gebhart/patrepeval huggingface dataset:
Development of a decision-making biomarker for CRTH2 antagonism in clinical studies (2015)

Biomarkers have shown to improve success rates in the development of novel drugs, providing essential information in the early phases of clinical development for decision-making. Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) is pursued as a drug target for a number of inflammatory diseases. CRTH2 antagonists block the activation and migration of key inflammatory cells such as eosinophils, basophils, and Th2 cells. The mechanism of action of CRTH2 antagonists was established in cells isolated from human blood. Biomarkers derived from these experiments were included in clinical studies to investigate the mechanism of action and potency of CRTH2 antagonists in human. For clinical phase I studies with the CRTH2 antagonist ACT-453859, a follow-up molecule of setipiprant, inclusion of the most precise and robust pharmacodynamic (PD) biomarker with a clinically relevant target effect was desired to aid phase II dose selection. Candidate biomarkers such as IL-13 secretion from Th2 cells and CRTH2, CD11b and CD203 modulation on basophils and eosinophils in whole blood were compared in terms of signal intensity and variability. Blockade of CRTH2 receptor internalization was finally chosen as PD biomarker and rigorously tested in a feasibility study. The assay showed excellent robustness, an intra-assay precision of 5% and inter-subject variability smaller than 15%. Based on phase II clinical study results with setipiprant, 90% CRTH2 receptor blockade was defined as clinically relevant PD effect. This target PD effect provides the means to take decisions based on the data generated in the phase I clinical studies with ACT-453859. Focal points • Bedside Biomarkers offer a great potential to influence decisions taken during early clinical development. For clinical phase I studies with the CRTH2 antagonist ACT-453859, a follow-up molecule of setipiprant, inclusion of a biomarker was desired to aid phase II dose selection. In order to facilitate decision-making, we developed a biomarker that delivers high quality data under clinical circumstance and defined a relevant target biomarker effect. • BenchsideIn-vitro experiments with human whole blood identified CRTH2 receptor internalization on basophils and eosinophils as the most precise and robust biomarker. Clinical results obtained with setipiprant in a seasonal allergic rhinitis study were used to define the clinically relevant target biomarker effect of 90% CRTH2 receptor blockade. Proof for the chosen target biomarker effect remains to be demonstrated in phase II clinical studies with ACT-453859.
mGlu2 Receptor Positive Allosteric Modulators (2016)

Positive allosteric modulation of the metabotropic glutamate type 2 (mGlu2) receptor has emerged as a promising mechanism for the treatment of central nervous system diseases, with the potential to provide a new and more effective avenue for the treatment of schizophrenia. Since the first discovery of mGlu2 receptor positive allosteric modulators (PAMs) multiple families of mGlu2 modulators have been reported. This chapter summarises the state of the art of the mGlu2 PAM arena by reviewing the different chemotypes reported to date, their proposed binding modes and the development status of those that have advanced into clinical evaluation.
Supplemental Figure 10 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer (2023)

&lt;p&gt;Supplemental Figure 10&lt;/p&gt;
Optimum quantum well width for III-nitride nonpolar and semipolar laser diodes (2009)

The advantage of using wider quantum wells in III-nitride lasers offered by nonpolar/semipolar technology is limited by narrower valence subband separation, thermal hole redistribution, and resulting optical gain degradation in wider wells. We show that corresponding increase in radiative carrier lifetime in wider quantum wells can lower the laser threshold, thus inferring the existence of an optimum quantum well width for laser design.
Spin-transfer switching of orthogonal spin-valve devices at cryogenic temperatures (2014)

We present the quasi-static and dynamic switching characteristics of orthogonal spin-transfer devices incorporating an out-of-plane magnetized polarizing layer and an in-plane magnetized spin valve device at cryogenic temperatures. Switching at 12 K between parallel and anti-parallel spin-valve states is investigated for slowly varied current as well as for current pulses with durations as short as 200 ps. We demonstrate 100% switching probability with current pulses 0.6 ns in duration. We also present a switching probability diagram that summarizes device switching operation under a variety of pulse durations, amplitudes, and polarities.
Glycolytic Gene Expression in Saccharomyces cerevisiae (1991)

The regulation of glycolytic gene expression in Saccharomyces cerevisiae has been studied in this thesis.
Advanced Wireless Local Positioning via Compressed Sensing (2018)

Wireless local positioning systems are based on measurements of signal time of flights and/or bearing angles to determine the position of an active transmitter in 3-D space. Traditional time-of-flight and angle measurements with such positioning systems require many data samples at high rates to fulfill the Nyquist criterion. Moreover, in multipath channels the ability of classical signal processing methods to resolve the delay and bearing vectors of the multiple transmission paths is strictly limited by the radio frequency bandwidth and aperture size. In this paper, we show that the wireless channel is ideally suited for the application of compressed sensing. We can thus reduce the number of samples without major losses in localization performance, or we can improve the resolution. After introducing a general model of a localization task with multipath propagation, and following the definition of key parameters of existing systems, we review the necessary data processing stages with compressed sensing and verify its excellent applicability. Finally, measurements are presented to verify the theoretical predictions experimentally.
Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector (2019)

A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV vaccine vector. We introduced genes for different variants of the HIV-1 envelope protein Env, i.e., secreted or membrane-anchored, intact or mutated furin cleavage site or different C-termini, into the genome of VSV-GP. We found that the addition of the Env antigen did not attenuate VSV-GP replication. All HIV-1 Env variants were expressed in VSV-GP infected cells and some were incorporated very efficiently into VSV-GP particles. Crucial epitopes for binding of broadly neutralizing antibodies against HIV-1 such as MPER (membrane-proximal external region), CD4 binding site, V1V2 and V3 loop were present on the surface of VSV-GP-Env particles. Binding of quaternary antibodies indicated a trimeric structure of VSV-GP incorporated Env. We detected high HIV-1 antibody titers in mice and showed that vectors expressing membrane-anchored Env elicited higher antibody titers than vectors that secreted Envs. In rabbits, Tier 1A HIV-1 neutralizing antibodies were detectable after prime immunization and titers further increased after boosting with a second immunization. Taken together, VSV-GP-Env is a promising vector vaccine against HIV-1 infection since this vector permits incorporation of native monomeric and/or trimeric HIV-1 Env into a viral membrane.
Tumour Burden Influence on Individual Rituximab Exposure and Response: Pharmacokinetic - Pharmacodynamic Approach by Using a Syngenic Bioluminescent Murine Model. (2007)

Abstract Immunotherapy with the humanised monoclonal anti-CD20 antibody rituximab represents an interesting therapeutic option for patients with B-cell Non-Hodgkin’s Lymphoma. Early clinical trials have shown that rituximab exposure was variable in patients receiving similar doses and that clinical response was related to rituximab concentrations. The aim of our study was to evaluate the influence of tumour burden on rituximab exposure and response to treatment. 8.103 cells of murine T-lymphoma cells (EL4) transduced with human CD20 cDNA (EL4-hCD20) and stably transfected with luciferase plasmid (EL4-hCD20-luc) were injected to C57Bl6J mice by i.v. route. Tumour detection, disease dissemination and progression were evaluated by in vivo bioluminescence imaging. Quantitative imaging analysis was performed after background noises and cosmic rays elimination. Rituximab concentrations were carried out by ELISA method. One dose of rituximab was injected thirteen day after lymphoma cell infusion, a time need for the development of disseminated disease. In the control group without rituximab, all mice developed disseminated lymphoma and died within 30 days whereas we found a significant dose/response relationship with increased doses of rituximab (from 150 μg to 1000 μg). At 500μg of rituximab, we found an important variability in response to treatment with about 23% of mice cured, 59% in partial response and 18% with progressive diseases. For all of these mice, tumour burden, determined before rituximab injection were calculated taking into account their size and bioluminescent activities corrected by the absorption coefficient of light according to the site localisation. Thus, we have demonstrated a significant correlation between tumour burden and response to rituximab and survival. Mice with the lower tumour burden having increased remission rates and survival. Using a pharmacokinetic-pharmacodynamic (PK-PD) model we also demonstrated that tumour burden influence rituximab exposure and response. There is a connection between tumour burden and rituximab efficiency (r2 = 0.938). Such results should have consequences for the rituximab use in human and in pre-clinical assessment of new anti-CD20 antibodies. D.D. is supported by a grant from Région Centre. This study has been supported by Association pour la Recherche contre le Cancer (Grant number: 3229), by the Institut National du Cancer and Cancéropôle Grand Ouest (MAb IMPACT - IMProving ACTivation of FcγRIIIa-expressing effector cells, pharmacogenetic-based optimisation of monoclonal antibody therapy for cancer-federative project) and by Roche France.
Real-World Robustness for Hybrid Vehicle Optimal Energy Management Strategies Incorporating Drivability Metrics (2014)

Hybrid vehicle fuel economy and drive quality are coupled through the “energy management” controller that regulates power flow among the various energy sources and sinks. This paper studies energy management controllers designed using shortest path stochastic dynamic programming (SP-SDP), a stochastic optimal control design method which can respect constraints on drivetrain activity while minimizing fuel consumption for an assumed distribution of driver power demand. The performance of SP-SDP controllers is evaluated through simulation on large numbers of real-world drive cycles and compared to a baseline industrial controller provided by a major auto manufacturer. On real-world driving data, the SP-SDP-based controllers yield 10% better fuel economy than the baseline industrial controller, for the same engine and gear activity. The SP-SDP controllers are further evaluated for robustness to the drive cycle statistics used in their design. Simplified drivability metrics introduced in previous work are validated on large real-world data sets.
Effect of Carbon on the Performance of Lithium-Air Secondary Battery (2014)

Three different carbon blacks (Vulcan, Ketjen Black, and 1:1 mixture of the two) are used as cathode catalysts for a lithium/air secondary battery, and their electrochemical properties are investigated. The surface morphology change after discharge is examined using scanning electron microscopy (SEM), and the discharge products are analyzed using Fourier transform-infrared spectroscopy (FT-IR). In order to measure the electrochemical properties, the charge and discharge measurements are conducted at a constant current density of 0.2 mA/cm, which monitors the voltage change. Electrochemical impedance spectroscopy (EIS) analyses are also performed in order to examine the change in the charge transfer resistance during the charge-discharge process. Compared with both the Ketjen black and Vulcan, the 1:1 mixture of the two carbon blacks exhibits the best performance as a cathode for the Li/air secondary battery, which results from a synergistic effect that exploits-both carbon blacks. †(Received July 3, 2013)
Quantitative evaluation of visual function in patients with cornea verticillata associated with Fabry disease (2019)

Although cornea verticillata associated with Fabry disease does not affect the visual acuity and letter contrast sensitivity, more comprehensive testing of visual function by the inclusion of straylight and grating contrast sensitivity measurements shows clear functional deficits in these patients.
gocc (2011)

Self-adaptive systems have recently attracted attention because of their ability to cope with changing environments, including system intrusions or faults. Such software must modify itself to better fit its environment, and one of the approaches by which we expect this capability to be achieved is the introduction of multiple control loops to assess the situation and to determine whether a change in behaviors or configurations is necessary and how to implement the change. Development of such systems with multiple control loops complicates the task of identifying components, and could be greatly aided by appropriate tool support. In this paper, we propose an architectural compiler for self-adaptive systems, which generates architectural configurations from the goal-oriented requirements descriptions. We also present a framework for generating such configurations with this compiler and a pattern in the requirements description. We evaluate the framework experimentally and show that it helps to generate suitable configurations that have high performance, and that the compiler scales well to large input models.
Bovine seminal plasmin is a DNA unwinding protein (1988)

The duplex DNA unwinding ability of seminal plasmin from bovine semen was examined by treatment of plasmid‐protein complexes with calf thymus topoisomerase I and resolution of the topoisomer distributions by agarose gel electrophoresis. Binding of seminal plasmin results in a moderate degree of unwinding of supercoiled plasmid. The elongation of the RNA chain by E.coli RNA polymerase over promoter containing template is not inhibited by seminal plasmin. However, the reinitiation of transcription is blocked in such cases indicating that seminal plasmin inhibits transcription by binding to the initiation site of RNA polymerase.
Building high-performance applications and services in Java (1997)

Article Building high-performance applications and services in Java: an experiential study Share on Authors: Sandeep K. Singhal IBM T.J. Watson Research Center IBM T.J. Watson Research CenterView Profile , Binh Q. Nguyen IBM Corporation IBM CorporationView Profile , Michael Fraenkel IBM Corporation IBM CorporationView Profile , Richard Redpath IBM Corporation IBM CorporationView Profile , Jimmy Nguyen IBM Corporation IBM CorporationView Profile Authors Info & Claims OOPSLA '97: Addendum to the 1997 ACM SIGPLAN conference on Object-oriented programming, systems, languages, and applications (Addendum)January 1997 Pages 16–20https://doi.org/10.1145/274567.274571Published:01 January 1997 2citation274DownloadsMetricsTotal Citations2Total Downloads274Last 12 Months1Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
MODULATION OF GPCR PHARMACOLOGY FROM THE EXTRACELLULAR VESTIBULE (2021)

G-protein coupled receptors (GPCRs) are considered important therapeutic targets due to their pathophysiological significance and pharmacological relevance. Endogenous ligands bind to the orthosteric binding pocket (OBP) embedded in the intrahelical space of the receptor. During the last years, however, it has been turned out that in many receptors there is secondary binding pocket (SBP) located in the extracellular vestibule that is much less conserved. In some cases it serves as a stable allosteric site harbouring allosteric ligands that modulate the pharmacology of orthosteric binders. In other cases it is used by bitopic compounds occupying both the OBP and SBP. In these terms, SBP binding moieties might influence the pharmacology of the bitopic ligands. Together with others, our research group showed that SBP binders contribute significantly to the affinity, selectivity, functional activity, functional selectivity and binding kinetics of bitopic ligands.
Developing high quality jacquard products on RSJ warp knitting machine (2004)

RSJ Jacquard raschel machine can be used to produce fine mesh fabric or densed elastic jacquard fabric. The products are mainly used in lingerie, foundation garment, sportswear and other sectors. In this thesis, how to develop top grade jacquard fabric is discussed in detail.
Associations of Plasma Bioactive Adrenomedullin Levels with Cardiovascular Risk Factors in BRCA1/2 Mutation Carriers (2022)

<b>Background</b> Cardiovascular disease (CVD) is an important cause of morbidity and mortality in breast cancer survivors. Effective screening modalities to identify CVD risk are lacking in this population. Adrenomedullin (ADM) has been suggested as a biomarker for subclinical cardiac dysfunction in the general population. Levels of ADM have been proven to be responsive to lifestyle changes that lead to improved cardiovascular health. As <i>BRCA1/2</i> mutation carriers are deemed to be at an increased risk for CVD, the aim of this study was to examine plasma ADM levels in a cohort of <i>BRCA</i> mutation carriers and to assess their association with cardiovascular risk factors. <b>Methods</b> Plasma ADM concentrations were measured in 292 female <i>BRCA1/2</i> mutation carriers with and without a history of breast cancer. Subjects were classified into high versus low ADM levels based on the median ADM level in the entire cohort (13.8 pg/mL). Logistic regression models were used to estimate the odds ratios (OR) of having elevated ADM levels by several cardiovascular risk factors. <b>Results</b> Of all women (median age: 43 years), 57.5% had a previous diagnosis of breast cancer. The median time between diagnosis and study entry was three years (range: 0 - 32 years). Women presenting with metabolic syndrome had 22-fold increased odds of having elevated ADM levels (p < 0.001). Elevated ADM levels were associated with lower cardiorespiratory fitness (OR = 0.88, p < 0.001) and several parameters of obesity (p < 0.001). ADM levels were higher in women who have ever smoked (OR = 1.72, p = 0.02). ADM levels were not associated with a previous diagnosis of breast cancer (p = 0.28). <b>Conclusions</b> This is the first study in <i>BRCA</i> mutation carriers that has linked circulating ADM levels to traditional cardiovascular risk factors. The long-term clinical implications of these findings are yet to be determined.
Rear Contact and BSF Formation for Local Al-BSF Solar Cells (2012)

This work studies the performance of commercially available Al pastes for the rear side contact formation with an industrially feasible process. The pastes are specifically designed for local Al-BSF/PERC (Passivated emitter and rear cell) cells. With this type of metallization, fill factors (FF) up to 80% are demonstrated, to our knowledge, the highest FF ever reported on fully screen printed PERC cells with industrial type emitter. Additionally, the use of an AlSi eutectic (12.7% Si) target for PVD sputtering is evaluated in comparison to a reference process using a pure Al target with the same kind of deposition technique. It was found that the thickness of the Al p+ BSF layer realized with the 12.7% Si containing Al target is systematically thicker than the reference due to a smaller metal Si interface. With this method, solar cells have been fabricated showing a potential efficiency above 20%, with standard Ag front screen printing on 60 Ω/□ emitter.
Improving Computational Efficiency of 3D Point Cloud Reconstruction from Image Sequences (2013)

The Levenberg-Marquardt optimization is normally used in 3D point cloud reconstruction from image sequences which is computationally expensive. This paper presents a two-stage camera pose estimation approach where an initial camera pose is obtained during the first stage and a refinement is performed during the second stage. This approach does not require the use of the Levenberg-Marquardt optimization and LU matrix decomposition for computing the projection matrix, thus providing a more computationally efficient 3D point cloud reconstruction as compared to the existing approaches. The results obtained using real video sequences indicate that the introduced approach generates lower re-projection errors as well as faster 3D point cloud reconstruction.
Corynebacterium glutamicum as a Host for Synthesis and Export of d -Amino Acids (2011)

A number of d-amino acids occur in nature, and there is growing interest in their function and metabolism, as well as in their production and use. Here we use the well-established l-amino-acid-producing bacterium Corynebacterium glutamicum to study whether d-amino acid synthesis is possible and whether mechanisms for the export of these amino acids exist. In contrast to Escherichia coli, C. glutamicum tolerates d-amino acids added extracellularly. Expression of argR (encoding the broad-substrate-specific racemase of Pseudomonas taetrolens) with its signal sequence deleted results in cytosolic localization of ArgR in C. glutamicum. The isolated enzyme has the highest activity with lysine (100%) but also exhibits activity with serine (2%). Upon overexpression of argR in an l-arginine, l-ornithine, or l-lysine producer, equimolar mixtures of the d- and l-enantiomers accumulated extracellularly. Unexpectedly, argR overexpression in an l-serine producer resulted in extracellular accumulation of a surplus of d-serine (81 mM d-serine and 37 mM l-serine) at intracellular concentrations of 125 mM d-serine plus 125 mM l-serine. This points to a nonlimiting ArgR activity for intracellular serine racemization and to the existence of a specific export carrier for d-serine. Export of d-lysine relies fully on the presence of lysE, encoding the exporter for l-lysine, which is apparently promiscuous with respect to the chirality of lysine. These data show that d-amino acids can also be produced with C. glutamicum and that in special cases, due to specific carriers, even a preferential extracellular accumulation of this enantiomer is possible.
Human immune cells as space travelers. (1999)

Experiments in space have shown that T lymphocyte function is altered in more than 50% of space crew members. There is strong evidence that such effect is due to stress rather than to weightlessness per se. However the health of astronauts was never threatened so far. Experiments in-vitro with cultures of human peripheral blood lymphocytes (not from astronauts) have shown that T cell function is dramatically reduced. Recent work with the random positioning machine, a new instrument to simulate conditions similar to microgravity, indicate that there are direct gravitational effects on the genetic expression of interleukin-2 and of its receptor in T lymphocytes.