gebhart/patrepeval huggingface dataset:
Lymphotoxin alpha gene in Crohn's disease patients: absence of implication in the response to infliximab in a large cohort study (2006)

A haplotype in the lymphotoxin alpha (LTA) gene has been associated with a lack of response to infliximab in a small cohort of Crohn's disease (CD) patients. The present study aimed to confirm the implication of this haplotype in the response to infliximab in a larger cohort of Caucasian patients. The response to the first infusion with infliximab was evaluated in 214 Caucasian patients with either luminal (n=150) or fistulising (n=64) CD. Clinical response was based on the decrease in CD Activity Index (luminal) or on the evolution in the fistula discharge (fistulising). Biological response was assessed in 139 patients who had elevated C-reactive protein (CRP) before treatment and for whom CRP values were also available after treatment. A positive biological response was defined as a decrease in CRP of at least 25%. The patients were genotyped for six polymorphisms in the LTA gene. A positive clinical response was present in 65.4% of the patients and a positive biological response was observed in 80.6% of the patients. No association was found with any of the studied polymorphisms, nor with the previously published LTA haplotype and the response to infliximab. We could not confirm an association between the LTA locus and clinical or biological response to infliximab in a large cohort of CD patients.
Cross-modulated Few-shot Image Generation for Colorectal Tissue Classification (2023)

In this work, we propose a few-shot colorectal tissue image generation method for addressing the scarcity of histopathological training data for rare cancer tissues. Our few-shot generation method, named XM-GAN, takes one base and a pair of reference tissue images as input and generates high-quality yet diverse images. Within our XM-GAN, a novel controllable fusion block densely aggregates local regions of reference images based on their similarity to those in the base image, resulting in locally consistent features. To the best of our knowledge, we are the first to investigate few-shot generation in colorectal tissue images. We evaluate our few-shot colorectral tissue image generation by performing extensive qualitative, quantitative and subject specialist (pathologist) based evaluations. Specifically, in specialist-based evaluation, pathologists could differentiate between our XM-GAN generated tissue images and real images only 55% time. Moreover, we utilize these generated images as data augmentation to address the few-shot tissue image classification task, achieving a gain of 4.4% in terms of mean accuracy over the vanilla few-shot classifier. Code: \url{https://github.com/VIROBO-15/XM-GAN}
A <i>Survivin</i> Gene Signature Predicts Aggressive Tumor Behavior (2005)

Gene signatures that predict aggressive tumor behavior at the earliest stages of disease, ideally before overt tissue abnormalities, are urgently needed. To search for such genes, we generated a transgenic model of survivin, an essential regulator of cell division and apoptosis overexpressed in cancer. Transgenic expression of survivin in the urinary bladder did not cause histologic abnormalities of the urothelium. However, microarray analysis revealed that survivin-expressing bladders exhibited profound changes in gene expression profile affecting extracellular matrix and inflammatory genes. Following exposure to a bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN), survivin transgenic animals exhibited accelerated tumor progression, preferential incidence of tumors as compared with premalignant lesions, and dramatically abbreviated survival. Conversely, transgenic expression of a survivin Thr34-->Ala dominant-negative mutant did not cause changes in gene expression or accelerated tumor progression after OH-BBN treatment. Therefore, survivin expression induces global transcriptional changes in the tissue microenvironment that may promote tumorigenesis. Detection of survivin or its associated gene signature may provide an early biomarker of aggressive tumor behavior before the appearance of tissue abnormalities.
Mutagenesis of Beryllium-Specific TCRs Suggests an Unusual Binding Topology for Antigen Recognition (2011)

Unconventional Ags, such as metals, stimulate T cells in a very specific manner. To delineate the binding landscape for metal-specific T cell recognition, alanine screens were performed on a set of Be-specific TCRs derived from the lung of a chronic beryllium disease patient. These TCRs are HLA-DP2-restricted and express nearly identical TCR Vβ5.1 chains coupled with different TCR α-chains. Site-specific mutagenesis of all amino acids comprising the CDRs of the TCRA and TCRB genes showed a dominant role for Vβ5.1 residues in Be recognition, with little contribution from the TCR α-chain. Solvent-exposed residues along the α-helices of the HLA-DP2 α- and β-chains were also mutated to alanine. Two β-chain residues, located near the proposed Be binding site of HLA-DP2, played a dominant role in T cell recognition with no contribution from the HLA-DP2 α-chain. These findings suggest that Be-specific T cells recognize Ag using an unconventional binding topology, with the majority of interactions contributed by TCR Vβ5.1 residues and the HLA-DP2 β1-chain. Thus, unusual docking topologies are not exclusively used by autoreactive T cells, but also for the recognition of unconventional metal Ags, such as Be.
Alveolar Dead Space as a Predictor of Severity of Pulmonary Embolism (2000)

The V(D)alv/V(T)alv correlates with the lung perfusion defect and the pulmonary artery pressures in subjects with PE. These findings show the potential for V(D)alv/V(T)alv to quantify the embolic burden of PE.
Experimental analysis of exome-scale mutational signature of glycidamide, the reactive metabolite of acrylamide (2018)

Abstract Acrylamide, a probable human carcinogen, is ubiquitously present in the human environment, with sources including heated starchy foods, coffee and cigarette smoke. Humans are also exposed to acrylamide occupationally. Acrylamide is genotoxic, inducing gene mutations and chromosomal aberrations in various experimental settings. Covalent haemoglobin adducts were reported in acrylamide-exposed humans and DNA adducts in experimental systems. The carcinogenicity of acrylamide has been attributed to the effects of glycidamide, its reactive and mutagenic metabolite capable of inducing rodent tumors at various anatomical sites. In order to characterize the pre-mutagenic DNA lesions and global mutation spectra induced by acrylamide and glycidamide, we combined DNA-adduct and whole-exome sequencing analyses in an established exposure-clonal immortalization system based on mouse embryonic fibroblasts. Sequencing and computational analysis revealed a unique mutational signature of glycidamide, characterized by predominant T:A&gt;A:T transversions, followed by T:A&gt;C:G and C:G&gt;A:T mutations exhibiting specific trinucleotide contexts and significant transcription strand bias. Computational interrogation of human cancer genome sequencing data indicated that a combination of the glycidamide signature and an experimental benzo[ a ]pyrene signature are nearly equivalent to the COSMIC tobacco-smoking related signature 4 in lung adenocarcinomas and squamous cell carcinomas. We found a more variable relationship between the glycidamide‐ and benzo[ a ]pyrene-signatures and COSMIC signature 4 in liver cancer, indicating more complex exposures in the liver. Our study demonstrates that the controlled experimental characterization of specific genetic damage associated with glycidamide exposure facilitates identifying corresponding patterns in cancer genome data, thereby underscoring how mutation signature laboratory experimentation contributes to the elucidation of cancer causation. A 40-word summary Innovative experimental approaches identify a novel mutational signature of glycidamide, a metabolite of the probable human carcinogen acrylamide. The results may elucidate the cancer risks associated with exposure to acrylamide, commonly found in tobacco smoke, thermally processed foods and beverages.
Identification of the active site tyrosine of Flp recombinase. Possible relevance of its location to the mechanism of recombination. (1990)

A combination of site-directed mutagenesis and amino acid sequence analysis identifies Tyr-343 of Flp recombinase as the residue that covalently attaches to DNA during the strand-cleavage step of recombination. This residue is part of the invariant His-Arg-Tyr triad of the Int family of recombinases. Tyr-343 is located in a highly protease-accessible (and hence "open") region of Flp. This placement may provide the conformational flexibility required for the dual role of Tyr-343 in recombination: nicking of the DNA strands to initiate recombination and joining of the nicked strands across partner substrates to complete recombination. In-frame insertion of a few amino acids close to Tyr-343 (and to its amino-terminal side) does not affect substrate recognition by Flp but abolishes its catalytic function.
An Embodied Brain Model of the Human Foetus (2016)

Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system.
A Universal Peptide Matrix Interactomics Approach to Disclose Motif-Dependent Protein Binding (2021)

Protein-protein interactions mediated by intrinsically disordered regions are often based on short linear motifs (SLiMs). SLiMs are implicated in signal transduction and gene regulation yet remain technically laborious and notoriously challenging to study. Here, we present an optimized method for a protein interaction screen on a peptide matrix (PRISMA) in combination with quantitative MS. The protocol was benchmarked with previously described SLiM-based protein-protein interactions using peptides derived from EGFR, SOS1, GLUT1, and CEBPB and extended to map binding partners of kinase activation loops. The detailed protocol provides practical considerations for setting up a PRISMA screen and subsequently implementing PRISMA on a liquid-handling robotic platform as a cost-effective high-throughput method. Optimized PRISMA can be universally applied to systematically study SLiM-based interactions and associated post-translational modifications or mutations to advance our understanding of the largely uncharacterized interactomes of intrinsically disordered protein regions.
Single‐cell spatial transcriptomics analysis of a regenerating liver (2022)

Liver, the largest gland in the body performs more than 500 functions. It is comprised of lobules, which are the functional metabolic units formed by a central vein in the center, and multiple portal triads at the periphery. Each portal triad is composed of a portal vein, hepatic artery and bile duct. Blood enters the lobule through portal vein and hepatic artery and moves through sinusoids that are lined by the sinusoidal endothelial cells (LSECs) and eventually exits through the central vein. Hepatocytes line the other side of the endothelial cells along the porto‐central axis. Intriguingly, the hepatocytes located across the lobule express genes differently based on their proximity to portal triad (zone‐1) versus central vein (zone‐3). This process of metabolic zonation ensures division of labor making hepatocytes more efficient in performing their endowed functions of synthesis, metabolism and detoxification based on their location in specific zones. Recent studies have begun to show that zonation of gene expression exists not only in hepatocytes but also in other minority cell types of the liver including cholangiocytes, endothelial cells, macrophages and stellate cells. Liver is also a unique organ with an innate capability to regenerate following toxicant‐induced injury or surgical resection. The process of regeneration is ensured by replication of all surviving cells in the liver. Very little is known about how metabolic zonation changes during the process of regeneration and how the various functions performed by the liver are maintained while the hepatocytes and other cells undergo replication towards attaining the pre‐hepatectomy mass. Here, we perform Molecular Cartography TM , a single cell spatial transcriptomics technique, to address changes in the both the expression and location of both zonated and non‐zonated genes in various cell types of the liver following partial hepatectomy. We address how these one hundred carefully selected genes undergo dynamic regulation as cells in the remnant liver attempt to maintain both function and proliferate to restore liver mass. In our current study we identify dynamic changes in spatiotemporal regulation of multiple important genes associated with most proliferation and function of cells during the process of liver regeneration.
Fabrication and Characterization of Rapidly Oxidized p-Type Cu<sub>2</sub>O Films from Cu Films and their Application to Heterojunction Thin-Film Solar Cells (2013)

In this study, we report that the metal Cu deposited on a glass substrate is formed into a stable p-type Cu 2 O film with excellent properties through rapid thermal oxidation (RTO). The pre-deposited Cu film layer went through thermal oxidation in the temperature range of 200–500 °C in O 2 and air ambient, and the electrical and optical properties were intensively investigated. The optimized p-type Cu 2 O film heat-treated at a temperature of 200 °C in an air ambient has a carrier concentration of 1.25×10 17 cm -3 , mobility of 0.51 cm 2 V -1 s -1 , and resistivity of 9.86 Ω cm; its optical band gap reaches about 2.4 eV. Using the p-type Cu 2 O film with i- and n-type amorphous silicon layers, heterojunction thin-film solar cells were fabricated on glass substrates. These transparent solar cells employed Ga-doped ZnO films as top and bottom electrodes. Solar cells with Cu 2 O film oxidized at 200 °C in an air ambient have an open circuit voltage of 0.36 V, short-circuit current of 15.2 mA/cm 2 , and photoelectric conversion efficiency of 1.98%.
Volume Pledge is Not Associated with Better Short-Term Outcomes After Lung Cancer Resection (2020)

The Volume Pledge was not associated with better outcomes except for a marginally shorter length of stay. A re-examination of volume-outcome relationships for hospitals and surgeons yielded mixed results that did not reveal a practical alternative for volume-based quality improvement efforts.
Seismic velocities of unconsolidated sands: Part 2 — Influence of sorting- and compaction-induced porosity variation (2006)

Abstract Unaccounted-for porosity variation in unconsolidated sediments can cloud the interpretation of the sediment's seismic velocities for factors such as fluid content and pressure. However, an understanding of the effects of porosity variation on the velocities can permit the remote characterization of porosity with seismic methods. We present the results of a series of measurements designed to isolate the effects of sorting- and compaction-induced porosity variation on the seismic velocities and their pressure dependences in clean, unconsolidated sands. We prepared a set of texturally similar sand and glass-bead samples with controlled grain-size distributions to cover an initial porosity range from 0.26 to 0.44. We measured the compressional- and shear-wave velocities and porosity of dry samples over a series of hydrostatic pressure cycles from 0.1to20MPa. Over this rangeof porosities, the velocities of the dry samples at a given pressure vary by &amp;lt;15%. However, the water-saturated compressional-wave velocities, modeled with Gassmann fluid substitution, demonstrate a consistent increase with decreasing porosity. In both the dry and water-saturated cases, the porosity trend at a given pressure is approximately described by the isostress (harmonic) average between the moduli of the highest-porosity sample at that pressure and the moduli of quartz, the predominant mineral component of the samples. Empirical power-law fit coefficients describing the pressure dependences of the dry bulk, shear, and constrained (P-wave) moduli from each sample also demonstrate no significant, systematic relationship with the porosity. The porosity dependence of the water-saturated bulk and constrained moduli is primarily contained in the empirical coefficient representing the modulus at zero pressure.
Photopolymers for holographic recording : from standard to self-processing materials (1993)

There has been a recent surge of interest in photopolymerizable materials in the field of holographic recording. Such materials exhibiting sensitivity in the UV, visible and near IR domains are now available. They are used for transmission or reflexion holography and generate permanent thick phase gratings. In spite of their poor photosensitivity compared to silver halide emulsions, they are interesting candidates for many holographic applications such as real time interferometry. The direct generation of images with no post-treatment, nor repositioning is their most attractive feature. A recording system which is sensitive in the 450-550 nm range and which is the most avanced version of the materials developed in Mulhouse, is used to exemplify the performances of self-developing polymer layers in the fields of interferometry, optical correlation or HOE.
P4‐070: A PROGRAM OF PRE‐SYMPTOMATIC EVALUATION OF EXPERIMENTAL OR NOVEL TREATMENTS FOR ALZHEIMER'S DISEASE (PREVENT‐AD): DESIGN, METHODS, AND PERSPECTIVES (2014)

Brain changes in Alzheimer's disease (AD) occur decades before appearance of the first symptoms of dementia. This pre-symptomatic stage of AD presents an opportunity to test interventions that can slow the disease process and thereby delay the onset of dementia. Efficiency of this work is enhanced by enrolling persons who have a first-degree relative with AD dementia.We describe a program in such subjects designed to test whether specific interventions will likely delay dementia onset. Our new Centre for Studies on Prevention of AD (StoP-AD) is assembling such a high-risk cohort and testing effects of potential prevention strategies in pre-symptomatic individuals. The Centre's first intervention trial will examine the effects of the nonsteroidal anti-inflammatory drug naproxen over two years. Endpoints include neuropsychological measures, sensory faculties (olfaction / central auditory processing), classic AD biomarkers in cerebrospinal fluid (CSF), and structural and functional magnetic resonance imaging (MRI). To date, we have evaluated 361 people for eligibility, enrolling 192. Of these, 118 are in the naproxen trial while 74 others undergo annual observations pending possible enrollment in future trials. APOE, BDNF, HMGR Intron M and BChE K genotypes have been determined for 177 participants. Some 40% of those enrolled in the naproxen trial have agreed to a series of four lumbar punctures (LPs), and 100 LPs have been assayed to data for concentrations of total tau, P-tau, Aβ1-40 and A β 1-42. MRI and fMRI modalities include fine structural analysis, regional volumes, resting state connectivity, regional cerebral blood flow (ASL), white matter pathology and task-based fMRI. Data are managed using an adaptation of the LORIS database. Early analyses of baseline data suggest that many of the endpoints correlate with age and, more importantly, with one-another (suggesting a common underlying driver or drivers independent of age). We offer the first description of a new Centre's study design and progress to date. A second trial, now in planning, will evaluate effects of an inducer of synthesis of the cholesterol transport protein apoE, which promotes neural regeneration and repair.
Estimation of an affine motion (2009)

This paper discusses the 3D affine motion estimation problem using two cameras via observations of a single feature point. The unknown parameters to be estimated include the nine rotational parameters, the three translational parameters, and the 3D position. One camera assumes a parabolic projection. The other camera is the conventional camera that has a planar projection surface. The parabolic camera is needed due to its ability of estimating the nine rotational parameters independently of the other camera. The conventional camera is utilized to solve the depth ambiguity problem. A closed-loop nonlinear observer is developed for the affine motion estimation problem. Simulation results are presented to show the robustness of the proposed motion estimation scheme.
Vocalizing large time series efficiently (2018)

We vocalize query results for time series data. We describe a holistic approach that integrates query evaluation and vocalization. In particular, we generate only those parts of the query result that are relevant for voice output. We exploit the fact that voice output has to be concise and simple to be understandable for listeners. Hence, the problem of generating voice output reduces to choosing between several coarse-grained alternatives. To make that choice, it is sufficient to evaluate the time series at a few carefully chosen locations. We use techniques from the area of optimal experimental design to choose optimal sampling points. Our algorithm is iterative and generates in each iteration a set of promising voice description candidates. We consider multiple metrics when generating voice descriptions, including the accuracy of description as well as its complexity and length. Then, we choose a near-optimal batch of sampling points to refine our choice between promising candidates. We compare this algorithm experimentally against several baselines, demonstrating superior performance in terms of execution time and output quality. We also conducted a user study, showing that it enables users to execute simple exploratory data analysis via voice descriptions alone. We also compare against visual interfaces and sonification (i.e., non-speech sound) interfaces in terms of user performance.