gebhart/patrepeval huggingface dataset:
A First in man study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RP7214, a Dihydroorotate Dehydrogenase (DHODH) inhibitor in Healthy Subjects (2022)

RP7214 is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This paper describes the results from a Phase 1 study that evaluated safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy subjects. Target engagement of DHODH was also evaluated. A randomized, double-blind, placebo-controlled trial of single-dose (100, 200, and 400 mg QD) and multiple doses (200 and 400 mg BID for 7 days) followed by food effect at a single dose of 200 mg was conducted. A total of 18 healthy volunteers (HVs) (6 subjects in each of three cohorts) in the SAD part, 12 (6 subjects each in two cohorts) in the MAD part, and 12 in the food effect study were enrolled. RP7214 was well tolerated at all dose levels. None of the subjects reported any RP7214-related adverse events. RP7214 showed dose-proportional pharmacokinetics after single and multiple dosing. Steady-state concentrations were reached within about 3–6 days. The mean plasma half-life of RP724 at steady-state was approximately 13h. RP7214 showed accumulation on multiple dosing.. Food did not impact the absorption of RP7214. RP7214 showed dose-dependent inhibition of DHODH as measured by analyzing accumulating DHO levels, confirming target engagement. The rapid absorption and high systemic exposure of RP724 with a favorable safety profile shows the potential for the development of RP7214 in SARS-CoV-2 infection and acute myeloid leukemia. (NCT04680429). Keywords: RP7214, dihydroorotate dehydrogenase, SAD, MAD, HV
Five-year analysis from the ESPRIT 10-year postmarketing surveillance registry of adalimumab treatment for moderate to severe psoriasis (2015)

No new safety signals were observed with adalimumab treatment during this initial 5-year registry review. Observed number of deaths was below expected. As-observed effectiveness remained stable through 60 months.
Inï¬‚uence of dry friction on the irreversibility of cycloidal speed reducer (2013)

Gears with involute profile have been used broadly as power transmission mechanisms. High speed reduction ratios can be obtained with trains of gears, resulting in high power losses due to friction. Compound planetary gears allow obtaining high speed reduction ratios with a lower number of gears involved in the power transmission, hence transmitting it with higher efficiency. Although high efficiency is a main requisite for speed reducers, for some applications it may be desirable to have an irreversible mechanism. A modern trend in power transmission systems is to use cycloidal profile gears. These systems present low backlash, high load capability and higher efficiency due to the rolling motion. Furthermore, their large transmission ratio in single stage allows more compact designs. The present paper deals with the development of a simplified model for the calculation of efficiency of cycloidal speed reducers. The followed approach takes into account the main parameters influencing the efficiency, in particular, the friction and the geometrical properties of the components. The resulting model is used to investigate the relation among efficiency and reduction ratio in order to define the conditions for the irreversibility. A test bench is developed for the validation of the results.
Synthesis of [11C]carbonyl-labeled cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate ([11C-carbonyl]PK68) as a potential PET tracer for receptor-interacting protein 1 kinase (2022)

In the present study, we successfully radiosynthesized [<sup>11</sup>C]PK68 as a potential PET tracer and evaluated its brain uptake. We are planning to optimize the chemical structure of [<sup>11</sup>C]PK68 and conduct further PET studies on it using pathological models.
Vaccination with synthetic constructs expressing cytomegalovirus immunogens is highly T cell immunogenic in mice (2012)

There is no licensed vaccine or cure for human cytomegalovirus (CMV), a ubiquitous β-herpesvirus infecting 60-95% of adults worldwide. Infection can cause congenital abnormalities, result in severe disease in immunocompromised patients, and is a major impediment during successful organ transplantation. In addition, it has been associated with numerous inflammatory diseases and cancers, as well as being implicated in the development of essential hypertension, a major risk factor for heart disease. To date, limited data regarding the identification of immunogenic viral targets has frustrated CMV vaccine development. Based upon promising clinical data suggesting an important role for T cells in protecting against disease in the transplantation setting, we designed a novel panel of highly-optimized synthetic vaccines encoding major CMV proteins and evaluated their immune potential in murine studies. Vaccination induced robust CD8+ and CD4+ T cells of great epitopic breadth as extensively analyzed using a novel modified T cell assay described herein. Together with improved levels of CMV-specific T cells as driven by a vaccine, further immune evaluation of each target is warranted. The present model provides an important tool for guiding future immunization strategies against CMV.
An Equilibrium Model for Diffusion-Limited Solid-State Polycondensation (2000)

A model for unsteady-state solid-state polycondensation (SSP) is developed and is applied to the polymerization of poly(bisphenol A carbonate) and poly(ethylene terephthalate) (PET). The model assumes that diffusion of the reaction condensate in the solid polymer is the rate-limiting step in the overall polymerization kinetics. Therefore, the reversible polycondensation reaction is at local equilibrium throughout the polymer particle at all times. The model is applicable to the three general types of step-growth polymerization: AB, A2, and A2 + B2 polycondensation. Through comparison with the predictions of a full kinetic model for polycarbonate synthesis, it is demonstrated that the equilibrium model provides an upper bound on molecular weight and its rate of increase. Model predictions are also compared to experimental data for PET SSP. These comparisons show that the equilibrium model provides a useful tool for understanding the effects of temperature and particle size as well as for establishing a lower bound on the diffusion coefficient of the reaction condensate in the solid polymer.
Integrated pharmacokinetics and pharmacodynamics of Ro 48–6791, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects (1997)

This first study with Ro 48-6791 in humans has shown that this benzodiazepine is approximately four to six times as potent as midazolam, but has a comparable onset and duration of action.
A 111-149-GHz, Compact Power-combined Amplifier With 17.5-dBm $P_{sat}$, 16.5% PAE in 22-nm CMOS FD-SOI (2022)

This paper presents a 4-way, 3-stage power-combined CMOS SOI power amplifier (PA) operating from 111–149 GHz. Pseudo-differential stages and 4-way parallel power combining increases the output power from power cells matched to 50 Ohms. Using sub-quarter wavelength (SQWL)-type coupled-line balun (CLB), low-loss output matching networks achieve higher power-added efficiency (PAE). Fabricated in 22-nm FD-SOI CMOS technology, the PA occupies 0.113mm2 core area generates 17.5-dBm saturated output power (P <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sat</inf> ) and 16.5% peak PAE. To the author's knowledge, this work demonstrates the highest PAE in a CMOS SOI process at D-band.
Fibers from Liquid Crystalline Polymers (2001)

No AccessStructure Formation in Polymeric FibersApr 2001Fibers from Liquid Crystalline PolymersDavid R. Salem, Stephen Z. D. Cheng, Fuming Li, Christopher Y. Li, Kevin W. McCreight, Yeocheol Yoon, Frank W. HarrisDavid R. Salem, Stephen Z. D. Cheng, Fuming Li, Christopher Y. Li, Kevin W. McCreight, Yeocheol Yoon, Frank W. Harrishttps://doi.org/10.3139/9783446456808.007SectionsAboutPDF ToolsAdd to FavoritesDownload CitationTrack CitationsCopy LTI LinkPDF key 'share (en)' returned an object instead of string.FacebookTwitterEmailLinkedIn previous chapternext chapter FiguresReferencesRelatedDetails 2001Pages: 247-295Print ISBN: 978-3-446-18203-5eISBN: 978-3-446-45680-8 Copyright & Permissions© 2001 Carl Hanser Verlag GmbH & Co. KGPDF downloadLoading ...
Abstract LB-156: Improved T cell survival, tumor localization and tumor eradication by folate receptor-alpha redirected T cells is achieved by provision of CD137 costimulatory signaling (2011)

Abstract Human T cells engineered to express a chimeric immune receptor (CIR) specific for folate receptor-alpha (FRα) have shown robust anti-tumor activity against epithelial cancers in vitro but not in the clinic due to their inability to persist and home to tumor in vivo. To address these issues, we constructed CIRs containing an FRα-specific scFv (MOv19) coupled to the T cell receptor CD3ζ chain signaling module alone or in combination with the CD137 (4–1BB) costimulatory motif in tandem. Primary human T cells transduced to express conventional MOv19-ζ or costimulated MOv19-BBζ CIRs secreted various proinflammatory cytokines and exerted cytotoxic function when cocultured with FRα+ tumor cells in vitro. However, only transfer of human T cells expressing the costimulated MOv19-BBζ CIR mediated tumor regression in immunodeficient mice bearing large, established FRα+ human cancer. MOv19-BBζ CIR T cell infusion mediated tumor regression in models of metastatic intraperitoneal, subcutaneous, and lung-involved human ovarian cancer. Importantly, tumor response was associated with the selective survival and tumor localization of human T cells in vivo and was only observed in mice receiving costimulated MOv19-BBζ CIR T cells. T cell persistence and anti-tumor activity were primarily antigen-driven, however, antigen-independent CD137 signaling by CIR did improve T cell persistence but not anti-tumor activity in vivo. Our results show that anti-FRα CIR outfitted with CD137 costimulatory signaling in tandem overcome issues of T cell persistence and tumor localization that limit the conventional FRα T cell targeting strategy to provide potent antitumor activity in vivo. Based upon these encouraging findings, we are preparing to open an anti-FRα CIR protocol for ovarian cancer in mid-2011, pending FDA approval. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-156. doi:10.1158/1538-7445.AM2011-LB-156
DTCO of sequential and monolithic CFET SRAM (2023)

Sequential and monolithic complementary FET (CFET) have become the most attractive device options for continuing the area scaling of SRAM beyond 5-&Aring;-compatible technology (A5). The stacked architecture of CFET has eradicated the need for PMOS and NMOS (PN) separation and thereby enables cell height scaling of 40% compared to 10-&Aring;-compatible technology (A10) forksheet (FS) SRAM. However, the routing becomes challenging with aggressive area scaling. This work proposes interconnect designs for A5 CFET SRAM and explores process integration options for corresponding solutions.
Study of the influence of surface roughness parameters on the frictional characteristics of materials (2019)

Abstract The study of surface roughness parameters and their correlation with coefficient of friction (COF) is of great importance for metal-mechanic applications. Evidence suggests that R a (surface roughness average) is not directly related to COF under sliding conditions. In this study, the relation between surface roughness parameters, namely R a , R t (maximum height of the profile), Δa (mean slope of the profile), and COF, as well as their interactions, were particularly studied. The materials were of an aluminium alloy Al A380. Samples were chemically attacked to modify their surface roughness characteristics. Six different conditions were tested: Al A380 with the surface attacked with an alkaline substance for 0, 2.5, 5, 15, 30 and 60 min. The value of COF was determined using a T-05 block-on-ring tribotester, and surface roughness data was obtained using an optical 3D surface measurement system. MathWorks MATLAB software was used to process the data. Results show that Δa has a strong positive correlation with COF during sliding conditions, whereas both R a and R t may vary without directly affecting COF, contrary to the commonly used industry standard.
Application of hybrid‐simulation to fragility assessment of the telescoping self‐centering energy dissipative bracing system (2013)

SUMMARY Substructure hybrid simulation has been the subject of numerous investigations in recent years. The simulation method allows for the assessment of the seismic performance of structures by representing critical components with physical specimens and the rest of the structure with numerical models. In this study the system level performance of a six‐storey structure with telescoping self‐centering energy dissipative (T‐SCED) braces is validated through pseudo‐dynamic (PsD) hybrid simulation. Fragility curves are derived for the T‐SCED system. This paper presents the configuration of the hybrid simulation, the newly developed control software for PsD hybrid simulation, which can integrate generic hydraulic actuators into PsD hybrid simulation, and the seismic performance of a structure equipped with T‐SCED braces. The experimental results show that the six‐storey structure with T‐SCED braces satisfies performance limits specified in ASCE 41. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Electrophysiological characterization of activation state-dependent Cav2 channel antagonist TROX-1 in spinal nerve injured rats (2015)

Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury.
Synthesis of Tetragonal BaTiO3by Microwave Heating and Conventional Heating (1997)

Hydrothermal synthesis of barium titanate was done by both microwave heating and conventional heating. The synthesis process was evaluated by examining samples at different processing times by X-ray diffraction. For samples produced by both heating methods, the metastable cubic phase crystallized first and gradually transformed to a tetragonal phase. Microwave synthesis showed advantages of shortened crystallization time, increased c/a ratio, and upon sintering led to a larger degree of increased c/a ratio. Elemental analysis showed a smaller Ti/Ba ratio and larger relative amount of Cl- ion in the microwave-treated sample than those in a conventionally treated sample. Sintering at 850 °C for both samples resulted in the samples exhibiting a clear transition temperature of around 125 °C as measured by DSC.
Gapped and gapless phases of frustration-free spin-12 chains (2015)

We consider a family of translation-invariant quantum spin chains with nearest-neighbor interactions and derive necessary and sufficient conditions for these systems to be gapped in the thermodynamic limit. More precisely, let ψ be an arbitrary two-qubit state. We consider a chain of n qubits with open boundary conditions and Hamiltonian Hn(ψ) which is defined as the sum of rank-1 projectors onto ψ applied to consecutive pairs of qubits. We show that the spectral gap of Hn(ψ) is upper bounded by 1/(n − 1) if the eigenvalues of a certain 2 × 2 matrix simply related to ψ have equal non-zero absolute value. Otherwise, the spectral gap is lower bounded by a positive constant independent of n (depending only on ψ). A key ingredient in the proof is a new operator inequality for the ground space projector which expresses a monotonicity under the partial trace. This monotonicity property appears to be very general and might be interesting in its own right. As an extension of our main result, we obtain a complete classification of gapped and gapless phases of frustration-free translation-invariant spin-1/2 chains with nearest-neighbor interactions.
Murine IgG1 Complexes Trigger Immune Effector Functions Predominantly via FcγRIII (CD16) (1998)

Abstract Previously, we have demonstrated that phagocytosis of IgG1-coated particles by macrophages in vitro is impaired by deletion of FcγRIII in mice, suggesting that IgG1 may interact preferentially with FcγRIII. In the present study, the biologic relevance of this observation was addressed by triggering various effector functions of the immune system in FcγRIII−/− mice, using panels of mAbs of different IgG subclasses. Both binding and phagocytosis of IgG1-coated sheep or human erythrocytes by FcγRIII−/− macrophages in vitro were strongly impaired, indicating that the impaired ingestion of complexed IgG1 by FcγRIII−/−macrophages is due to a defect in binding. An in vivo consequence of the defective phagocytosis was observed by resistance of FcγRIII-deficient mice to experimental autoimmune hemolytic anemia, as shown by a lack of IgG1-mediated erythrophagocytosis in vivo by liver macrophages. Furthermore, trapping of soluble IgG1-containing immune complexes by follicular dendritic cells in mesenteric lymph nodes from FcγRIII−/− mice was abolished. Whole blood from FcγRIII−/− mice was unable to induce lysis of tumor cells in the presence of IgG1 antitumor Abs. Finally, IgG1 mAbs proved unable to mount a passive cutaneous anaphylaxis in FcγRIII−/− mice. Together, these results demonstrate that IgG1 complexes, either in particulate or in soluble form, trigger in vitro and in vivo immune effector functions in mice predominantly via FcγRIII.
Self-timed vertacolor dichromatic vision sensor for low power pattern detection (2008)

This paper proposes a simple focal plane pattern detector architecture using a novel pixel sensor based on the dichromatic vertacolor structure. Additionally, the sensor transfers dichromatic intensity values using a self-timed time-to- first-spike scheme, which provides high dynamic range imaging. The intensity information is transmitted using the address event representation protocol. The spectral information is sampled automatically at each intensity reading in a ratioed way that maintains high dynamic range. A test chip consisting of 20 pixels has been fabricated in 1.5 um 2P 2M CMOS and characterized. The combined pattern detector/ imager core consumes 45 uA at 5 V supply voltage.
Alignment and wavefront control systems of the National Ignition Facility (2004)

The National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory is a stadium-sized facility containing a 192-beam Nd glass laser. Its 1.053-µm output is frequency converted to produce 1.8-MJ, 500-TW pulses in the ultraviolet. Refer to the companion overview articles in this issue for more information. High-energy-density and inertial confinement fusion physics experiments require the ability to precisely align and focus pulses with single-beam energy up to 20 KJ and durations of a few nanoseconds onto millimeter-sized targets. NIF's alignment control system now regularly provides automatic alignment of the four commissioned beams prior to every NIF shot in approximately 45 min, and speed improvements are being implemented. NIF utilizes adaptive optics for wavefront control, which significantly improves the ability to tightly focus each laser beam onto a target. Multiple sources of both static and dynamic aberration are corrected. This article provides an overview of the NIF automatic alignment and wavefront control systems, and provides data to show that the facility is expected to meet its primary requirements to position beams on the target with an accuracy of 50-µm rms over the 192 beams and to focus the pulses into a 600-µm spot.
Absolute quantum yields in NaYF4:Er,Yb upconverters – synthesis temperature and power dependence (2012)

We investigate the temperature and power dependence of the emission quantum yield of NaYF4:Er,Yb upconverters. We show that the quantum yields may vary by almost three orders of magnitude. We demonstrate that formation of the hexagonal phase of this material is not in itself sufficient to guarantee high upconversion efficiency.
Optimal shipboard power system management via mixed integer dynamic programming (2005)

Power systems involve continuous and discrete components and controls. The modeling of 'hybrid' power systems using a logical specification to define the transition dynamics of the discrete subsystem is described. A computational tool for reduction of the logical specification to a set of inequalities is discussed. The use of the transformed model in a dynamic programming approach to the design of optimal feedback controls is described. Examples are given.
Utilization of the IEEE802.11 power save mode with IP paging (2005)

Mobile communication systems increasingly adopt Internet protocol solutions for transport of control and data traffic. To optimize scalability of the mobile communication infrastructure as well as to save scarce radio bandwidth and mobile energy resources, mobile devices can enter a power save mode and refrain from sending superfluous location information towards the network in case the device is idle. Such systems utilize paging to locate and reactivate mobile devices in power save mode, as well as to initiate re-establishment of routing information in the network. The well accepted wireless LAN standard IEEE802.11 supports mechanisms for power saving while a mobile terminal is associated with a particular access point. But paging control of mobile devices in power save mode beyond the scope of a single access point is not part of the standard IEEE802.11 application. In this paper, we propose a mechanism to integrate and utilize existing IEEE802.11 power save mode with an IP paging architecture and protocol without the need to modify the IEEE802.11 standard. In addition to the IP paging protocol operation, the proposal covers an appropriate addressing and identification scheme, which can be utilized for other access technologies as well. An analytical evaluation of energy and paging delay costs allows estimation of the proposed mechanism's efficiency, which might be sub-optimal for high load conditions, but appropriate to support migration scenarios towards future heterogeneous access mobile communication networks.