gebhart/patrepeval huggingface dataset:
Reversible Inhibition of Testicular Steroidogenesis and Spermatogenesis by a Potent Gonadotropin-Releasing Hormone Agonist in Normal Men (1981)

We studied the antifertility effects of a potent gonadotropin-releasing hormone agonist, D-Trp6-Pro9-N-ethylamide-LHRH (LHRHA) in eight normal men, who received daily subcutaneous injections for six to 10 weeks. Plasma testosterone levels fell substantially in all eight. Plasma 17-hydroxyprogesterone and serum estradiol-17 beta levels decreased concordantly with plasma testosterone. Impotence developed in five men between the sixth and seventh weeks of treatment, with resolution in each case within two weeks of stopping treatment. Serum gonadotropin levels also fell during treatment, briefly rebounding above basal levels when therapy ended. Sperm density and motility fell t a nadir during the seventh to 18th week after therapy. In six subjects sperm levels fell to 6 X 10(6) sperm per milliliter or less, and in the other two they decreased 70 and 86 per cent below basal mean values. Sperm density returned to pretreatment levels in all men during the 10-to-14-week recovery period. These results are consistent with LHRHA-induced pituitary "desensitization" but do not exclude a direct inhibitory effect of LHRHA on testicular steroidogenesis and spermatogenesis.
Blocking intracellular degradation of the erythropoietin and asialoglycoprotein receptors by calpain inhibitors does not result in the same increase in the levels of their membrane and secreted forms (1996)

The erythropoietin receptor (EPO-R), a type 1 membrane glycoprotein, is degraded mainly in the lysosomes or endosomes, whereas the asialoglycoprotein receptor (ASGP-R) H2a subunit, a type 2 membrane glycoprotein, is degraded exclusively in the endoplasmic reticulum. The present study describes compounds that inhibit the intracellular degradation of these receptors in an efficient manner. However, the levels of cell-surface expression and secretion of their soluble exoplasmic domains were not enhanced to the same extent. The calpain inhibitors N-acetyl-leucyl-leucyl-norleucinal (ALLN) and N-acetyl-leucyl-leucyl-methional (ALLM) inhibited EPO-R degradation profoundly. After 3 h of chase using Ba/F3 cells and NIH 3T3 fibroblasts expressing the EPO-R, virtually all of the receptor molecules were degraded, whereas 80% of the pulse-labelled receptor remained intact in the presence of the inhibitor. EPO-R cell-surface expression was elevated 1.5-fold after 1 h of incubation with ALLN. In the absence of protein synthesis, ALLN caused the accumulation of non-degraded EPO-R molecules in endosomes and lysosomes, as determined by double immunofluorescence labelling of NIH 3T3 cells expressing EPO-Rs. In Ba/F3 cells expressing a soluble EPO-R, ALLN treatment increased secretion of the soluble exoplasmic domain of the EPO-R 2-5-fold. Similarly, in NIH 3T3 cells singly transfected with the ASGP-R H2a subunit cDNA, ALLN inhibited degradation of the ASGP-R H2a subunit precursor, as well as the degradation of the 35 kDa proteolytic fragment corresponding to the receptor ectodomain, by 3-6-fold. However, accumulation of secreted proteolytic fragment in the medium was augmented in the presence of ALLN by only 1.75-fold. In cells expressing the G78R mutant of the ASGP-R H2a subunit, which is not cleaved to the 35 kDa fragment [Yuk and Lodish (1993) J. Cell Biol. 123, 1735-1749], degradation of the precursor was inhibited. Overall, our data suggest the involvement of cysteine proteinases located in the endoplasmic reticulum, as well as in post-Golgi compartments, in degradation of the EPO-R and the ASGP-R H2a subunit. The much lower effect of the inhibitory compounds on cell-surface and secreted forms of the EPO-R and ASGP-R H2a subunit illustrates the complexity and the tight regulation of the cellular localization and stability of membrane proteins.
Extracting a Knowledge Base of Mechanisms from COVID-19 Papers (2020)

The COVID-19 pandemic has spawned a diverse body of scientific literature that is challenging to navigate, stimulating interest in automated tools to help find useful knowledge. We pursue the construction of a knowledge base (KB) of mechanisms -- a fundamental concept across the sciences encompassing activities, functions and causal relations, ranging from cellular processes to economic impacts. We extract this information from the natural language of scientific papers by developing a broad, unified schema that strikes a balance between relevance and breadth. We annotate a dataset of mechanisms with our schema and train a model to extract mechanism relations from papers. Our experiments demonstrate the utility of our KB in supporting interdisciplinary scientific search over COVID-19 literature, outperforming the prominent PubMed search in a study with clinical experts.
The Cassini Ion Mass Spectrometer: Performance Metrics and Techniques (2011)

The Cassini Plasma Spectrometer (CAPS) Ion Mass Spectrometer (IMS) uses a unique electric field configuration coupled with precise sub-nanosecond timing to produce a high mass-resolution plasma analyzer with both broad energy an mass ranges. The IMS maintains a spectrographic mass resolution (m/Δm) of ≥50 over a mass range of 1 to 40amu for singly charged positive ions in the energy range of 0.001 to 15ke V. Ions having energies between 15 and 50keV are measured with a lower mass resolution of ∼7.5 as are ions below 15keV which are neutralized or negatively ionized by passage through thin carbon foils at the entrance to the mass analysis section. Bot high and medium mass resolution measurements are made simultaneously on incoming ions of all masses. The total angular acceptance is 11° × 160° and areal acceptance is ∼1cm 2 per pixel. An overview of the design and results of the laboratory testing of the IMS are presented here.
Effect of Age, Castration, and Testosterone Replacement on the Development and Restoration of Canine Benign Prostatic Hyperplasia (1987)

No AccessJournal of Urology1 Jun 1987Effect of Age, Castration, and Testosterone Replacement on the Development and Restoration of Canine Benign Prostatic Hyperplasia S.J. Berry, D.S. Coffey, J.D. Strandberg, and L.L. Ewing S.J. BerryS.J. Berry More articles by this author , D.S. CoffeyD.S. Coffey More articles by this author , J.D. StrandbergJ.D. Strandberg More articles by this author , and L.L. EwingL.L. Ewing More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)44530-7AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Effect of Age, Castration, and Testosterone Replacement on the Development and Restoration of Canine Benign Prostatic Hyperplasia." The Journal of Urology, 137(6), p. 1324 © 1987 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 137Issue 6June 1987Page: 1324 Advertisement Copyright & Permissions© 1987 by The American Urological Association Education and Research, Inc.MetricsAuthor Information S.J. Berry More articles by this author D.S. Coffey More articles by this author J.D. Strandberg More articles by this author L.L. Ewing More articles by this author Expand All Advertisement PDF downloadLoading ...
P0727P-CRESYL SULFATE AND INDOXYL SULFATE: A POSSIBLE ROLE AS BIOMARKERS IN THE PREDICTION OF RENAL FUNCTION AND CKD PROGRESSION (2020)

Abstract Background and Aims Uremic toxins are markedly accumulated in chronic kidney disease (CKD) patients. Among these two protein-bound compounds, indoxyl sulfate (IXS) and p-cresyl sulfate (PCS) derived from gut bacterial transformation, play an important role. Recent evidences demonstrate their toxic effects in vitro and may contribute in vivo to CKD progression and mortality in uremic patients. For this reason, bacterial metabolism and its metabolites are therapeutic targets in CKD. While, several studies have evaluated possible associations between these two compounds and renal function decline in CKD, while no study has evaluated them according to the stage of progression (CKD stage). In this study, PCS and IXS are considered to highlight the possible role as biomarkers in the prediction of renal function and CKD progression (GFR stage 1-5). Method In our observational, prospective study we evaluated total (t) and free (f) PCS and IXS plasmatic fractions using Ultra High Performance Liquid Chromatography Infinity 1260 (Agilent technologies) coupled to an API 3200™ triple quadrupole mass spectrometry (ABSciex). Data were shown as mean ± SD or median (25th-75th). Statistical analysis was done by SPSS version 24.0 Results We evaluated 80 CKD patients: 54.68 ± 12.88 yrs, 39 F and 41 M. The median creatinine was 1.58 (0.90-3.32) mg/dL, median urea 58.50 (42.0-121.25) mg/dL and eGFR (CKD-EPI) 42 (17.25-85.75) mL/min/1.73 m2. On the table 1, it was summarized the levels of PCS and IXS in all patients and classified by GFR (G) stages. We found the statistically significant increase of total and free fractions of PCS (p&amp;lt;0.001) and IXS (p&amp;lt;0.001) with the progression of CKD by G stage and inverse strong correlation between eGFR (CKD-EPI) and PCSt (Spearman's Rho (r)=-0.70, p&amp;lt;0.001), PCSf (r=-0.75, p&amp;lt;0.001), IXSt (r=-0.76, p&amp;lt;0.001), IXSf (r=-0.82, p&amp;lt;0.001). Moreover, the increase of PCS and IXS predicts the eGFR decline significantly, according to the linear regression model using eGFR as dependent variable: PCSt (R-squared (R2)= 0.34, p&amp;lt;0.001). PCSf (R2=0.21, p&amp;lt;0.001). IXSt (R2=0.27, p&amp;lt;0.001). IXSf (R2=0.19, p&amp;lt;0.001). By multivariate analysis, the total compounds of both toxins remain predictive of eGFR: PCSt (β=-0.72, p=0.003; 95%CI:-2.43;-0.54) and IXSt (β=-0.70, p=0.011; 95%CI:-5.15;-0.70). Conclusion In conclusion, in our study we show the strong correlations between and PCS and IXS and eGFR and we found the significantly increase of PCS and IXS (total and free) with the progression of CKD in all G stage (1-5). We highlight the use of mass spectrometry in the evaluation of renal function especially in the earliest stages of CKD with the possibility of measuring minimum concentrations of PCSf and IXSf. Assuming the predictive value of PCS and IXS towards the reduction of eGFR, we could hypothesize the identification of cut-offs based on confidence intervals, for the prediction and progression of renal function impairment.
Inwardly rectifying potassium channels (K<sub>IR</sub>) in GtoPdb v.2021.3 (2021)

The 2TM domain family of K channels are also known as the inward-rectifier K channel family. This family includes the strong inward-rectifier K channels (Kir2.x) that are constitutively active, the G-protein-activated inward-rectifier K channels (Kir3.x) and the ATP-sensitive K channels (Kir6.x, which combine with sulphonylurea receptors (SUR1-3)). The pore-forming α subunits form tetramers, and heteromeric channels may be formed within subfamilies (e.g. Kir3.2 with Kir3.3).
Pulsatile blood flow in the entire coronary arterial tree: theory and experiment (2006)

The pulsatility of coronary circulation can be accurately simulated on the basis of the measured branching pattern, vascular geometry, and material properties of the coronary vasculature. A Womersley-type mathematical model is developed to analyze pulsatile blood flow in diastole in the absence of vessel tone in the entire coronary arterial tree on the basis of previously measured morphometric data. The model incorporates a constitutive equation of pressure and cross-section area relation based on our previous experimental data. The formulation enables the prediction of the impedance, the pressure distribution, and the pulsatile flow distribution throughout the entire coronary arterial tree. The model is validated by experimental measurements in six diastolic arrested, vasodilated porcine hearts. The agreement between theory and experiment is excellent. Furthermore, the present pulse wave results at low frequency agree very well with previously published steady-state model. Finally, the phase angle of flow is seen to decrease along the trunk of the major coronary artery and primary branches toward the capillary vessels. This study represents the first, most extensive validated analysis of Womersley-type pulse wave transmission in the entire coronary arterial tree down to the first segment of capillaries. The present model will serve to quantitatively test various hypotheses in the coronary circulation under pulsatile flow conditions.
Plasmonic Nanoparticle-Based Digital Cytometry to Quantify MUC16 Binding on the Surface of Leukocytes in Ovarian Cancer (2020)

Although levels of the circulating ovarian cancer marker (CA125) can distinguish ovarian masses that are likely to be malignant and correlate with severity of disease, serum CA125 has not proved useful in general population screening. Recently, cell culture studies have indicated that MUC16 may bind to the Siglec-9 receptor on natural killer (NK) cells where it downregulates the cytotoxicity of NK cells, allowing ovarian cancer cells to evade immune surveillance. We present evidence that the presence of MUC16 can be locally visualized and imaged on the surface of peripheral blood mononuclear cells (PBMCs) in ovarian cancer via a novel "digital" cytometry technique that incorporates: (i) OC125 monoclonal antibody-conjugated gold nanoparticles as optical nanoprobes, (ii) a high contrast dark-field microscopy system to detect PBMC-bound gold nanoparticles, and (iii) a computational algorithm for automatic counting of these nanoparticles to estimate the quantity of surface-bound MUC16. The quantitative detection of our technique was successfully demonstrated by discriminating clones of the ovarian cancer cell line, OVCAR3, based on low, intermediate, and high expression levels of MUC16. Additionally, PBMC surface-bound MUC16 was tracked in an ovarian cancer patient over a 17 month period; the results suggest that the binding of MUC16 on the surface of immune cells may play an early indicator for recurrent metastasis 6 months before computational tomography-based clinical diagnosis. We also demonstrate that the levels of surface-bound MUC16 on PBMCs from five ovarian cancer patients were greater than those from five healthy controls.
GFAP expression and social deficits in transgenic mice overexpressing human sAPPα (2013)

Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed β-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.
Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction (2015)

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354573.
Recent developments in using mechanistic cardiac modelling for drug safety evaluation (2016)

On the tenth anniversary of two key International Conference on Harmonisation (ICH) guidelines relating to cardiac proarrhythmic safety, an initiative aims to consider the implementation of a new paradigm that combines in vitro and in silico technologies to improve risk assessment. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative (co-sponsored by the Cardiac Safety Research Consortium, Health and Environmental Sciences Institute, Safety Pharmacology Society and FDA) is a bold and welcome step in using computational tools for regulatory decision making. This review compares and contrasts the state-of-the-art tools from empirical to mechanistic models of cardiac electrophysiology, and how they can and should be used in combination with experimental tests for compound decision making.
Lessons and challenges in automating data dependability (2004)

Designing and managing dependable systems is a difficult endeavor. In this paper, we describe challenges in this vast problem space, including provisioning and allocating shared resources, adaptively managing system dependability, expressing dependability goals, interactively exploring the design space, and designing end-to-end service dependability. We outline the optimization-based approach we've used to tackle the data dependability portion of this space, and describe how we can extend that approach to address an even larger dependability scope.
Use of ABR flow control in wireless ATM systems (2002)

This paper will propose how available bit rate (ABR), and in particular the flow control mechanisms inherent to it, could be applied to provide consistent resource management of both fixed and, in particular, radio resources in a wireless ATM network integrated into fixed ATM. The paper also includes some preliminary simulation results, showing the efficiency of the proposed scheme. The ABR flow control mechanism can successfully be used also to protect the capacity limited radio interface in a wireless ATM system. This is useful when wireless ATM systems must support bursty data traffic. Our simulations have shown that the proposed way of using the ABR flow control allows efficient radio interface operation with a rather limited and predictable amount of buffering capacity in the access points. This is essential in providing adequate cell loss performance of low cost access points. The radio interface utilisation is also quite high, one more important characteristic when designing wireless systems.
Prognostic value of PET/CT and CT in T‐cell lymphoblastic lymphoma/leukaemia patients: A retrospective cohort study of 145 patients (2023)

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BioAssay Research Database (BARD): chemical biology and probe-development enabled by structured metadata and result types (2014)

BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource.
Crossroads in GDNF therapy for Parkinson's disease (2006)

The development of a neuroprotective or neuroregenerative therapy for Parkinson's disease (PD) would be a major therapeutic advance. Unfortunately, results from a recent controlled clinical study delivering the neurotrophic factor, glial-derived neurotrophic factor (GDNF), directly into brain did not demonstrate efficacy and safety of such a treatment. A critical review of available data suggests that there are questions that need to be answered before the future of GDNF as a therapy for PD can be determined.
P4‐181: In vitro study on [3H]THK523 binding to brain tissues of Alzheimer's disease (2012)

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Neurofibrillary tangles (NFTs) are one of the pathological hallmarks found in AD brains. NFTs in the brain are tightly associated with the severity of dementia, indicating the contribution of NFTs to neuronal dysfunction. NFTs are a therapeutic target of AD for disease modifying therapy. A PET tracer for imaging NFTs in the brain would be valuable in the development of new therapies for AD. Recently, [18 F]THK523 was reported as a novel in vivo tau imaging ligand for AD(1). Here we report our study on in vitro THK523 binding in AD brain tissues using [3 H]THK523. Frozen brains of human and mouse were used in the study, including AD and non-AD. [3 H]THK523 was synthesized in house. Autoradiography (ARG) was performed using frozen brain slices with [3 H]THK523. Unlabeled Pittsburgh Compound-B (PIB) was used as a blocking compound in addition to self block. Immunohistochemistry (IHC) was carried out with brain slices adjacent to those in the ARG study using antibodies for amyloid plaques (6E10) and NFTs (PHF6). In human AD brain slices of hippocampus, we observe displaceable [3 H]THK523 binding by self block in the entorihnal cortex and hippocampus, which co-localizes with positive PHF6 staining by IHC in the adjacent brain slices. But, unlike self block (1 μ M), PIB at 300 nM shows minimal inhibition of [3 H]THK523 binding sites in those brain regions. This is consistent with the report about [3 H]THK523 binding to tau pathology. However, in human AD brain slices of cerebral cortex, we observe displaceable and punctate [3 H]THK523 binding in the gray matter, similar to the pattern of positive 6E10 staining of β -amyloid plaques by IHC in the adjacent slices. In addition, PIB (300 nM) shows full inhibition of punctate [3 H]THK523 binding in cortex gray matter. This is inconsistent with the reported binding selectivity of [3 H]THK523 as a tau imaging ligand. The data suggest [3 H]THK523 not only binds to tau pathology but also to β -amyloid plaques in AD brain slices. The study indicates further investigation is necessary to determine utility of THK523 as a selective tau imaging tracer.