gebhart/patrepeval huggingface dataset:
A Novel Potent and Selective Inhibitor of Glycogen Synthase Kinase‐3 (GSK‐3) (2018)

Glycogen synthase kinase 3 (GSK‐3) is a multi‐tasking serine/threonine protein kinase that is constitutively active and has over 50 known substrates. There are two isoforms of GSK‐3, GSK‐3α and GSK‐3β, which share nearly identical sequences in their catalytic domains. GSK‐3 has been shown to regulate critical cellular functions and has been implicated in several human diseases including pathological inflammation, diabetes, and Alzheimer's. Elevated expression/activity of GSK‐3 can result in dysfunctional inflammatory cytokine production which can be a key component of pathological processes. While GSK‐3 inhibitors have been identified and there are ongoing clinical trials involving GSK‐3 inhibitors (e.g. Tideglusib), given the challenge of finding compounds that selectively inhibit a specified kinase and the plethora of known substrates for GSK‐3, there is a critical need for the identification of novel, specific inhibitors of GSK‐3. Our group has identified a small organic compound, COB‐187, that exhibits potent inhibition of GSK‐3 activity in a non‐cell‐based molecular assay. An extensive screen utilizing 414 kinase assays (representing 404 unique kinases) revealed that COB‐187 is highly specific for GSK‐3 and inhibits the activity of both GSK‐3 isoforms. COB‐187 inhibited the activity of GSK‐3 with greater potency than Tideglusib and was significantly more selective. This result led us to hypothesize that COB‐187 inhibits cellular GSK‐3 activity. Thus, PMA differentiated THP‐1 human macrophages (ATCC, Manassas, VA) were used to investigate the effect of COB‐187 on cellular GSK‐3 function. GSK‐3 is known to phosphorylate β‐catenin at Ser33/37/Thr41 which targets this protein for degradation. Thus, a hallmark of GSK‐3 inhibition is a decrease in Ser33/37/Thr41 phosphorylation and an increase in β‐catenin levels. In addition, there is an increase in β‐catenin phosphorylation at Ser675. Western blot analysis of protein isolated from COB‐187 treated (5 hr.) THP‐1 cells compared to carrier control (DMSO) treated cells, revealed a dose‐dependent reduction in β‐catenin phosphorylation at Ser33/37/Thr41 and consequent increase in β‐catenin levels as well as an increase in phosphorylation at Ser675. Immunocytochemistry showed increased levels of β‐catenin and localization to the nucleus in COB‐187 treated cells. The human cytokine proteome profiler array kit from R&amp;D systems (Minneapolis, MN) revealed marked a reduction in the expression of inflammatory cytokines (e.g. IL‐1β, TNF‐α, IFN‐γ, CXCL10) in LPS stimulated THP‐1 macrophages treated with COB‐187. Based on these results, COB‐187 appears to be a specific and potent GSK‐3 inhibitor and might represent an avenue for the development of novel small molecule therapeutics for diseases caused by aberrant GSK‐3 activity. Support or Funding Information NIH R15GM110602 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
A Broad Symmetry Criterion for Nonparametric Validity of Parametrically Based Tests in Randomized Trials (2011)

Pilot phases of a randomized clinical trial often suggest that a parametric model may be an accurate description of the trial's longitudinal trajectories. However, parametric models are often not used for fear that they may invalidate tests of null hypotheses of equality between the experimental groups. Existing work has shown that when, for some types of data, certain parametric models are used, the validity for testing the null is preserved even if the parametric models are incorrect. Here, we provide a broader and easier to check characterization of parametric models that can be used to (i) preserve nonparametric validity of testing the null hypothesis, i.e., even when the models are incorrect, and (ii) increase power compared to the non- or semiparametric bounds when the models are close to correct. We demonstrate our results in a clinical trial of depression in Alzheimer's patients.
Controlling potential barrier height by changing V-shaped pit size and the effect on optical and electrical properties for InGaN/GaN based light-emitting diodes (2015)

The internal quantum efficiency (IQE) of InGaN/GaN multiple quantum wells (MQWs) with blue light emission was improved by inserting an InGaN/GaN superlattice (SL) beneath the MQWs. While the SL technique is useful for improving the light-emitting diode (LED) performance, its effectiveness from a multilateral point of view requires investigation. V-shaped pits (V-pits), which generate a potential barrier and screen the effect of the threading dislocation, are one of the candidates for increasing the light emission efficiency of LEDs exceptionally. In this research, we investigated the relationship between the V-pit and SL and revealed that the V-pit diameter is strongly correlated with the IQE by changing the number of SL periods. Using scanning near-field optical microscopy and photoluminescence measurements, we demonstrated the distinct presence of the potential barrier formed by the V-pits around the dislocations. The relationship between the V-pit and the number of SL periods resulted in changing the potential barrier height, which is related to the V-pit diameter determined by the number of SL periods. In addition, we made an attempt to insert pit expansion layers (PELs) composed of combination of SL and middle temperature grown GaN layer instead of only SL structure. As a result of the evaluation of LEDs using SL or PEL, the EL intensity was strongly related to pit diameter regardless of the structures to form the V-pits. In addition, it was clear that larger V-pits reduce the efficiency droop, which is considered to be suppression of the carrier loss at high injection current.
Impact of donor extracellular vesicle release on recipient cell “cross-dressing” following clinical liver and kidney transplantation (2020)

In several murine models of transplantation, the "cross-dressing" of recipient antigen presenting cells (APCs) with intact donor major histocompatibility complex (MHC) derived from allograft-released small extracellular vesicles (sEVs) has been recently described as a key mechanism in eliciting and sustaining alloimmune responses. Investigation of these processes in clinical organ transplantation has, however, been hampered by the lack of sensitivity of conventional instruments and assays. We have employed advanced imaging flow cytometry (iFCM) to explore the kinetics of allograft sEV release and the extent to which donor sEVs might induce cross-dressing following liver and kidney transplantation. We report for the first time that recipient APC cross-dressing can be transiently detected in the circulation shortly after liver, but not kidney, transplantation in association with the release of HLA-bearing allograft-derived sEVs. In liver transplant recipients the majority of circulating cells exhibiting donor HLA are indeed cross-dressed cells and not passenger leukocytes. In keeping with experimental animal data, the downstream functional consequences of the transfer of circulating sEVs harvested from human transplant recipients varies depending on the type of transplant and time posttransplant. sEVs released shortly after liver, but not kidney, transplantation exhibit immunoinhibitory effects that could influence liver allograft immunogenicity.
Cyclin-dependent kinase Inhibitors Inspired by Roscovitine: Purine Bioisosteres (2012)

Roscovitine is a synthetic inhibitor of cyclin-dependent kinases that is currently undergoing clinical trials as a candidate drug for some oncological indications. Its discovery prompted many research teams to further optimize its structure or to initiate their own related but independent studies. This article reviews known roscovitine bioisosteres that have been prepared as CDK inhibitors using different core heterocycles. The individual bioisostere types have been described and explored to a different extent, which complicates direct comparisons of their biochemical activity - only six direct analogs containing different purine bioisosteres have been prepared and evaluated side by side with roscovitine. Only four types of bioisosteres have demonstrated improved biological properties, namely pyrazolo[ 1,5-a]-1,3,5-triazines, pyrazolo[1,5-a]pyrimidines, pyrazolo[1,5-a]pyridines and pyrazolo[4,3-d]pyrimidines.
Proteins and Their Interactions With Small Molecules Studied byComputer Simulations. (2002)

The presentation introduce an on-going research project focused
on proteins and their interactions with small molecules. Two
systems are studied by computer simulations; (1)
cyclin-dependent kinase-2 (cdk2) and its inhibition by
purine-like compounds, and (2) haloalkane dehalogenases.
Cyclin-dependent kinases are enzymes controlling the cell
division cycle. A deregulation of cdk has been proved to occur
in human primary tumors and in tumor cell lines. It evoked
potential application of cdk inhibitors in cancer therapy.
Haloalkane dehalogenases are bacterial enzymes cleaving the
carbon-halogen bond of the halogenated aliphatic compounds by a
hydrolytic mechanism. These enzymes have a potential
application in detoxification of subsurface pullutants and
recovery of industrial side products.
Progress in Photonic-Crystal Surface-Emitting Lasers (2019)

Photonic-crystal surface-emitting lasers (PCSELs) have attracted considerable attention as a novel semiconductor laser that surpasses traditional semiconductor lasers. In this review article, we review the current progress of PCSELs, including the demonstration of large-area coherent oscillation, the control of beam patterns, the demonstration of beam steering, and the realization of watt-class and high-beam-quality operation. Furthermore, we show very recent progress in the exploration of high brightness of more than 300 MW cm−2 sr−1, obtained with a high output power of about 10 W while maintaining a high beam quality M2 ~ 2. The PCSELs with such high performances are expected to be applied to a variety of fields, such as laser-based material processing, optical sensing (light-detection and ranging (LiDAR)), and lighting, as they retain the benefits of compact and high-efficiency semiconductor lasers.
System Design of Adjustable Speed Drives, Part 2: System Simulation and ac Line Interactions (2012)

Part 1 of System Design of Adjustable Speed Drives [1] investigated the second-order effects that occur as interactions between adjustable speed drives (ASDs) and system-connected equipment, specifically with regard to commonmode (CM) voltage and ground noise current injected in the system and differential-mode (DM) voltage spikes on the load due to ASD semiconductor switching [1]. This article (Part 2) continues the investigation by proposing high-frequency ASDs, cable, and motor models used in system simulation to identify and mitigate the complex DM or CM injected. Theoretical component models were bridged with field experience to simulate and resolve a practical low-voltage (LV) field example of parallel high horsepower inverters having instantaneous overcurrent (IOC) trip issues due to circulating CM currents between inverters and ground. Component models are also used in a system electromagnetic interference (EMI) simulation example of a power structure, which induced line-to-ground noise current in an industrial plant ground grid.
Nouvel activateur solide de catalyseurs organométalliques pour la polymérisation des oléfines (2005)

Cette these concerne le developpement d’un nouvel activateur solide de complexes organometalliques pour la polymerisation des olefines. Les complexes mono-sites ont permis des avancees en terme d’activites en polymerisation et de controles des proprietes des polymeres, inaccessibles jusqu’alors avec les catalyseurs Ziegler-Natta ; cependant, leur industrialisation reste encore marginale. Leur heterogeneisation au moyen d’un support-activateur doit permettre leur emploi dans des unites de production, economiquement et ecologiquement plus favorables, comme celles employees industriellement en catalyse Phillips et Ziegler-Natta et ainsi exploiter leurs proprietes au niveau industriel. Des activateurs solides ont ete developpes non pas en rendant heterogene des activateurs connus mais en synthetisant un solide capable d’etre un activateur des complexes. Ces activateurs ont ete employes en polymerisation avec des complexes metallocenes et post-metallocenes. Les systemes catalytiques ont des activites superieures ou egales a celles obtenues en solution, tout en conservant les proprietes des polymeres. Les polymeres ont une morphologie en forme de grains spheriques
A Comparison of Proppant Erosion during Slurry Injection (2014)

Abstract During frac-pack treatments, proppant erosion is often a limiting factor for the allowable flow rate and total volume of proppant pumped during the job. Each completion assembly has a rating based on limited amounts of full scale erosion testing which is typically provided for one or two types of proppant. Previous testing results have shown that different types of proppant, such as lightweight ceramic (LWC), intermediate strength proppant (ISP), and high-strength proppant (HSP) have different erosion rates. A jet impingement test facility was used to compare different sources of proppant for each of the commonly used proppant types. The test facility was designed to replicate the downhole conditions, while providing the capability to control the test parameters. A nozzle diameter was selected to represent the typical flow-structure size within the completion equipment and a linear gel with proppant loadings between 2 and 10 PPA was selected for the test slurry. The test coupons were low-alloy steel with a representative heat treatment of the material used for downhole equipment. The results were analyzed by measuring mass removal and the 3D erosion profile to compare the overall erosion rate in each test, as well as the erosion profile produced by the various proppants. Furthermore, the proppant was inspected using a laser confocal microscope to provide comparisons between proppant types and sources. The test results, presented in this paper, show that different sources of proppant within a single type of proppant can lead to significantly different erosion rates. Comparison between two sources of HSP showed that there can be a variation in erosion rate of over 60% and that the variation in erosion rate can double when comparing two sources of ISP. These results have verified that proposed changes, such as changing the proppant from what was tested originally for the frac-job operation, can affect the erosion within the completion equipment. Therefore, it is of critical importance to evaluate the possible effects of any change to ensure that the rating of the tool will not be exceeded.
NO/cG MP-dependent ADP-ribosylation of Actin Mediates the Estrogen Increase in Permeability of Cultured Human Cervical/Vaginal Epithelia (1999)

Reproductive Biology, and Physiology and Biophysics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio, USA.
Processability, Thermal, Mechanical, and Morphological Properties of Novolac Type-Epoxy Resin-Based Carbon-Carbon Composite (2004)

The objectives of this study are to investigate the feasibility of utilizing novolac type-epoxy resin to prepare carbon-carbon(C-C) composite and to study the properties of the composite. Different postcuring times, temperatures, and carbonization heat treatment temperatures were used to treat the novolac type-epoxy resin. The changes in the thermal, physical, and mechanical properties during the carbonization processing are also investigated. The results show that the matrix cured at a higher postcuring time and temperature possesses a significant weight loss on the postcure process and limits the weight loss on carbonization processing. Increasing the postcure time and temperature will improve the mechanical properties of composite after carbonization, however, higher postcure time and temperature will cause additional matrix and fabric damage. In the carbonization process, the mechanical properties and density of C-C composite decrease rapidly after 400 C. When heat treatment temperature is increased to 800 C, mechanical properties and density of composite will remain constant and then increase slightly.
Food menu selection support system (2012)

This paper proposes a food menu selection support system to realize a safe dietary life considering constraint conditions. Nowadays, people have greater choice in food menu selection due to diversification of diet such as food choices available by dining out in restaurants and ready-made foods. Some people, such as food allergy and dialysis patients, however, are excluded from these benefits by dietary constraints...Food menu planning is difficult for people found to be allergic to certain foods, people on dialysis, or people who are recuperating at home after leaving hospital. To address these issues, we propose a food menu selection support system that considers the constraint conditions of individuals for a safe dietary life. The system supports various individual situations such as home, hospital, school, kindergarten and elder care residence.
Surgical Anatomy of the Knee A Review of Common Open Approaches. (2016)

Knee-related complaints are among the most commonly encountered conditions by orthopaedic surgeons. Knee pathology varies widely and includes arthritis, deformities, fractures, infections, neuromuscular disorders, oncologic diseases, and soft-tissue injury. While nonoperative treatment modalities (activity modification, medications, injections, and physical therapy) are typically used as primary interventions, surgical treatment may ultimately become necessary. The purpose of this review is to discuss the most common open approaches to the knee, with an emphasis on surgically relevant anatomy for each approach. Understanding of the anatomy of the knee joint and associated neurovascular structures is necessary in order to avoid intraoperative complications and optimize postoperative recovery.
Effectiveness—Essential for Cost-effectiveness—Reply (2022)

In Reply We thank Cliff, Kelkar, and Mattke for their thoughtful comments.1 Cliff and Kelkar identify many reasons to question the efficacy of aducanumab and donanemab. We find their specific points convincing and agree that neither drug has demonstrated its efficacy reliably.
Amorphous In–Ga–Zn–O Dual-Gate TFTs: Current–Voltage Characteristics and Electrical Stress Instabilities (2012)

We studied the electrical characteristics and electrical stress instabilities of amorphous In-Ga-Zn-O (-IGZO) dual-gate thin-film-transistors (DG TFTs). A threshold voltage of the bottom-gate (BG)-driven -IGZO DG TFTs showed a linear dependence on the top-gate (TG) voltage. The slope of this dependence is associated with the ratio of the TG to BG insulator capacitance. The BG-driven DG TFT showed linear field-effect mobility comparable to that of a single-gate (SG) TFT without the TG electrode and a smaller saturation field-effect mobility and a larger subthreshold swing in comparison to the SG TFT. These characteristics were explained by the BG-driven DG TFT model formulated by taking the TG bias effect into account. The TG interface showed worse stability under an electric bias stress in comparison to the BG interface. It was also found that a negative voltage applied to the TG improved the stability of the DG TFT under a constant-current stress. These observations suggest that the BG-driven -IGZO DG TFTs with the appropriate negative TG voltage applied can simultaneously show both normally off characteristics and higher stability than the SG TFTs.
Differential Rod Contouring is Essential for Improving Vertebral Rotation in Patients With Adolescent Idiopathic Scoliosis (2017)

4.
Frequency and Pitch (2019)

Adiscussion of audio tones in the physics classroom will include mention of their frequency. The frequency of a periodic signal is a well-defined quantity that can readily be measured. A concept related to frequency is that of pitch. Pitch is a perceived quantity that cannot be measured directly and is most important when listeners characterize periodic acoustic signals. The distinction between frequency and pitch is often simplified or even overlooked entirely. Several examples are presented here that clearly illustrate that pitch and frequency are not always simply related.
A Heterogeneous Kinetics Model for Triplet Exciton Transfer in Solid-State Upconversion (2019)

High internal quantum efficiency semiconductor nanocrystal (NC)-based photon upconversion devices are currently based on a single monolayer of active NCs. Devices are therefore limited in their external quantum efficiency based on the low number of photons absorbed. Increasing the number of photons absorbed is expected to increase the upconversion efficiency, yet experimentally increasing the number of layers does not appreciably increase the upconverted light output. We unravel this mystery by combining kinetic modeling and transient photoluminescence spectroscopy. The inherent energetic disorder stemming from the polydispersity of the NCs means that the kinetics are governed by a stochastic transfer matrix. By drawing the rates from a probabilistic distribution and constructing a reaction network with realistic connectivity, we are able to fit complex photoluminescence traces with a very simple model. We use this model to explain the thickness-dependent performance of the upconversion devices and can attribute the reduced efficiencies to the low excitonic diffusivity of the exciton within the NC layers and increased back transfer of the created singlets from the organic annihilator rubrene. We suggest some avenues for overcoming these limitations in future devices.
Minimum variance distortionless response (MVDR) modeling of voiced speech (2002)

In this paper we propose the MVDR method, which is based upon the minimum variance distortionless response (MVDR) spectrum estimation method, for modeling voiced speech. Developed to overcome some of the shortcomings of linear prediction models, the MVDR method provides better models for medium and high pitch voiced speech. The MVDR model is an all-pole model whose spectrum is easily obtained from a modest non-iterative computation involving the linear prediction coefficients thereby retaining some of the computational attractiveness of LPC methods. With the proper choice of filter order, which is dependent on the number of harmonics, the MVDR spectrum models the formants and spectral powers of voiced speech exactly. An efficient reduced model order MVDR method is developed to further enhance its applicability. An extension of the reduced order MVDR method for recovering the correct amplitudes of the harmonics of voiced speech is also presented.
Hybrid Graphene-WS2 Mach-Zehnder modulator on passive silicon waveguide (2021)

2D materials such as graphene have attracted a lot of interest in recent years because of their unique electrical and optical properties [1] - [3] . For example, a graphene Mach-Zehnder modulator (MZM) with 2.8Vmm modulation efficiency and 5GHz bandwidth has been demonstrated in the literature [2] . However, one of the challenges for current graphene MZM is graphene’s relatively high insertion loss. Potential solutions have been proposed, such as improving the quality of graphene or operating the device within graphene’s transparency region [4] . Recently, transition metal dichalcogenides (TMDC) have shown a strong electro-refraction effect in the C band, accompanied by only a limited loss increase [3] , which is promising for high efficiency, low loss Mach-Zehnder modulators and switches.