gebhart/patrepeval huggingface dataset:
Targeting the Loss of the <i>von Hippel-Lindau</i> Tumor Suppressor Gene in Renal Cell Carcinoma Cells (2007)

Late-stage clear cell renal carcinoma poses a formidable clinical challenge due to the high mortality rate associated with this disease. Molecular and genetic studies have identified functional loss of the von Hippel-Lindau (VHL) gene as a frequent and crucial event in the development of the malignant phenotype of clear cell renal carcinomas. Loss of VHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. The objective of this study was to evaluate the possibility of targeting VHL loss through pharmacologic means. Chromomycin A3 (ChA3) was identified through in silico analysis of existing publicly available drug profiles from the National Cancer Institute as an agent that seemed to selectively target VHL-deficient clear cell renal carcinoma cells. Genotype-selective toxicity was first determined through short-term viability assays and then confirmed with clonogenic studies. Coculture of fluorescently labeled VHL-deficient and VHL-positive cells showed discriminate killing of the VHL-deficient cells with ChA3. Mechanistically, overexpression of hypoxia-inducible factor (HIF)-2alpha in VHL-positive clear cell renal carcinoma cells phenocopied loss of VHL with respect to ChA3 toxicity, establishing ChA3 as a HIF-dependent cytotoxin. This study shows the feasibility of selectively targeting the loss of the VHL tumor suppressor gene in clear cell renal carcinoma for potential clinical benefit and may have greater ramifications in the development of new targeted therapies for the treatment of cancer and other genetic diseases.
An Interactive Tool for Supporting Error Analysis for Text Mining (2010)

This demo abstract presents an interactive tool for supporting error analysis for text mining, which is situated within the Summarization Integrated Development Environment (SIDE). This freely downloadable tool was designed based on repeated experience teaching text mining over a number of years, and has been successfully tested in that context as a tool for students to use in conjunction with machine learning projects. 1
Numerical comparison of different penalty modified barrier functions for optical tomography problems (2009)

Fluorescent contrast agents have been proposed for near-infrared (NIR) diagnostic breast imaging problems as the most efficient process for inducing optical contrast. We have developed a penalty modified barrier function method (PMBF) with constrained truncated Newton and trust region methods (CONTN) for fluorescence-enhanced NIR diagnostic imaging for both noncontact (area illumination/collection) and contact (point illumination/collection) measurement techniques. A simple logarithmic penalty function has been used in the PMBF/CONTN algorithm with linear convergence. The motivation of this paper is to compare the efficiency and performance of this method with many alternative penalty barrier function methods, (a) hyperbolic penalty function, (b) quadratic-logarithm penalty function, (c) logarithmic exponential penalty function for proper selection of a penalty function that will be the most suitable for optical reconstruction problems. In this paper a numerical comparison of different penalty function methods has been made using experimental measured data in a clinically relevance volume in three-dimensions. Our objective is to continue development of sophisticated constrained optimization PMBF/CONTN method to provide high resolution three dimensional tomography a reality.
Quantitative assessment of the effect of anode surface roughness on diagnostic X-ray spectra: A Monte Carlo simulation study (2009)

An experimental measurement study involving surface profilometry and scanning electron microscopy (SEM) combined with MCNP4C-based Monte Carlo simulations was performed to evaluate anode surface roughness in aged X-ray tubes and to quantitatively predict its impact and relevance on generated diagnostic X-ray spectra. Surface profilometry determined that the center-line average roughness in the most aged x-ray tube evaluated in our study was around 50 ?m. SEM measurements also revealed valuable details about the morphology of cracks and irregularities on the anode's focal path. An image-based modeling method was followed for defining more realistic models from the surface-cracked anodes into MCNP's environment. In this approach, the matrices of focal spot images were numerically processed such that the mean depth of cracks along with their spatial pattern to be incorporated into pixel values in agreement with the measured average depths. By invoking MCNP4C's Gaussian energy broadening (GEB), the correctness of this code in simulating diagnostic x-ray spectra was well validated against experimentally-measured spectra. The simulated spectra in surface deteriorated anode models were compared with those simulated in perfectly plain anodes considered as reference. From these comparisons, an intensity loss of 4.5% and 16.8% was predicted for anodes aged by 5 and 50 ?m-deep cracks in conditions of 50 kVp, 6 degree target angle, 2.5 mm Al total filtration. By deploying several point detectors (F5 tallies) along the anode-cathode direction and averaging exposure over them, it was found that for a 12 degree anode roughened by 50 ?m-deep cracks, the reduction of overall exposure is 14.9% and 13.1% for 70 and 120 kVp tube voltages, respectively. Finally, change in patient entrance skin dose (ESD), as a result of anode roughness, was assessed under various conditions in a chest X-ray radiography examination. In conclusion, anode surface roughness can have a non negligible effect on output spectra in aged X-ray imaging tubes and as such, depending on X-ray tube's workload, its impact should be carefully considered in medical X-ray imaging systems.
ChemInform Abstract: Proton‐Conductive Metal—Organic Frameworks (2016)

Abstract Review: 85 refs.
Bioactives in Blueberries Improve Insulin Sensitivity in Obese, Insulin-Resistant Men (2010)

Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)×m 22 ×min 21 ). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n =1 5) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants’ body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 6 0.5 mg×kg FFM 21 ×min 21 ) than in the placebo group (0.4 6 0.4 mg×kg FFM 21 ×min 21 )( P =0 .04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants. J. Nutr. 140: 1764‐1768, 2010.
Biosynthesis of Resorcylic Acid Lactone Lasiodiplodin in<i>Lasiodiplodia theobromae</i> (2009)

The biosynthesis of lasiodiplodin (1) and its (5S)-5-hydroxylated derivative (2) were investigated by the administration of (13)C-labeled acetates to Lasiodiplodia theobromae. The labeling patterns of biosynthetically (13)C-labeled 1 and 2 were determined by (13)C-NMR and INADEQUATE spectra, demonstrating the octaketide origins of 1 and 2. Taking into account the biosynthetic study of resorcylic acid lactones, the involvement of highly reduced acyl intermediates in the biosynthesis of lasiodiplodins was presumed; thus, we synthesized (2)H-labeled hypothetical acyl intermediates of 1, 9-hydroxydecanoic acid (4) and its N-acetylcysteamine thioester (SNAC, 5). When L. theobromae was incubated with 5 mM of a (2)H-labeled intermediate, the (2)H-label from the intermediate was incorporated at the expected position of 1. These incorporation studies revealed that 1 was produced via a pathway which closely resembles that of resorcylic acid lactone biosynthesis.
Justify Your Answer: The Role of Written Think Aloud in Script Concordance Testing (2016)

Written TA can optimize SCT by demonstrating when correct examinee responses are based on guessing or uncertainty rather than robust clinical rationale. TA can also enhance SCT by allowing examinees to provide justification for responses that otherwise would have been considered incorrect and by identifying questions that are frequently misinterpreted to avoid including them in future examinations. TA also has significant value in differentiating between acceptable variations in expert clinician responses and deviance associated with faulty rationale or question misinterpretation; this could improve SCT reliability. A written TA protocol appears to be a valuable tool to assess trainees' clinical reasoning and can strengthen the quantitative assessment provided by SCT.
Alpha1-antitrypsin deficiency: a clinical-genetic overview (2011)

Severe α1-antitrypsin deficiency (AATD) is an inherited disorder, leading to development of emphysema in smokers at a relatively young age with disability in their forties or fifties. The emphysema results from excessive elastin degradation by neutrophil elastase as a result of the severe deficiency of its major inhibitor α1-antitrypsin (AAT). The AAT expression is determined by the SERPINA1 gene which expresses codominant alleles. The three most common alleles are the normal M, the S with plasma levels of 60% of normal, and the severely deficient Z with levels of about 15% of normal. Homozygosity for the Z mutant allele is associated with retention of abnormal AAT in the liver, which may lead to neonatal hepatitis, liver disease in children, and liver disease in adults. Regular intravenous infusions of purified human AAT (AAT augmentation therapy) have been used to partially correct the biochemical defect and protect the lung against further injury. Two randomized controlled trials showed a trend of slower progression of emphysema by chest computerized tomography. Integrated analysis of these two studies indicated significantly slower progression of emphysema. AAT is quantified by immunologic measurement of AAT in serum, the phenotype characterized by isoelectric focusing, the common genotypes by targeted DNA analysis, and by sequencing the coding region of the gene when the AAT abnormality remains undefined. AATD is often unrecognized, and diagnosis delayed. Testing for AATD is recommended in patients with chronic irreversible airflow obstruction, especially in those with early onset of disease or positive family history. Testing is also recommended for immediate family members of those with AATD, asthmatics with persistent airflow obstruction, and infants and older subjects with unexplained liver disease. There are over 100 different AAT gene variants; most are rare and only some are associated with clinical disease.
Effective screen for amyloid &beta; aggregation inhibitor using amyloid &beta;-conjugated gold nanoparticles (2010)

The abnormal aggregation of amyloid β (Aβ) and its subsequent intra- and extracellular accumulation constitute the disease-causing cascade of Alzheimer's disease (AD). The detection of Aβ aggregates and senile plaque formation, however, is nearly impossible during early pathogenesis, and the absence of a convenient screen to validate the activity of Aβ aggregation regulators impedes the development of promising drug targets and diagnostic biomarkers for AD. Here, we conjugated amyloid β42 (Aβ42) peptide to gold nanoparticles (AuNPs) to visualize Aβ42 aggregation via Aβ42 aggregation-induced AuNP precipitation. AuNP-Aβ42 precipitate was quantified by optical density measurements of supernatants and thioflavin T binding assay. Transmission electron microscopy (TEM) analysis also showed reduced interparticle distance of AuNPs and confirmed the Aβ42 aggregation-induced AuNP precipitation. Transthyretin, a widely known Aβ aggregation inhibitor, limited AuNP-Aβ42 precipitation by preventing Aβ42 aggregation. Finally, according to TEM analysis, Aβ42-conjugated AuNPs treated with blood-driven serum revealed the differentiated aggregation patterns between normal and AD. These findings may open a scientific breakthrough in finding a possible diagnostic and prognostic tool for neurodegenerative diseases involving abnormal protein aggregation as their key pathogenesis processes.
Measuring Flux Density Of Monatomic Oxygen (1991)

Improved version of catalytic-probe technique yields more accurate measurements of flux density of neutral, monatomic oxygen. Two probes measure heat of recombination on catalytic surface. Principal application of technique in experiments in which oxygen plasmas used to examine degradation of various materials by monatomic oxygen.
RamA, a Protein Required for Reductive Activation of Corrinoid-dependent Methylamine Methyltransferase Reactions in Methanogenic Archaea (2008)

Archaeal methane formation from methylamines is initiated by distinct methyltransferases with specificity for monomethylamine, dimethylamine, or trimethylamine. Each methylamine methyltransferase methylates a cognate corrinoid protein, which is subsequently demethylated by a second methyltransferase to form methyl-coenzyme M, the direct methane precursor. Methylation of the corrinoid protein requires reduction of the central cobalt to the highly reducing and nucleophilic Co(I) state. RamA, a 60-kDa monomeric iron-sulfur protein, was isolated from Methanosarcina barkeri and is required for in vitro ATP-dependent reductive activation of methylamine:CoM methyl transfer from all three methylamines. In the absence of the methyltransferases, highly purified RamA was shown to mediate the ATP-dependent reductive activation of Co(II) corrinoid to the Co(I) state for the monomethylamine corrinoid protein, MtmC. The ramA gene is located near a cluster of genes required for monomethylamine methyltransferase activity, including MtbA, the methylamine-specific CoM methylase and the pyl operon required for co-translational insertion of pyrrolysine into the active site of methylamine methyltransferases. RamA possesses a C-terminal ferredoxin-like domain capable of binding two tetranuclear iron-sulfur proteins. Mutliple ramA homologs were identified in genomes of methanogenic Archaea, often encoded near methyltrophic methyltransferase genes. RamA homologs are also encoded in a diverse selection of bacterial genomes, often located near genes for corrinoid-dependent methyltransferases. These results suggest that RamA mediates reductive activation of corrinoid proteins and that it is the first functional archetype of COG3894, a family of redox proteins of unknown function.
Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor (2015)

DNA-encoded small-molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, this technology has been used with soluble protein targets that are produced and used in a purified state. Here, we describe a cell-based method for identifying small-molecule ligands from DNA-encoded libraries against integral membrane protein targets. We use this method to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs). The method is simple and broadly applicable to other GPCRs and integral membrane proteins. We have extended the application of DNA-encoded library technology to membrane-associated targets and demonstrate the feasibility of selecting DNA-tagged, small-molecule ligands from complex combinatorial libraries against targets in a heterogeneous milieu, such as the surface of a cell.
Activation of the Promoter of the Orphan Receptor SHP by Orphan Receptors That Bind DNA as Monomers (1999)

Small heterodimer partner (SHP) is an orphan nuclear receptor that lacks a conventional DNA binding domain. It interacts with several other members of the nuclear receptor superfamily and inhibits receptor transactivation. In order to characterize the regulation of SHP expression, a number of receptors and other transcription factors were tested for effects on the SHP promoter. Among these, the orphan receptor steroidogenic factor-1 (SF-1) was found to potently transactivate the SHP promoter. Detailed footprinting studies show that the SHP promoter contains at least five SF-1 binding sites, and mutagenesis studies demonstrate each of the three strongest binding sites is required for SF-1 transactivation. SHP is coexpressed with SF-1 in adrenal glands, but is also expressed in tissues that lack SF-1, including liver. However, liver expresses a close relative of SF-1, the orphan fetoprotein transcription factor (FTF), and FTF can also transactivate the SHP promoter. These results suggest that alterations in the levels or activities of SF-1 or FTF could modulate SHP expression in appropriate tissues and thereby affect a variety of receptor dependent signaling pathways.
Phosphorylation by a G protein-coupled kinase inhibits signaling and promotes internalization of the monocyte chemoattractant protein-1 receptor. Critical role of carboxyl-tail serines/threonines in receptor function (1996)

Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine family of chemotactic cytokines and signals via activation of a G protein-coupled seven-transmembrane domain receptor to mediate chemotaxis. Monocyte activation is limited by desensitization and internalization of the MCP-1R, but these mechanisms are not well understood. In this study, we show that the type B MCP-1R (MCP-1RB/CCR2B) is rapidly phosphorylated and internalized in response to nanomolar concentrations of MCP-1. Co-expression of CCR2B in Xenopus oocytes with beta-adrenergic receptor kinase 2 (beta ark2), but not beta ark1 or rhodopsin kinase, specifically blocked receptor activation by MCP-1. Mutation of serine (Ser) and threonine (Thr) residues in the terminal carboxyl-tail of the receptor, which are potential targets of beta ark-mediated phosphorylation, prevented inhibition of receptor activation by beta ark2 in microinjected oocytes. Finally, a construct in which multiple Ser and Thr residues in the carboxyl-tail were changed to alanine significantly prolonged the agonist-dependent intracellular calcium flux and inhibited receptor internalization in transfected human embryonic kidney (HEK)-293 cells. These studies demonstrate that phosphorylation of Ser and Thr residues in the carboxyl-tail of CCR2B mediates receptor desensitization and internalization and may serve to limit the chemotactic response of leukocytes to MCP-1 and related chemokines.
Evaluation of mRNA Biomarkers to Identify Risk of Hospital Acquired Infections in Children Admitted to Paediatric Intensive Care Unit (2016)

To our knowledge, this is the first study of mRNA biomarkers of HAI in the paediatric population. Increased mRNA expressions of anti-inflammatory cytokine and modulation of apoptotic genes suggest the development of immunosuppression in critically ill children. Immune monitoring using a panel of genes may offer a novel stratification tool to identify HAI risk.
Deep Learning for Frame Error Probability Prediction in BICM-OFDM Systems (2018)

In the context of wireless communications, we propose a deep learning approach to learn the mapping from the instantaneous state of a frequency selective fading channel to the corresponding frame error probability (FEP) for an arbitrary set of transmission parameters. We propose an abstract model of a bit interleaved coded modulation (BICM) orthogonal frequency division multiplexing (OFDM) link chain and show that the maximum likelihood (ML) estimator of the model parameters estimates the true FEP distribution. Further, we exploit deep neural networks as a general purpose tool to implement our model and propose a training scheme for which, even while training with the binary frame error events (i.e., ACKs / NACKs), the network outputs converge to the FEP conditioned on the input channel state. We provide simulation results that demonstrate gains in the FEP prediction accuracy with our approach as compared to the traditional effective exponential SIR metric (EESM) approach for a range of channel code rates, and show that these gains can be exploited to increase the link throughput.
Finding a Stable Route Through AODV by Using Route Fragility Coefficient as Metric (2006)

The widespread applications of Mobile Ad hoc Networks (MANET) and scarce network resources have lead to the development of many protocols in this field. The need of time is to find a protocol which makes efficient use of resources and improves the overall performance of network. This paper focuses on enhancing the performance of Ad Hoc on Demand Distance Vector (AODV) routing protocol by choosing Route Fragility Coefficient (RFC) as its metric. This metric causes AODV to find a stable route. The stable route is characterized as the one which has less dynamism and in which nodes stay close to each other. Simulation results are provided to demonstrate improvement in throughput and reduction in routing protocol overhead with increased mobility. The performance metrics are measured by varying the maximum speed of the nodes and size of the network.
A concentric array for low and medium frequencies (1990)

It is shown that a concentric array of improved directivity Corum elements disposed about a central tower, driven by appropriate source amplitudes, produces a Fourier series approximation to any desired vertically polarized radiation pattern in the plane of the array. The antenna system is of special interest to broadcasters (where protected contours and interference levels are legally constrained) and also to other medium- and low-frequency users who require a vertically polarized directional array. An elementary example of the pattern synthesis technique is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The Analysis of Panel Data under a Markov Assumption (1985)

Abstract Methods for the analysis of panel data under a continuous-time Markov model are proposed. We present procedures for obtaining maximum likelihood estimates and associated asymptotic covariance matrices for transition intensity parameters in time homogeneous models, and for other process characteristics such as mean sojourn times and equilibrium distributions. Generalizations to handle covariance analysis and to the fitting of certain nonhomogeneous models are presented, and an example based on a longitudinal study of the smoking habits of school children is discussed. Questions of embeddability and estimation are examined.