gebhart/patrepeval huggingface dataset:
Metabolism and disposition of EXP631—A novel antidepressant analgesic (1993)

EXP631, 4-(3-thienyl)-alpha, alpha,1-trimethyl-4-piperidine-methanol hemi-fumarate salt (I), is a centrally acting non-opioid analgesic compound with monoamine uptake blocking properties. EXP631 has analgesic effects in several animal models. It is intended to be used for the treatment of moderate to moderately severe acute and chronic pain. To characterize the disposition of EXP631, the plasma levels of EXP631 were determined in rats and dogs after single intravenous and oral doses. In rats, EXP631 was rapidly absorbed following a single oral solution dose of 5-20 mg kg-1 with maximum plasma levels detected within 1.2 h post dose. The absorption was complete with an oral bioavailability of 92-131%. The pharmacokinetics was dose independent as measured by either Cmax or AUC values. In fasted dogs, EXP631 was absorbed rapidly and well (F = 81%) from an oral solution with the maximum concentration detected at 20 min post dose. In fed dogs, the absorption from capsules was slower (1.38 h) compared to the solution, but the absorption was complete (F = 115%). An N-desmethyl metabolite (II) was found in both rat and dog plasma samples. The structure was confirmed by mass spectroscopy, nuclear magnetic resonance spectroscopy and comparative chromatographic retention times. The metabolite is inactive as an analgesic.
Electrostatic Interaction with the Bacterial Cell Envelope Tunes the Lytic Activity of Two Novel Peptidoglycan Hydrolases (2022)

Peptidoglycan (PG) hydrolases, due to their crucial role in the metabolism of the bacterial cell wall (CW), are increasingly being considered suitable targets for therapies, and a potent alternative to conventional antibiotics. In the light of contradictory data reported, detailed mechanism of regulation of enzymes activity based on electrostatic interactions between hydrolase molecule and bacterial CW surface remains unknown. Here, we report a comprehensive study on this phenomenon using as a model two novel PG hydrolases, SpM23_A, and SpM23_B, which although share the same bacterial host, similarities in sequence conservation, domain architecture, and structure, display surprisingly distinct net charges (in 2D electrophoresis, pI 6.8, and pI 9.7, respectively). We demonstrate a strong correlation between hydrolases surface net charge and the enzymes activity by modulating the charge of both, enzyme molecule and bacterial cell surface. Teichoic acids, anionic polymers present in the bacterial CW, are shown to be involved in the mechanism of enzymes activity regulation by the electrostatics-based interplay between charged bacterial envelope and PG hydrolases. These data serve as a hint for the future development of chimeric PG hydrolases of desired antimicrobial specificity. <b>IMPORTANCE</b> This study shows direct relationship between the surface charge of two recently described enzymes, SpM23_A and SpM23_B, and bacterial cell walls. We demonstrate that by (i) surface charge probing of bacterial strains collection, (ii) reduction of the net charge of the positively charged enzyme, and (iii) altering the net charge of the bacterial surface by modifying the content and composition of teichoic acids. In all cases, we observed that lytic activity and binding strength of SpM23 enzymes, are regulated by electrostatic interactions with the bacterial cell envelope and that this interaction contributes to the determination of the spectrum of susceptible bacterial species. Moreover, we revealed the regulatory role of charged cell wall components, namely, teichoic and lipoteichoic acids, over the SpM23 enzymes. We believe that our findings make an important contribution to understand the means of hydrolases activity regulation in the complex environment of the bacterial cell wall.
Cannabidiol protects an <i>in vitro</i> model of the blood–brain barrier from oxygen‐glucose deprivation via PPARγ and 5‐HT<sub>1A</sub> receptors (2015)

These data suggest that preventing permeability changes at the BBB could represent an as yet unrecognized mechanism of CBD-induced neuroprotection in ischaemic stroke, a mechanism mediated by activation of PPARγ and 5-HT1A receptors.
Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification (2017)

Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.
Synthesis of Trifluorovinyl Ethers Incorporating Functionalized Hydrocarbon Ether Groups:  Insight into the Mechanism of Trifluorovinyl Ether Formation from Trimethylsilyl 2-Alkoxy-2,3,3,3-tetrafluoropropionates (1997)

Novel trifluorovinyl ethers (TFVEs, ROCFCF2), where R is an oligoether, were synthesized from the corresponding sodium alkoxide and hexafluoropropene oxide. The sodium alkoxide ring opened hexafluoropropene oxide at the more highly substituted carbon (C2) to give the 2-alkoxy-2,3,3,3-tetrafluoropropionic acid ester incorporating 2 equiv of the alcohol, ROCF(CF3)CO2R. Hydrolysis of the ester and reaction of the resulting sodium 2-alkoxy-2,3,3,3-tetrafluoropropionate with chlorotrimethylsilane gave the trimethylsilyl 2-alkoxy-2,3,3,3-tetrafluoropropionate, ROCF(CF3)CO2Si(CH3)3. Gas phase vacuum thermolysis of the trimethylsilyl ester at 140−150 °C gave the corresponding TFVEs in 55−63% yields. Thus, 1-[2-(ethoxyethoxy)ethoxy]-1,2,2-trifluoroethene and 1-[2-(2-tert-butoxyethoxy)ethoxy]-1,2,2-trifluoroethene were synthesized from 2-(2-ethoxyethoxy)ethanol and 2-(2-tert-butoxyethoxy)ethanol, respectively. Interestingly, thermolysis of sodium or potassium 2-alkoxy-2,3,3,3-tetrafluoropropionates resulted in negligible to low yields of TFVEs.1 For example, thermolysis of sodium 2-[2-(ethoxyethoxy)ethoxy]-2,3,3,3-tetrafluoropropionate gave a trifluoroacetate ester, 2-(2-ethoxyethoxy)ethyl trifluoroacetate. Variable temperature 19F NMR spectroscopy of trimethylsilyl 2-[2-(ethoxyethoxy)ethoxy]-2,3,3,3-tetrafluoropropionate suggests that an equilibrium exists between two structural conformations of these trimethylsilyl esters: one in which there is an intramolecular “interaction” of silicon with fluorine and one in which there is no silicon−fluorine interaction. This interaction may affect the outcome of the trimethylsilyl ester thermolysis.
On the condition of adaptive neurofuzzy models (2002)

Learning within fuzzy and neurofuzzy systems is becomingly increasingly important as researchers try to infer qualitative, vague information from quantitative, numeric data. The fuzzy representation of an adaptive neurofuzzy system is important both for initialisation and validation purposes, where a designer needs to interpret the knowledge stored in a network. Therefore it is important to study the convergence and rate of convergence characteristics of the parameters in a neurofuzzy model and investigate how this depends on the system's structure. This paper considers how the condition of the input fuzzy sets determines the convergence and generalisation abilities of the network and describes several new results about instantaneous least mean square training rules.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Evaluation of the CO<sub>2</sub> Poisoning Effect on a Highly Active Cathode SrSc<sub>0.175</sub>Nb<sub>0.025</sub>Co<sub>0.8</sub>O<sub>3-δ</sub> in the Oxygen Reduction Reaction (2016)

A solid oxide fuel cell (SOFC) is a highly efficient device for converting chemical energy to electrical energy. In addition to the efforts to reduce the operating temperature of SOFCs to below 600 °C, research studies of the basic mechanism of CO2 poisoning on cathode materials are envisioned to improve the operation of dual-chamber SOFCs using ambient air. In this work, we comparatively studied the CO2 poisoning effect on two highly active perovskites SrSc(0.175)Nb(0.025)Co(0.8)O(3-δ) (SSNC) and Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-δ) (BSCF), using complementary characterization techniques, e.g., powder X-ray diffraction (XRD), Fourier transform-infrared (FT-IR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), CO2-temperature-programmed desorption (CO2-TPD), and electrochemical impedance spectroscopy (EIS). The SSNC cathode shows better tolerance to CO2 as compared with BSCF, which is attributed to the absence of Ba, higher average metal-oxygen bond energy (ABE) of SSNC, and the higher acidity of Nb(5+) cations, whereas the oxygen vacancy concentration plays a less important role.
Betatron Application in Mobile and Relocatable Inspection Systems for Freight Transport Control (2016)

Accelerators with energy level up to 4 MeV having high level of penetration ability by steel equivalent are the popular to control oversize cargo transported by road, by railway and by river. Betatron's usage as cyclic induction accelerator has some advantages in comparison with linear accelerators and other sources. Tomsk Polytechnic University has developed many types of betatrons, most of them are being produced by separate affiliated company " Foton ". Article is shown the results of application of the betatrons in inspection custom systems.
Towards a Novel Metadata Information Service for Distributed Data Management (2007)

The trend in Grid computing towards more data intensive applications, accessing more and more relational databases and requiring advanced integration of secondhand and publicly available data sources, is still upstanding. Rich metadata information about these data sources plays a vital role for efficient distributed data management. There is a lack of service oriented monitoring tools providing a rich set of metadata for data sources, in contrast to the established usage of monitoring and metadata information tools for network and computational Grid resources. We allow the improved integration and exploitation of data sources in service-oriented architectures by providing a service oriented monitoring tool, named DSMON, for them – initially focusing on relational databases. Our approach supports coarse and fine grained information about heterogeneous relational databases via a uniform interface and provides a homogeneous view on the available metadata. This paper presents novel usage scenarios needing a monitoring service as well as important requirements to be fulfilled by such a service. Our research prototype is not bound to a specific data access middleware nor necessarily tightly coupled with other components. Therefore it can play a vital role in any service oriented infrastructure targeted towards advanced data access, integration and management. The functionality and performance of the DSMON prototype is demonstrated for commonly used relational databases such as MySQL, PostGRE and Oracle. DSMON is an essential component of a more general metadata information service, called DSMIS, for data sources providing advanced funtionalities like prediction of the future behavior of a data source and external metadata updates. We introduce its overall architecture and discuss its novel functionalities.
Time-optimal nonlinear feedback control for the NPSAT1 spacecraft (2006)

NPSAT1 is a small satellite being built at the Naval Postgraduate School, and due to launch in January 2006. It uses magnetic actuators and a pitch momentum wheel for attitude control. In this paper, a novel time-optimal sampled-data feedback control algorithm is introduced for closed-loop control of NPSAT1 in the presence of disturbances. The feedback law is not analytically explicit; rather, it is obtained by a rapid re-computation of the open-loop time-optimal control at each update instant. The implementation of the proposed controller is based on a shrinking horizon approach and does not require any advance knowledge of the computation time. Preground-test simulations show that the proposed control scheme performs well in the presence of parameter uncertainties and external disturbance torques
Electron reflectance of multiquantum barrier (MQB) (1986)

In the letter we propose a new multi-quantum structure, namely a multiquantum barrier (MQB). The reflectivity of an electron from the MQB is given theoretically and it is shown that the effective potential barrier of MQB can be higher than that of a classical bulk barrier.
Spin-Transfer Torque Magnetic Memory as a Stochastic Memristive Synapse for Neuromorphic Systems (2015)

Spin-transfer torque magnetic memory (STT-MRAM) is currently under intense academic and industrial development, since it features non-volatility, high write and read speed and high endurance. In this work, we show that when used in a non-conventional regime, it can additionally act as a stochastic memristive device, appropriate to implement a "synaptic" function. We introduce basic concepts relating to spin-transfer torque magnetic tunnel junction (STT-MTJ, the STT-MRAM cell) behavior and its possible use to implement learning-capable synapses. Three programming regimes (low, intermediate and high current) are identified and compared. System-level simulations on a task of vehicle counting highlight the potential of the technology for learning systems. Monte Carlo simulations show its robustness to device variations. The simulations also allow comparing system operation when the different programming regimes of STT-MTJs are used. In comparison to the high and low current regimes, the intermediate current regime allows minimization of energy consumption, while retaining a high robustness to device variations. These results open the way for unexplored applications of STT-MTJs in robust, low power, cognitive-type systems.
Longitudinal patterns of repetitive behavior in toddlers with autism (2020)

Recent evidence suggests that restricted and repetitive behaviors may differentiate children who develop autism spectrum disorder (ASD) by late infancy. How these core symptoms manifest early in life, particularly among infants at high-risk for the disorder, is not well characterized.
Zoledronic acid repolarizes tumour‐associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway (2009)

It is unknown whether zoledronic acid (ZA) at clinically relevant doses is active against tumours not located in bone. Mice transgenic for the activated ErbB-2 oncogene were treated with a cumulative number of doses equivalent to that recommended in human beings. A significant increase in tumour-free and overall survival was observed in mice treated with ZA. At clinically compatible concentrations, ZA modulated the mevalonate pathway and affected protein prenylation in both tumour cells and macrophages. A marked reduction in the number of tumour-associated macrophages was paralleled by a significant decrease in tumour vascularization. The local production of vascular endothelial growth factor and interleukin-10 was drastically down-regulated in favour of interferon-γ production. Peritoneal macrophages and tumour-associated macrophages of ZA-treated mice recovered a full M1 antitumoral phenotype, as shown by nuclear translocation of nuclear factor kB, inducible nitric oxide synthase expression and nitric oxide production. These data indicate that clinically achievable doses of ZA inhibit spontaneous mammary cancerogenesis by targeting the local microenvironment, as shown by a decreased tumour vascularization, a reduced number of tumour-associated macrophages and their reverted polarization from M2 to M1 phenotype.
Determination of molecular motion in membranes using periodic pattern photobleaching. (1978)

The lateral diffusion of a fluorescent phospholipid probe in oriented multibilayers of dimyristoylphosphatidylcholine has been measured by observing the redistribution of fluorescence after photobleaching of the membranes in a periodic pattern of parallel stripes. The diffusion constant D of the fluorescent lipid was found to vary between 1.5 X 10(-11) cm2/sec at 9.6 degrees and 2.0 X 10(-10) at 22.5 degrees in the monoclinic phase. Preliminary studies of dipalmitoylphosphatidylcholine liposomes in the Lbeta' and Pbeta' phases yielded diffusion constants of the order of 10(-11) cm2/sec. These data are relevant to earlier discussions of the rate of complement activation by hapten-sensitized liposomal membranes [Brûlet, P. and McConnell, H. M. (1976) Proc. Natl. Acad. Sci. USA 73,2977--2981; Parce, J. W., Henry, N. and McConnell, H.M. (1978) Proc. Natl. Acad. Sci. USA 75, 1515--1518)]. We have also used this method to study the motion of fluorescent antibodies bound to murine EL-4 tumor cells. Pattern photobleaching techniques have the advantages that cellular or liposomal translation has no major adverse effect on the measurements, that certain nondiffusive motions can be detected and characterized, and that diffusive or other motions can be recorded photographically.
A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy (2019)

This paper provides a brief review of the history, proposed pharmacological mechanisms, safety issues, and clinical applications of the medicine 3,4-methylenedioxymethamphetamine (MDMA). Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic stress disorder (PTSD). In this review paper other potential therapeutic applications for MDMA therapy are described, including contemporary studies treating anxiety associated with autism and the authors' ongoing study exploring the potential role for MDMA-assisted psychotherapy to treat alcohol use disorder. MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021. This means that if clinical efficacy criteria are achieved, MDMA would become a medicine.
Substance P-induced cadherin expression and its signal transduction in a cloned human corneal epithelial cell line (2000)

Although the absence of Substance P (SP), a neurotransmitter in the trigeminal nerve, has been speculated as a cause for developing neurotrophic keratitis, its exact pathogenesis is still not clarified. In a previous report, we showed with electron microscopic examination that epithelial cell attachment was weakened in denervated corneas. In this study, SV40-transformed human corneal epithelial cells (HCE-Ts) were used to explore the molecular mechanisms responsible for mediating regulation of E-cadherin expression in response to Substance P receptor stimulation. Expression of the mRNAs for specific SP receptors, neurokinin (NK)-1R, NK-2R, and NK-3R, was demonstrated with RT-PCR. The cells were treated with various concentrations of SP in vitro, and the expression of an adhesion molecule E-cadherin was analyzed by immunofluorescence, immunoblotting, and enzyme-linked immunosorbent assay (ELISA) using an anti-E-cadherin antibody. E-cadherin expression was increased by SP in a dose-dependent manner both in the cytosolic fraction and in the cell membrane fraction. This increase in E-cadherin expression was completely inhibited by Calphostin C (PKC inhibitor) and KN-62 (CaMK inhibitor), but not by H-89 (PKA inhibitor), indicating that SP-induced E-cadherin expression involves the activation of protein kinase C (PKC) and calmodulin kinase (CaMK). SP did not affect cell proliferation at all. All these findings indicate that SP induced E-cadherin expression through PKC and CaMK activation and suggest that a lack of SP may account in part for the pathogenesis of neurotrophic keratitis.
Characterisation of dual gate lateral inversion layer emitter transistor (2002)

The design, fabrication and characterisation of a dual gate lateral inversion layer emitter transistor (DGLILET) is described. It resembles an anode shorted LIGBT in its structure but has two MOS gates. The second gate controls injection of minority carriers and the resulting conductivity modulation in the device. Owing to this feature the DGLILET can operate as a bipolar device in the on-state and a majority carrier device in switching, causing a low on-state drop combined with low switching losses. The reduction in overall losses makes the device attractive for use in power and high voltage integrated circuits. In addition, the snapback effect present in the anode shorted LIGBT is effectively removed in the DGLILET resulting in a versatile power-switching device. An integrated gate drive circuit has also been designed to drive the two gates of the DGLILET.
Implementing High-performance Complex Matrix Multiplication via the 3m and 4m Methods (2017)

In this article, we explore the implementation of complex matrix multiplication. We begin by briefly identifying various challenges associated with the conventional approach, which calls for a carefully written kernel that implements complex arithmetic at the lowest possible level (i.e., assembly language). We then set out to develop a method of complex matrix multiplication that avoids the need for complex kernels altogether. This constraint promotes code reuse and portability within libraries such as Basic Linear Algebra Subprograms and BLAS-Like Library Instantiation Software (BLIS) and allows kernel developers to focus their efforts on fewer and simpler kernels. We develop two alternative approaches—one based on the 3 m method and one that reflects the classic 4 m formulation—each with multiple variants, all of which rely only on real matrix multiplication kernels. We discuss the performance characteristics of these “induced” methods and observe that the assembly-level method actually resides along the 4 m spectrum of algorithmic variants. Implementations are developed within the BLIS framework, and testing on modern hardware confirms that while the less numerically stable 3 m method yields the fastest runtimes, the more stable (and thus widely applicable) 4 m method’s performance is somewhat limited due to implementation challenges that appear inherent in nature.
An On-Chip Noise Canceller with High Voltage Supply Lines for Nanosecond-Range Power Supply Noise (2007)

An on-chip noise canceller with high voltage supply lines for the nanosecond-range power supply noise is proposed. The canceller fabricated with 90-nm CMOS achieves 68% noise reduction with 2.0% power increase. Under the same noise reduction conditions, the area penalty for the canceller is 1/77 and 1/45 of those for the additional on-chip decoupling capacitors and the power supply lines respectively.