gebhart/patrepeval huggingface dataset:
Results From the First‐in‐Human Study With Ozanimod, a Novel, Selective Sphingosine‐1‐Phosphate Receptor Modulator (2017)

The sphingosine-1-phosphate 1 receptor (S1P<sub>1R</sub> ) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P<sub>1R</sub> and S1P<sub>5R</sub> receptors in clinical development for the treatment of chronic immune-mediated, inflammatory diseases. This first-in-human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose-escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose-limiting toxicities. The most common ozanimod-related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady-state volume of distribution (73-101 L/kg), moderate oral clearance (204-227 L/h), and an elimination half-life of approximately 17 to 21 hours. Ozanimod produced a robust dose-dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose-dependent negative chronotropic effect was observed following the first dose, with the dose-escalation regimen attenuating the first-dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once-daily regimens under clinical investigation.
Genetic Evidence for the Reduction of Brassinosteroid Levels by a BAHD Acyltransferase-Like Protein in Arabidopsis   (2012)

Brassinosteroids (BRs) are a group of steroidal hormones involved in plant development. Although the BR biosynthesis pathways are well characterized, the BR inactivation process, which contributes to BR homeostasis, is less understood. Here, we show that a member of the BAHD (for benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, and deacetylvindoline 4-O-acetyltransferase) acyltransferase family may play a role in BR homeostasis in Arabidopsis (Arabidopsis thaliana). We isolated two gain-of-function mutants, brassinosteroid inactivator1-1Dominant (bia1-1D) and bia1-2D, in which a novel BAHD acyltransferase-like protein was transcriptionally activated. Both mutants exhibited dwarfism, reduced male fertility, and deetiolation in darkness, which are typical phenotypes of plants defective in BR biosynthesis. Exogenous BR treatment rescued the phenotypes of the bia1-1D mutant. Endogenous levels of BRs were reduced in the bia1-1D mutant, demonstrating that BIA1 regulates endogenous BR levels. When grown in darkness, the bia1 loss-of-function mutant showed a longer hypocotyl phenotype and was more responsive to exogenous BR treatment than the wild-type plant. BIA1 expression was predominantly observed in the root, where low levels of BRs were detected. These results indicate that the BAHD acyltransferase family member encoded by BIA1 plays a role in controlling BR levels, particularly in the root and hypocotyl in darkness. Taken together, our study provides new insights into a mechanism that maintains BR homeostasis in Arabidopsis, likely via acyl conjugation of BRs.
1.1-µm Band Extended Wide-Bandwidth Wavelength-Swept Laser Based on Polygonal Scanning Wavelength Filter (2021)

We demonstrated a 1.1-µm band extended wideband wavelength-swept laser (WSL) that combined two semiconductor optical amplifiers (SOAs) based on a polygonal scanning wavelength filter. The center wavelengths of the two SOAs were 1020 nm and 1140 nm, respectively. Two SOAs were connected in parallel in the form of a Mach-Zehnder interferometer. At a scanning speed of 1.8 kHz, the 10-dB bandwidth of the spectral output and the average power were approximately 228 nm and 16.88 mW, respectively. Owing to the nonlinear effect of the SOA, a decrease was observed in the bandwidth according to the scanning speed. Moreover, the intensity of the WSL decreased because the oscillation time was smaller than the buildup time. In addition, a cholesteric liquid crystal (CLC) cell was fabricated as an application of WSL, and the dynamic change of the first-order reflection of the CLC cell in the 1-µm band was observed using the WSL. The pitch jumps of the reflection band occurred according to the electric field applied to the CLC cell, and instantaneous changes were observed.
Speech dysfunction in early Parkinson's disease (1995)

The purpose of this study is to determine if subjects in the early stages of untreated Parkinson's disease (PD) or PD treated with deprenyl alone suffer from motor speech abnormalities. Speech defects are common in advanced PD, including disturbances of respiration, phonation, and articulation. We studied 12 subjects with early PD (Hoehn and Yahr stage < or = 2, mean duration disease 3.2 years) who were not taking symptomatic therapy and tested them under two conditions: on and off deprenyl. None of the subjects was depressed or demented (Mini Mental Status mean 29.9/30; Hamilton Depression Rating mean 2.7/52). All functioned independently (Schwab and England Activities of Daily Living mean 93.1/100). Acoustic and speech productions were assessed using the DSP Sona-Graph 5500 and an evaluation of dysarthria. All 12 had at least two characteristics of dysarthria on examination, although 8 were not aware of it. Vocal tremor was identified on narrow band spectrogram for four subjects. Deprenyl did not have a consistent effect on speech. Ten subjects had no detectable change in speech on deprenyl, one was worse, and one was improved.
Development of an Ultimate-high-efficiency Motor by utilizing High-Bs Nanocrystalline Alloy (2019)

In order to increasing the efficiency of axial gap motors, a motor was designed to achieve an efficiency of 98% based on the IE 5-11kW motor (motor efficiency of 96%). Based on the design, we created a prototype with ceramic housings, thinned coil conductors, and nanocrystalline materials for the stator core as real items to reduce losses. We verified its effect by evaluating the motor characteristics. As a result, it was confirmed that the prototype can achieve a motor efficiency of 98.3% at 3,000min-1 and 11kW rated driving. Moreover, in the temperature rise test, it was demonstrated that class B type (130°C) could be achieved.
Generating functions and lower bounds on rates for limited error-correcting codes (1991)

Runlength-limited (RLL) and digital-sum-limited (DSL) codes are considered. For these codes the finite and asymptotic lower bounds on achievable rates for the given minimum Hamming distance are derived. Using generating functions and trellis diagram techniques, the authors prove the existence of RLL- and DSL-codes of rate R and minimum distance d= delta n, such that R>or=2.log lambda /sub 1/(0)-min(log lambda /sub 1/(z)- delta .log z), 0<or=z<or=1, for large enough code length n. The value lambda /sub 1/(z) is the maximum modulus eigenvalue of a certain matrix that is dependent on the limitations and some parameter z. The bounds for the limited codes improve the lower bound of H. C. Ferreira (1984).<<ETX>>
Draft Genome Sequences of Three Penicillin-Resistant Neisseria gonorrhoeae Strains Isolated in Cincinnati, Ohio, in 1994 (2021)

Here, we report the draft genome sequences of three penicillin-resistant <i>Neisseria gonorrhoeae</i> isolates. We include associated data on MICs and genetic relationships to other <i>N. gonorrhoeae</i> strains collected from across the United States. Resistance mutations known to contribute to reduced penicillin susceptibility are annotated in each genome.
Engineered Nonlinearities in Transparent Conducting Oxides (2017)

Towards the fabrication of all-dielectric nanophotonic devices with tunable capabilities, we combined interband and intraband nonlinearities in aluminum-doped zinc oxide thin films thus enlarging the material bandwidth and gaining ultra-fast control over the transmitted spectrum.
ASSESSMENT OF MULTIANTIGEN PRINT IMMUNOASSAY AND RAPID LATERAL-FLOW TEST FOR THE DETECTION OF MYCOBACTERIUM BOVIS INFECTION IN MALAYAN TAPIR (TAPIRUS INDICUS) (2021)

A multiantigen print immunoassay (MAPIA) and rapid test (RT) developed and validated for detection of mycobacterial antibodies in elephants (<i>Elephas maximus</i> and <i>Loxodonta africana</i>) was assessed in Malayan tapir (<i>Tapirus indicus</i>). Retrospective analysis of banked serum from one <i>Mycobacterium bovis</i> infected and seven presumably uninfected tapir was performed by MAPIA and RT. A sample collected 2 mon prior to the death of a culture-confirmed <i>M. bovis</i>-infected tapir served as a positive control. Seroreactivity of this sample was demonstrated via both MAPIA and RT testing. Seven uninfected animals, including four without postmortem evidence of mycobacterial disease and three that remain healthy, were negative controls; none demonstrated seroreactivity to key antigens with either test. These results suggest that MAPIA and RT have potential utility for rapid detection of <i>M. bovis</i> infection in Malayan tapir.
Genetically Modified Her2-Specific T Cells Recognize Low and High Her2 Expressing Breast Cancer Cells. (2005)

Abstract Background: Only patients with breast cancers expressing high levels of Her2 benefit from anti-Her2 monoclonal antibodies such as trastuzumab. In the present study we investigated in vitro, if chimeric T-cell receptors (TCR), which combine the antigen-specificity of monoclonal antibodies with the effector function of T cells can overcome this limitation. Material and Methods: T cells from healthy donors were transduced with retroviral vectors containing the Her2-specific chimeric TCR gene with a CD28-zeta signaling domain (Her2-CD28-zeta). The specificity of the genetically modified T cells was determined by their ability 1) to kill breast cancer cell lines in cytoxicity assays, and 2) to proliferate and secrete cytokines (IFN-γ and IL-2) after stimulation with breast cancer cell lines. The following panel of cell lines was used: autologous PHA blasts, MDA-MB-468 (both Her2-negative), MCF-7 (Her2-low), Her218 and SKBR-3 (both Her2-high). Results: Her2-CD28-zeta expressing T cells killed low and high Her2-positive breast cancer cell lines in cytotoxicity assays, where as Her2-negative T cells were not killed. Stimulation of T cells with breast cancer cell lines expressing both high and low levels of Her2 resulted in T-cell proliferation and secretion of IFN-γ and IL-2 in a HER2 dependent manner. Discussion: We demonstrate that breast cancer cells with low levels of expression of Her2 can effectively activate T cells expressing Her2-specific chimeric T cell receptor, induce T-cell proliferation, and the production of IL-2, an important T-cell growth factor. These results indicate that T cells expressing chimeric TCRs could possibly extend the application of Her2 targeted therapies to malignancies expressing low levels of Her2.
Receding-Horizon Optimization of Unbalanced Distribution Systems with Time-Scale Separation for Discrete and Continuous Control Devices (2018)

This paper presents a method for the optimal control of discrete and continuous devices in an unbalanced three-phase distribution network with significant renewable generation. A hierarchical control scheme is presented where the discrete mechanical assets are dispatched at a slow time-scale as a mixed-integer program (MIP) and the continuous DERs are controlled at a fast time-scale as a convex program. The optimization programs are operated at two time scales as they manage controllable grid resources with different levels of responsiveness and flexibility. The MIP optimizes slow mechanical assets to position voltage robustly against uncertain net-load and a three-phase SOCP program is used to solve the fast loss-minimization optimization for the continuously operated DERs while providing corrective control against the intermittent and variable renewable net-load generation. The scheme is presented on the IEEE-13 node test feeder.
Penetration of Dexamethasone into Brain Glucocorticoid Targets Is Enhanced in mdr1A P-Glycoprotein Knockout Mice (1998)

Mice with a genetic disruption of the multiple drug resistance (mdr1a) gene were used to examine the effect of the absence of its drug-transporting P-glycoprotein product from the blood-brain barrier on the distribution and cell nuclear uptake of [ 3 H]-dexamethasone in the brain. [ 3 H]-dexamethasone (4 g/kg mouse) was administered sc to adrenalectomized mdr1a (/) and mdr1a (/) mice. One hour later, the mice were decapitated, and the radioactivity was measured in homogenates of cerebellum, blood, and liver following extraction of the radioactive steroid. The frontal brain was cut in sections for autoradiography.
Using Hydrogen Bonds to Direct the Assembly of Crowded Aromatics (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Sustained Transgene Expression via Hydrogel-Mediated Gene Transfer Results from Multiple Transfection Events (2018)

Sustained delivery of therapeutic genes in vitro and in vivo has a wide range of applications in studying biology and in developing therapies for treating disease or repairing tissue. Nonviral vectors such as cationic polymers still present promising approaches; however, bolus transfection methods with polyethylenimine-based DNA polyplexes suffer from considerable levels of cytotoxicity and short-lived transgene expression levels. Here, we designed and characterized a hyaluronic acid-based porous hydrogel system for nonviral gene delivery by loading with surface-associated DNA polyplexes. With this, we observed tunable, enhanced, and sustained transgene expression over 30 days of cell culture with better cell viability and marked improvements over comparable bolus transfection techniques. Finally, we investigated mechanisms thought to be responsible for the sustained expression profile, finding that multiple transfection events are likely responsible for the observed sustained expression.
IP Over ICN Goes Live (2018)

Information-centric networking (ICN) has long been advocating for radical changes to the IP-based Internet. However, the upgrade challenges that this entails have hindered ICN adoption. To break this loop, the POINT project proposed a hybrid, IP-over-ICN, architecture: IP networks are preserved at the edge, connected to each other over an ICN core. This exploits the key benefits of ICN, enabling individual network operators to improve the performance of their IP-based services, without changing the rest of the Internet. We provide an overview of POINT and outline how it improves upon IP in terms of performance and resilience. Our focus is on the successful trial of the POINT prototype in a production network, where real users operated actual IP-based applications.
Growth of Aligned Multiwall Carbon Nanotubes and the Effect of Adsorbates on the Field Emission Properties (2003)

In attempt to decipher the field emission characteristics of multiwall carbon nanotubes (MWCNTs), we have developed a fabrication method based on plasma enhanced chemical vapour deposition (PECVD) to provide utmost control of the nanotube structure such as their alignment, individual position, diameter, length and morphology. We investigated the field emission properties of these nanotubes to elucidate the effect of adsorbates on the nanotubes. Our results show that although the adsorbates cause an apparent lowering of the required turn on voltage/field of the nanotubes, the adsorbates undesirably cause a saturation of the current, large temporal fluctuations in the current, and also a deviation of the emission characteristics from Fowler‐Nordheim like emission. The adsorbates are easily removed by extracting an emission current of 1 uA per nanotube or using a high applied electric field (∼25V/um).
Study on Welding Inherent Deformations in Welded Structural Materials (2008)

It is meaningful to predict welding deformation in practical time and to apply these data in welding industry. In this paper, the inherent deformations of beading on plate welding and fillet welding are studied. A 3D thermal-elastic-plastic FEM based on interactive substructure method (ISM) is used to predict the welding deformations. Experiments are carried out to verify the computation results. Based on the computation results, the inverse analysis method is proposed to estimate the inherent deformations. Using inherent deformations, welding deformation can be accurately reproduced by elastic FEM which is much more practical and efficient. Finally, a database of inherent deformations on bead on plate welding and fillet welding including 8 different materials is developed. Meanwhile, the relationship of welding heat input and inherent deformations is discussed. The effectiveness of this method is also confirmed by experimental results.
beta-Endorphin augments the cytolytic activity and interferon production of natural killer cells. (1986)

We have investigated the in vitro effects of the neurohormone beta-endorphin (b-end) on natural killer (NK) activity and interferon (IFN) production mediated by large granular lymphocytes (LGL). LGL-enriched fractions from peripheral blood mononuclear cells (PBMC) from normal human volunteers were obtained by fractionation over discontinuous Percoll gradients. LGL were preincubated with or without various concentrations of b-end or the closely related peptides alpha-endorphin (a-end), gamma-endorphin (g-end), or D-ALA2-beta-endorphin (D-ALA2-b-end), a synthetic b-end analogue. NK activity was assayed on 51Cr-labeled K562 target cells. Preincubation of LGL effectors (but not K562 targets) for 2 to 18 hr with concentrations of b-end between 10(-7) M and 10(-10) M produced significant augmentation of NK cytolytic activity (mean percentage increase: 63%). The classic opiate antagonist naloxone blocked the enhancing effect when used at a 100-fold molar excess relative to b-end. Neither a-end nor g-end could augment NK activity, whereas D-ALA2-b-end produced an enhancement comparable with that produced by b-end. In addition, incubation of LGL with b-end in the presence of phytohemagglutinin or poly I:C significantly augmented IFN production. These findings demonstrate that b-end enhances NK activity and IFN production of purified LGL, and suggests that b-end might bind to an opioid receptor on LGL that can be blocked by naloxone. These results lend support to the concepts of regulation of the immune response by neurohormones and the functional relationship between the nervous and immune systems.
In-vivo evaluation of the PUCA-pump, a new left ventricular assist device (2004)

The PUlsatile CAtheter-pump is a new assist device meant for short term support. The device can be inserted into the left ventricle through the subclavian or axillary artery and can pump 2.5–3 L/min. The pump system consists of a 21 Fr catheter with a build in two-way valve, which is connected to a single port membrane pump positioned outside the body, driven by a commercially available IABP pump driver.
ChemInform Abstract: Sol—Gel Microencapsulation of Odorants and Flavors: Opening the Route to Sustainable Fragrances and Aromas (2014)

Abstract Review: 43 refs.
Common Variants on Chromosome 9p21 Are Associated with Normal Tension Glaucoma (2012)

Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10(-8), odds ratio (OR)= 2.00 with 95% confidence interval (CI) 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10(-11), OR= 2.13 with 95% CI 1.69-2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.
Electrical limit of silver nanowire electrodes: Direct measurement of the nanowire junction resistance (2016)

We measure basic network parameters of silver nanowire (AgNW) networks commonly used as transparent conducting electrodes in organic optoelectronic devices. By means of four point probing with nanoprobes, the wire-to-wire junction resistance and the resistance of single nanowires are measured. The resistance RNW of a single nanowire shows a value of RNW=(4.96±0.18) Ω/μm. The junction resistance RJ differs for annealed and non-annealed NW networks, exhibiting values of RJ=(25.2±1.9) Ω (annealed) and RJ=(529±239) Ω (non-annealed), respectively. Our simulation achieves a good agreement between the measured network parameters and the sheet resistance RS of the entire network. Extrapolating RJ to zero, our study show that we are close to the electrical limit of the conductivity of our AgNW system: We obtain a possible RS reduction by only ≈20% (common RS≈10 Ω/sq). Therefore, we expect further performance improvements in AgNW systems mainly by increasing NW length or by utilizing novel network geometries.
Intérêt biologique des métabolites oxygénés de l’acide alpha-linolénique, projet Oxylino (2016)

Présentation «flash» : projet de recherche (Oxylino) en cours inter-collaboratif du Dr Frédéric Capel
Nanozymes in Pesticides Detection (2021)

Pesticides are widely used to protect crops from diseases and pests and to increase yield. However, due to their notoriously high toxicity and overuse, pesticide residues present in foods pose a great threat to the safety of human health and the environment. The fabrication and development of analytical techniques to detect pesticide residues in foods have been beset with various difficulties, including the complex sample matrix and ultralow levels of the target analyte. In recent years, nanozyme, the multifunctional nanomaterial with enzyme-mimicking activity, has been widely applied in pesticide residue determination. This chapter summarizes the latest progress in nanozyme-assisted analytical techniques for pesticide determination, including colorimetric, fluorescent, electrochemical, chemiluminescent, etc. The most common raw materials involved in nanozyme synthesis are noble metals, iron oxide, and graphene oxide. The reported nanozymes have exhibited high catalytic activities of biological enzymes, such as peroxidase, oxidase, laccase, phosphonate hydrolase, etc. By using nanozyme-assisted methods, sensitive and selective detection of many pesticides, such as organophosphorus and organochlorine, have been achieved. Furthermore, by cooperating with nanozyme, molecule recognition elements have also been widely applied in pesticide detection. In general, nanozyme-assisted novel techniques demonstrate huge potential in the detection of pesticide residues.