gebhart/patrepeval huggingface dataset:
Simple functionalized quaternary ammonium salts as stable silicawall modifiers for CE-MS analysis of biological molecules (2012)

Capillary electrophoresis is today a well consolidated analytical technique, applied to almost all research fields where molecules’ separation is crucial. This technique has been quickly developed in all its structural components like the detectors, the electrophoretic modes and the automation. But there is still a weak point just at the core of the technique: the fused silica capillary. Our group has been committed since several years to synthesize silica wall modifiers characterized by the following properties: to be simple molecules cheap to produce, chemically stable, easy and fast to use also by unskilled operators, reliable and, even more importantly, compatible with MS detectors without the risk of leakage or instrument fouling. Here we present the main properties, as silica wall modifiers and EOF modulators, of some compounds that we have synthesized and tested on the analysis of proteins and molecules of biological origin. These modifiers are, basically, functionalized quaternary ammonium salts: some of them, although being small and simple molecules, show the peculiar property of eliciting a very quick and very stable association with the silica surface, comparable with that of covalently bonded silica coatings. Due to their high stability and low molecular mass, potential release phenomena are minimized, so that these coatings do not interfere with mass detections and are not dangerous to mass spectrometry instrumentation.
Mondo: Unifying diseases for the world, by the world (2022)

Abstract There are thousands of distinct disease entities and concepts, each of which are known by different and sometimes contradictory names. The lack of a unified system for managing these entities poses a major challenge for both machines and humans that need to harmonize information to better predict causes and treatments for disease. The Mondo Disease Ontology is an open, community-driven ontology that integrates key medical and biomedical terminologies, supporting disease data integration to improve diagnosis, treatment, and translational research. Mondo records the sources of all data and is continually updated, making it suitable for research and clinical applications that require up-to-date disease knowledge.
Supplementary Table 3 from Impact of Screening Test Performance and Cost on Mortality Reduction and Cost-effectiveness of Multimodal Ovarian Cancer Screening (2023)

&lt;p&gt;XLS file - 64K, Impact of screening frequency on mortality reduction and cost-effectiveness of ovarian cancer screening strategies&lt;/p&gt;
Crystal structure of the M 5 muscarinic acetylcholine receptor (2019)

The human M<sub>5</sub> muscarinic acetylcholine receptor (mAChR) has recently emerged as an exciting therapeutic target for treating a range of disorders, including drug addiction. However, a lack of structural information for this receptor subtype has limited further drug development and validation. Here we report a high-resolution crystal structure of the human M<sub>5</sub> mAChR bound to the clinically used inverse agonist, tiotropium. This structure allowed for a comparison across all 5 mAChR family members that revealed important differences in both orthosteric and allosteric sites that could inform the rational design of selective ligands. These structural studies, together with chimeric swaps between the extracellular regions of the M<sub>2</sub> and M<sub>5</sub> mAChRs, provided structural insight into kinetic selectivity, where ligands show differential residency times between related family members. Collectively, our study provides important insights into the nature of orthosteric and allosteric ligand interaction across the mAChR family that could be exploited for the design of selective drugs.
Efficient production of long double-stranded RNAs applicable to agricultural pest control by Corynebacterium glutamicum equipped with coliphage T7-expression system (2021)

RNA-based pesticides exert their function by suppressing the expression of an essential gene in the target pest through RNA interference caused by double-stranded RNA (dsRNA). Here, we selected target genes for growth suppression of the solanaceous crop pests ladybird beetle (Henosepilachna vigintioctopunctata) and Colorado potato beetle (Leptinotarsa decemlineata)-the death-associated inhibitor of apoptosis protein 1 gene (diap1), and an orthologous gene of the COPI coatomer protein complex (copI), respectively. We constructed a cost-competitive overproduction system for dsRNA using Corynebacterium glutamicum as a host bacterium. The dsRNA expression unit was equipped with two sets of promoters and terminators derived from coliphage T7, and the convergent expression system was designed to be selectively transcribed by T7 RNA polymerase. This expression system efficiently overproduced both target dsRNAs. On culture in a jar fermentor, the yield of diap1-targeting dsRNA (approximately 360 bp) was > 1 g per liter of culture. Long-chain diap1-targeting dsRNAs (up to around 1 kbp) could be produced without a substantial loss of efficiency. dsRNA accumulated in C. glutamicum significantly suppressed larval growth of H. vigintioctopunctata. The dsRNA expression technology developed here is expected to substantially reduce dsRNA production costs. Our method can be applied for a wide range of industrial uses, including agricultural pest control. KEY POINTS: • Overexpression of dsRNA was achieved in C. glutamicum using a coliphage T7 system. • The best strain produced > 1 g/L of the target dsRNA species, for use as an insecticide. • The developed system efficiently produced long dsRNA species, up to ~ 1 kbp.
Technique de mesure temporelle des pertes fer en régime symétrique et asymétrique : application à l'optimisation des régulateurs magnétiques (2014)

L'étude expérimentale des pertes et du comportement des circuits magnétiques se heurte au caractère non linéaire de ces composants. Si des mesures petit signal restent adaptées à l'évaluation des pertes cuivre, dont les caractéristiques restent indépendantes du niveau de courant, le comportement des noyaux magnétiques en dépend fortement en plus des formes des courants et tensions appliqués. Souvent suspectées d'un manque de précision, les mesures temporelles présentent un grand intérêt lorsqu'il s'agit de caractériser des composants magnétiques fortement non linéaires. On montrera notamment que les performances des oscilloscopes actuels moyennant quelques précautions permettent de les utiliser même à des fréquences élevées. Une méthode originale de caractérisation en régime asymétrique sera notamment présentée et appliquée à des inductances saturables qui constituent le composant clé des alimentations à régulation magnétique.
Dietary Whey Protein Modulates the Liver Glycogen Level and Glycoregulatory Enzymes Activity in Exercised Rats (2004)

0159 The depletion of glycogen storages has been associated with fatigue during constantload exercise. Therefore, it is important to examine some regulatory enzyme activities of the carbohydrate metabolism and determine the reasons for the glycogen accumulation in the liver. PURPOSE: We investigated whether dietary whey protein, as compared with dietary casein or soy protein, affected the storage of glycogen and glycoregulatory enzymes activity in sedentary or exercised rats liver. METHODS: 32 male Sprague-Dawley rats (ca. 130 g) were used. After acclimation, all rats were divided into one sedentary or three exercised groups (n = 8). In the sedentary group, casein was the source of dietary protein, while the three exercised groups were fed either casein, whey protein or soy protein. All experimental diets contained 20% protein. Rats were allowed free access to food and water for 4 weeks. Rats in the exercised groups were trained using a motor-driven treadmill for 30 min/day, 4 days/week. The running speed was 20 m/min, 7o inclination during the first 5 min, and 25 m/min, 7o inclination during the last 25 min. At end of the training period, all the rats were sacrificed after 12 h starvation in the resting state and 24 h after the end of the last training. Under ether anesthesia, arteriovenous blood was collected. Liver was quickly removed, washed and frozen at−80o C until assay. RESULTS: The whey protein group showed a significant increase of hepatic glycogen as compared with the other two exercised groups. The activities of 6-phosphofructokinase and pyruvate kinase (glycolysis limiting enzymes) were significantly lower in rats fed whey protein compared to those in rats fed casein. On the other hand, hepatic fructose 1, 6-bisphosphatase activity (gluconeogenesis limiting enzyme) was significantly increased in rats fed whey protein as compared with those fed casein or soy protein. Furthermore, a significant decrease in liver lipogenic enzyme activities (malic enzyme, glucose 6-phosphate dehydrogenase, acetyl-CoA carboxylase and fatty acid synthase) was observed in rats fed whey or soy protein compared with those fed casein diet. Besides, hepatic alanine aminotransferase activity and the level of alanine in serum were increased in the whey protein group as compared with the casein or soy protein group. CONCLUSION: We demonstrated that a whey protein diet favored the increase of the liver glycogen, due to a decrease of glycolysis and lipogenic limiting enzyme activities, as well as to the activation of gluconeogenesis from alanine via alanine aminotransferase.
Strained SQW GaInP/AlInP visible lasers fabricated by a novel shutter control method in gas source molecular beam epitaxy (1992)

AlGaInP strained layer QW lasers were extensively studied thus far by metalorganic chemical vapor deposition (MOCVD), producing very low threshold current densities1,2 and high optical power.3,4 In this paper, we report what we believe to be the first successful operation of SSQ GaInP/AlInp visible lasers grown by gas source molecular beam epitaxy (GSMBE).3 A novel shutter control method carried out during one monolayer (ML) growth was employed to produce tensile and compressive GaInP layers. Very low threshold current densities of 329 A/cm2 and 1.95 kA/cm2 were achieved for compressive (700 nm in wavelength) and tensile (632 nm), respectively.
S4. Supplementary Results: Prior ADT Treatment from Muscadine Grape Skin Extract (MPX) in Men with Biochemically Recurrent Prostate Cancer: A Randomized, Multicenter, Placebo-Controlled Clinical Trial (2023)

&lt;p&gt;Section S4 shows increased lengthening in PSADT for patients with SOD2 Ala/Ala genotype were seen in ADT naive patients.&lt;/p&gt;
Criteria of Activation of Powdery Materials by a Preliminary Mechanical Treatment (1983)

γ-Fe2O3 was vibration ball-milled with varying amplitude, α, from 8 to 24mm and grinding time. The enthalpy increase, ΔH*, due to mechanical treatment was measured by a differential scanning calorimeter. Pretreated sample was subsequently heated at 693K for 60min, and the fractional transformation into α-phase, a1, was obtained. Both ΔH* and a1 increased monotonically with grinding time with leveling off at longer milling time. The tendency of a level off was different, however, between ΔH* and a1. ΔH* increased monotonically with increasing amplitude whereas a1 showed a maximum at α = 10mm. The correlation between a1 and the lattice disturbance, the latter being obtained from the relative intensity of X-ray diffraction peaks, was not uniquely determined, but depended on the amplitude. This suggests that the same lattice disturbance does not always lead to the same degree of acceleration of the subsequent reaction. The reason was discussed on the basis of the content of ΔH* and the nuclei-growth mechanism of γ→α transformation of Fe2O3.
ChemInform Abstract: CRYSTAL AND MOLECULAR STRUCTURE OF THREE ISOMERS OF DICHLORODIAMMINEDIHYDROXOPLATINUM(IV): CIS‐TRANS ISOMERIZATION ON RECRYSTALLIZATION FROM WATER (1984)

Abstract Die Strukturen des cis,cis,trans‐ (I) (P4 2 /n, Z=4), trans,trans,trans‐ (II) (P2 1 /c, Z=2) und cis,trans,cis‐Isomeren (III) (P2 1 /m, Z=2) von PtCl 2 (NH 3 ) 2 (OH) 2 werden röntgenographisch bestimmt.
Fixed Point Theory Approach to Exponential Convergence in LTV Continuous Time Consensus Dynamics with Delays (2013)

The problem of continuous linear time varying consensus dynamics is addressed in the presence of constant communication delays. We make a Fixed Point Theory argument with the use of contraction mappings and we state sufficient conditions for exponential convergence to a consensus value with prescribed convergence rate.
Power Minimization Via Rate Splitting in Downlink Cloud-Radio Access Networks (2020)

Minimizing the power consumption in mobile communication networks while guaranteeing quality of service (QoS) requirements is essential in light of the unprecedented increase in the number of connected devices and the associated data traffic. Conventional cloud-radio access networks (C-RAN) assume treating interference as noise (TIN) while dealing with the provisioning of wireless interference. This paper considers a C-RAN system, where a central processor (CP) at the cloud is connected to several base-stations (BSs) via limited capacity fronthaul links. The paper then assumes a communication scheme where the CP applies rate splitting (RS) to the messages requested by the users, and enables common message decoding (CMD) at the receivers side. The paper addresses the problem of minimizing the weighted transmit power subject to minimum QoS and fronthaul capacity constraints, which is generally a non-convex and difficult problem to solve. We, therefore, propose an iterative approach based on inner-convex approximations (ICA) to obtain a stationary point of the optimization problem. The simulations show the power savings achieved by the proposed RS-CMD scheme as compared to the conventional TIN, especially at high QoS requirements.
A new paradigm of bacteria-gut interplay brought through the study of <bold>Shigella</bold> (2010)

Bacteria-gut epithelial interplay and the mucosal immune response are the most critical issues in determining the fate of bacterial infection and the severity of diseases. Shigella species (abbreviated here as Shigella), the causative agent of bacillary dysentery (shigellosis), are highly adapted human pathogens that are capable of invading and colonizing the intestinal epithelium, which results in severe inflammatory colitis. Shigella secrete a large and diverse number (more then 50) of effectors via the type III secretion system (TTSS) during infection, some of which are delivered into the surrounding bacterial space and some others into the host cell cytoplasm and nucleus. The delivered effectors mimic and usurp the host cellular functions, and modulate host cell signaling and immune response, thus playing pivotal roles in promoting bacterial infection and circumventing host defense systems. This article overviews the pathogenic characteristics of Shigella, and highlights current topics related to the bacterial infectious stratagem executed by the TTSS-secreted effectors. Though bacterial stratagems and the molecular mechanisms of infection vary greatly among pathogens, the current studies of Shigella provide a paradigm shift in bacterial pathogenesis.
Negative regulation of cell growth and differentiation by TSG101 through association with p21 Cip1/WAF1 (2002)

TSG101 was discovered in a screen for tumor susceptibility genes and has since been shown to have a multiplicity of biological effects. However, the basis for TSG101's ability to regulate cell growth has not been elucidated. We report here that the TSG101 protein binds to the cyclin/cyclin-dependent kinase (CDK) inhibitor (CKI) p21(Cip1/WAF1) and increases stability of the p21 protein in HEK293F cells and differentiating primary keratinocytes, suppressing differentiation in a p21-dependent manner. In proliferating keratinocytes where the p21 protein is relatively stable, TSG101 does not affect the stability or expression of p21 but shows p21-dependent recruitment to cyclin/CDK complexes, inhibits cyclin/CDK activity, and causes strong growth suppression to a much greater extent in p21+/+ than in p21-/- cells. Conversely, suppression of endogenous TSG101 expression by an antisense TSG101 cDNA causes doubling of the fraction of keratinocytes in the S phase of the cell cycle as occurs during p21 deficiency. Our results indicate that TSG101 has a direct role in the control of growth and differentiation in primary epithelial cells, and that p21 is an important mediator of these TSG101 functions.
Abstract AP31: TARGETING PD–L1/PD1 PATHWAY THROUGH BET PROTEIN INHIBITION IN EPITHELIAL OVARIAN CANCER (2017)

Abstract BACKGROUND: Expression of programmed death ligand 1 (PD-L1) is up-regulated in many cancers and has been found to suppress antitumor immunity through binding to its receptor programmed death 1 (PD-1). Blockade of PD-1/PD-L1 signaling axis enhances antitumor immunity in many cancers including epithelial ovarian cancer (EOC). Despite the importance of PD-L1 in tumor immunity, the epigenetic regulation of PD-L1 expression remains poorly understood. AIMS: To determine the roles of epigenetic components in regulating PD-L1 gene expression and modulating antitumor immunity. METHODS: Toward this goal, I screened a small molecule library of epigenetic inhibitors and examined their inhibition on PD-L1 expression in EOC cells to identify the positive hits. To further confirm PD-L1 inhibition in vivo, C57BL/6 mice are injected with luciferase expressing mouse ovarian cancer ID8 cells and treated with or without epigenetic inhibitors, PD-L1 expression in both tumor cells and immune cells are examined, tumor growth and survival are also monitored. RESULTS: BET inhibitors suppresses both constitutive and IFNγ induced PD-L1 expression in EOC cells through targeting BRD4. Further ChIP-seq and ChIP assay demonstrate that BRD4 directly binds to PD-L1 gene promoter and regulated its transcription. BET inhibitor JQ1 suppresses PD-L1 expression in both tumor cells and immune cells including dendritic cells and macrophages in mice bearing ID8 mouse ovarian cancer cells. Moreover, the BET inhibitor suppresses the tumor growth and improves the survival of EOC bearing mice through activating antitumor T cells. CONCLUSION: Taken together, we demonstrated that BRD4 can directly regulate PD-L1 expression in EOC cells by binding to the promoter of PD-L1 encoding gene, suppressing PD-L1 expression with BET inhibitors blocks PD1/PD-L1 signaling and enhances antitumor immunity in vivo. These findings indicate that pharmacological inhibition of BET proteins represent a new therapeutic strategy for EOC by targeting PD-L1 expression. Citation Format: Hengrui Zhu, Fee Bengsch, Nikolaos Svoronos, Melanie R. Rutkowski, Benjamin G. Bitler, Michael J. Allegrezza, Yuhki Yokoyama, James E. Bradner, Jose R. Conejo-Garcia, Rugang Zhang. TARGETING PD–L1/PD1 PATHWAY THROUGH BET PROTEIN INHIBITION IN EPITHELIAL OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP31.
FUS is sequestered in nuclear aggregates in ALS patient fibroblasts (2014)

Mutations in the RNA-binding protein FUS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We investigate whether mutant FUS protein in ALS patient-derived fibroblasts affects normal FUS functions in the nucleus. We investigated fibroblasts from two ALS patients possessing different FUS mutations and a normal control. Fibroblasts from these patients have their nuclear FUS protein trapped in SDS-resistant aggregates. Genome-wide analysis reveals an inappropriate accumulation of Ser-2 phosphorylation on RNA polymerase II (RNA Pol II) near the transcription start sites of 625 genes for ALS patient cells and after small interfering RNA (siRNA) knockdown of FUS in normal fibroblasts. Furthermore, both the presence of mutant FUS protein and siRNA knockdown of wild-type FUS correlate with altered distribution of RNA Pol II within fibroblast nuclei. A loss of FUS function in orchestrating Ser-2 phosphorylation of the CTD of RNA Pol II is detectable in ALS patient-derived fibroblasts expressing mutant FUS protein, even when the FUS protein remains largely nuclear. A likely explanation for this loss of function is the aggregation of FUS protein in nuclei. Thus our results suggest a specific mechanism by which mutant FUS can have biological consequences other than by the formation of cytoplasmic aggregates.
Plasticized Single-Ion Polymer Conductors:  Conductivity, Local and Segmental Dynamics, and Interaction Parameters (2007)

This paper considers high-quality conductivity data for plasticized ionomers in the context of polymer local and segmental processes. Dielectric spectroscopy was conducted on a neat PEO-based ionomer and six mixtures containing 6 wt % plasticizer with a wide range of dielectric constants. Conductivity increased dramatically but remained Vogel Fulcher Tamman (VFT)-like for all plasticized ionomers, indicating that the mechanism of ion transport was unchanged. Relaxation times of the polymer local beta and segmental alpha processes were analyzed for the plasticized ionomers, providing activation energies and relaxation strengths for the beta process and VFT fitting parameters for the alpha process. The glass transition temperature T(g) of the mixtures was found to be the critical characteristic governing conductivity, based on four criteria: VFT-like behavior of conductivity, decrease in the conductivity-segmental coupling index upon the addition of plasticizer, statistical insignificance of solvent quality (dielectric constant, donor number, and viscosity) on conductivity, and the creation of a conductivity master curve as a function of T(g)-normalized temperature.
JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B (2022)

JNJ-73763976 and JNJ-73763924 had short plasma half-lives and exposure generally increased in a dose-proportional manner; there were no pharmacokinetic differences between Japanese and non-Japanese healthy adults. JNJ-73763989 with or without JNJ-56136379 and NA was generally safe and well tolerated.
Effects of reduced glutathione (GSH) on oxaliplatin pharmacokinetics (OXA pk) and on Pt-DNA adducts formation in advanced colorectal cancer patients treated by FOLFOX4 regimen (2007)

2559 Background: Neurotoxicity is a common OXA toxicity in FOLFOX4 regimen for patients with advanced colorectal cancer. Recently, Cascinu et al. (JCO 2002; 20: 3478–3483) provided evidence that GSH reduces the OXA-induced neurotoxicity, but GSH influence on the formation of Pt-DNA adducts still remains unknown. This study evaluated the effect of GSH addition on OXA pk and on Pt-DNA adducts formation Table of Contents Methods: 28 patients were given twelve FOLFOX4 courses and randomized to receive either GSH 1,500 mg/m 2 or normal saline solution (placebo) before OXA iv infusion. OXA pk and Pt-DNA adducts formation were evaluated at courses 5, 9 and 12. Total and ultrafiltered platinum were analyzed by atomic adsorption, Pt-DNA adducts in leukocytes (as model for tumour tissue) by adsorptive stripping voltammetry. Pk analysis were done by non-compartmental analysis, statistical analysis by non-parametric Mann-Whitney test. Results: Median total and ultrafiltered platinum median C max and AUC tot values were comparable to previously reported ones, being higher in the placebo arm, due to a moderate reduction of platinum clearance. The formation of Pt-DNA adducts was more pronounced in GSH arm (median value 20.3 Pt atoms/10 6 nucleotides vs. 5.7 Pt atoms/10 6 nucleotides), even not statistically significant. Conclusions: The addition of GSH to FOLFOX4 regimen is able to reduce the OXA-induced neurotoxicity, without affecting either the OXA pk behaviour or the formation of Pt-DNA adducts, without modifying FOLFOX4 clinical efficacy. [Table: see text] No significant financial relationships to disclose.