gebhart/patrepeval huggingface dataset:
First Clinical Experience With TRV130: Pharmacokinetics and Pharmacodynamics in Healthy Volunteers (2013)

TRV130 is a G protein-biased ligand at the µ-opioid receptor. In preclinical studies it was potently analgesic while causing less respiratory depression and gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A first-in-human study was conducted with ascending doses of TRV130 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV130 was well-tolerated over the dose range 0.15 to 7 mg administered intravenously over 1 hour. TRV130 geometric mean exposure and Cmax were dose-linear, with AUC0-inf of 2.52 to 205.97 ng h/mL and Cmax of 1.04 to 102.36 ng/mL across the dose range tested, with half-life of 1.6-2.7 hours. A 1.5 mg dose of TRV130 was also well-tolerated when administered as 30, 15, 5, and 1 minute infusions. TRV130 pharmacokinetics were modestly affected by CYP2D6 phenotype: clearance was reduced by 53% in CYP2D6 poor metabolizers.TRV130 caused dose- and exposure-related pupil constriction, confirming central compartment µ-opioid receptor engagement. Marked pupil constriction was noted at 2.2, 4, and 7 mg doses. Nausea and vomiting observed at the 7 mg dose limited further dose escalation. These findings suggest that TRV130 may have a broad margin between doses causing µ-opioid receptor-mediated pharmacology and doses causing µ-opioid receptor-mediated intolerance.
Interferon-β1b in the treatment of secondary progressive MS (2001)

IFN-beta1b may delay sustained deterioration in patient-reported HrQoL in SP-MS. Methods of interpreting change in HrQoL are currently insufficiently developed to determine how clinically important these changes are for this population.
Designing Power Module Health Monitoring Systems Based on Converter Load Profile (2020)

This article presents a method for designing converter systems embedding power modules for a specified degradation monitoring performance in real-time applications. It builds upon prior work which identified specific variations in three-dimensional transient heat transfer with interface and interconnect state-of-health. This article contributes a joint, module-converter concurrent design method to quantify opportunities and limits in using chip-based temperature sensing to integrate electrothermal impedance spectroscopy <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in situ</i> . Challenges intrinsic to modules, such as many, closely packed heat sources, are quantified. This article also examines spatial degrees-of-freedom for placing additional degradation sensing temperature detectors. Experimental measurements of transient thermal frequency response show trends that can be exploited to push temperature sensors against their signal-to-noise ratio limits. Overall, the design method relies on circuit topology and modulation details; it is directed toward early-stage converter development. To that end, an included harmonic loss modeling step immediately provides a designer with feedback about the feasibility of a degradation sensing concept.
Comprehensive analysis of melanoma antigen specific T cell repertoire: EPIMAX (EPItope MAXimum) (2007)

3016 Background: We have demonstrated in phase I clinical trial treating 20 patients with metastatic melanoma that dendritic cells (DCs) loaded with killed allogeneic tumor cells can elicit immune and clinical responses. Loading DC vaccines with killed allogeneic tumor cells allows: i) presentation of antigens via both MHC class I and class II, ii) strong help, iii) applicability to any cancer, and iv) loading tumor antigen independent of HLA haplotype of the patient. However, this renders the immunomonitoring step complex as the antigens and their restriction elements are unknown. To address this issue, we developed EPIMAX. Methods: EPIMAX measures simultaneously cell proliferation and secretion of multiple cytokines that distinguish Type 1, Type 2 cytokines and IL-10 secretion using Luminex. Briefly, 5x10 5 CFSE-labeled PBMCs are plated with peptide pools of overlapping peptide libraries from appropriate antigens. After 48hrs, supernatants are transferred for cytokine determination. After an additional 6 days of culture, cell proliferation is analyzed by flow cytometry after staining for surface markers CD4 and CD8. Results: We demonstrated that EPIMAX permits us to assess: i) Specificity and breadth of induced immune responses, ii) Type of induced immunity (Type I, Type II, IL-10), and iii) Function of specific T cells as measured by cytokine secretion and proliferation. To date 8 patients with stage IV melanoma were analyzed at baseline and after vaccination with DCs loaded with killed allogeneic melanoma cells. We assessed epitopes derived from MART-1, NY-ESO1, TRP-1 and gp100. Analysis of CD8+T cells: We have identified 15 melanoma antigen CD8+T cell epitopes in 8 patients. These include: three Tc0 epitopes (IL2), and twelve Tc1 epitopes triggering IP-10 secretion. Analysis of CD4+T cells: We have identified 15 melanoma antigen CD4+T cell epitopes in 5 patients. These include: nine Th0 epitopes (IL2), four Th1 epitopes (IFNγ) and two Th2 epitopes (IL13). Finally, we analyzed secretion of IL-10 and found thus far IL-10 secreting CD4+T cells in seven patients. Further studies demonstrated that these T cells have regulatory function. Conclusions: EPIMAX permits comprehensive assessment of melanoma antigen specific T cell repertoire. No significant financial relationships to disclose.
OA cartilage derived chondrocytes encapsulated in poly(ethylene glycol) diacrylate (PEGDA) for the evaluation of cartilage restoration and apoptosis in an in vitro model. (2011)

Osteoarthritis (OA) is characterized by cartilage attrition, subchondral bone remodeling, osteophyte formation and synovial inflammation. Perturbed homeostasis caused by inflammation, oxidative stress, mitochondrial dysfunction and proapoptotic/antiapoptotic dysregulation is known to impair chondrocyte survival in joint microenvironments and contribute to OA pathogenesis. However, the molecular mechanisms underlying the programmed cell death (apoptosis) of chondral cells are not yet well defined. The present study was conducted to evaluate apoptosis of chondrocytes from knee articular cartilage of patients with OA. The aim of this study was to investigate and compare the apoptosis through the expression of caspase-3 in tissue explants, in cells cultured in monolayer, and in cells encapsulated in a hydrogel (PEGDA) scaffold. Chondrocytes were also studied following cell isolation and encapsulation in poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Specifically, articular cartilage specimens were assessed by histology (Hematoxlyn and Eosin) and histochemistry (Safranin-O and Alcian Blue). The effector of apoptosis caspase-3 was studied through immunohistochemistry, immunocytochemistry and immunofluorescence. DNA strand breaks were evaluated in freshly isolated chondrocytes from human OA cartilage using the TUNEL assay, and changes in nuclear morphology of apoptotic cells were detected by staining with Hoechst 33258. The results showed an increased expression of caspase-3 in tissue explants, in pre-confluent cells and after four passages in culture, and a decreased expression of caspase-3 comparable to control cartilage in cells encapsulated in hydrogels (PEGDA) after 5 weeks in culture. The freshly isolated chondrocytes were TUNEL positive. The chondrocytes after 5 weeks of culture in hydrogels (PEGDA) showed the formation of new hyaline cartilage with increased cell growth, cellular aggregations and extracellular matrix (ECM) production. This is of particular relevance to the use of OA cells and tissue engineering in the therapeutic approach to patients.
Targeting the Metabotropic Glutamate Receptor mGluR4 for the Treatment of Diseases of the Central Nervous System (2005)

Over the last several years a great deal of interest has been focused on the metabotropic glutamate receptors as potential targets for the treatment of a variety of disorders of the central nervous system. Recently, selective agonist or allosteric potentiators of mGluR4, one of the group III mGluRs, have been proposed as potential novel therapeutics for the palliative treatment of Parkinson's disease and some forms of epilepsy. mGluR4 stands out amongst the group III mGluRs due to its relatively restricted localization and apparent role in several key neuronal circuits. Work from a number of laboratories has led to the development of more selective tools for the study of mGluR4, as well as refined models of the structure and function of this receptor. In addition, a growing body of literature suggests that mGluR4 plays a key neuroprotective role in broad spectrum of neurodegenerative disorders. It is hoped that this increased understanding of the role of mGluR4 combined with more detailed structural information will spur the development of better pharmacological tools, and ultimately to novel clinical therapy.
SUMMARY AND RECOMMENDATIONS OF RECYCLED MATERIALS IN ROADSIDE SAFETY DEVICES (2001)

In response to the increased interest in the use of recycled materials such as plastics, rubber, paper, and glass, etc., the Texas Department of Transportation (TxDOT) sponsored project 0-1458, entitled Recycled Materials in Roadside Safety Devices. The purpose of this project was to investigate and explore the use of recycled materials in roadside safety applications with the goal of product implementation. This report summarizes a three-phase research program intended to evaluate the use of recycled materials in roadside safety devices. In the first phase, information regarding recycled material manufacturers and their products was acquired through an extensive literature review and survey of research organizations, state and federal transportation agencies, professional and trade societies, and manufacturers. In the second phase of this project, products were further evaluated through a series of static and dynamic laboratory tests. The testing focused on the applications of Type II barricades, guardrail posts, guardrail offset blocks, and sign supports which were identified as areas with high potential that lacked suitable recycled alternatives. The products showed a wide range in behavior due to different material compositions. Phase III consisted of full-scale crash testing of selected products to validate laboratory results, verify their crashworthiness, and assist with the development of performance specifications. Three products were evaluated for use as temporary sign supports. Another product was evaluated for use as guardrail posts and offset blocks in strong post W-beam guardrail. Performance specifications were prepared for these applications and are included as appendices in the summary report.
Thickness-dependent structural, magnetic and transport properties of epitaxial Co2FeAl Heusler alloy thin films (2012)

We report on a systematic study of the structural, magnetic properties and the anomalous Hall effect, in the Heusler alloy Co2FeAl (CFA) epitaxial films on MgO(001), as a function of film thickness. It was found that the epitaxial CFA films show a highly ordered B2 structure with an in-plane uniaxial magnetic anisotropy. An analysis of the electrical transport properties reveals that the lattice and magnon scattering contributions to the longitudinal resistivity. Independent on the thickness of films, the anomalous Hall resistivity of CFA films is found to be dominated by skew scattering only. Moreover, the anomalous Hall resistivity shows weakly temperature dependent behavior, and its absolute value increases as the thickness decreases. We attribute this temperature insensitivity in the anomalous Hall resistivity to the weak temperature dependent of tunneling spin-polarization in the CFA films, while the thickness dependence behavior is likely due to the increasing significance of interface or free surface electronic states.
Modeling and Optimization of a Vortex Induced Vibration Fluid Kinetic Energy Harvester (2014)

In this contribution a fluid kinetic energy harvester excited by vortex induced vibration (VIV) is proposed. In terms of describing and verifying the interaction between the structural and the fluidic domain, a two-way Fluid Structure Interaction (FSI) simulation has been carried out. In order to optimize the harvester, different designs have been investigated to improve the performance. Subsequently, a demonstrator setup for testing the manufactured harvester has been assembled. The experimental results were compared with that of FSI-simulations. By applying the optimized harvester structure, the vortex induced pressure could be enhanced 4 times compared to convetional structures. The results show that the VIV energy harvester deliver 1 μW power output under 2 m/s air flows.
Testing telediagnostic thyroid ultrasound in Peru: a new horizon in expanding access to imaging in rural and underserved areas (2021)

Thyroid VSI telediagnostic ultrasound demonstrated both excellent visualization of the thyroid gland and agreement with standard of care thyroid ultrasound for nodules and thyroid size evaluation. This system could be deployed for evaluation of palpable thyroid abnormalities, nodule follow-up, and epidemiological studies to promote global health and improve the availability of diagnostic imaging in underserved communities.
Antibody responses to P. falciparum blood stage antigens and incidence of clinical malaria in children living in endemic area in Burkina Faso (2017)

On the basis of the data presented in this study, we conclude that the induction of humoral immune response to tested malaria antigens is related to age, transmission season level and incidence of clinical malaria.
Molecular dynamics study of the proton pump cycle of bacteriorhodopsin (1993)

Retinal isomerization reactions, which are functionally important in the proton pump cycle of bacteriorhodopsin, were studied by molecular dynamics simulations performed on the complete protein. Retinal isomerizations were simulated in situ to account for the effects of the retinal-protein interactions. The protein structure employed was that described in Nonella et al. [Nonella, M., Windemuth, A., & Schulten, K. (1991) Photochem. Photobiol. 54, 937-948]. We investigated two mechanisms suggested previously for the proton pump cycle, the 13-cis isomerization model (C-T model) and the 13,14-dicis isomerization model. According to these models, retinal undergoes an all-trans-->13-cis or an all-trans-->13,14-dicis photoisomerization as the primary step of the pump cycle. From the simulations emerged a consistent picture of isomerization reactions and their control through the retinal-protein interactions which favors the 13,14-dicis isomerization model. Electrostatic interactions between the protonated Schiff base and its counterion are found to direct the stereochemistry of retinal in the photocycle: this and other interactions steer retinal toward the 13,14-dicis geometry in the primary photoreaction, toward the 13-cis geometry after its deprotonation, and to the all-trans isomeric form after its reprotonation. We also propose a catalytic mechanism involving hydrogen bonding of the Schiff base to main chain oxygen atoms of Val-49 and Thr-89 for the 13-cis-->all-trans thermal reisomerization of retinal. The all-trans-->13-cis primary photoreaction required by the "C-T" model was found to be inhibited by the Schiff base-counterion interaction, but the possibility of such a reaction can not be excluded. In order to investigate the "C-T" model, we enforced an all-trans-->13-cis photoisomerization in a simulation and monitored the subsequent protein conformational changes. The effects of internal water molecules on retinal isomerization reactions were studied by placing 16 water molecules in the proton conduction channel. The results indicate that water affects the nature of the Schiff base counterion and the nature of the primary photoreaction. Water chains, formed between positively and negatively charged protein groups in the proton conduction channel, are suggested to be involved in the reprotonation and deprotonation of retinal.
Effect of left-handed materials in surface plasmon excitation and propagationlength (2019)

We investigated the dispersion relation of surface plasmons (SPs) excited in a medium comprised of a left-handed material (LHM) layer. We investigated different light polarizations in SP excitation along an LHM-metal interface. We studied SP excitation through a classical Kretschmann geometry, employing an LHM interlayer between a dielectric and a metal layer. Using this three-layer configuration, we investigated the effect of LHM medium on characterizing SP propagation length, which is directly related to the energy of the surface waves.
Inducement of Azimuthal Molecular Orientation of Pentacene by Imprinted Periodic Groove Patterns for Organic Thin‐Film Transistors (2008)

A new strategy for control of the in-plane orientation of pentacene is introduced using nanometer-scale periodic groove patterns as an alignment layer. Compared to pentacene films that are not aligned, an enhanced field effect mobility of 1.67 cm2 V−1 s−1 has been achieved when the optimal π-orbital overlap direction is parallel to the direction of the current flow. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2008/adma200701076_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Transcatheter direct mitral annuloplasty with Cardioband: feasibility and efficacy trial in an acute preclinical model (2016)

Transcatheter direct annuloplasty with a surgical-like adjustable device is feasible in the porcine animal model. The humanised porcine model has been instrumental in demonstrating feasibility and in establishing the procedural steps.
Synthesis, Reduction Potentials, and Antitubercular Activity of Ring A/B Analogues of the Bioreductive Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824) (2008)

The nitroimidazooxazine S-1 (PA-824) is a new class of bioreductive drug for tuberculosis. A series of related bicyclic nitroheterocycles was synthesized, designed to have a wide range of one-electron reduction potentials E(1) (from -570 to -338 mV, compared with -534 mV for S-1). The observed E(1) values closely correlated with the sigma(m) values of the heteroatom at the 4/8-position of the adjacent six-membered ring. Although the compounds spanned a range of E(1) values around that of S-1, only the nitroimidazothiazines showed significant antitubercular activity (at a similar level of potency), suggesting that E(1) is not the main driver of efficacy. Furthermore, there was a correlation between activity and the formation of imidazole ring-reduced products at the two-electron level, pointing to the potential importance of this reduction pathway, which is determined by the nature of the substituent at the 2-position of the 4-nitroimidazole ring.
Sulfheme Proteins (1972)

Abstract The optical spectrum of carboxysulfmyoglobin (sulf-MbCO), which is prepared in 90% purity, has been studied both at 4° and near liquid nitrogen temperature. An assignment of the spectral transitions further supports the conclusion that the prosthetic group of sulfmyoglobin is an iron chlorin. Sulfmyoglobin has been found to exhibit a rectangular hyperbolic CO binding curve with a p½ of 9 to 10 mm Hg at 4° and pH 8. This represents an affinity at least 1500-fold lower than that of myoglobin under the same conditions. The infrared C—O stretching frequency of CO bound to the iron of ferrous sulfmyoglobin has been found to be 1953.5 ± 0.5 cm-1, about 10 cm-1 higher than that of CO bound to myoglobin. A linear relationship has been found which correlates the logarithms of the O2 and CO affinity constants with the carbonyl stretching frequency, which is taken here as a measure of the electron density at the iron. It is suggested that most of the decrease in O2 and CO affinity of sulfmyoglobin, as compared to myoglobin, can be attributed to the lowering of electron-density at the iron of the prosthetic group. Finally, a photochemical method is described for the conversion of carboxysulfmyoglobin back to carboxymyoglobin.
Implementation trade-offs in using a restricted data flow architecture in a high performance RISC microprocessor (1995)

The implementation of a superscalar, speculative execution SPARC-V9 microprocessor incorporating Restricted Data Flow principles required many design trade-offs. Consideration was given to both performance and cost. Performance is largely a function of cycle time and instructions executed per cycle while cost is primarily a function of die area. Here we describe our Restricted Data Flow implementation and the means with which we arrived at its configuration. Future semiconductor technology advances will allow these trade-offs to be relaxed and higher performance Restricted Data Flow machines to be built.
Towards a tactical software defined network (2016)

Tactical military networks present a challenging environment for the delivery of information services. A tactical network must support a dynamically changing force in the face of physical and electronic threats and where bandwidth is scarce. The network manager faces an almost impossible task to deliver vital information with the required quality of service in the face of changing operational priorities. This paper describes a structured methodology to assess emerging technologies such as Software Defined Networks (SDN) which can deliver increased agility and reduce the operator burden in tactical networks. It presents initial results from the application of this methodology.
Novel synthetic plasmid and Doggybone™ DNA vaccines induce neutralizing antibodies and provide protection from lethal influenza challenge in mice (2015)

Nucleic acid-based vaccines (NAVs) are a promising alternative to conventional influenza vaccines with the potential to increase influenza vaccine availability due to their simplicity in design and rapid speed of production. NAVs can also target multiple influenza antigens and control flu variants. Traditionally NAVs have been DNA plasmids however, we are continuing to explore new methods that may enhance vaccine efficacy. Recently new focus has been on RNA cassettes as NAVs. RNA vaccines combine conceptual advantages in that they focus on delivery of only the coding cassette. However, RNA vaccines have a short half-life and cause interferon-induced fevers. Here we describe a new NAV approach where we study delivery of a linear DNA cassette [Doggybone linear closed DNA [(dbDNA)] produced by an enzymatic process that yields an antigen expression cassette comprising a promoter, DNA antigen, poly A tail, and telomeric ends. This focused approach has many of the advantages of plasmid DNA as well as a minimal cassette size similar to RNA strategies. For this study, we characterized the specific CD4(+) and CD8(+) T cell responses and determined the hemagglutination inhibition (HI) titers induced by dbDNA and compared the responses with those of an optimized plasmid DNA (pDNA) vaccine encoding the same H1N1 influenza A/PR/8/34 HA gene. Immunizations with the constructs resulted in similar humoral and cellular immune responses. Both constructs induced high-titer HI antibodies and fully protected animals from lethal viral challenge. The data obtained from this study provides important validation for further development of novel vector approaches.