gebhart/patrepeval huggingface dataset:
Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus (2016)

Infection with human cytomegalovirus (HCMV) is a threat for pregnant women and immunocompromised hosts. Although limited drugs are available, development of new agents against HCMV is desired. Through screening of the LOPAC library, we identified emetine as HCMV inhibitor. Additional studies confirmed its anti-HCMV activities in human foreskin fibroblasts: EC50-40±1.72 nM, CC50-8±0.56 μM, and selectivity index of 200. HCMV inhibition occurred after virus entry, but before DNA replication, and resulted in decreased expression of viral proteins. Synergistic virus inhibition was achieved when emetine was combined with ganciclovir. In a mouse CMV (MCMV) model, emetine was well-tolerated, displayed long half-life, preferential distribution to tissues over plasma, and effectively suppressed MCMV. Since the in vitro anti-HCMV activity of emetine decreased significantly in low-density cells, a mechanism involving cell cycle regulation was suspected. HCMV inhibition by emetine depended on ribosomal processing S14 (RPS14) binding to MDM2, leading to disruption of HCMV-induced MDM2-p53 and MDM2-IE2 interactions. Irrespective of cell density, emetine induced RPS14 translocation into the nucleus during infection. In infected high-density cells, MDM2 was available for interaction with RPS14, resulting in disruption of MDM2-p53 interaction. However, in low-density cells the pre-existing interaction of MDM2-p53 could not be disrupted, and RPS14 could not interact with MDM2. In high-density cells the interaction of MDM2-RPS14 resulted in ubiquitination and degradation of RPS14, which was not observed in low-density cells. In infected-only or in non-infected emetine-treated cells, RPS14 failed to translocate into the nucleus, hence could not interact with MDM2, and was not ubiquitinated. HCMV replicated similarly in RPS14 knockdown or control cells, but emetine did not inhibit virus replication in the former cell line. The interaction of MDM2-p53 was maintained in infected RPS14 knockdown cells despite emetine treatment, confirming a unique mechanism by which emetine exploits RPS14 to disrupt MDM2-p53 interaction. Summarized, emetine may represent a promising candidate for HCMV therapy alone or in combination with ganciclovir through a novel host-dependent mechanism.
Mediation of the Effect of Laquinimod on Disability Progression in Relapsing-Remitting Multiple Sclerosis (RRMS) (P3.195) (2014)

OBJECTIVE: To explore whether laquinimod's effect on disability progression is mediated through its effect on relapses and new T2 lesions. BACKGROUND: Laquinimod treatment is associated with significant reduction of disability progression in RRMS relative to placebo. However, whether effects on relapses and MRI parameters contribute to the effect on disability progression has not yet been elucidated. DESIGN/METHODS: Pooled individual patient data from the ALLEGRO and BRAVO studies were used for this analysis. Treatment response to laquinimod vs. placebo on 6-month confirmed disability progression, defined as an increase of EDSS 蠅1 point from baseline for patients with baseline EDSS ≤5, or increase of EDSS 蠅0.5 for patients with baseline EDSS >5, was assessed by a baseline-adjusted logistic regression model with number of relapses and number of new T2 lesions during the first year of the study independently added to the model. A Freedman’s (1992) proportion of treatment effect explained by each potential surrogate was used to interpret the results. RESULTS: The initial logistic model yielded reductions of 44% (OR=0.56, P=.005; 95% CI [0.40; 0.78]) in the odds for disability progression confirmed for 6 months with laquinimod vs. placebo. This result is consistent with the 46% reduction previously reported using survival analysis (HR=0.54, P=.0001; 95% CI [0.392; 0.739]). Treatment response when adjusting for relapses or new T2 lesions activity during the first year was only mildly changed (to a 40% reduction) or remained similar (46% reduction) to the response achieved in the initial model. Proportion of treatment response on disability progression explained by relapses during the first year was 11%. CONCLUSIONS: The observed treatment effect of laquinimod in reducing disability progression is not strongly mediated through its effects on either relapses or new T2 lesions activity. This finding supports laquinimod’s novel mechanism of action, i.e., affecting irreversible tissue damage independently from acute inflammatory activity. Study Supported by: Teva Pharmaceutical Industries, Petach Tiqva, Israel.
Structural Modifications of <i>N</i>-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-Aryl-1-piperazinehexanamides: Influence on Lipophilicity and 5-HT<sub>7</sub> Receptor Activity. Part III (2008)

Starting from the previously reported 5-HT 7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8-31 were designed with the primary aim to obtain new compounds endowed with suitable physicochemical properties for rapid and extensive penetration into the brain. The affinities for 5-HT 7, 5-HT 1A, and D 2 receptors of compounds 8-31 were assessed, and several compounds displayed 5-HT 7 receptor affinities in the nanomolar range. Among these, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT 7 receptor affinity (Ki = 0.58 nM), high selectivity over 5-HT 1A and D 2 receptors (324- and 245-fold, respectively), and agonist properties (maximal effect = 82%, EC 50 = 0.60 microM). After intraperitoneal injection in mice, 25 rapidly reached the systemic circulation and entered the brain. Its brain concentration-time profile paralleled that in plasma, indicating that 25 rapidly and freely distributes across the blood-brain barrier. Compound 25 underwent N-dealkylation to the corresponding 1-arylpiperazine metabolite.
An ITLDD CMOS process with self-aligned reverse-sequence LDD/channel implantation (1991)

An advanced inverse-T LDD (ITLDD) CMOS process has been developed. This process features self-aligned lightly-doped-drain/channel implantation for improved hot-carrier protection. Selective polysilicon deposition is used to define the thick polysilicon gate regions with a thin polysilicon gate regions overlying the lightly doped n/sup -/ and p/sup +/ regions. Since the thick poly gate regions are defined by nitride sidewall spacers, optical lithography can be used to define sub-half-micrometer gate length MOSFETs. The LDD implants are performed after the n/sup +/ and p/sup +/ implants are annealed, resulting in MOSFET's with improved short-channel behavior due to the smaller lateral source/drain diffusion.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Deformation Microstructures of Two-Phase Intermetallic Alloy Composed of Ni<sub>3</sub>Al and Ni<sub>3</sub>V in Single Crystalline Form (2012)

Two-phase single-crystal intermetallic alloys composed of Ni 3 Al (L1 2 ) and Ni 3 V (D0 22 ) with some orientations were compressed at various temperatures, and their deformation microstructures were observed by transmission electron microscopy (TEM). The deformation at room temperature was governed by the glide motion of dislocations in the primary Ni 3 Al precipitates and the activation of the microtwins in the Ni 3 V variant structures in the channel regions. The interfaces between the primary Ni 3 Al precipitates and the Ni 3 V variant structures are suggested to work as the barriers to the dislocation motion. While, at temperature above the peak temperature (873 K), the deformation microstructures of the two-phase intermetallic alloy exhibited the ribbon-like deformation microstructures penetrating the constituent phases i.e. through the interfaces between primary Ni 3 Al precipitates and the Ni 3 V variant structures in the channel regions. It was also suggested that the superior strength in the two-phase intermetallic alloys is due to the high flow strength of the Ni 3 V phases and to the interfacial hardening receiving when the dislocations activated in the primary Ni 3 Al precipitates propagate to the channel regions.
Fabricating capacitive micromachined ultrasonic transducers with direct wafer-bonding and LOCOS technology (2008)

We present an improved fabrication method for capacitive micromachined ultrasonic transducers (CMUTs). Recently, a process was developed to fabricate CMUTs using direct wafer-bonding instead of the traditional sacrificial release method. This paper presents a method based on local oxidation of silicon (LOCOS) and direct wafer-bonding to improve the controllability of gap heights and the parasitic capacitance. Critical vertical dimensions are determined by a thermal oxidation process, which allows tight vertical tolerances (≪ 10 nm) with unmatched uniformity over the entire wafer. Using this process we successfully fabricated CMUTs with gap heights as small as 40 nm with a uniformity of ± 2 nm over the entire wafer.
Pulsed laser triggered high speed microfluidic fluorescence activated cell sorter (2012)

We report a high speed and high purity pulsed laser triggered fluorescence activated cell sorter (PLACS) with a sorting throughput up to 20,000 mammalian cells s(-1) with 37% sorting purity, 90% cell viability in enrichment mode, and >90% purity in high purity mode at 1500 cells s(-1) or 3000 beads s(-1). Fast switching (30 μs) and a small perturbation volume (~90 pL) is achieved by a unique sorting mechanism in which explosive vapor bubbles are generated using focused laser pulses in a single layer microfluidic PDMS channel.
Pathogenesis of a novel porcine parainfluenza virus type 1 isolate in conventional and colostrum deprived/caesarean derived pigs (2021)

Two experimental challenge studies were conducted to evaluate the pathogenesis of a porcine parainfluenza virus type 1 (PPIV-1) isolate. Four-week-old conventional (CON) pigs were challenged in Study 1 and six-week-old caesarean derived/colostrum deprived (CDCD) pigs were challenged in Study 2. Results indicate that PPIV-1 shedding and replication occur in the upper and lower respiratory tracts of CON and CDCD pigs as detected by RT-qPCR and immunohistochemistry. Mild macroscopic lung lesions were observed in CON pigs but not in CDCD pigs. Microscopic lung lesions were mild and consisted of peribronchiolar lymphocytic cuffing and epithelial proliferation in CON and CDCD pigs. Serum neutralizing antibodies were detected in the CON and CDCD pigs by 14 and 7 days post inoculation, respectively. This study provides evidence that in spite of PPIV-1 infection and replication in challenged swine, significant clinical respiratory disease was not observed.
Solution Chemistry Engineering towards Large-Scale Perovskite Photovoltaics (2017)

Organic-inorganic hybrid halide perovskites have recently emerged as a new class of light absorbers with a rapid progress and impressive efficiencies (>22%) for solar conversion applications. Despite the rapid progress demonstrated by these light absorbers, there is still a lack of understanding of some fundamental material/physical/chemical properties of these materials. There is also a significant processing gap between the lab-scale spin coating and scalable deposition methods toward future roll-to-roll manufacturing. In this presentation, I will show the challenges associated scaling up perovskite solar cells with respect to the sensitivity of perovskite crystallization/formation using different process conditions. I will present our recent studies toward a better understanding and control of perovskite nucleation, grain growth, and microstructure evolution using solution processing [1,2]. The precursor chemistry and growth conditions are found to affect significantly the structural and electro-optical properties of perovskite thin films. We find that the solution chemistry of the perovskite precursor ink is critical for scalable deposition perovskite thin films [3]. But this has largely been underexplored. To address this issue, we present a rational design of perovskite precursor film formation to achieve uniform and compact thin films using scalable deposition methods. Using these high-quality perovskite films, we have obtained device efficiencies approaching the values achieved by using lab-scale spin coating deposition. High efficiency perovskite PV mini-modules have also been demonstrated with scalable depositions. These findings make a significant advance towards commercialization of the perovskite PV technology. These results and others will be discussed.
WIDE-BANDWIDTH, HIGH FRAME RATE ELECTRICAL IMPEDANCE TOMOGRAPHY / SPECTROSCOPY - A Code Division Multiplexing (CDM) Approach (2008)

We present a proposal and proof-of-concept, experimental results for a new type of electrical impedance tomography / spectroscopy system that makes use of code division multiplexing to achieve two important technological advances. Assigning each channel an orthogonal code allow all the impedance measurements to be made simultaneously in time, thereby increasing the frame rate; and the use of pseudorandom input signals allows a very wide range of frequencies to be sampled simultaneously in each channel.
Fault-tolerant fault tolerance for component-based automation systems (2013)

To guarantee high availability, automation systems must be fault-tolerant. To this end, they must provide redundant solutions for the critical parts of the system. Classical fault tolerance patterns such as standby or N-modular redundancy provide system stability in the case of a fault. Fault tolerance is subsequently degraded or, depending on the number of deployed replicas, often even unavailable until the system has been repaired.
Cannabinoids and Capsaicin Improve Liver Function Following Thioacetamide-Induced Acute Injury in Mice (2008)

The similar pattern found between the effect of cannabinoids and their antagonists on brain and liver indicated that the therapeutic effect might be directed by the improvement in both organs through CB2 receptors and/or TRPV1 receptors. Modulation of these systems may have therapeutic potential.
Space Vehicle Maneuver Method to Lower Collision Risk to an Acceptable Level (2003)

A method for determining the maneuver required by a space vehicle to reduce its collision probability with another tracked object below a predefined threshold was developed. The methodology employs efficient computationalschemes for computing collision probability, propagating space vehicles, and three-dimensional root finding. The collision probability calculation was improved by reducing a two-dimensional integral to a one-dimensional integral, thereby realizing a significant reduction in computational effort. In addition, a method to circumvent high-fidelity propagation of the space objects from the time of the maneuver to the time of closest approach was found. The method essentially replaces high-fidelity propagation with simple two-body Keplerian propagation. A gradient technique is used to find the maneuver direction. The maneuver magnitude is found using a one-dimensional root finding scheme that takes advantage of the linear relationship between the maneuver velocity and resulting displacement. The method was applied to an actual case involving two geostationary satellites whose collision probability was unacceptably high. For various times before closest approach, the maneuver required to reduce the collision probability below a required threshold was found and provided to satellite operators. A maneuver time was selected and the associated maneuver was executed by satellite operators. Postmaneuver tracking of the satellites indicated that the maneuver worked as planned and reduced the collision probability to the desired level.
Growth Hormone-Mediated Breakdown of Body Fat: Effects of GH on Lipases in Adipose Tissue and Skeletal Muscle of Old Rats Fed Different Diets (2003)

Lipid storage and breakdown is mainly controlled by lipoprotein lipase and hormone-sensitive lipase. The aim of this work was to elucidate whether growth hormone mediated loss of adipose tissue involves a concerted action on tissue lipases, and to what degree such events are modulated by dietary regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory action on hormone-sensitive lipase. We also propose that growth hormone's effects on tissue lipases and blood lipids are modulated by dietary regimen.
State of the art of corrugated horn antennas that combine horizontal and vertical corrugations (2005)

In the present paper the state of the art, possibilities, advantages and disadvantages of the patented corrugated horn antennas that combine horizontal and vertical corrugations is being covered. These rather new type and probably not very well known yet, corrugated horn profiles; combine in the same horn antenna both horizontal and vertical corrugations. This horn antenna produces with reasonable bandwidth, low crosspolarisation, and low sidelobe levels in a physical size smaller than any other solutions. In fact, designs from 15 to 30 dB directivity have been prepared and some of them have been manufactured, tested and arranged for an emerging market that is being served by Flann Microwave Ltd. at present.
Concept for a lunar He-3 transporter using an in-orbit modified shuttle external tank (1989)

A concept is presented for the transport of gaseous He-3 in temperature equilibrium with the liquid hydrogen and liquid oxygen in a modified lunar shuttle external tank. The concept first describes the internal modifications to accommodate He-3, and then, the external modifications to incorporate a propulsion system and an aerobrake. Estimates of the system masses and an assessment of propulsion requirements show the round trip capability. The concept also includes a description of the lunar orbit servicing and transfer operations.
Differentiation of Peripheral Blood Monocytes into Dendritic Cells (2005)

Dendritic cells (DCs) are potent antigen-presenting cells (APC) that are important in the initiation and control of cellular immune responses. Commonly used in T cell-stimulation experiments, DCs are typically "matured" in vitro with microbial products or proinflammatory cytokines, and then loaded with antigens from any number of sources, including peptides, whole proteins, cell lysates, RNA, microbes, or killed tumor cells. This unit presents a simple and commonly used method for the generation of mature human dendritic cells--differentiating them from peripheral blood monocytes.
Spatially encoded phase‐contrast MRI—3D MRI movies of 1D and 2D structures at millisecond resolution (2011)

This work demonstrates that the principles underlying phase-contrast MRI may be used to encode spatial rather than flow information along a perpendicular dimension, if this dimension contains an MRI-visible object at only one spatial location. In particular, the situation applies to 3D mapping of curved 2D structures which requires only two projection images with different spatial phase-encoding gradients. These phase-contrast gradients define the field of view and mean spin-density positions of the object in the perpendicular dimension by respective phase differences. When combined with highly undersampled radial fast low angle shot (FLASH) and image reconstruction by regularized nonlinear inversion, spatial phase-contrast MRI allows for dynamic 3D mapping of 2D structures in real time. First examples include 3D MRI movies of the acting human hand at a temporal resolution of 50 ms. With an even simpler technique, 3D maps of curved 1D structures may be obtained from only three acquisitions of a frequency-encoded MRI signal with two perpendicular phase encodings. Here, 3D MRI movies of a rapidly rotating banana were obtained at 5 ms resolution or 200 frames per second. In conclusion, spatial phase-contrast 3D MRI of 2D or 1D structures is respective two or four orders of magnitude faster than conventional 3D MRI.
Short‐term forecasting of the daily load curve for residential electricity usage in the Smart Grid (2013)

We propose a model of the daily load curve for residential electricity usage, including in particular the effects of dynamic price incentives on the demand response, a topic of considerable interest in the emerging Smart Grid. The model is based on a time series and stochastic regression framework in which the observed daily load curve is represented in terms of a set of periodic smoothing‐spline basis functions, with the basis function coefficients evolving according to a linear Gaussian state‐space model that incorporates level shifts, day of the week and holiday adjustments, and weather effects, as well as the dynamic price‐incentive effects mentioned earlier. Model parameters are estimated from observational time‐series data using maximum‐likelihood methods, with the computations being efficiently carried out using Kalman filtering recursions. The resulting fitted model can be used for short‐term load forecasting by providing a forward sequence of price‐incentive signals and weather projections over the forecast period. This proposed modeling and forecasting methodology have many advantages over competing methods in the literature, including the ability to model intraday load‐substitution effects that are induced by the specified dynamic pricing schedules, the ability to use fine‐grained (5–15 min interval) observational data without greatly increasing the computational cost of the estimation and forecasting procedures, the ability to use informative prior distributions for any model parameters that cannot be reliably estimated from the available observational data, and the ability to update model forecasts based on the latest sequence of partial observational data without having to store the entire time‐series history. Copyright © 2013 John Wiley & Sons, Ltd.
Rescaling of metal oxide nanocrystals for energy storage having high capacitance and energy density with robust cycle life (2015)

Nanocrystals are promising structures, but they are too large for achieving maximum energy storage performance. We show that rescaling 3-nm particles through lithiation followed by delithiation leads to high-performance energy storage by realizing high capacitance close to the theoretical capacitance available via ion-to-atom redox reactions. Reactive force-field (ReaxFF) molecular dynamics simulations support the conclusion that Li atoms react with nickel oxide nanocrystals (NiO-n) to form lithiated core-shell structures (Ni:Li2O), whereas subsequent delithiation causes Ni:Li2O to form atomic clusters of NiO-a. This is consistent with in situ X-ray photoelectron and optical spectroscopy results showing that Ni(2+) of the nanocrystal changes during lithiation-delithiation through Ni(0) and back to Ni(2+). These processes are also demonstrated to provide a generic route to rescale another metal oxide. Furthermore, assembling NiO-a into the positive electrode of an asymmetric device enables extraction of full capacitance for a counter negative electrode, giving high energy density in addition to robust capacitance retention over 100,000 cycles.