind of fish...\" \"Here you go.\" \"", "Thanks.\" \"", "Whoo!\" \"", "Come on, girl, let's get some fish.\" \"", "You're dropping on me.\" \"", "Let's go.\" \"", "Let's go.\" \"", "Whoo!\" \"", "All right, listen up, you fucking faggots!\" \"", "We got fresh beer on tap, so I want you to fall in.\" \"", "Let's go.\" \"", "Cole, come on.\" \"", "Come on.\" \"", "Here.\" \"", "Here, precious motherfucker.\" \"", "She can handle it.\" \"", "You can't.\" \"", "Yeah, one time in, uh, high school, freshman year, me and my boys... we needed to go to the liquor store, pick up a...\" \"I'd take the whole fucking thing down by myself.\" \"", "Why don't you bring me over a hot dog?\" \"", "♪ Whoo, boy ♪\" \"Come on, man.\" \"", "♪ Look at them girls go ♪\" \" Whoo!\" \" ", "Oh, oh!\" \"", "Yeah, get her!\" \"", "Get her!\" \"", "♪ I know what I'm talking about ♪\" \"Ohh!\" \" ", "Let's go.\" \" ", "Can I get your autograph?\" \"", "Oh.\" \"[ ", "Hip-hop music plays in distance ]\" \"Mnh.\" \"", "Shit.\" \"", "That's... sorry.\" \"", "Hey.\" \" ", "It's real nice.\" \" ", "That ain't... that ain't mine.\" \" ", "That's the communal stash.\" \" ", "Mm-hmm.\" \"", "Is this what you like?\" \"", "Slow down a little bit, all right?\" \"", "Oh.\" \"", "Yeah.\" \"", "Don't move.\" \"", "Mnh, stop, okay?\" \"", "Hey, stop!\" \"", "Fuck!\" \"", "I'm sorry.\" \"", "Fuck you, bitch!\" \"", "Hey, where have you been?\" \"", "You all right?\" \"", "Hey, come here.\" \"", "What's wrong?\" \"", "What's wrong?\" \"", "I'm fine.\" \"", "Hey, Cole.\" \"", "Shit.\" \"", "Shit.\" \"", "4-7-1, wake up.\" \"", "No, no.\" \"", "Not again.\" \"", "Leave me alone.\" \"", "Come on, on your feet.\" \"", "Back to the door.\" \"", "You know the drill.\" \"", "Fuck you.\" \"", "Sleep tight.\" \"", "Hey.\" \"", "Hey, what's up?\" \"", "Is 471 still on his frequent flyer program?\" \"", "Yup.\" \"", "Mecca?\" \"", "Well, it damn sure ain't pointing to Disneyland.\" \"", "He's quite the artist.\" \"", "Mm-hmm.\" \"", "The guy's a regular \"poocasso.\"\" \"", "What... you haven't heard that one yet?\" \"", "What will you do with that?\" \"", "Write it up and hand it off to G.I.S.\" \"Intelligence gathering for that?\" \"", "That's the S.O.P.\" \"Seems like a waste of time.\" \"", "Yeah, well, that also seems to be the S.O.P. Around here.\" \"", "You know... hey, will you go get the chaplain for me?\" \"", "I need him to search that Qur'an.\" \"", "Yeah.\" \"", "It's small in here.\" \"", "Yeah, you ain't kidding.\" \"[ ", "Indistinct conversations in distance ]\" \" Hey, Bergen.\" \" ", "Yeah, what's up?\" \"", "You know what that brevity code means?\" \" \"", "Alfred Hitchcock on the block\"?\" \" ", "Yeah.\" \"", "That is a shrink visited the detainee.\" \" ", "Really?\" \" ", "Yeah.\" \"", "There's a whole bunch of 'em in here.\" \"", "Dude's a head case.\" \" ", "Thanks.\" \" ", "Yeah, man.\" \"", "Hey.\" \"", "Hey.\" \"", "Tough week, huh?\" \"", "Yeah.\" \"", "I mean, like, I handle it, you know.\" \"", "I'm not tripping or anything.\" \"", "It's just...\" \"No, yeah.\" \"", "Um, yeah, me too.\" \"", "Yeah.\" \"", "It's kind of a weird situation, though.\" \"", "I know, right?\" \"", "Fucking detainees, man.\" \"", "What's their fucking problem?\" \" ", "Well, where were you?\" \" ", "Yeah.\" \"", "Hey, do you guys get any of that detainee chow?\" \"", "That shit looks good.\" \"", "Nope.\" \"", "We're not supposed to touch it if there's any left over, either.\" \"", "Fuck!\" \"", "Fucking detainees...\" \"they get all the breaks, right?\" \"", "Have you ever read Harry Potter?\" \"", "The kids' book?\" \"", "No, why?\" \"", "No reason.\" \"", "You know Sudoku?\" \"", "Yeah, sure.\" \"", "You know, I have done all these books here, so I have to make my own, you know?\" \"", "Well...\" \"It's pretty.\" \"", "You know, it's not just the drawing.\" \"", "You know what I mean?\" \"", "The numbers are very hard to figure out.\" \"", "You... you cannot just put any number in.\" \"", "Yeah, I know.\" \"", "Those men who do these books, you know, they do it all by computers.\" \"", "But to do it in your head, it's... it's...\" \"it's hard.\" \"", "You must be very smart, but...\" \"I have gone to university, you know?\" \"", "Are you sure it works?\" \"", "Of course it works, yes.\" \"", "What?\" \"", "You don't believe me?\" \"", "Okay.\" \"", "Come here.\" \"", "I will give it to you.\" \"", "You can...\" \"I want you to keep it.\" \"", "Now, you can see it for yourself, but you don't tell me that it's fake 'cause you cannot solve it.\" \"", "Yeah?\" \"", "No, thanks.\" \"", "You... you don't like puzzles?\" \"", "No, it's just... it's just the rules.\" \"", "Rule?\" \"", "Okay, okay.\" \"", "Bring this box.\" \" ", "I will put it in the box and...\" \" Hey, I can't.\" \"", "I'm sorry.\" \"", "Why?\" \"", "You... you... you think this paper will hurt you somehow, huh?\" \"", "Huh?\" \"", "You think that I will kill you with this piece of paper?\" \"", "Huh?\" \"", "You say the rules.\" \"", "What does fucking rule says?\" \"", "Maybe you think that you're getting disease from me.\" \"", "Yeah?\" \"", "That is it, maybe?\" \"", "That's why you guys are always wearing your rubber gloves.\" \"", "You guys don't even like to touch us.\" \" ", "You don't...\" \" Hey, calm down.\" \"", "I didn't say that.\" \"", "No.\" \"", "You know, you...\" \"let me tell you.\" \"", "You figured it out all, you know?\" \"", "This was a secret message.\" \"", "Look at this.\" \"", "I was going to send this to all my Al-qaedas friends in New York,\" \" and this was my big escape plan.\" \" ", "Don't... don't do that.\" \"", "Gone.\" \"", "See?\" \"", "Whhht!\" \"", "It's now in their hands, okay?\" \"", "I was trying to be nice with you.\" \"", "I-I-I wasn't being asshole to you.\" \"", "I don't know why you are being asshole to me.\" \"", "I am not being an asshole to you.\" \"", "I...\" \"I think you... yes, yes, yes, you are.\" \"", "Yes.\" \"", "Fuck you!\" \"", "You locked up us here for years!\" \"", "For what?\" \"!\" \"", "To show the world that you are good guy and we are bad guy?\" \"!\" \"", "Fuck you!\" \"", "You and America are the bad guy!\" \" ", "You American are the real terrorists!\" \" ", "Hey, keep it down!\" \"", "I looked for your book, you know?\" \"", "YourHarry Potter book...\" \"it's not in the library.\" \"", "You're fooling with me, huh?\" \"", "No.\" \"", "No, it's really not there.\" \"", "You're sure it's not there?\" \"", "Huh?\" \"", "Are you sure the book is not there 'cause, you know, once, one of these guards...\" \"he told me that he has seen it in the library.\" \"", "You know... you know, he... he... he... he was... keep telling me each week that, \"I will bring it next week.\" \"", "I will bring it next week,\" but he never bring it for me.\" \"", "He's probably fucking with you.\" \"", "It's not there.\" \"", "I'm sorry for... asking you too much about these books.\" \"", "You know, it... it's been a very long time that I have been waiting.\" \"", "And sometimes, I think that it's making me crazy...\" \"A little, you know?\" \"", "Not knowing how all these things are going to end.\" \"", "It's been a long time that I'm waiting.\" \"", "For the book?\" \"", "Yeah.\" \"", "Yeah, for the book.\" \"", "You understand what I am saying?\" \"", "I can...\" \"I can imagine what it would be like.\" \"", "Can you?\" \"", "Mm.\" \"", "I...\" \"Try to.\" \"", "Then...\" \"I will also try.\" \"", "Hey, 3-6-1...\" \"Chicken piccata is really good today...\" \"better than normal.\" \"", "You want some?\" \"", "Come on.\" \"", "No takers?\" \"", "Come on, please?\" \"", "Well, that makes this day five.\" \"", "You all know what's coming next.\" \"", "You want to call it off?\" \"", "I'll take that as a \"no.\"\" \"", "Mmm.\" \"", "Butter pecan.\" \"", "Bon appatit.\" \"", "How long are we gonna keep doing this?\" \"", "As long as they can.\" \"", "Attention on deck.\" \"", "That's the ringleader?\" \"", "Yes, sir.\" \"", "What's he want this time?\" \"", "Uh, I'm not sure, sir.\" \"", "Sir.\" \"", "Yes?\" \"", "I think I heard him say something about an elliptical machine, sir.\" \"", "You think they're gonna give him one?\" \"", "Why not?\" \"", "It would be easier than this.\" \"", "Yeah, but it'd take forever to get down here.\" \"", "Are you kidding me?\" \"", "They'll just take ours.\" \"", "Who's winning?\" \"", "You guys... that's who.\" \"", "I don't know about that.\" \"", "You got your elliptical machine.\" \"", "Yeah.\" \"", "You gonna use it?\" \"", "No.\" \"", "No one will use it.\" \"", "Why'd you demand it?\" \"", "I didn't demand this... mahmoud did.\" \"", "Why'd he demand it?\" \"", "I don't know.\" \"", "Go ask Mahmoud.\" \"", "Maybe because he's an asshole?\" \"", "So what's the count today?\" \"", "Oh.\" \"", "I've only gotten to 12 kicks today.\" \"", "Do you know what I hear today?\" \"", "Well, someone says sabir in \"A\" block...\" \"they said he hit 40 last week.\" \" ", "40?\" \" ", "Yeah.\" \"", "That's what they say.\" \"", "I don't know.\" \"", "I'm not so sure 'cause, well, no one has seen this, you know... only the guards, and those guards...\" \"they wouldn't say.\" \"", "You think you can beat 40?\" \"", "I don't know.\" \"", "I still think that he's made this up, you know.\" \"", "I tell you what...\" \"you beat 40, I'll vouch for you.\" \"", "Yeah?\" \"", "Yeah.\" \"", "Okay.\" \"", "2...3...4...5... 6...7...8...\" \"You're a long way away from 40.\" \" ", "What was that?\" \" ", "8.\" \"", "Are you sure?\" \" ", "Wasn't that 48?\" \" ", "I'm sure.\" \" ", "You saw 48.\" \" ", "I didn't.\" \"", "I mean, come on.\" \"", "Those guys... they don't believe you, anyway.\" \"", "Not gonna lie for you.\" \"", "You know, compliant detainees get to play on a real field together?\" \"", "Uh-huh.\" \"", "They are lucky.\" \"", "If you stop acting up, they'll transfer you.\" \" ", "You know that, right?\" \" ", "Mm-hmm.\" \"", "And you don't care?\" \"", "It's those guys who don't care, blondie.\" \"", "You know, they don't care about anything, just the things that make their life easier.\" \"", "You guys always say, \"follow these rules...\" \"we will let you watch TV,\" huh?\" \"", "But if I follow your rules, what does it means?\" \"", "It means that I'm agreeing that you have the right to give me rules, huh?\" \"", "Well, you don't.\" \"", "You don't have the right to give me rules.\" \"", "So, me...\" \"I never agree to follow your rules...\" \"Never.\" \"", "You know, maybe you think I'm stupid for this.\" \" ", "No, you're not stupid.\" \" ", "No.\" \"", "I mean, maybe you're right, but...\" \"You're definitely not stupid.\" \"", "You went to university.\" \"", "You're making fun of me, huh?\" \"", "Yeah, you're making fun...\" \"you're laughing at me, huh?\" \"", "Come on.\" \"", "Look at you.\" \"", "You're laughing at me, huh?\" \" ", "What's that about?\" \" ", "Nothing.\" \"", "They don't like you talking to me, huh?\" \"", "Private...\" \"Get over here.\" \"", "Neither do they, huh?\" \"", "Yes, Corporal?\" \"", "What were you just talking about over there?\" \"", "With Ali?\" \"", "No, with detainee 471.\" \" ", "Nothing.\" \" ", "Uh-huh.\" \"", "All right.\" \"", "Well, if you ain't talking about nothing, then you don't need to be talking, right?\" \"", "Hey!\" \"", "Hey, I did 20 kicks!\" \"", "Hey!\" \"", "I did 20 kicks!\" \"", "Did you see that, blondie?\" \"", "I swear I did 20!\" \"", "I swear I did!\" \"", "I'm gonna need your help on the showers today.\" \"", "The showers?\" \"", "I know you don't want to, but all my extra men are dealing with some dickhead in delta pod that decided to cover his entire cell in poop.\" \"", "I can't work showers.\" \"", "They won't even look me in the eye.\" \" ", "They think they're gonna shower?\" \" ", "Well, that's their problem.\" \"", "I mean, at least it'll speed things up.\" \" ", "S.O.P. Clearly states we are not...\" \" I know what S.O.P. Says.\" \"", "What's the matter?\" \"", "Can't handle it?\" \"", "You want me to get one of my other guys, pull him away from doing whatever the hell he's doing, so he can do it for you?\" \"", "No.\" \"", "Forget her.\" \"", "Get your ass in there.\" \"", "Let's go, skippy.\" \"", "Get undressed.\" \"", "Clock's ticking.\" \"", "Get your pants off.\" \"", "And shorts off.\" \"", "Come on.\" \"", "Get your fucking shorts off.\" \"", "Get your fucking shorts off, or I'll call in an Irf and we'll get them to take them off for you.\" \"", "Get them off.\" \"", "You guarding the fence, or you guarding him?\" \"", "This is completely out of line.\" \"", "Let me ask you something... are you a soldier, or are you a female soldier?\" \"", "'Cause I don't have these kind of problems with soldiers.\" \"", "You got to watch him.\" \"", "That's your job.\" \"", "Look at him.\" \"", "Hey, Cole, I thought that was you.\" \"", "What are you doing back here?\" \" ", "Drinking.\" \" ", "No shit.\" \"", "What's wrong?\" \"", "You had a bad day or something?\" \"", "Not particularly.\" \"", "Not as bad as yours, I hear.\" \"", "What do you mean?\" \"", "I heard some detainee just covered his cell on feces.\" \"", "Probably wasn't fun.\" \"", "When... today?\" \"", "On delta pod?\" \"", "No, it was just pretty quiet all day.\" \"", "Yeah.\" \"", "Must have been another pod.\" \"", "No, nothing like that happened on any of the pods.\" \"", "If it did, I would've saw it.\" \"", "Come in, boys!\" \"", "It's shot time!\" \"", "That's what I'm talking about!\" \"", "Oh, hey.\" \"", "What do you want?\" \"", "Jackie Chan got one.\" \"", "Shh!\" \"", "Shh!\" \"", "I'm not following you here.\" \"[ ", "Soldiers shouting cadences in distance ]\" \"Private first class Cole reporting as ordered, sir.\" \"", "At ease.\" \"", "Have a seat, private.\" \"", "Candy?\" \"", "No, thank you, sir.\" \"", "I've read your report.\" \"", "I've also spoken to corporal ransdell.\" \"", "In your report, you say that you were escorting a detainee to the showers after rec... is that correct?\" \"", "Affirmative.\" \"", "And you filed the report because this was uncomfortable.\" \"", "Well...\" \"No, I-it made him uncomfortable.\" \" ", "Who?\" \" ", "The detainee.\" \"", "So you filed against a fellow soldier because the detainee was uncomfortable?\" \"", "It was not the proper way to treat him, sir.\" \"", "Did the detainee take a shower?\" \"", "Yes, sir.\" \"", "Sounds like he wasn't that uncomfortable with it, then.\" \"", "It was a blatant violation of standard operating procedure, which is why I filed the report.\" \"", "Since you knew what was happening was against S.O.P., what exactly were you doing there?\" \"", "I was ordered to be there, sir.\" \"", "Corporal ransdell gave you a direct order?\" \"", "He had lied about being shorthanded.\" \"", "Did he order you, or did he lie to you?\" \"", "Sir...\" \"'Cause it seems to me there'd be no point to lie to you if he simply ordered you.\" \" ", "He... he...\" \" And there's nothing going on?\" \"", "You don't have a personal relationship with him, nothing going on outside the wire?\" \"", "No, sir.\" \"", "Is that what he told you?\" \"", "4-7-1, the detainee... you two are friends.\" \"", "No, sir.\" \"", "You're not friendly with him?\" \" ", "No, sir.\" \" ", "You don't talk to him?\" \"", "We have spoken.\" \"", "I am...\" \"Not...\" \"I...\" \" Like I said in my report...\" \" I've read your report.\" \"", "I know what it says.\" \"", "I also know what corporal ransdell says about it.\" \"", "But what I don't know and will probably never know is what is really going on here.\" \"", "Do you like it here, son?\" \"", "Sir?\" \"", "Do you like it here...\" \"In Guantanamo bay?\" \"", "Yes, sir.\" \"", "It's fine.\" \"", "I hate it.\" \"", "This ain't the kind of post a guy makes his stars on.\" \"", "Nobody gives you a medal when you do it right... they just give you a demotion when you do it wrong.\" \"", "My granddad... he flew 25 missions over Germany, blew up a dozen Nazi installments.\" \"", "What do we get?\" \"", "We get to babysit a bunch of sheep farmers.\" \"", "Like I said, I hate it here, and, yet, here I am.\" \"", "And do you know why?\" \"", "I'm here because my commanding officer told me to come here.\" \"", "Yes, sir.\" \"", "The review board will have, uh, a hearing for both of you next month.\" \" ", "I didn't do...\" \" You're dismissed.\" \"", "Yes, sir.\" \"", "Good morning, sir.\" \" ", "Hey.\" \" ", "Hey.\" \"", "How's your Enchilada?\" \"", "It's about as good as it looks.\" \"", "I should have went with the chicken fingers.\" \"", "Hard to mess those up, right?\" \"", "Hear about what happened on delta pod?\" \"", "What?\" \"", "Another cocktail?\" \"", "No.\" \"", "A dude tried to hang himself last night.\" \"", "How?\" \"", "It's not even possible.\" \"", "We watch these guys 24-7.\" \"", "No, not a detainee.\" \"", "It was a... it was a guard.\" \"", "The dude tied himself off to a ceiling fan and... get this... the piece of shit pulled out of the wall.\" \"", "Can you believe that shit?\" \"", "The dude's life got saved by shitty army contractors.\" \"", "It's funny, right?\" \"", "He's lucky.\" \"", "It's crazy though, right... that he tried to kill himself?\" \"", "I mean, I get it.\" \"", "It's a tough mission, you know.\" \"", "But what the fuck, man?\" \"", "It's our fucking job.\" \"", "You got to get over it, you know?\" \"", "Yeah.\" \"", "I know.\" \"", "It's got to be hard for some people, though.\" \"", "It's...\" \"It's not as black and white as they said it was gonna be.\" \"", "What's that mean?\" \"", "I don't know what he was expecting, but I'm sure it wasn't this.\" \"", "Come on, though.\" \"", "It's not as bad as that.\" \"", "A lot of these guys aren't even that tough.\" \"", "Exactly.\" \"", "Makes you feel fucking guilty.\" \"", "It's like...\" \"Guilty?\" \"", "Come... what the fuck you got to feel guilty for?\" \"", "No, man.\" \"", "Hell, you shouldn't feel guilty about shit.\" \"", "These motherfuckers did 9/11, and now they're in jail... end of story.\" \"", "The motherfuckers that did 9/11 died there.\" \"", "You know what your problem is?\" \"", "You've been talking too much to the fucking translators.\" \"", "They've gotten all in your head, and you've forgotten how lucky you really are.\" \"", "We could be in Iraq right now.\" \"", "You realize that?\" \"", "I mean, you'd rather be dodging cocktails than bullets, right?\" \"", "No.\" \"", "Whatever.\" \"", "10 minutes, faggots.\" \"", "Smoke 'em if you got 'em.\" \"", "Hey...\" \"You smoke now?\" \"", "Yeah.\" \"", "What are you gonna do, Cole?\" \"", "Tell on it?\" \"", "Based on the detainees' preferences...\" \"Yo.\" \" ", "What's up?\" \" ", "Here you go.\" \"", "You've been transferred.\" \"", "What?\" \"", "Where?\" \"", "Night shift.\" \"", "Yeah.\" \"", "Just, uh, skip tomorrow.\" \"", "Rotate in on the next.\" \"", "Your new O.I.C. Will come get you.\" \"", "It's all there.\" \"", "Why?\" \"", "Why?\" \"", "Shit, Cole.\" \"", "You know ain't no why in the army.\" \"", "Hey.\" \"", "Hey.\" \"", "Is that clock right?\" \"", "Yeah.\" \"", "So...\" \"W-where is blondie?\" \"", "Huh?\" \"", "Detainee 1-0-8 was heard singing a song in Arabic that had the English words \"bin laden\" in it.\" \"", "At 1700 hours, detainee 9-1 complained that his chow smelled rotten.\" \"", "He was given another meal, which he said tasted bad.\" \"", "At 1900, detainee 2-3-5 was given a water bottle.\" \"", "He drank it, asked for another, and proceeded to drink six more bottles in the span of five minutes.\" \"", "He then complained of feeling bad.\" \"", "We had 2-5 moves scheduled, 2-8 moves completed.\" \"", "Atten-hut!\" \"", "Honor bound.\" \"", "To defend freedom.\" \"", "Blondie?\" \"", "Blondie?\" \"", "It is you.\" \"", "Hey, don't... don't get up.\" \"", "Go back to sleep.\" \"", "No.\" \"", "No.\" \"", "No.\" \"", "I..\" \"I...\" \"I...\" \"I can never sleep well... you know, here, anyway.\" \"", "I didn't...\" \"I didn't know they kept the lights on all night.\" \"", "All day and all night.\" \"", "How is it that you're here?\" \"", "I mean, uh, you're a night guard.\" \"", "Oh.\" \"", "Um, I'm sorry.\" \"", "You cannot say.\" \"", "I-It's okay.\" \"", "No.\" \"", "Actually, uh I snitched on someone.\" \"", "What... what... what is it... snitch?\" \"", "It's like golden snitch and...\" \"No.\" \"", "Um, to snitch on someone is, uh...\" \"It's to tell...\" \"like, if someone does something wrong, you turn them in.\" \"", "Who... who did you snitch on?\" \"", "I can't say.\" \"", "It's moptop, huh?\" \"", "What... what did he do to you?\" \"", "You should get some sleep.\" \"", "See you later.\" \"", "I'm not gonna tell you what he did.\" \"", "Okay.\" \"", "So, tell me this one...\" \"how did you end up here?\" \"", "I told you... they reassigned me.\" \"", "No, no.\" \"", "How did you end up here in this place?\" \"", "How did you end up here?\" \"", "Me?\" \"", "How did I end up here?\" \"", "I could tell you that I was not with Al-Qaeda or a terrorist or... you wouldn't believe me, anyway.\" \"", "Nobody believes me here.\" \"", "So you're from Germany?\" \"", "Yeah.\" \"", "You remember.\" \"", "Yeah.\" \"", "Yeah.\" \"", "Yeah.\" \"", "From Germany, yeah.\" \"", "Actually, I was, you know, from Bremen.\" \"", "Do you know the city...\" \"Bremen?\" \"", "Bremen?\" \" ", "You don't know?\" \" ", "No.\" \"", "I can't even say it.\" \"", "Huh?\" \"", "Sprechen Sie Deutsch?\" \" ", "No speakDeutsch?\" \" ", "Mm, Dutch?\" \" ", "What?\" \" ", "Nein.\" \"", "Um, no.\" \"", "Have you been in Germany before?\" \"", "No?\" \" ", "No.\" \" ", "No.\" \"", "No.\" \"", "I'd like to... plan to.\" \"", "So, tell me... where have you been?\" \"", "I mean, you're...\" \"you're probably gonna laugh.\" \"", "Me?\" \"", "Laugh?\" \"", "No.\" \"", "At you?\" \"", "Uh, I-I never laugh at you.\" \"", "This is my first time out of the country...\" \"I mean, it's pretty lame, right?\" \"", "No.\" \"", "No, it's not.\" \"", "It's... you're... you're young.\" \"", "You're very young, and you're...\" \"you're a beginner, huh?\" \"", "Yeah.\" \"", "There are more people on this base than in my hometown.\" \"", "Small, huh?\" \"", "Yeah, tiny... gets smaller every day.\" \"", "And is this the reason that you came here?\" \"", "Part of it, yeah.\" \"", "What is the other part?\" \"", "A lot of reasons.\" \"", "Um...\" \"I wanted to do something.\" \"", "You know, I...\" \"I wanted to do something important.\" \"", "Yeah.\" \"", "I understand.\" \"", "Hey.\" \"", "Thank you.\" \"", "It's hard making the switch, huh?\" \"", "Yeah, it's all right.\" \"", "It takes a few days.\" \"", "Of course, uh, you won't be a night owl for...\" \"for too long, right?\" \"", "I guess not.\" \"", "Or...\" \"I hated the day shift... bunch of detainees chatting your ear off.\" \"", "I'd hate that.\" \"", "Thanks for the coffee.\" \"", "Hey.\" \"", "Are you still awake?\" \"", "What day is today?\" \"", "Wednesday.\" \"", "No, what date is today?\" \"", "Um, July 14th.\" \"", "So you're leaving next month?\" \"", "Yeah.\" \"", "How'd you know that?\" \"", "They always change the guards in August.\" \"", "So, when... when you leave, will you sign up again here?\" \"", "Like, you know, there are guards here that have been for many years.\" \"", "No, I don't think so.\" \"", "So you want to go to your home, your...\" \"your small town?\" \"", "No.\" \"", "What do you want to do, then?\" \"", "I don't know yet.\" \"", "Travel, maybe.\" \"", "Go to Bremen.\" \"", "I don't like this month.\" \"", "Always these new guards...\" \"Treating us like very bad guys.\" \"", "They'll learn...\" \"Like I did.\" \"", "What did you learn?\" \"", "Huh?\" \"", "Tell me.\" \"", "You must learn something, huh, when I throw that shit on you... you learned something, huh?\" \"", "Or when we're trying to kill ourselves here, with hunger strike, you learned something..\" \"Huh?\" \"", "You said.\" \"", "So tell me... what is that?\" \"", "I want to know.\" \"", "What did you learn?\" \"", "Only you think you know, but you know nothing.\" \"", "You know nothing about me.\" \"", "You and me...\" \"We are at war.\" \"", "I don't see it like that.\" \"", "Then you see nothing.\" \"", "What is that?\" \"", "Hey, hey, hey, hey!\" \"", "If... if you call on your radio, you're not going to make it.\" \"", "You're not going to make it.\" \"", "Bring it down.\" \"", "Bring it down.\" \"", "Mm-hmm.\" \"", "Mm-hmm.\" \"", "Okay.\" \"", "Just don't do anything crazy, okay?\" \"", "You think I'm crazy?\" \"", "No.\" \"", "No, I said just don't...\" \"don't do anything crazy.\" \"", "Is this crazy to you?\" \"", "If you was me, you wouldn't do this?\" \"", "Give me one reason why... one.\" \"", "Maybe to try to not... not die in this...\" \"this fucking shithole.\" \"", "I don't like to die in this shithole!\" \"", "But one way or another, this is the place I will die.\" \"", "Look, you don't know that.\" \"", "You can't know that.\" \"", "Ali, things can change.\" \"", "Things... things can always change.\" \"", "You... you can't just, uh...\" \"you can't just fucking give up.\" \" ", "You got to...\" \" Give up, blondie... what is \"give up\"?\" \"", "Three years ago, they took me to these interrogations.\" \"", "And one of your guys here, one of those guys who don't wear uniform...\" \"he told me that I'm innocent.\" \"", "He told me that he knows I'm innocent, but I still cannot go home...\" \"Because there's no country, no city, no fucking person in this planet will take me because I've been here.\" \"", "I have no place to go, blondie.\" \"", "This is the only thing that can change something.\" \"", "Everything okay?\" \"", "Yeah.\" \"", "Yeah, everything's fine.\" \"", "Um.\" \"", "My... my radio's...\" \"it's...it's on the Fritz.\" \"", "Can you get me another one?\" \"", "Uh, yeah.\" \"", "Blondie, you... you are a good guy.\" \"", "Yeah, thanks.\" \"", "Am I a bad guy or a good guy to you?\" \"", "Ali...\" \"It doesn't matter right now.\" \"", "It's the only time it matters.\" \"", "So you're gonna just... you're gonna be a martyr?\" \"", "Is that what you think you're... you think you're gonna go to heaven?\" \"", "That's what you want to do?\" \"", "I don't believe in this anymore.\" \"", "Well, then, why are you doing this?\" \"", "Look at me.\" \"", "You're asking me why do I want to die, but you don't see that I'm not even living.\" \"", "You guys control everything.\" \"", "You tell us what to eat, when to sleep.\" \"", "Even when we don't want to eat, you tell me we must.\" \"", "It is your life... it is not ours.\" \"", "I don't expect you to understand that.\" \"", "I-I like you.\" \"", "I do.\" \"", "But... but you'll never understand this.\" \"", "It's Amy.\" \"", "You keep calling me \"blondie,\" but...\" \"My name's Amy Cole from Moore haven, Florida.\" \"", "And I like you, Ali.\" \"", "I really do.\" \"", "Ah, fuck!\" \"", "Hey, hey!\" \"", "Is there a... is there a zoo in Bremen?\" \"", "What?\" \"", "When I was a kid, I went to the zoo with my dad.\" \"", "It was just outside where we lived and, uh...\" \"It's really small, one of those zoos where they keep the animals locked up in these... these tiny, little cages, these tiny, little, like, concrete boxes with tires in them or something.\" \"", "I was really excited about going.\" \"", "I really wanted to see something outside my town.\" \"", "I wanted to be...\" \"I wanted to be so close to something so wild and...\" \"It just wasn't okay.\" \"", "I didn't..\" \"I didn't like it.\" \"", "And my dad kept trying to fucking tell me that it was okay, that... that this lion could never go back home because... because he wouldn't be able to survive in the wild, having been locked up for so long.\" \"", "Okay.\" \"", "You're trying to tell me that the zoo people... they are not guilty.\" \"", "They have no choice.\" \"", "No.\" \"", "I thought they had a choice.\" \"", "If they had the choice, they should've given it to him.\" \"", "They should have let the lion choose.\" \"", "You're the new guy, huh?\" \"", "Tell me... how do you like it here?\" \"", "Do you want a book or not?\" \"", "Hold on your horses, big ear.\" \"", "No one here goes anywhere.\" \"", "At least, I'm... what... what is that book there, the big one?\" \"", "No.\" \"", "No, the b... the big one.\" \"", "The... the big yellow book!\" \"", "The big... the yellow big book!\" \"", "Yes, that... give it to me.\" \"", "Yeah, give that book.\" \"[ ", "Introduction to the antlers' \"kettering\" plays ]\" \"♪ I wish that I had known in that first minute we met ♪\" \"♪ the unpayable debt that I owe to you ♪\" \"♪ because you'd been abused by the bone that refused you ♪\" \"♪ and you hired me to make up for that ♪\" \"♪ while I was checking vitals, I suggested a smile ♪\" \"♪ you didn't talk for a while ♪\" \"♪ you were freezing ♪\" \"♪ you said you hated my tone ♪\" \"♪ it made you feel so alone ♪\" \"♪ and so you told me I ought to be leaving ♪\" \"♪ but something kept me standing by that hospital bed ♪\" \"♪ I should have quit, but, instead, I took care of you ♪\" \"♪ you made me sleep all uneven ♪\" \"♪ and I didn't believe them when they told me that there was no saving you ♪\"" ]

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[ "Proposal for a better integration of bacterial lysis into the production of plasmid DNA at large scale.", "\nThe paper addresses the question of how to achieve bacterial lysis in large-scale plasmid DNA production processes, where conventional alkaline lysis may become awkward to handle. ", "Bacteria were grown in shaker flasks and a bioreactor. ", "Suboptimal growth conditions were found advantageous for stable plasmid production at high copy numbers (up to 25mg/L could be achieved). ", "Cells were harvested by filtration in the presence of a filter aid. ", "A linear relationship between the biomass and the optimal filter aid concentration in terms of back pressure could be established. ", "Bacteria-containing filter cakes were washed with isotonic buffer and lysis was achieved in situ by a two-step protocol calling for fragilisation of the cells followed by heat lysis in a suitable buffer. ", "RNA and other soluble cell components where washed out of the cake during this step, while the plasmid DNA was retained. ", "Afterwards a clear lysate containing relatively pure plasmid DNA could be eluted from the cake mostly as the desired supercoiled topoisomer, while cell debris and genomic DNA were retained. ", "Lysis is, thus, integrated not only with cell capture but also with a significant degree of isolation/purification, as most impurities were considerably reduced during the procedure." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "[Mixed odontogenic tumors. ", "Studies on the significance of correlations between ameloblastic fibroma, ameloblastic fibro-odontoma and odontoma].", "\nThe purpose of the present study was to evaluate the interrelationship between the mixed odontogenic tumors. ", "A population of 292 cases--9 cases from our own files, 283 cases taken from the literature--was considered. ", "Data concerning age, sex distribution and site of occurrence of the different lesions were statistically analyzed. ", "The results showed a significant prevalence of odontomas in the anterior region and a highly significant correlation for age and site distribution in relation to the various lesions. ", "It is supposed that ameloblastic fibroma, ameloblastic fibro-odontoma and odontoma represent different maturational stages of the same lesion whose histogenesis is linked to the odontogenic process." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Sunday, May 15, 2005\n\nI know a lot of writers, and in private, after a few cocktails, they all admit the same thing:\n\nThey watch their Amazon listings.", "\n\nIt's a maddening thing to watch your Amazon Sales Rank go up and down and down and down, sometimes on an hourly basis.", "\n\nEven more ulcer-inducing is when a thoughtful reader decides to bash your book with a hatred so intense I can't help but wonder if I'd done something horrible to them in a previous life, such as murdered their spouse or interrupted them while they were watching Jerry Springer.", "\n\nOddly enough, many of these readers didn't even buy my book---they checked it out at the library. ", "The experience was obviously so traumatic that they took up the noble cause of protecting potential buyers from wasting their hard-earned money by posting these warnings on Amazon, because we all know that once we see a bad Amazon review, there's NO WAY we'd ever order THAT book, no sir.", "\n\nBut, in deference to these guardians of moral outrage, I too have once posted a bad Amazon review.", "\n\nAfter waiting 13 years for the sequel to Silence of the Lambs (which I loved), I was one of those crazy folks in line at 7AM the day that Hannibal was released. ", "And I didn't like it. ", "I really didn't like it. ", "So I posted a negative Amazon review. ", "And as you all well know, my negative review immediately stopped everyone from buying Hannibal, and the book only sold about a dozen copies all around the world thanks to my bitter rant, and Thomas Harris is now living a pauper's existence, unable to find work.", "\n\nSince then I've continued to review books, but I only review the ones that I like. ", "I figure life is too short to be negative.", "\n\nSince then I've also gotten reviews that made my review of Hannibal seem quaint by comparison.", "\n\nKarma is a bitch.", "\n\nBut bad reviews don't bother me at all. ", "Everyone has an opinion, and all opinions are valid. ", "Bad press is better than no press at all, and I'm happy to be read, even if the reader hated every word.", "\n\nSo I would like to publicly thank everyone who has reviewed me, both good and bad, and hope that you'll continue to do so to see if I get better or worse with each successive book.", "\n\nOkay, so I've finally finished revamping my homepage, JAKonrath.com, and though it still needs some tweaking, I'm happy with the look and the navigation.", "\n\nI added MUCHO content. ", "Besides more tips for new writers, I've added a ton of info on marketing and self-promotion for published writers. ", "I've also added more stories, articles, pictures, downloads, and a free e-book.", "\n\nThe e-book is a technothriller that I wrote pre-Jack Daniels series. ", "It's available in a few different formats, and yours for the reasonable price of zero dollars.", "\n\nIs this a dumb idea, giving away a free book? ", "I dunno. ", "Might be. ", "We'll see what the future holds..." ]

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[ "Wednesday, February 10, 2016\n\nI'm no gamer but I love Razer Inc's peripherals. ", "At both home and work I use their BlackWidow keyboards, DeathAdder mice, and Goliathus mousepads. ", "They're reliable and they look and feel great. ", "Sadly, today I discovered something about them that is not so great: The Razer Game Scanner Service.", "\n\nSome service installed on my computer was pumping tons of messages to my computer's debug console, writing the same message several times a second: \"GameScannerService(RzProcessManager) (0xb20) (0xcb4).\" ", "It didn't take long to figure out that this service is part of the Razer Comms package, which must have installed along with the default Razer Synapse applications that you're prompted to install when you plug a new Razer device into your computer. ", "I don't even have any games installed on this computer, so I obviously don't need this service- but I've got a much bigger problem: This is a Windows logo-certified commercial product that's installed on literally millions of machines around the world that's pumping thousands and thousands of lines of useless information to the debug consoles of those computers all the time. ", "That's a huge waste of collective CPU resources, and it's just plain terrible design. ", "Release-build software shouldn't ever dump anything to the debug console, ever. ", "How in the world did this get past Razer QA and Microsoft's certification labs?", "\n\nSince I don't need the service, I just disabled it in the Services control panel:\n\nLaunch Services.msc.", "\n\nLocate Razer Game Scanner in the list of services.", "\n\nDouble-click the service's entry, then click Stop and set the Startup type field to Disabled and then click OK.", "\n\nDepending on the features you need, you might be able to simply uninstall Razer Synapse from the Programs and Features control panel.", "\n\nThursday, February 4, 2016\n\nMy Samsung Galaxy S5 phone received a couple of software updates earlier this week, and beginning yesterday a mysterious new icon appeared on both my lock screen and my home screen...\n\nThe icon obscured anything beneath it, and if I tried to drag it out of the way my phone's screen would dim like it was covered by a gray transparent overlay. ", "Once this happened I was also no longer able to touch the screen or use the phone's physical buttons. ", "The only way I could regain use of my phone was to pop out the battery and then pop it back in and restart.", "\n\nThis is what the icon looked like:\n\nHere's how it appeared on my lock screen.", "\n\nAnd this is how it appeared on my home screen, with the \"Launch Quick Remote\" bubble.", "\n\nI had never seen this icon before, it covered up stuff on my screen, and touching it rendered the phone useless. ", "What in the *bleep* was going on?", "\nMy web searches came up empty, but I ultimately figured out how to fix the problem. ", "It appears that the recent software updates AT&T pushed to my phone this week included an app called Peel Smart Remote, which seems to be some kind of universal remote app for your phone. ", "I've never used it before, and have no desire to start. ", "My first thought was to simply remove the app. ", "Unfortunately, that's not possible on my phone- it's apparently part of AT&T's bundled image for the S5. ", "I was still able to get rid of the icon though. ", "Here's how:\n\nRegaining control over your phone:\n\nMy phone is an AT&T Samsung Galaxy S5 (Model number:\nSAMSUNG-SM-G900A) and it's currently running Android version 5.0\n(Lollipop). ", "With that model it's really easy to just pop off the back cover, pry out the battery, and then replace it and power the phone back on. ", "Once the phone boots back up you should be able to use your screen and buttons to perform the steps in the next section.", "\n\nIf your phone doesn't have a replaceable battery that you can easily pop out, commenter BiggestU passed along this tip: \"You can power off by simultaneously holding down\nthe power button and the volume down button for at least 7 seconds. ", "Wait\na minute, then turn the power back on again.\" (", "I will add that when I\ndid this the phone restarted automatically, instead of shutting down- but it definitely does the\ntrick.)", "\n\nAnother commenter, Renay, suggests that there might be a way to regain control of your phone without restarting: \"When the screen is stuck, briefly press Vol-up, Home, and Power together. ", "It will give control back immediately.\"", "\n\nGetting rid of the icon:\n\nOnce you have control over your phone, open up the Settings app and locate the Application manager.", "\n\nLocate Peel Smart Remote in the list and tap it to open its info.", "\n\nYou will probably find that the app cannot be uninstalled. ", "However, you should be able to disable it. ", "Press the Disable button.", "\n\nWhen you return to the list of apps you should now find that Peel Smart Remote is disabled. ", "If you restart your phone now, you should no longer see the icon.", "\n\nThat's all there is to it. ", "I'm still left with some lingering questions, though:\n\nWhy are Peel/Samsung/AT&T putting this dumb icon on my screen without telling me what the *bleep* it's for?", "\n\nWhat purpose is this thing supposed to serve anyway when tapping it makes my phone unusable?", "\n\nIn the App Age, where both documentation and customer support are but distant memories, we may never know...\n\nMonday, February 1, 2016\n\nI was really frustrated when Waves and MusicLab omitted the ability for users to choose where to install their products in Waves Central and RealEight. ", "Even though I've got a kickin' rad DAW PC, my primary system drive is a small SSD and I don't have room on it for anything other than my operating system and my personal files. ", "Neither Waves nor MusicLab would help me move their products to a different drive (I asked), so I came up with a different solution...\n\nIn version 1.1.0.0 of UltimatePluginTool, I've added the ability to relocate entire folders to any other folder or drive on your computer in a way that doesn't affect your existing programs. ", "If you've ever moved a Native Instruments product to another drive and then tried to use Maschine or Komplete Kontrol afterward, you know that relocating an application usually requires more work than simply dragging around some files. ", "Well, the new Relocate Plugin Content wizard of UltimatePluginTool addresses those problems by leaving a symbolic link in the old location where your files used to reside which silently redirects any applications who look there to the new, correct location.", "\n\nThe wizard can move the files for you or just create the link if you've already relocated the files. ", "The user guide included with the download has full instructions, and I've posted a video tutorial that walks you through three different examples of the Relocate Plugin Content wizard in action.", "\n\nEven though I added this feature specifically because I wanted to move some of my music applications to a different drive, UltimatePluginTool's Relocate Plugin Content wizard isn't limited to music software. ", "You can seamlessly locate pretty much any folder on your PC to another directory or drive. ", "I've already used it to move a number of applications onto a secondary \"programs and plugins\" drive. ", "Liberate your applications and unburden your drives!", "\n\nSupport UltimatePluginTool\n\nI develop and maintain free software on my own time. ", "I don't charge a fee because I want everyone to have equal access to my programs- but if something I wrote helped you and you'd like to express your thanks in a concrete way, you can send a donation of any amount via PayPal. ", "Support from my visitors covers my hosting and licensing costs, and gives me incentive to keep putting out cool new utilities.", "\n\nIf you wish to help out, you can enter a donation amount below and then click on the Donate button. ", "You do not need a PayPal account in\norder to donate! ", "Just click the \"Don't have a PayPal account\" option on the page that comes up after you click the Donate button. ", "The\ndonation amount is in U.S. Dollars (USD).", "\n\nAmount: $\n\nNote: You might receive a personal \"thank you\" from me in response, but I won't sign you up for any mailing lists and you won't hear from me again unless you contact me first. ", "Thanks for your consideration!" ]

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[ "Q:\n\nThere exist $x_{1},x_{2},\\cdots,x_{k}$ such two inequality $|x_{1}+x_{2}+\\cdots+x_{k}|\\ge 1$\n\nEdit: This problem 1 is a 2014 Sydney mathematics competition problem (8th grade). ", "It seems difficult to solve.", "\n\nShow that:\nThere exist complex numbers $x_{1},x_{2},\\cdots,x_{k}(k\\ge 2)$ such that:\n $$\\begin{cases}\n|x^2_{1}+x^2_{2}+\\cdots+x^2_{m}|\\le\\frac{1}{2} \\text{ for all } m \\le k\\\\\n|x_{1}+x_{2}+\\cdots+x_{k}|\\ge 1.", "\n\\end{cases}$$\n\nA:\n\nLet $x_i=\\frac{1}{k}$ for $i=1$ to $k$. Then both inequalities hold.", "\n\nA:\n\nFor $k=1,$ there is no solution as $|x_1|\\ge 1 \\Rightarrow |x_1^2|\\ge1.$\nFor $k\\ge 2,$ set $x_j=(-i)^j\\frac{-i}{\\sqrt2}$ for all $j.$ Now let $S_m=|x^2_1+\\cdots+x^2_m|.$ For an even $m,$ it should be clear that $S_m=0.$ For an odd $m,$ we have $S_m=|\\frac12|=\\frac12.$\nNow let $T_k=|x_1+\\cdots+x_k|.$ If $k>1$ then considering that $|x_1+x_2|=1$ we get $T_{2k}=|k(x_1+x_2)|=k$ and $T_{2k+1}=|k(x_1+x_2)+\\frac1{\\sqrt 2}|\\ge k.$ The result follows.", "\n\n" ]

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[ "Circulating levels of endothelin in cirrhosis.", "\nCurrent information concerning endothelin in cirrhosis is conflicting. ", "Plasma endothelin concentration has been found to be increased in some studies and normal or reduced in others. ", "The present study was aimed to investigate the plasma levels of endothelin in cirrhosis and to assess whether it is involved in the renal and hemodynamic disturbances and neurohumoral changes present in this condition. ", "Renal function, plasma renin activity, and plasma concentration of aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic factor, and endothelin were measured in 9 healthy subjects, 7 compensated cirrhotics, and 25 cirrhotics with ascites (10 with functional renal failure). ", "Cirrhotics with ascites with and without functional renal failure showed higher endothelin levels (15.6 +/- 6.4 and 15.7 +/- 4.6 pg/mL, respectively; mean +/- SD) than compensated cirrhotics (6.4 +/- 1.8 pg/mL) and healthy subjects (3.4 +/- 1.0 pg/mL) (analysis of variance, F = 21.84; P < 0.001). ", "These patients also showed higher plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic factor, although plasma endothelin levels only correlated significantly with plasma atrial natriuretic factor (r = 0.73, P < 0.001) and antidiuretic hormone concentrations (r = 0.59, P < 0.001). ", "In 7 additional nonazotemic cirrhotics with ascites, plasma renin activity and the plasma concentration of aldosterone and endothelin were measured before and 24 hours after the intravenous administration of a saline solution of human serum albumin. ", "Volume expansion markedly suppressed renin and aldosterone but not endothelin (21.03 +/- 7.34 vs. 23.97 +/- 14.29 pg/mL). ", "Circulating plasma levels of endothelin are elevated in cirrhosis with ascites and do not decrease following plasma volume expansion." ]

{ "pile_set_name": "PubMed Abstracts" }

[ 0.0008200673037208617, 0.0006565045332536101, 0.0006168499239720404, 0.0005893969791941345, 0.0007131697493605316, 0.0008335415623150766, 0.0007906525279395282, 0.0008736848249100149, 0.0006615880411118269, 0.0006646408583037555 ]

[ "package com.huawei.okhttp3;\n\nimport com.huawei.okhttp3.internal.", "Util;\nimport com.huawei.okio.", "Buffer;\nimport com.huawei.okio.", "BufferedSink;\nimport com.huawei.okio.", "ByteString;\nimport java.io.", "IOException;\nimport java.util.", "ArrayList;\nimport java.util.", "List;\nimport java.util.", "UUID;\nimport javax.annotation.", "Nullable;\n\npublic final class MultipartBody extends RequestBody {\n public static final MediaType ALTERNATIVE = MediaType.get(\"multipart/alternative\");\n private static final byte[] COLONSPACE = {58, 32};\n private static final byte[] CRLF = {13, 10};\n private static final byte[] DASHDASH = {45, 45};\n public static final MediaType DIGEST = MediaType.get(\"multipart/digest\");\n public static final MediaType FORM = MediaType.get(\"multipart/form-data\");\n public static final MediaType MIXED = MediaType.get(\"multipart/mixed\");\n public static final MediaType PARALLEL = MediaType.get(\"multipart/parallel\");\n private final ByteString boundary;\n private long contentLength = -1;\n private final MediaType contentType;\n private final MediaType originalType;\n private final List<Part> parts;\n\n MultipartBody(ByteString boundary2, MediaType type, List<Part> parts2) {\n this.boundary = boundary2;\n this.originalType = type;\n this.contentType = MediaType.get(type + \"; boundary=\" + boundary2.utf8());\n this.parts = Util.immutableList(parts2);\n }\n\n public MediaType type() {\n return this.originalType;\n }\n\n public String boundary() {\n return this.boundary.utf8();\n }\n\n public int size() {\n return this.parts.size();\n }\n\n public List<Part> parts() {\n return this.parts;\n }\n\n public Part part(int index) {\n if (index > size() - 1) {\n return null;\n }\n return this.parts.get(index);\n }\n\n @Override // com.huawei.okhttp3.RequestBody\n public MediaType contentType() {\n return this.contentType;\n }\n\n @Override // com.huawei.okhttp3.RequestBody\n public long contentLength() throws IOException {\n long result = this.contentLength;\n if (result !", "= -1) {\n return result;\n }\n long writeOrCountBytes = writeOrCountBytes(null, true);\n this.contentLength = writeOrCountBytes;\n return writeOrCountBytes;\n }\n\n @Override // com.huawei.okhttp3.RequestBody\n public void writeTo(BufferedSink sink) throws IOException {\n writeOrCountBytes(sink, false);\n }\n\n /* JADX DEBUG: Multi-variable search result rejected for r3v0, resolved type: com.huawei.okio.", "Buffer */\n /* JADX DEBUG: Multi-variable search result rejected for r4v0, resolved type: com.huawei.okio.", "BufferedSink */\n /* JADX DEBUG: Multi-variable search result rejected for r3v1, resolved type: com.huawei.okio.", "Buffer */\n /* JADX DEBUG: Multi-variable search result rejected for r4v1, resolved type: com.huawei.okio.", "BufferedSink */\n /* JADX DEBUG: Multi-variable search result rejected for r4v2, resolved type: com.huawei.okio.", "BufferedSink */\n /* JADX DEBUG: Multi-variable search result rejected for r3v2, resolved type: com.huawei.okio.", "Buffer */\n /* JADX WARN: Multi-variable type inference failed */\n private long writeOrCountBytes(@Nullable BufferedSink sink, boolean countBytes) throws IOException {\n BufferedSink sink2;\n long byteCount = 0;\n Buffer byteCountBuffer = 0;\n if (countBytes) {\n sink2 = new Buffer();\n byteCountBuffer = sink2;\n } else {\n sink2 = sink;\n }\n int partCount = this.parts.size();\n for (int p = 0; p < partCount; p++) {\n Part part = this.parts.get(p);\n Headers headers = part.headers;\n RequestBody body = part.body;\n sink2.write(DASHDASH);\n sink2.write(this.boundary);\n sink2.write(CRLF);\n if (headers !", "= null) {\n int headerCount = headers.size();\n for (int h = 0; h < headerCount; h++) {\n sink2.writeUtf8(headers.name(h)).write(COLONSPACE).writeUtf8(headers.value(h)).write(CRLF);\n }\n }\n MediaType contentType2 = body.contentType();\n if (contentType2 !", "= null) {\n sink2.writeUtf8(\"Content-Type: \").writeUtf8(contentType2.toString()).write(CRLF);\n }\n long contentLength2 = body.contentLength();\n if (contentLength2 !", "= -1) {\n sink2.writeUtf8(\"Content-Length: \").writeDecimalLong(contentLength2).write(CRLF);\n } else if (countBytes) {\n byteCountBuffer.clear();\n return -1;\n }\n sink2.write(CRLF);\n if (countBytes) {\n byteCount += contentLength2;\n } else {\n body.writeTo(sink2);\n }\n sink2.write(CRLF);\n }\n sink2.write(DASHDASH);\n sink2.write(this.boundary);\n sink2.write(DASHDASH);\n sink2.write(CRLF);\n if (!", "countBytes) {\n return byteCount;\n }\n long byteCount2 = byteCount + byteCountBuffer.size();\n byteCountBuffer.clear();\n return byteCount2;\n }\n\n static StringBuilder appendQuotedString(StringBuilder target, String key) {\n target.append('\\\"');\n int len = key.length();\n for (int i = 0; i < len; i++) {\n char ch = key.charAt(i);\n if (ch == '\\n') {\n target.append(\"%0A\");\n } else if (ch == '\\r') {\n target.append(\"%0D\");\n } else if (ch !", "= '\\\"') {\n target.append(ch);\n } else {\n target.append(\"%22\");\n }\n }\n target.append('\\\"');\n return target;\n }\n\n public static final class Part {\n final RequestBody body;\n @Nullable\n final Headers headers;\n\n public static Part create(RequestBody body2) {\n return create(null, body2);\n }\n\n public static Part create(@Nullable Headers headers2, RequestBody body2) {\n if (body2 == null) {\n throw new NullPointerException(\"body == null\");\n } else if (headers2 !", "= null && headers2.get(\"Content-Type\") !", "= null) {\n throw new IllegalArgumentException(\"Unexpected header: Content-Type\");\n } else if (headers2 == null || headers2.get(\"Content-Length\") == null) {\n return new Part(headers2, body2);\n } else {\n throw new IllegalArgumentException(\"Unexpected header: Content-Length\");\n }\n }\n\n public static Part createFormData(String name, String value) {\n return createFormData(name, null, RequestBody.create((MediaType) null, value));\n }\n\n public static Part createFormData(String name, @Nullable String filename, RequestBody body2) {\n if (name !", "= null) {\n StringBuilder disposition = new StringBuilder(\"form-data; name=\");\n MultipartBody.appendQuotedString(disposition, name);\n if (filename !", "= null) {\n disposition.append(\"; filename=\");\n MultipartBody.appendQuotedString(disposition, filename);\n }\n return create(Headers.of(\"Content-Disposition\", disposition.toString()), body2);\n }\n throw new NullPointerException(\"name == null\");\n }\n\n private Part(@Nullable Headers headers2, RequestBody body2) {\n this.headers = headers2;\n this.body = body2;\n }\n\n @Nullable\n public Headers headers() {\n return this.headers;\n }\n\n public RequestBody body() {\n return this.body;\n }\n }\n\n public static final class Builder {\n private final ByteString boundary;\n private final List<Part> parts;\n private MediaType type;\n\n public Builder() {\n this(UUID.randomUUID().toString());\n }\n\n public Builder(String boundary2) {\n this.type = MultipartBody.", "MIXED;\n this.parts = new ArrayList();\n this.boundary = ByteString.encodeUtf8(boundary2);\n }\n\n public Builder setType(MediaType type2) {\n if (type2 == null) {\n throw new NullPointerException(\"type == null\");\n } else if (type2.type().equals(\"multipart\")) {\n this.type = type2;\n return this;\n } else {\n throw new IllegalArgumentException(\"multipart !", "= \" + type2);\n }\n }\n\n public Builder addPart(RequestBody body) {\n return addPart(Part.create(body));\n }\n\n public Builder addPart(@Nullable Headers headers, RequestBody body) {\n return addPart(Part.create(headers, body));\n }\n\n public Builder addFormDataPart(String name, String value) {\n return addPart(Part.createFormData(name, value));\n }\n\n public Builder addFormDataPart(String name, @Nullable String filename, RequestBody body) {\n return addPart(Part.createFormData(name, filename, body));\n }\n\n public Builder addPart(Part part) {\n if (part !", "= null) {\n this.parts.add(part);\n return this;\n }\n throw new NullPointerException(\"part == null\");\n }\n\n public MultipartBody build() {\n if (!", "this.parts.isEmpty()) {\n return new MultipartBody(this.boundary, this.type, this.parts);\n }\n throw new IllegalStateException(\"Multipart body must have at least one part.\");", "\n }\n }\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\nSystem cannot find the directory of current running process in “C:\\Windows\\Fonts” folder\n\nI have a file running from this directory:\nC:\\Windows\\Fonts\\com4.{208d2c60-3aea-1069-a2d7-08002b30309d}, When I want to open that directory it says System cannot find the specified path and when I want to delete the file inside that folder with PowerShell, it says Access Denied!", "\nHow can I delete the file and folder?", "\n\nA:\n\nCOM4 is a special reserved 'DOS Device' name. ", "Files or Folders with these types of names can not be created or accessed by normal means. ", "Also the appended string .{208d2c60-3aea-1069-a2d7-08002b30309d} is the Shell CLSID for My Network Places, It will cause the folder with this appended sting to appear as such in Windows Explorer to hide the contents.", "\nIt can be renamed to a normal name so it can be be accessed afterwards. ", "But since it is located in the system folder C:\\Windows\\Fonts, Administrative rights are needed for doing so.", "\nIn an elevated Command Prompt (CMD.EXE) this command can be used to rename the folder\nren \"\\\\.\\C:\\Windows\\Fonts\\com4.{208d2c60-3aea-1069-a2d7-08002b30309d}\" \"NewName\"\nBut for the rename to be successful, any program(Most probably a malware as you mentioned) that is running from this folder must be terminated beforehand.", "\nA malware can have other protections mechanisms to prevent you from doing any of the above actions or easily undo what you have done, So you should protect your system with an updated Antivirus product and keep it updated until it is detected and removed completely.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Agape Health Clinic open Saturday\n\nComment\n\nPrattTribune - Pratt, KS\n\nWriter\n\nPosted Nov. 27, 2012 at 9:00 AM\nUpdated Nov 27, 2012 at 9:06 AM\n\nPosted Nov. 27, 2012 at 9:00 AM\nUpdated Nov 27, 2012 at 9:06 AM\n\nPratt, Kan.\n\nThe Agape Health Clinic will be open for low income, uninsured patients on Dec. 1 at Chandler Hall on Pratt Community College. ", "Doors open at 8 a.m. and patients are asked to be registered by 10:30 a.m. to see a physician.", "\n\nThe next dental clinic is Feb. 9. ", "Patients wishing to take advantage of that extractions-only clinic must be seen at a regular clinic." ]

{ "pile_set_name": "Pile-CC" }

[ 0.0006145149818621576, 0.0006366916350089014, 0.0006296812207438052, 0.0005800306098535657 ]

[ "This cleanser is a true beauty product; it does more than just remove makeup and impurities from face and eye. ", "Its emollient action leaves skin supple and is the perfect preparation for your skin, morning and night. ", "Includes nourishing Rosehip and Evening Primrose oils and Aloe Vera to moisturise and soften your skin.", "\n\n9/10 \"Perfect texture - creamy-rich but not greasy or too thick: easy to dispense and removed every last trace of make-up including waterproof eye make-up; skin felt very moisturised. ", "One of the best products I tested.\"", "\nThe Green Beauty Bible, Sarah Stacey & Josephine Fairley." ]

{ "pile_set_name": "Pile-CC" }

[ 0.0017589996568858624, 0.00558330537751317, 0.005590643733739853, 0.0007742181769572198, 0.0005350902792997658, 0.0006380237173289061 ]

[ "Photograph of a group of British officers on board the S.S. Tenasserim, taken by Willoughby Wallace Hooper in 1885. ", "The photograph is one of a series documenting the Third Anglo-Burmese War (1885-86) made by Hooper while serving as Provost Marshal with the British army. ", "On 3 November 1885 he left Madras (Chennai), in India, on board the Tenasserim with troops of the Royal Artillery and arrived in Rangoon in Burma (Myanmar) on 8 November. ", "Hooper was a dedicated amateur photographer who also worked in collaboration with an army veterinary surgeon, George Western, and his subjects in India had included ethnographical studies, the life of the British, and the Madras famines of 1876-78. ", "The Burma war series of photographs is considered “one of the most accomplished and comprehensive records of a nineteenth century military campaign”. ", "They were published in 1887 as ‘Burmah: a series of one hundred photographs illustrating incidents connected with the British Expeditionary Force to that country, from the embarkation at Madras, 1st Nov, 1885, to the capture of King Theebaw, with many views of Mandalay and surrounding country, native life and industries’. ", "There were two editions, one with albumen prints, one with autotypes, and a series of lantern slides was also issued. ", "A political scandal arose following allegations by a journalist that Hooper had acted sadistically in the process of photographing the execution by firing squad of Burmese rebels. ", "The subsequent court of inquiry concluded that he had behaved in a “callous and indecorous” way and the affair raised issues of the role of the photograph in documenting human suffering and the conduct of the British military during a colonial war. ", "The war culminated in the annexation of Upper Burma on 1 January 1886 by the British and the exile of King Thibaw (reigned 1878-1885), the last of the Burmese kings, and his Queen Supayalat, to India." ]

{ "pile_set_name": "Pile-CC" }

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[ "Abortion and family-binding models: fertility limitation in Hungary.", "\nThis paper demonstrates how family-building models can be used for checking the quality of abortion data. ", "A family-building model, called FERMODA, is presented and used to check whether the available data on abortion for Hungary are consistent with Hungarian data on other aspects of family building. ", "Model cohorts are generated, using in FERMODA the proportions of women married and the birth and abortion rates of two selected Hungarian cohorts. ", "The estimates obtained from the simulated cohorts concerning use of contraception are compared with the information available on contraception, and, on the basis of this comparison, a judgment is made about the quality of abortion data for Hungary." ]

{ "pile_set_name": "PubMed Abstracts" }

[ 0.0005925925215706229, 0.0006465932819992304, 0.0005896278889849782, 0.0007512945448979735, 0.0006063166656531394 ]

[ "1. ", "Field of the Invention\nThe present invention relates to a method of manufacturing a sensor and a sensor.", "\n2. ", "Description of the Related Art\nConventionally known sensors include oxygen sensors configured such that a detection element assuming a tubular shape (hereinafter also referred to as a tubular detection element) is housed in a metallic shell. ", "Some oxygen sensors employ a tubular detection element having a flange portion, which is integrally formed at a substantially central position in the axial direction such that the flange portion faces rearward and projects radially outward. ", "The tubular detection element is disposed in the metallic shell such that the flange portion is engaged directly or via another member (such as a packing) with a stepped portion projecting radially inward from the wall surface of a through-hole of the metallic shell.", "\nMeanwhile, recently proposed oxygen sensors employ a detection element having a plate shape (a detection element having a laminated structure; hereinafter also referred to as a plate-type detection element) in place of a detection element having a tubular shape. ", "Such a plate-type detection element does not have an integrally formed flange portion for engaging a stepped portion of a metallic shell. ", "Thus, the plate-type detection element employs a tubular insulator on which an engagement surface is formed for engaging the stepped portion of the metallic shell, so that the plate-type detection element can be held by the metallic shell. ", "More specifically, the insulator and the plate-type detection element are fixedly united, and the engagement surface of the insulator serves as the engagement surface of the flange portion and is engaged with the stepped portion of the metallic shell, whereby the plate-type detection element is held by the metallic shell (refer to Patent Document 1).", "\nUse of the insulator as a flange portion enables attachment of a plate-type detection element to a metallic shell designed for use with a tubular detection element. ", "Thus, sensors employing a tubular detection element and sensors using a plate-type detection element can share metallic shells as common components. ", "Such sharing of components reduces component costs in the production of sensors.", "\nMeanwhile, some oxygen sensors that employ a detection element having a plate shape are configured such that an insulating holder, a powder-compacted filler, and an insulating sleeve are arranged in layers so as to surround the plate-type detection element from all radial directions. ", "In the process of manufacturing such a sensor, after the insulating holder and the powder-compacted filler are disposed within a metallic shell, a plate-type detection element to which the insulating sleeve is attached is inserted through an element-insertion through-hole of the powder-compacted filler and through an element-insertion through-hole of the insulating holder, whereby the plate-type detection element and the metallic shell are joined together. ", "Subsequently, pressure is applied to the powder-compacted filler. ", "Compression stress of the powder-compacted filler causes the plate-type detection element to be held in the metallic shell, thereby uniting the plate-type detection element and the metallic shell (refer to Patent Document 2).", "\n[Patent Document 1]\nJapanese Patent Application Laid-Open (kokai) No. ", "2002-174622 (FIGS. ", "1 and 3)\n[Patent Document 2]\nJapanese Patent Application Laid-Open (kokai) No. ", "2002-168823 (FIG. ", "1)\n3. ", "Problems to be Solved by the Invention:\nHowever, the conventional oxygen sensor disclosed in above-mentioned Patent Document 1 employs a glass seal material to fixedly join the insulator and the detection element. ", "Glass welding requires high-temperature thermal processing. ", "Since high-temperature thermal processing may crack (fracture) the detection element with an abrupt change in temperature, thermal processing time must be set long with a slow rate of raising the temperature so as to prevent fracturing of the detection element. ", "However, in the process of manufacturing a sensor, increasing the high-temperature thermal processing time reduces manufacturing efficiency.", "\nMeanwhile, the conventional oxygen sensor disclosed in above-mentioned Patent Document 2 employs a powder-compacted filler (a ring member formed through compaction of a powder substance (hereinafter also referred to as a powder-compacted ring)) in place of the glass seal material, thereby eliminating the need of a thermal processing step for glass welding and thus avoiding reduced sensor manufacturing efficiency, which could otherwise result from increasing the high-temperature thermal processing time.", "\nThe powder-compacted ring can be formed into, for example, an annular shape having an element-insertion through-hole formed at a central portion. ", "The element-insertion through-hole has a cross-sectional area slightly greater than that of the plate-type detection element so as to allow insertion of the plate-type detection element therethrough.", "\nHowever, in manufacturing a sensor that uses a powder-compacted ring having an element-insertion through-hole formed in the above-mentioned shape, the following assembly work becomes troublesome: after the powder-compacted ring is disposed in a through-hole of a metallic shell, a plate-type detection element and the metal shell are assembled together such that the detection element is inserted into the element-insertion through-hole of the powder-compacted ring. ", "Specifically, when the plate-type detection element is to be inserted into the element-insertion through-hole, the plate-type detection element must be set to an angular orientation (an angular position around its axis) so as to be insertable into the element-insertion through-hole. ", "Particularly, in the case of a metallic shell configured such that the powder-compacted ring is disposed deep in its through-hole, identifying the angular orientation of the element-insertion through-hole of the powder-compacted ring becomes difficult; as a result, assembling the plate-type detection element and the metallic shell becomes troublesome." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Q:\n\nConvert Mapbox Vector Tiles to Longitude and Latitude\n\nI am using Mapbox's QA Tiles and Python to access OSM data. ", "While the tile-based approach is very handy I got stuck with how the geometry is saved. ", "Apparently, coordinates are optimized for Mapbox's rendering needs and are 'vector tile grid coordinates'. ", "To my surprise, I can't find any reference that would help me to understand what they actually did.", "\nIn my case, I want to check if a location (as latitude and longitude) are within an OSM area (Polygon or Multipolygon). ", "This is what I got from the QA tile:\n{\n \"osm\": {\n \"version\": 2, \n \"features\": [\n {\n \"geometry\": {\n \"type\": \"Point\", \n \"coordinates\": [\n 95810, \n 1041260\n ]\n }, \n \"type\": 1, \n \"properties\": {\n \"@uid\": 144382, \n \"backrest\": \"yes\", \n \"@id\": 3072121792, \n \"@timestamp\": 1410453825, \n \"@changeset\": 25372130, \n \"amenity\": \"bench\", \n \"@user\": \"SHuehne\", \n \"@version\": 1, \n \"@type\": \"node\"\n }, \n \"id\": 0\n },\n …\n ]\n \"extent\": 1048576\n }\n}\n\nThis is the example node in OSM, the QA tile is z=12, x=2163, y=1435.", "\n\nA:\n\nI kept on reading and I guess I found the answer myself. ", "I won't delete the answer, maybe someone else will bump into the same problem.", "\nmapbox-vector-tile is the library I use and its documentation explains how they transformation are done: https://github.com/tilezen/mapbox-vector-tile#coordinate-transformations-for-encoding\n\nA:\n\n@linqu's answer the best for Python as per your question.", "\nA JS implementation which extracts the VT geometry as GeoJSON is at https://github.com/mapbox/vector-tile-js/blob/master/lib/vectortilefeature.js#L129\nOther JS tools which can help:\n\nhttps://github.com/mapbox/vector-tile-js\nhttps://github.com/mapbox/vt2geojson\n\n" ]

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[ "Main menu\n\nProject Overview\n\nBiofuels and biobased products can substantially improve environmental quality, rural economies, and national security. ", "Realizing this opportunity will require the efforts of scientists and engineers who have an appreciation for the complexity and degree of interrelation of sustainable production of fuels from biomass. ", "Kansas State University is well positioned in this regard for preparing students to become research and educational leaders who can meet the evolving needs of the bio-based energy industry through a deep appreciation of the interrelated impact of economic, technological, agricultural, and societal issues. ", "This IGERT proposal presents an integrated interdisciplinary graduate program for achieving transformative advances in the development of next-generation biorefineries.", "\n\nEligible Ph.D. applicants (U.S. citizen or permanent resident) are encouraged to apply to Kansas State University’s National Science Foundation (NSF)-sponsored Integrative Graduate Education and Research Training (IGERT) program. ", "An IGERT trainee will receive two years (and possibly a third year) of an annual stipend of $30,000 and an additional $10,500 annual allowance for tuition, insurance, as well as resources for specialized training, internships, research and travel funds.", "\n\nResearch Objectives: Developing technology and policies to take us from crops to commuting requires an understanding of and appreciation for integration of feedstock production, collection and transportation, biomass conversion, and product utilization. ", "IGERT trainees will be organized within interdisciplinary core teams working toward solutions of integrated problems within three major categories: technology, agriculture, and socioeconomic issues. ", "Each team will work together to advance the science, technology, and policy of a specific technological subject. ", "For example: how can a biomass conversion system be designed which achieves high yield of fuels and chemicals while retaining economic viability of modestly scaled facilities? ", "Answering this question requires expertise and input from scientists and engineers with understanding of the biomass conversion technology, economics of biomass production and facility operation, and the social impact on the affected communities. ", "This mode of multidisciplinary interaction is central to each IGERT project.", "\n\nBroader Impacts: Training and research components of this project will lead to development of new technologies and practices which result in a substantial enhancement in the sustainability of the conversion of biomass to fuels. ", "As a result of this program, decisions regarding biofuels production will be guided by not only by technological and agricultural feasibility but also by the impact of the proposed technology on society.", "\n\nEducation Objectives: This IGERT program will train students using discovery, learning, and engagement techniques. ", "Trainee dissertation projects will be conducted in an integrated, concurrent fashion with overlapping faculty supervisory committee membership, regular joint meetings, and with dissertation chapter(s) and publications addressing the collaborative, integrated research issues and results. ", "New learning opportunities are provided to trainees in planned classroom, seminar, workshop, certificate program, and field experience activities. ", "This learning will be deepened for trainees and expanded to undergraduate researchers through research mentorship opportunities. ", "Engagement is assured through collaboration with agricultural biomass producers and bioenergy industrial partners. ", "These program features also ensure trainees embody scholarship elements of discovery, integration, application, and teaching in their graduate program.", "\n\nWith support from NSF and partners, this IGERT project will directly fund the Ph.D. studies of trainees for two years and possibly a third year. ", "These IGERT trainees will be paired with undergraduate researchers and faculty members to form core research teams addressing the scientific barriers facing sustainable biorefineries. ", "Teams will interact with industrial practitioners and researchers from Europe and Brazil. ", "Through this highly integrated network of researchers, significant advances to the establishment of sustainable biorefineries are expected. ", "Sustainable biorefineries can lead to a significant reduction in greenhouse gas emissions and improvements in the economic viability of our agrarian communities." ]

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