gebhart/patrepeval huggingface dataset:
Synthesis and Biological Evaluation of 3-Aryl-3-(4-phenoxy)-propionic Acid as a Novel Series of G Protein-Coupled Receptor 40 Agonists (2007)

High-throughput screening of a subset of the J&J compound library containing the carboxylic acid functional group uncovered a bromophenyl derivative as a moderate potent GPR40 agonist. Chemical elaboration of this bromophenyl led to the discovery of a novel series of GPR40 agonists with submicromolar potency. Among them, 22 and 24 behaved as full agonists when compared to the endogenous GPR40 ligand linolenic acid in a functional Ca+2 flux assay in HEK cells expressing GPR40 receptor. Several GPR40 agonists have also demonstrated the ability to induce glucose-mediated insulin secretion in the mouse MIN6 pancreatic beta-cell line. Our data supports the hypothesis that GPR40 may play an important role in fatty acid-mediated glucose-dependent insulin secretion. Compound 22 exhibited good pharmacokinetic profile in rat and may serve as a good candidate for in vivo study and may help to determine if GPR40 agonists would be beneficial in the treatment of type II diabetes.
P450s under Restriction (PURE) Screen Using HepaRG and Primary Human Hepatocytes for Discovery of Novel HBV Antivirals (2020)

Herein is reported a novel screening paradigm <b>PURE</b> (<i>P</i>450s <i>u</i>nder <i>re</i>striction) for the identification and optimization of hits as part of a hepatitis B virus (HBV) antiviral discovery program. To closely represent <i>in vivo</i> hepatocytes, differentiated HepaRG cells (dHRGs) and primary human hepatocytes (PHHs) were used as the basis for an HBV infection system. However, a significant challenge arose during potency evaluation in using cultured dHRGs and PHHs as screening platforms because, as with hepatocytes <i>in vivo</i>, these cells express active cytochrome P450 enzymes and thus can metabolize test compounds. The observed antiviral effects may be the cumulative result of a dynamic pool of parent compound and metabolites thus confounding structure activity relationship (SAR) interpretation and subsequent optimization design initiatives. We show here that <b>PURE</b> methodology restricts metabolism of HBV-infected dHRGs and PHHs and thus provides highly informative potency data for decision-making on key representative antiviral compounds.
SiC JFETs for Power Module Applications (2010)

Starting with the production of Infineon´s first silicon carbide (SiC) Schottky diodes in 2001, a lot of progress was achieved during recent years. Currently, a 3rd generation of MPS (merged pn Schottky) diodes is commercially available combining tremendous improvements with respect to surge current capability and reduced thermal resistance. In this work we present the implementation of SiC switches in power modules and a comparison of these units with the corresponding Si-based power modules. Also the frequency dependence of the total losses of the 1200V configurations using Si-IGBTs or SiC-JFETs as active device is shown, indicating that modules solution with a state of the art SiC JFET outperforms all other options for switching frequencies of 20 kHz and beyond. Additionally a total loss vs. frequency study will be presented. Furthermore, it is show that the switching losses of JFET based modules can be further reduced by reducing the internal distributed gate resistivity.
Over 10 000 Peptide Identifications from the HeLa Proteome by Using Single‐Shot Capillary Zone Electrophoresis Combined with Tandem Mass Spectrometry (2014)

Abstract Capillary zone electrophoresis (CZE)–tandem mass spectrometry (MS/MS) has recently attracted attention as a tool for shotgun proteomics. However, its performance for this analysis has so far fallen far below that of reversed‐phase liquid chromatography (RPLC)–MS/MS. The use of a CZE method with a wide separation window (up to 90 min) and high peak capacity (ca. 300) is reported. This method was coupled to an Orbitrap Fusion mass spectrometer through an electrokinetically pumped sheath‐flow interface for the analysis of complex proteome digests. Single‐shot CZE–MS/MS lead to the identification of over 10 000 peptides and 2100 proteins from a HeLa cell proteome digest in approximately 100 min. This performance is nearly an order of magnitude better than earlier CZE studies and is within a factor of two to four of the state‐of‐the‐art nano ultrahigh‐pressure LC system.
Improved High Performance Liquid Chromatographic Method for the Determination of Tris(Hydroxy-Methyl)Aminomethane (THAM) in Human Plasma, Erythrocytes, and Whole Blood (1998)

Abstract A sensitive high performance liquid chromatographic (HPLC) assay was developed to quantitate the organic amine proton-acceptor, tris(hydroxymethyl)aminomethane (THAM) in human plasma, erythrocytes, and whole blood. An aliquot of the sample was heat evaporated (200°C for 2 h), derivatized, extracted, and then injected onto a symmetry C8 column. The UV absorbance of the effluent was monitored at 237 nm. 2-Amino-2-methyl-1,3-propanediol was found to be an appropriate internal standard. The method has been applied to quantitate the samples from patients undergoing orthotopic liver transplantation. The assay has also been employed to assess the in vitro time of THAM-uptake into the erythrocytes from blood samples incubated at 37°C.
Pituitary-bone connection in skeletal regulation (2016)

Pituitary hormones have traditionally been thought to exert specific, but limited function on target tissues. More recently, the discovery of these hormones and their receptors in organs such as the skeleton suggests that pituitary hormones have more ubiquitous functions. Here, we discuss the interaction of growth hormone (GH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) with bone. The direct skeletal action of pituitary hormones therefore provides new insights and therapeutic opportunities for metabolic bone diseases, prominently osteoporosis.
Anthracyclines and regional myocardial damage in breast cancer patients. A multicentre study from the Working Group on Drug Cardiotoxicity and Cardioprotection, Italian Society of Cardiology (SIC) (2020)

The decrease of GLS is more precocious and pronounced in BC patients who received FEC + taxanes. Cardiac function further worsens after 6 months of adjuvant trastuzumab. All LV segments are damaged, with the anterior septum and the apex showing the greatest impairments.
Study on propagation characteristics in SHF (over 6 GHz) bands (2014)

In order to apply super high frequency (SHF) bands to small cells, we clarify basic propagation characteristics and shadowing loss due to human body shadowing in the SHF (over 6 GHz) bands based on measurements.
Dysregulation of the cell survival/anti-apoptotic NF-κB pathway by the novel humanized BM-ca anti-CD20 mAb: Implication in chemosensitization (2009)

Treatment of patients with relapsed or refractory low grade follicular B-NHL lymphoma with rituximab (chimeric anti-CD20 mAb) has resulted in approximately 50% response rate. The mechanism underlying the failure of rituximab to affect the remaining 50% of the patients is not clear, though their tumors express CD20. The in vivo effector functions of rituximab include ADCC, CDC and seldom apoptosis. In addition, we have reported that rituximab signals the cells and inhibits several intracellular cell survival pathways that are responsible for the immuno and chemo-sensitizing effects of rituximab on resistant B-NHL cell lines. The objective of this study was to develop novel and fully humanized anti-CD20 monoclonal antibodies with enhanced effector functions and molecular signaling that may potentiate their therapeutic efficacy. Novel humanized anti-CD20 monoclonal antibodies were derived from a chimerized form of murine anti-CD20 1K11791, shown to exert a more potent ADCC, CDC and apoptotic activities compared to rituximab. A representative humanized monoclonal antibody, BM-ca was used to examine its biological effect and molecular signaling using Ramos B-NHL cell line as a model. The studies were also performed in parallel with rituximab treatment for comparison. Ramos cells were treated with various concentrations of BM-ca monoclonal antibody. Inhibition of cell proliferation was observed in a concentration-dependent manner, suggesting cell signal perturbations must have occurred. Compared to untreated cells, treatment with BM-ca inhibited both the constitutively activated NF-kappaB and p38 MAPK pathways, as assessed by inhibition of both phospho-p65 and phospho-IkappaBalpha and phospho-p38, respectively, but not the unphosphorylated forms. BM-ca significantly induced the expression of the metastasis suppressor and immune surveillance cancer gene product, Raf-1 kinase inhibitor protein (RKIP). These alterations resulted in inhibition of anti-apoptotic gene products and sensitized Ramos cells to apoptosis by CDDP. In comparison with rituximab, BM-ca showed qualitative and quantitative differences in the above analyses. These findings demonstrate that BM-ca triggers CD20 expressing B-NHL cells resulting in a significant alteration of several gene products that regulate cell growth and chemoresistance.
YAMR (2010)

Multipath routing is a promising technique to increase the Internet's reliability and to give users greater control over the service they receive. However, past proposals choose paths which are not guaranteed to have high diversity. In this paper, we propose yet another multipath routing scheme (YAMR) for the interdomain case. YAMR provably constructs a set of paths that is resilient to any one inter-domain link failure, thus achieving high reliability in a systematic way. Further, even though YAMR maintains more paths than BGP, it actually requires significantly less control traffic, thus alleviating instead of worsening one of the Internet's scalability problems. This reduction in churn is achieved by a novel hiding technique that automatically localizes failures leaving the greater part of the Internet completely oblivious.
Quantitative analyses of [11C]Ro15-4513 binding to subunits of GABAA/benzodiazepine receptor in the living human brain (2009)

The reference tissue methods using pons as a reference region can be used for quantitative analysis of [¹¹C]Ro15-4513 binding. SRTM seemed less susceptible to noise than does graphical analysis.
Optimization-Based Cell Selection Method for Grid-Connected Modular Multilevel Converters (2015)

Modular multilevel converters (MMCs) are widely used in different applications. Due to low-loss operation, compactness, and high modularity, MMC is extremely attractive for high-voltage direct-current (HVDC) transmission systems. The HVDC station loss is highly related to the converter switching pulse pattern, which is generated by modulation algorithm and cell selection methods. This paper formulates the switching pulse pattern generation, as a versatile optimization problem. The problem constraints and objectives are formulated for HVDC applications and compared with similar problems in the field of computer science. To overcome the computational complexity in solving the introduced optimization problem, a heuristic method is proposed for cell selection algorithm. The method utilizes the current level in order to obtain lossless switching at zero-current crossings. The study of the proposed method, in a time-domain simulation platform, shows that the method can reduce the switching converter losses by 60% compared to carrier-based modulation, maintaining the same capacitor voltage ripple. Eventually, the practical functionality of the proposed method is verified in a real-time digital simulator, RTDS, for a 512-level converter in a point to point HVDC link. Although this paper focuses on HVDC, the mathematical model is applicable for any MMC application.
The entropic brain: effortful speech reflcted in organisation of the network graph (2015)

Uncertainty of incoming information increases the amount of mental effort. Scientists might have been interested in quantifying the amount of this mental effort, as evidenced by the great amount of research devoted to computing the energy used to deal with the uncertainty of an event. One of these measures is Shannon’s entropy, which was initially used as a measure of the level of uncertainty with respect to the outcome of an event (Shannon, 1948). As defined by Shannon, entropy is expected to increase as the level of disorder (uncertainty or task complexity) increases. Therefore, to evaluate how the brain deals with entropy, one could either locate the focal area showing activity that is positively correlated with the degree of uncertainty or consider information transfer. We speculated that a functionally effective brain would modulate its network to fit to the varying entropy, since computation in the brain is probabilistic. Therefore, we put forward two hypotheses: 1) the functional brain architecture will reflect the varying entropy, and 2) the entropy will be modality-specific. In order to test these hypotheses, we estimated several network properties of the magnetoencephalography time-series signals obtained from healthy monolingual listeners. We particularly focused on whether entropy reflects the modality-specific processing load, especially when the degrees of the processing load of the two events were similar in terms of the rate of accuracy and the length of response time between tasks. In order to manipulate both entropy and modality, we varied the processing complexity (easy vs. difficult) in either a linguistic or non-linguistic (pitch change detection vs. word intelligibility test) task. Using graph-theoretical measures, the global organisation measures of the network, such as its small-worldness, correlation coefficient, global efficiency, and characteristic path-lengths, were compared within the network extracted as a set of 78 brain atlas nodes. The results showed a significant main effect of task complexity on the brain network properties, demonstrating that task load is indeed ubiquitous regardless of task modality. Equally importantly, we also found a pronounced task-specific difference in the network properties between linguistic and non-linguistic modalities. Regardless of modality, in the effortful tasks, the characteristic path-length and the correlation-coefficient were significantly larger, whereas the linguistic tasks resulted in significantly higher small-worldness, with the hubs located at the usual language nodes. Our findings collectively suggest that task load is ubiquitous but is also modality-specific in the brain network properties, as evidenced by the specific network graph measures.
Incorporating the whole-mount prostate histology reconstruction program Histostitcher into the extensible imaging platform (XIP) framework (2012)

There is a need for identifying quantitative imaging (e.g. MRI) signatures for prostate cancer (CaP), so that computer-aided diagnostic methods can be trained to detect disease extent in vivo. Determining CaP extent on in vivo MRI is difficult to do; however, with the availability of ex vivo surgical whole mount histological sections (WMHS) for CaP patients undergoing radical prostatectomy, co-registration methods can be applied to align and map disease extent onto pre-operative MR imaging from the post-operative histology. Yet obtaining digitized images of WHMS for co-registration with the pre-operative MRI is cumbersome since (a) most digital slide scanners are unable to accommodate the entire section, and (b) significant technical expertise is required for whole mount slide preparation. Consequently, most centers opt to construct quartered sections of each histology slice. Prior to co-registration with MRI, however, these quartered sections need to be digitally stitched together to reconstitute a digital, pseudo WMHS. Histostitcher&copy; is an interactive software program that uses semi-automatic registration tools to digitally stitch quartered sections into pseudo WMHS. Histostitcher&copy; was originally developed using the GUI tools provided by the Matlab programming interface, but the clinical use was limited due to the inefficiency of the interface. The limitations of the Matlab based GUI include (a) an inability to edit the fiducials, (b) the rendering being extremely slow, and (c) lack of interactive and rapid visualization tools. In this work, Histostitcher&copy; has been integrated into the eXtensible Imaging Platform (XIP <sup>TM</sup> ) framework (a set of libraries containing functionalities for analyzing and visualizing medical image data). XIP <sup>TM</sup> lends the stitching tool much greater flexibility and functionality by (a) allowing interactive and seamless navigation through the full resolution histology images, (b) the ability to easily add, edit, or remove fiducials and annotations in order to register the quadrants and map the disease extent. In this work, we showcase examples of digital stitching of quartered histological sections into pseudo-WHMS using Histostitcher &copy; via the new XIP <sup>TM</sup> interface. This tool will be particularly useful in clinical trials and large cohort studies where a quick, interactive way of digitally reconstructing pseudo WMHS is required.
The Metabolic Syndrome From Pathophysiology to Novel Treatment Strategies (2001)

The Metabolic Syndrome denotes the clustering of several metabolic abnormalities that are associated with an increased risk of cardiovascular disease. Among other terms, the syndrome is also called Syndrome X or The Insulin Resistance Syndrome. The main features of the syndrome are obesity, insulin resistance(SLASH)hyperinsulinemia, dyslipidemia, impaired glucose tolerance(SLASH)type 2 diabetes and hypertension. This syndrome is estimated to affect over 30 million Americans, and its prevalence is predicted to increase dramatically over the next two decades. Because of the complexity of the syndrome, the underlying cause and contributing factors leading to the development of the syndrome have been difficult to unravel and is an area of intense investigation. It is well recognized that the development of the syndrome has a genetic and environmental component, which has lead to the implementation of strategies for the identification of individuals at risk for the disease and for intervention to reduce the risk factors in patients with the disease. However, it is unclear as to whether there is one target for effective pharmaceutical intervention, or whether polypharmacy is required to treat the individual features of the syndrome. This article will review the pathophysiology of the disease and the current and future pharmaceutical approaches for effective disease management.
Environnement de programmation pour ASN.1 (1993)

Ce rapport decrit un environnement de developpement d'applications distribuees base sur le langage ASN.1. Le langage ASN.1 normalise par l'ISO, est utilise pour specifier les structures de donnees echangees par les modules d'une application distribuee. Cet environnement a ete realise en Centaur (developpe par l'equipe CROAP) et est interface au generateur de stubs Mavros (developpe par l'equipe RODEO). L'environnement minimal comprend un analyseur syntaxique, un editeur et un verificateur de types qui facilitent l'edition syntaxique de descriptions ASN.1. Les afficheurs C et Lisp qui visualisent les declarations ASN.1 et l'interface avec le compilateur Mavros facilitent l'ecriture des clients et serveurs de l'application. Nous proposons egalement plusieurs outils dedies a la mise au point de programmes ASN.1 dont un optimiseur et un generateur de tests.
Tunable Gas Permeability of Polymer-Clay Nano Brick Wall Thin Film Assemblies (2010)

2-3 anti-reflective, 4 electrochromic, 5 and sensing behaviors. 6-7 These films are created by alternately exposing a substrate to positively- and negatively-charged molecules or particles, as shown in Figure 1(a). In this case, steps 1 – 4 are continuously repeated until the desired number of “bilayers” (or cationic-anionic pairs) is achieved. Each individual layer may be 1 – 100+ nm thick. The ability to control film composition down to the nm-level and process under ambient conditions are two key advantages of this deposition technique. In the present study, clay was deposited one layer at a time in conjunction with a polymeric mortar to create a nano-brick wall, shown in Figure 1(b), with an oxygen transmission rate (OTR) below 0.35 cc/m 2 day.
Standardized volume rendering for magnetic resonance angiography measurements in the abdominal aorta (2006)

All the standardized VRT methods compare favorably with MIP and VRT with freely selected parameters as regards interobserver variability. The partial range histogram method, although systematically overestimating vessel diameters, gives results closest to those of DSA.
Transmission and Serial Propagation of Enterocytozoon bieneusi from Humans and Rhesus Macaques in Gnotobiotic Piglets (1998)

For over a decade Enterocytozoon bieneusi infections in people with AIDS have been linked with chronic diarrhea and wasting. The slow scientific progress in treating these infections is attributed to the inability of investigators to cultivate the parasite, which has also precluded evaluation of effective therapies. We report here successful serial transmissions of E. bieneusi from patients with AIDS and from macaques with AIDS to immunosuppressed gnotobiotic piglets. One infected piglet was still excreting spores at necropsy 50 days after an oral challenge. Spores in feces were detected microscopically by trichrome stain and by PCR and within enterocytes by in situ hybridization and immunohistochemistry. E. bieneusi infection induced no symptoms. The development of an animal model for E. bieneusi will open up new opportunities for investigating this parasite.
Throughput Behavior in Multihop Multiantenna Wireless Networks (2009)

Multiantenna or MIMO systems offer great potential for increasing the throughput of multihop wireless networks via spatial reuse and/or spatial multiplexing. This paper characterizes and analyzes the maximum achievable throughput in multihop, MIMO-equipped, wireless networks under three MIMO protocols, spatial reuse only (SRP), spatial multiplexing only (SMP), and spatial reuse and multiplexing (SRMP), each of which enhances the throughput, but via a different way of exploiting MIMO's capabilities. We show via extensive simulation that as the number of antennas increases, the maximum achievable throughput first rises and then flattens out asymptotically under SRP, while it increases "almost" linearly under SMP or SRMP. We also evaluate the effects of several network parameters on this achievable throughput, and show how throughput behaves under these effects.