gebhart/patrepeval huggingface dataset:
Rethinking Endothelial Dysfunction as a Crucial Target in Fighting Heart Failure (2019)

Endothelial dysfunction is characterized by nitric oxide dysregulation and an altered redox state. Oxidative stress and inflammatory markers prevail, thus promoting atherogenesis and hypertension, important risk factors for the development and progression of heart failure. There has been a reemerging interest in the role that endothelial dysfunction plays in the failing circulation. Accordingly, patients with heart failure are being clinically assessed for endothelial dysfunction via various methods, including flow-mediated vasodilation, peripheral arterial tonometry, quantification of circulating endothelial progenitor cells, and early and late endothelial progenitor cell outgrowth measurements. Although the mechanisms underlying endothelial dysfunction are intimately related to cardiovascular disease and heart failure, it remains unclear whether targeting endothelial dysfunction is a feasible strategy for ameliorating heart failure progression. This review focuses on the pathophysiology of endothelial dysfunction, the mechanisms linking endothelial dysfunction and heart failure, and the various diagnostic methods currently used to measure endothelial function, ultimately highlighting the therapeutic implications of targeting endothelial dysfunction for the treatment of heart failure.
Identification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity (2009)

We screened 10,000 different cDNAs and identified a number of genes and pathways that have previously not been implicated in SREBP control and cellular cholesterol homeostasis. These findings further our understanding of lipid biology and should lead to new insights into lipid associated disorders.
Silicon Photonics for the Datacenter (2015)

To fully benefit from silicon photonics technology at the system-level, novel electro-optical assembly techniques are required enabling a close integration with the processor or switch chip. Optical coupling and signal distribution options are discussed.
Selectivity tuning over monometallic and bimetallic dehydrogenation catalysts: effects of support and particle size (2017)

Spectroscopic, kinetic and theoretical insights guide the design of PdCu dehydrogenation catalysts.
Development and Perspectives: Multifunctional Nucleic Acid Nanomedicines for Treatment of Gynecological Cancers (2023)

Gynecological malignancies are a significant cause of morbidity and mortality across the globe. Due to delayed presentation, gynecological cancer patients are often referred late in the disease's course, resulting in poor outcomes. A considerable number of patients ultimately succumb to chemotherapy-resistant disease, which reoccurs at advanced stages despite treatment interventions. Although efforts have been devoted to developing therapies that demonstrate reduced resistance to chemotherapy and enhanced toxicity profiles, current clinical outcomes remain unsatisfactory due to treatment resistance and unfavorable off-target effects. Consequently, innovative biological and nanotherapeutic approaches are imperative to strengthen and optimize the therapeutic arsenal for gynecological cancers. Advancements in nanotechnology-based therapies for gynecological malignancies offer significant advantages, including reduced toxicity, expanded drug circulation, and optimized therapeutic dosing, ultimately leading to enhanced treatment effectiveness. Recent advances in nucleic acid therapeutics using microRNA, small interfering RNA, and messenger RNA provide novel approaches for cancer therapeutics. Effective single-agent and combinatorial nucleic acid therapeutics for gynecological malignancies have the potential to transform cancer treatment by giving safer, more tailored approaches than conventional therapies. This review highlights current preclinical studies that effectively exploit these approaches for the treatment of gynecological malignant tumors and malignant ascites.
Single‐Crystalline W‐Doped VO<sub>2</sub> Nanobeams with Highly Reversible Electrical and Plasmonic Responses Near Room Temperature (2016)

Single‐crystalline vanadium dioxide (VO 2 ) nanostructures are of great interest because of their single‐domain metal‐to‐insulator transition. In this paper, single‐crystalline W‐doped VO 2 nanobeams are synthesized for optical and electrical applications. As a result of differences in the polarization of the beams along their transverse and longitudinal axes, dual‐surface plasmon resonance peaks at 1344 and 619 nm are generated, resulting in an increase in the solar modulating abilities of the VO 2 nanobeams. The conductivity of the single‐crystalline W‐doped VO 2 nanobeams changes by three to four orders of magnitude at the transition temperature, which is of great importance for electrical applications.
Determination of the molecular states of the processive endocellulase <i>Thermobifida fusca</i> Cel9A during crystalline cellulose depolymerization (2011)

Detailed understanding of cell wall degrading enzymes is important for their modeling and industrial applications, including in the production of biofuels. Here we used Cel9A, a processive endocellulase from Thermobifida fusca, to demonstrate that cellulases that contain a catalytic domain (CD) attached to a cellulose binding module (CBM) by a flexible linker exist in three distinct molecular states. By measuring the ability of a soluble competitor to reduce Cel9A activity on an insoluble substrate, we show that the most common state of Cel9A is bound via its CBM, but with its CD unoccupied by the insoluble substrate. These findings are relevant for kinetic modeling and microscopy studies of modular glycoside hydrolases.
P211 Identification of linear and conformational epitopes on the infliximab molecule (2022)

<h3>Introduction</h3> Antidrug antibodies (ADA) to infliximab occur commonly, may limit its therapeutic use, and are associated with a range of clinical outcomes. The aim of this study was to identify linear and conformational infliximab epitopes. <h3>Methods</h3> Pooled sera from 8 ADA positive inflammatory bowel disease patients treated with biosimilar infliximab, CT -P13 (Remsima ®, Celltrion, South Korea) with different clinical outcomes were used for selection of two phage display libraries: 1) Whole gene fragment library (GFL) &gt;10<sup>6</sup> clones to select linear epitopes was synthesised using ~400 infliximab in–frame gene fragments of 150 base pairs with overlapping amino acids (Twist Bioscience, US). After three rounds of selection, phagemid clones were picked and the diversity of sequences compared to pre–selection. 2) Random peptide library (RPL) (Ph.D.™–12, New England BioLabs, US) 10<sup>9</sup> clones of random 12–mer peptides was used to identify 'mimitopes'– sequences that mimic conformational epitopes. After four rounds of selection, 70 plaques from pre–selection, rounds 3 and 4 were sequenced from ADA+ and control selections. Bioinformatic epitope prediction tool Pepitope, (http://pepitope.tau.ac.il) predicted the conformational epitopes using the infliximab Fab 3D protein structure. <h3>Results</h3> There was enrichment of three sequences from the GFL: all mapped to complementarity determining regions (CDRs) (Figure 1). From the RPL, three random peptide sequences showed selective enrichment. Conformational mimotopes were predicted using these sequences: RPL light chain peptide 1: SVALNVKRAPVT (predicted mimotope S14 V13 S12 L11 N103 A84 R39 R45 G57 P59 I58 S60), RPL heavy chain peptide 2: YNKETPQTGFRA (predicted mimotope Y201 N162 N204 N206 T212 P126 K124 T123 S122 F153 A121) and RPL heavy chain peptide 3: FHGPSKISSGES (predicted mimotope L45 E46 G44 P41 S40 Q39 V95 T115 T114 G113 E6 S21). There was overlap of selected amino acids (G57 P59 I58 S60) in GFL light chain peptide 3 and RPL light chain peptide 1. <h3>Conclusions</h3> All three linear epitopes identified from the GFL mapped to infliximab CDRs – sites where ADA could affect function and have a neutralising role. The possible position of conformational epitopes has been predicted. Further work is needed to confirm specificity of ADA+ sera for these peptides.
QUANTITATIVE EVALUATION OF HYPOXIC HUMAN BETA CELLS IN ISLET CELLS USING ICYS/LSC AND HYPOXYPROBE-1. (2010)

Ichii, H.; Misawa, R.; Miki, A.; Mita, A.; Yamamoto, T.; Sakuma, Y.; Baker, S.; Inverardi, L.; Ricordi, C. Author Information
Data from &lt;i&gt;BRAF&lt;/i&gt; and &lt;i&gt;NRAS&lt;/i&gt; Locus-Specific Variants Have Different Outcomes on Survival to Colorectal Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Somatic mutation status at &lt;i&gt;KRAS, BRAF&lt;/i&gt;, and &lt;i&gt;NRAS&lt;/i&gt; is associated with prognosis in patients with advanced colorectal cancer (aCRC); however, it remains unclear whether there are intralocus, variant-specific differences in survival and other clinicopathologic parameters.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We profiled 2,157 aCRCs for somatic mutations in &lt;i&gt;KRAS, BRAF&lt;/i&gt;, and &lt;i&gt;NRAS&lt;/i&gt; and determined microsatellite instability status. We sought inter- and intralocus correlations between mutations and variant-specific associations with survival and clinicopathology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; &lt;i&gt;KRAS&lt;/i&gt; mutations were rarely found together and those in codons 12 and 13 conferred poor prognosis [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.28–1.61; &lt;i&gt;P&lt;/i&gt; = 6.4 × 10&lt;sup&gt;−10&lt;/sup&gt; and HR, 1.53; 95% CI, 1.26–1.86; &lt;i&gt;P&lt;/i&gt; = 1.5 × 10&lt;sup&gt;−05&lt;/sup&gt;, respectively]. For &lt;i&gt;BRAF,&lt;/i&gt; more c.1781A&gt;G (p.D594G) CRCs carried &lt;i&gt;RAS&lt;/i&gt; mutations [14% (3/21)] compared with c.1799T&gt;A (p.V600E) CRCs [1% (2/178), &lt;i&gt;P&lt;/i&gt; = 9.0 × 10&lt;sup&gt;−03&lt;/sup&gt;]. c.1799T&gt;A (p.V600E) was associated with poor prognosis (HR, 2.60; 95% CI, 2.06–3.28; &lt;i&gt;P&lt;/i&gt; = 1.0 × 10&lt;sup&gt;−15&lt;/sup&gt;), whereas c.1781A&gt;G (p.D594G) was not (HR, 1.30; 95% CI, 0.73–2.31; &lt;i&gt;P&lt;/i&gt; = 0.37); this intralocus difference was significant (&lt;i&gt;P&lt;/i&gt; = 0.04). More c.1799T&gt;A (p.V600E) colorectal cancers were found in the right colon [47% (47/100)], compared with c.1781A&gt;G (p.D594G) colorectal cancers [7% (1/15), &lt;i&gt;P&lt;/i&gt; = 3.7 × 10&lt;sup&gt;−03&lt;/sup&gt;]. For &lt;i&gt;NRAS&lt;/i&gt;, 5% (3/60) of codon 61 mutant colorectal cancers had &lt;i&gt;KRAS&lt;/i&gt; mutations compared with 44% (10/23) of codons 12 and 13 mutant colorectal cancers (&lt;i&gt;P&lt;/i&gt; = 7.9 × 10&lt;sup&gt;−05&lt;/sup&gt;). Codon 61 mutations conferred poor prognosis (HR, 1.47; 95% CI, 1.09–1.99; &lt;i&gt;P&lt;/i&gt; = 0.01), whereas codons 12 and 13 mutations did not (HR, 1.29; 95% CI, 0.64–2.58; &lt;i&gt;P&lt;/i&gt; = 0.48).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data show considerable intralocus variation in the outcomes of mutations in &lt;i&gt;BRAF&lt;/i&gt; and &lt;i&gt;NRAS&lt;/i&gt;. These data need to be considered in patient management and personalized cancer therapy. &lt;i&gt;Clin Cancer Res; 23(11); 2742–9. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Different t‐cell subtypes are associated with pathologically distinct forms of moloney leukemia virus (m‐mulv)‐induced lymphoma (1982)

The T-cell enzyme markers, terminal deoxy-nucleotidyltransferase (TDT) and 20 alpha hydroxysteroid dehydrogenase (20 alpha SDH), were used to classify lymphomas induced by the Moloney leukemia virus (M-MuLV). Different subtypes of T cells were shown to be involved in different types of lymphoma. Thymomas were TdT-positive and grew as subcutaneous solid tumors at the site of inoculation. Spleen cells from mice with generalized lymphoma were of two types. In the majority of cases the lymphomas consisted of 20 alpha SDH-positive cells that homed to spleen and lymph nodes upon transplantation. In a few cases the cells of enlarged spleens were TdT-positive and, like the TdT-positive thymomas, could be transplanted as subcutaneous tumors. Thus, TdT-positive and 20 alpha SDH-positive T-cell lymphomas can be distinguished by their homing properties. Preleukemic thymus cells from M-MuLV inoculated mice can, after transfer to 400 -R irradiated syngeneic hosts, induce new lymphomas by virus release or grow in an autonomous fashion in the recipients. Whether of donor or recipient type, these lymphomas are TdT-positive. In contrast, preleukemic bone marrow cells give lymphomas of donor type which are as heterogeneous for T-cell enzymes as are lymphomas induced by neonatal inoculation of M-MuLV.
The R28 protein of <i>Streptococcus pyogenes</i> is related to several group B streptococcal surface proteins, confers protective immunity and promotes binding to human epithelial cells (1999)

The R28 protein is a surface molecule expressed by some strains of Streptococcus pyogenes (group A streptococcus). Here, we present evidence that R28 may play an important role in virulence. Sequence analysis demonstrated that R28 has an extremely repetitive sequence and can be viewed as a chimera derived from the three surface proteins Rib, alpha and beta of the group B streptococcus (GBS). Thus, the gene encoding R28 may have originated in GBS. The R28 protein promotes adhesion to human epithelial cells, as shown by experiments with an R28-negative mutant and by the demonstration that antibodies to highly purified R28 inhibited adhesion. In a mouse model of lethal intraperitoneal S. pyogenes infection, antibodies to R28 conferred protective immunity. However, the virulence of an R28-negative mutant was similar to that of the parental strain in the intraperitoneal infection model. Together, these data indicate that R28 represents a novel type of adhesin expressed by S. pyogenes and that R28 may also act as a target for protective antibodies at later stages of an infection. We consider the hypothesis that R28 played a pathogenetic role in the well-known epidemics of childbed fever (puerperal fever), which were caused by S. pyogenes. A role for R28 in these epidemics is suggested by epidemiological data.
[Free nucleotides of nerve cells, in culture]. (1980)

In primary cultures the free nucleotide (FN) distribution pattern showed a slight increase of adenylic nucleotides in neuroblasts as compared to glioblasts. Significant differences in the FN distribution were found between primary cultures and clonal nerve cell lines.
Integrative Omics Approach to Identifying Genes Associated With Atrial Fibrillation (2019)

<u>Rationale:</u> GWAS (Genome-Wide Association Studies) have identified hundreds of genetic loci associated with atrial fibrillation (AF). However, these loci explain only a small proportion of AF heritability. <u>Objective:</u> To develop an approach to identify additional AF-related genes by integrating multiple omics data. <u>Methods and Results:</u> Three types of omics data were integrated: (1) summary statistics from the AFGen 2017 GWAS; (2) a whole blood EWAS (Epigenome-Wide Association Study) of AF; and (3) a whole blood TWAS (Transcriptome-Wide Association Study) of AF. The variant-level GWAS results were collapsed into gene-level associations using fast set-based association analysis. The CpG-level EWAS results were also collapsed into gene-level associations by an adapted SNP-set Kernel Association Test approach. Both GWAS and EWAS gene-based associations were then meta-analyzed with TWAS using a fixed-effects model weighted by the sample size of each data set. A tissue-specific network was subsequently constructed using the NetWAS (Network-Wide Association Study). The identified genes were then compared with the AFGen 2018 GWAS that contained more than triple the number of AF cases compared with AFGen 2017 GWAS. We observed that the multiomics approach identified many more relevant AF-related genes than using AFGen 2018 GWAS alone (1931 versus 206 genes). Many of these genes are involved in the development and regulation of heart- and muscle-related biological processes. Moreover, the gene set identified by multiomics approach explained much more AF variance than those identified by GWAS alone (10.4% versus 3.5%). <u>Conclusions:</u> We developed a strategy to integrate multiple omics data to identify AF-related genes. Our integrative approach may be useful to improve the power of traditional GWAS, which might be particularly useful for rare traits and diseases with limited sample size.
Evaluation of a multicomponent grading system for obstructive sleep apnoea: the Baveno classification (2021)

New findings on pathophysiology, epidemiology, and outcome have raised concerns on the relevance of the apnoea-hypopnoea index (AHI) in the classification of obstructive sleep apnoea (OSA) severity. Recently, a multicomponent grading system decision integrating symptomatology and comorbidities (Baveno classification), was proposed to characterise OSA and to guide therapeutic decisions. We evaluated whether this system reflects the OSA population, whether it translates into differences in outcomes, and whether the addition of AHI improves the scheme. A total of 14 499 OSA patients from the European Sleep Apnoea Database cohort were analysed. The groups were homogeneously distributed and were found to clearly stratify the population with respect to baseline parameters. Differences in sleepiness and blood pressure between the groups were analysed in a subgroup of patients after 24-36 months of treatment. Group A (minor symptoms and comorbidities) did not demonstrate any effect of treatment on outcome. However, groups B (severe symptoms, minor comorbidities), C (minor symptoms, severe comorbidities) and D (severe symptoms and comorbidities) were associated with improvement in either or both parameters with treatment. The AHI is an essential prerequisite of the diagnosis; however, adding the AHI did not improve the classification. Rather, it was inferior with respect to guiding the treatment decision. Thus, the Baveno classification allows a better stratification of the OSA population and may provide a better guidance for therapeutic decisions in OSA.
&lt;title&gt;Achieving safe autonomous landings on Mars using vision-based approaches&lt;/title&gt; (1992)

Autonomous landing capabilities will be critical to the success of planetary exploration missions, and in particular to the exploration of Mars. Past studies have indicated that the probability of failure associated with open-loop landings is unacceptably high. Two approaches to achieving autonomous landings with higher probabilities of success are currently under analysis. If a landing site has been certified as hazard free, then navigational aids can be used to facilitate a precision landing. When only limited surface knowledge is available and landing areas cannot be certified as hazard free, then a hazard detection and avoidance approach can be used, in which the vehicle selects hazard free landing sites in real-time during its descent. Issues pertinent to both approaches, including sensors and algorithms, are presented. Preliminary results indicate that one promising approach to achieving high accuracy precision landing is to correlate optical images of the terrain acquired during the terminal descent phase with a reference image. For hazard detection scenarios, a sensor suite comprised of a passive intensity sensor and a laser ranging sensor appears promising as a means of achieving robust landings.
Using NBN to predict biochemical relapse following image-guided radiotherapy (IGRT) for intermediate-risk prostate cancer (IR-PCa). (2014)

26 Background: Despite the use of clinical prognostic factors, 20 to 40% of patients with intermediate-risk prostate cancer (IR-PCa) fail local treatment for unexplained reasons. Given that an accurate DNA damage response (DDR) may be associated with genetic instability and radioresponse, we investigated whether copy number alterations (CNAs) in DDR genes are predictive or prognostic following local treatment. Methods: Using array comparative genomic hybridization (aCGH), we characterized CNAs in biopsies derived from 126 IR-PCa pts. who underwent image-guided radiotherapy (IGRT). We studied the DDR-sensing genes: MRE11A, RAD50, NBN, ATM, and ATR. The IGRT cohort (median dose: 76.4Gy; median follow-up: 7.8yrs) was compared to a radical prostatectomy (RP) cohort (154 pts. from Memorial Sloan-Kettering Cancer Center database; median follow-up: 4.8yrs). CNAs were then tested for their independent prognostic capability using Kaplan-Meir method and Cox proportional hazard models. Results: In our IGRT cohort, m,ost frequent DDR gene CNAs were: NBN 20 of 126 (15.9%), ATR 11of 126 (8.7%), and ATM 7 of 126 (5.5%). NBN CNAs were mainly gains (19/20) and strongly correlated with increased NBN-mRNA abundance compared to NBN-neutral cases (p=0.016). CNAs in DDR genes were not associated with GS, prostate-specific antigen, or T-stage. Importantly, NBN gain ranked among the top 3.3% of all genes in terms of its strength of association with the percent of the genome altered (PGA). After adjusting for clinical factors in a multivariate model, NBN gain was a significant independent predictor of 5 years-biochemical relapse-free rate (bRFR) following IGRT (48.6% versus 78.8%; HR = 3.14, 95% CI: 1.42-6.94, p=0.004). No DDR CNA was prognostic in the RP cohort. Increased NBN mRNA expression correlated to radioresistance in vitro (i.e. clonogenic surviving fraction after 3Gy) in five prostate cancer cell lines (R 2 = 0.665). This relationship was not observed for any of the other DDR genes. Conclusions: NBN copy number gain or increased expression correlates with tumor genomic instability, decreased bRFR (IGRT- but not surgery-treated pts.) and intrinsic prostate cancer cell radioresistance. If validated in independent IGRT cohorts, NBN gain could be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches.
GapMind for Carbon Sources: Automated annotations of catabolic pathways (2021)

Abstract GapMind for carbon sources is an automated tool for annotating catabolic pathways in bacterial and archaeal genomes. GapMind includes 62 compounds and identifies potential transporters and enzymes by their similarity to experimentally-characterized proteins. To improve GapMind’s coverage, we used high-throughput genetic data from 29 bacteria and systematically examined the gaps. We identified novel pathways or enzymes for the utilization of glucosamine, citrulline, myo-inositol, lactose, and phenylacetate, and we annotated 299 diverged enzymes and transporters. We also curated 125 proteins from published reports. For the 29 bacteria with genetic data, GapMind finds high-confidence paths for 85% of utilized carbon sources. In diverse bacteria and archaea, 38% of utilized carbon sources have high-confidence paths, which was improved from 27% by incorporating the fitness-based annotations and our curation. GapMind for carbon sources is available as a web server ( http://papers.genomics.lbl.gov/carbon ) and takes just 30 seconds for the typical genome.