tbuckley/cabot-search huggingface dataset:
Direct Detection and Timing of Aortic Valve Closure
Authors: D. M. MACCANON, F. AREVALO, E. C. MEYER
Journal: Circulation Research (1964)

A special electrical contacting device was developed and used to time the relationship between aortic valve closure and the aortic incisura in closed chest anesthetized dogs. High speed tracings showed that the aortic valve is closed at least 5 to 13 msec before the incisura. It is concluded that the aortic pressure incisura results from rebound of the aortic blood column and walls after valve closure and that the second heart sound is not caused by collision of the valve leaflets but by the same mechanical factors which are responsible for the incisura.
First Drug for Women With Constipation-Predominant IBS
Authors: Lester M. Crawford, Jr
Journal: JAMA (2002)

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BSmooth: from whole genome bisulfite sequencing reads to differentially methylated regions
Authors: Kasper D Hansen, Benjamin Langmead, Rafael A Irizarry
Journal: Genome biology (2012)

Abstract DNA methylation is an important epigenetic modification involved in gene regulation, which can now be measured using whole-genome bisulfite sequencing. However, cost, complexity of the data, and lack of comprehensive analytical tools are major challenges that keep this technology from becoming widely applied. Here we present BSmooth, an alignment, quality control and analysis pipeline that provides accurate and precise results even with low coverage data, appropriately handling biological replicates. BSmooth is open source software, and can be downloaded from http://rafalab.jhsph.edu/bsmooth .
Effect of intraluminal oxygen on endotoxin absorption in experimental occlusion of the superior mesenteric artery.
Authors: K Shute
Journal: Gut (1977)

Absorption of bacterial endotoxin has been shown to occur after release of the occluded superior mesenteric artery in the rat. A significant reduction in endotoxin absorption was observed as a result of the infusion of gaseous oxygen into the bowel lumen during the period of ischaemia (P less than 0-001). The methods of endotoxin identification and assay are described, and the possible reasons for this effect of intraluminal oxygen are discussed.
A Phase I and Pharmacokinetic Study of Temsirolimus (CCI-779) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients with Advanced Cancer
Authors: Manuel Hidalgo, Jan C. Buckner, Charles Erlichman, Marilyn S. Pollack, Joseph P. Boni, Gary Dukart, Bonnie Marshall, Lisa Speicher, Laurence Moore, Eric K. Rowinsky
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Patients with advanced cancer received temsirolimus (Torisel, CCI-779), a novel inhibitor of mammalian target of rapamycin, i.v. once daily for 5 days every 2 weeks to determine the maximum tolerated dose, toxicity profile, pharmacokinetics, and preliminary antitumor efficacy. Experimental Design: Doses were escalated in successive cohorts of patients using a conventional phase I clinical trial design. Samples of whole blood and plasma were collected to determine the pharmacokinetics of temsirolimus and sirolimus, its principal metabolite. Results: Sixty-three patients were treated with temsirolimus (0.75-24 mg/m2/d). The most common drug-related toxicities were asthenia, mucositis, nausea, and cutaneous toxicity. The maximum tolerated dose was 15 mg/m2/d for patients with extensive prior treatment because, in the 19 mg/m2/d cohort, two patients had dose-limiting toxicities (one with grade 3 vomiting, diarrhea, and asthenia and one with elevated transaminases) and three patients required dose reductions. For minimally pretreated patients, in the 24 mg/m2/d cohort, one patient developed a dose-limiting toxicity of grade 3 stomatitis and two patients required dose reductions, establishing 19 mg/m2/d as the maximum acceptable dose. Immunologic studies did not show any consistent trend toward immunosuppression. Temsirolimus exposure increased with dose in a less than proportional manner. Terminal half-life was 13 to 25 hours. Sirolimus-to-temsirolimus exposure ratios were 0.6 to 1.8. A patient with non–small cell lung cancer achieved a confirmed partial response, which lasted for 12.7 months. Three patients had unconfirmed partial responses; two patients had stable disease for ≥24 weeks. Conclusion: Temsirolimus was generally well tolerated on this intermittent schedule. Encouraging preliminary antitumor activity was observed.
Restoration of function of the ∆F508 mutation in cystic fibrosis
Authors: Stephen Rowan
Journal: Thorax (2012)

Restoration of function of the ΔF508 mutation in cystic fibrosisThe first nucleotide binding domain (NBD1) of the of ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR), is considered a potential drug target in cystic fibrosis but the links between this and CFTR misfolding remain unclear.NBD1 is one of the cytosolic domains of CFTR and is found in at least one allele of 90% of cystic fibrosis patients, significantly diminishing the folding efficiency of CFTR.The aim of this study was to clarify the role of NBD1 and structural consequences of the ΔF508 mutation in CFTR assembly.The isolated domains of thermodynamic and kinetic destabilisation from isolated NBD1 variants by the ΔF508 mutation were studied along with conformational stabilisation of ΔF508 NBD1.Thermodynamic and kinetic destabilisations in combination were shown to be responsible for the ΔF508 NBD1 misfolding.In full-length CFTR, the stability of NBD1 and NBD1-CL interface is needed for normal channel function.As ΔF508 causes impairment of both these domains, energetic and interface defects (NBD1-MSD2) need to be corrected simultaneously in ΔF508 CFTR for wild-type function.This study explains the limitations of some corrector molecules when targeted against a particular structural abnormality in CFTR.The understanding of interface mutation in such complicated multi-domain membrane proteins may lead to structure based combination corrector therapies.
Impaired immunity in harbour seals (Phoca vitulina) exposed to bioaccumulated environmental contaminants: review of a long-term feeding study.
Authors: R L de Swart, P S Ross, J G Vos, A D Osterhaus
Journal: Environmental Health Perspectives (1996)

Mass mortalities among seals and dolphins inhabiting contaminated marine regions have led to speculation about a possible involvement of immunosuppression associated with environmental pollution. To evaluate whether contaminants at ambient environmental levels can affect immune function of seals, we carried out an immunotoxicological study under semifield conditions. Two groups of 11 harbour seals (Phoca vitulina) originating from a relatively uncontaminated area were fed herring from either the highly polluted Baltic Sea or the relatively uncontaminated Atlantic Ocean. Changes in immune function were monitored over a 2 1/2-year period. The seals that were fed contaminated Baltic herring developed significantly higher body burdens of potentially immunotoxic organochlorines and displayed impaired immune responses as demonstrated by suppression of natural killer cell activity and specific T-cell responses. During a 2-week fasting experiment performed at the end of the feeding study, mobilization of organochlorines from the blubber did not lead to a strong increase of contaminant levels in the blood, and no enhancement of the existing immunosuppression was observed. These results demonstrate that chronic exposure to environmental contaminants accumulated through the food chain affects immune function in harbour seals, whereas short-term fasting periods, which are normal for seals, do not seem to pose an additional risk. The seals of this study were not exposed perinatally to high levels of environmental chemicals, and body burdens of organochlorines measured near the end of the study were lower than those generally observed in free-ranging seals inhabiting many contaminated regions. Therefore, it may be expected that environmental contaminants adversely affect immune function of free-ranging seals inhabiting contaminated regions at least as seriously as observed in these studies.
Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies
Authors: Takashi Sonoki, Lana Harder, Doug E. Horsman, Loraine Karran, Izumi Taniguchi, Tony G. Willis, Stefan Gesk, Doris Steinemann, Emanuele Zucca, Brigitte Schlegelberger, Francesc Solé, Andrew J. Mungall, Randy D. Gascoyne, Reiner Siebert, Martin J. S. Dyer
Journal: Blood (2001)
Recurrent and new hepatitis C virus infection after liver transplantation
Authors: James E. Everhart, Yuling Wei, Heather Eng, Michael R. Charlton, David H. Persing, Russell H. Wiesner, Jeffrey J. Germer, John R. Lake, Rowen K. Zetterman, Jay H. Hoofnagle
Journal: Hepatology (1999)

Chronic infection with the hepatitis C virus (HCV) is the most common reason for liver transplantation. We examined the results of laboratory tests for HCV on a cohort of patients who received a liver transplant between 1990 and 1994 at three large centers. Seven hundred twenty–two recipients and 604 donors were tested for antibody to HCV (anti–HCV) using a second–generation enzyme–linked immunoassay (EIA–2), followed by recombinant immunoblot (RIBA–2) and HCV RNA confirmation by reverse–transcription polymerase chain reaction (RT–PCR) (with genotyping and viral quantification). Diagnosis of posttransplantation infection required detection of serum HCV RNA that could be genotyped by sequencing or was repeatedly positive despite being unsequenceable. Twenty–five percent of transplantation candidates were seropositive for anti–HCV. Approximately 86% of anti–HCV-positive, 93% of RIBA–positive, and 97% of HCV RNA-positive candidates developed infection after transplantation. Pretransplantation HCV RNA was superior to RIBA–2 for predicting posttransplantation infection. Whereas HCV genotype was identified in nearly all candidates and changed little after transplantation, serum viral levels rose markedly after transplantation. Fifteen donors were either anti–HCV- or HCV RNA-positive. Recipients of grafts from donors with HCV RNA all developed infection, whereas infection was not detected in recipients of grafts from donors with anti–HCV but without detectable HCV RNA. The rate of new infection fell significantly ( P = .02) after the introduction of EIA–2 screening of blood. Donor and candidate markers for HCV predict posttransplantation infection
Transforming Growth Factor β1 Inhibits Fas Ligand Expression and Subsequent Activation-induced Cell Death in T Cells via Downregulation of c-Myc
Authors: Laurent Genestier, Shailaja Kasibhatla, Thomas Brunner, Douglas R. Green
Journal: The Journal of Experimental Medicine (1999)

Activation-induced cell death (AICD) is a process that regulates the size and the duration of the primary immune T cell response. In this report, we investigated the mechanisms involved in the regulation of AICD by transforming growth factor β1 (TGF-β1). We found that TGF-β1 decreased apoptosis of human T cells or T cell hybridomas after activation by anti-CD3. This decrease was associated with inhibition of Fas (Apo-1/CD95) ligand (FasL) expression, whereas Fas signaling was not affected by TGF-β1. In parallel, TGF-β1 inhibited c-Myc expression in T cell hybridomas, and ectopic expression of a chimeric molecule composed of c-Myc and the steroid binding domain of the estrogen receptor (Myc-ER) blocked both the inhibition of FasL and the decrease of AICD induced by TGF-β1, providing that 4-hydroxytamoxifen was present. These results identify one mechanism by which TGF-β1 blocks AICD to allow the clonal expansion of effector T cells and the generation of memory T cells during immune responses.
Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.
Authors: S R Mudaliar, F A Lindberg, M Joyce, P Beerdsen, P Strange, A Lin, R R Henry
Journal: Diabetes Care (1999)

OBJECTIVE: To study the pharmacokinetic and pharmacodynamic profile of insulin aspart (a new fast-acting human insulin analog) after subcutaneous administration in the deltoid, abdominal, and thigh sites and to compare this profile with regular human insulin (Novolin; Novo Nordisk A/S, Copenhagen). RESEARCH DESIGN AND METHODS: A total of 20 healthy subjects were studied in a single-center six-period double-blind randomized crossover trial with 6 study days and a washout period of 1 week between each single daily dose of the trial drug. Subjects were randomized to receive a single dose of 0.2 U/kg of insulin aspart or regular insulin on each of the 6 study days in three different sites (the deltoid, the abdomen, and the thigh) during a 10-h euglycemic clamp (two drugs and three injection sites). Pharmacokinetic and pharmacodynamic measurements were derived from blood sample measurements of glucose, insulin, and C-peptide during these clamps. RESULTS: The pharmacodynamic data from the euglycemic clamp study showed that, regardless of injection site, the maximal glucose infusion rate (GIR Cmax) was greater and occurred at an earlier time (GIR Tmax) after administration of insulin aspart than regular insulin (GIR Cmax: abdomen 813 vs. 708, deltoid 861 vs. 736, and thigh 857 vs. 720 g/min, P &amp;lt; 0.05 for all; GIR Tmax: abdomen 94 vs. 173, deltoid 111 vs. 192, and thigh 145 vs. 193 g/min, P &amp;lt; 0.05 for all). Pharmacokinetic parameters were also consistent with faster absorption and higher peak insulin concentrations after insulin aspart administration. From all sites, the peak insulin concentration (Cmax) was higher and occurred earlier (Tmax) after administration of insulin aspart than of regular insulin (Cmax: abdomen 501 vs. 260, deltoid 506 vs. 252, thigh 422 vs. 220 pmol/l, P &amp;lt; 0.001 for all sites; Tmax: abdomen 52 vs. 109, deltoid 54 vs. 98, and thigh 60 vs. 107 min, P &amp;lt; 0.01 for all sites). The absorption and glucose-lowering action of insulin aspart did not differ between sites (similar GIR Cmax, Tmax, and area under the curve parameters). However, the duration of the glucose-lowering effect was up to 34 min shorter (P &amp;lt; 0.01) for the abdomen injections than for the deltoid or thigh injections (lower time of 50% glucose disposal). In addition, the amount of glucose infused was significantly lower by 10-14% in the abdomen than in other sites. CONCLUSIONS: Subcutaneous administration of insulin aspart causes a more rapid and intense maximal effect compared with regular insulin during euglycemic clamp studies in nondiabetic subjects. Abdominal administration of insulin aspart has a shorter duration of glucose-lowering effect compared with administration in the deltoid or thigh.
Evaluation of pleural diseases with FDG-PET imaging: preliminary report
Authors: T. Bury, P. Paulus, A. Dowlati, J. L. Corhay, P. Rigo, M. F. Radermecker
Journal: Thorax (1997)

Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) is an accurate method for differentiating benign from malignant disease. The use of FDG-PET for the aetiological diagnosis of pleural disease was investigated in 25 patients.PET was performed on each subject before invasive procedures were used to determine the aetiological diagnosis. The PET data were analysed by visual interpretation of coronal, sagittal, and transverse slices.Sixteen patients were found to have malignant pleural disease and nine had benign disease. All patients with histologically confirmed malignant disease showed FDG uptake within the pleural thickening which was intense in 14 cases and moderate in two. PET imaging showed the absence of FDG uptake and correctly categorised seven non-malignant lesions. Two patients with infectious pleural diseases showed a localised and moderate FDG uptake.Our preliminary results suggest that FDG-PET could be an effective tool for differentiating between benign and malignant pleural diseases.
Attention, saccade programming, and the timing of eye-movement control
Authors: Ralph Radach, Heiner Deubel, Dieter Heller
Journal: Behavioral and Brain Sciences (2003)

E-Z Reader achieves an impressive fit of empirical eye movement data by simulating core processes of reading in a computational approach that includes serial word processing, shifts of attention, and temporal overlap in the programming of saccades. However, when common assumptions for the time requirements of these processes are taken into account, severe constraints on the time line within which these elements can be combined become obvious. We argue that it appears difficult to accommodate these processes within a largely sequential modeling framework such as E-Z Reader.
Large-Scale Parsimony Analysis of Metazoan Indels in Protein-Coding Genes
Authors: F. Belinky, O. Cohen, D. Huchon
Journal: Molecular Biology and Evolution (2009)

Insertions and deletions (indels) are considered to be rare evolutionary events, the analysis of which may resolve controversial phylogenetic relationships. Indeed, indel characters are often assumed to be less homoplastic than amino acid and nucleotide substitutions and, consequently, more reliable markers for phylogenetic reconstruction. In this study, we analyzed indels from over 1,000 metazoan orthologous genes. We studied the impact of different species sampling, ortholog data sets, lengths of included indels, and indel-coding methods on the resulting metazoan tree. Our results show that, similar to sequence substitutions, indels are homoplastic characters, and their analysis is sensitive to the long-branch attraction artifact. Furthermore, improving the taxon sampling and choosing a closely related outgroup greatly impact the phylogenetic inference. Our indel-based inferences support the Ecdysozoa hypothesis over the Coelomata hypothesis and suggest that sponges are a sister clade to other animals.
MULTIMODALITY IN VIVO IMAGING SYSTEMS: Twice the Power or Double the Trouble?
Authors: Simon R. Cherry
Journal: Annual Review of Biomedical Engineering (2006)

Many different types of radiation have been exploited to provide images of the structure and function of tissues inside a living subject. Each imaging modality is characterized by differing resolutions on the spatial and temporal scales, and by a different sensitivity for measuring properties related to morphology or function. Combinations of imaging modalities that integrate the strengths of two modalities, and at the same time eliminate one or more weaknesses of an individual modality, thus offer the prospect of improved diagnostics, therapeutic monitoring, and preclinical research using imaging approaches. This review discusses the advantages and challenges in developing multimodality imaging systems for in vivo use, highlights some successful combinations that are now routinely used in the clinic and in research, and discusses recent advances in multimodality instrumentation that may offer new opportunities for imaging.
Two simple clinical tests for predicting onset of medial tibial stress syndrome: shin palpation test and shin oedema test
Authors: Phil Newman, Roger Adams, Gordon Waddington
Journal: British Journal of Sports Medicine (2012)

To examine the relationship between two clinical test results and future diagnosis of (Medial Tibial Stress Syndrome) MTSS in personnel at a military trainee establishment.Data from a preparticipation musculoskeletal screening test performed on 384 Australian Defence Force Academy Officer Cadets were compared against 693 injuries reported by 326 of the Officer Cadets in the following 16 months. Data were held in an Injury Surveillance database and analysed using χ² and Fisher's Exact tests, and Receiver Operating Characteristic Curve analysis.Diagnosis of MTSS, confirmed by an independent blinded health practitioner.Both the palpation and oedema clinical tests were each found to be significant predictors for later onset of MTSS. Specifically: Shin palpation test OR 4.63, 95% CI 2.5 to 8.5, Positive Likelihood Ratio 3.38, Negative Likelihood Ratio 0.732, Pearson χ² p<0.001; Shin oedema test OR 76.1 95% CI 9.6 to 602.7, Positive Likelihood Ratio 7.26, Negative Likelihood Ratio 0.095, Fisher's Exact p<0.001; Combined Shin Palpation Test and Shin Oedema Test Positive Likelihood Ratio 7.94, Negative Likelihood Ratio <0.001, Fisher's Exact p<0.001. Female gender was found to be an independent risk factor (OR 2.97, 95% CI 1.66 to 5.31, Positive Likelihood Ratio 2.09, Negative Likelihood Ratio 0.703, Pearson χ² p<0.001) for developing MTSS.The tests for MTSS employed here are components of a normal clinical examination used to diagnose MTSS. This paper confirms that these tests and female gender can also be confidently applied in predicting those in an asymptomatic population who are at greater risk of developing MTSS symptoms with activity at some point in the future.