gebhart/patrepeval huggingface dataset:
p-Substituted N-acetyl-L-(S)- and D(R)-.alpha.-amino-N-phenylsuccinimides and -glutarimides. Substituent effects on stereoselective anticonvulsant activity (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTp-Substituted N-acetyl-L-(S)- and D(R)-.alpha.-amino-N-phenylsuccinimides and -glutarimides. Substituent effects on stereoselective anticonvulsant activityDonald T. Witiak, Shiv K. Seth, Eugene R. Baizman, Stuart L. Weibel, and Harold H. WolfCite this: J. Med. Chem. 1972, 15, 11, 1117–1123Publication Date (Print):November 1, 1972Publication History Published online1 May 2002Published inissue 1 November 1972https://pubs.acs.org/doi/10.1021/jm00281a007https://doi.org/10.1021/jm00281a007research-articleACS PublicationsRequest reuse permissionsArticle Views116Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A Break in the Brake Mechanism in Diabetes (2008)

The importance of insulin and glucagon as fine regulators of glycemic excursions is well established (1). Alterations in gastric emptying are generally not considered important contributors to postprandial hyperglycemia until late complications of diabetes such as gastroparesis have occurred (2,3). It is now emerging that the rate of gastric emptying may be a major determinant of postprandial glycemic excursions in healthy subjects, as well as in type 1 and type 2 diabetic patients (4).

Gastroparesis is a relatively rare complication that occurs late in diabetes because of irreversible intestinal nerve damage (4); it must be distinguished from the physiological inhibitory effects of acute hyperglycemia on gastric motility (5,6). The latter has been proposed as a defense mechanism existing to minimize postprandial hyperglycemia by reducing the rate of efflux of glucose into the circulation from the gut (7). This may be of special importance for people with type 1 diabetes who have a reduced ability to delay gastric emptying in response to hyperglycemia (8). Cross-sectional studies suggest that an inverse relationship between the rate of gastric emptying and blood glucose concentration also exists in type 2 diabetic patients (4) and, thus, that similar regulatory mechanisms may exist in both conditions.

### Extrinsic pathway.

Normally, the rate of gastric emptying is tightly regulated as a result of neural and hormonal feedback triggered by the interaction of nutrients within the small intestine known as the ileal break mechanism or “extrinsic pathway” of control. This feedback is caloric-load dependent, relates to the length of small intestine exposed to nutrient, and regulates the overall rate of emptying to about 2–3 kcal/min (9,10). When food reaches the intestine, L- and K-cells in the distal small bowel are stimulated to produce glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), respectively, both of …
In vitro efficacy of artemisinin-based treatments against SARS-CoV-2 (2021)

Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration-response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC<sub>50</sub>) in different cell types: 7-12 µg/mL), followed by artemether (53-98 µg/mL), A. annua extracts (83-260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC<sub>50</sub> values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.
Expression of Mcl‐1 in mantle cell lymphoma is associated with high‐grade morphology, a high proliferative state, and p53 overexpression (2002)

Abstract Mantle cell lymphoma (MCL) is a distinct type of B‐cell non‐Hodgkin's lymphoma characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. Defects in apoptosis may contribute to pathogenesis. This study evaluated the expression of the anti‐apoptotic protein Mcl‐1 in two MCL cell lines and five frozen MCL tumours (four small‐cell, one blastoid/large‐cell) using western blot analysis. Mcl‐1 expression was also assessed in 36 formalin‐fixed, paraffin wax‐embedded MCL tumours (24 small‐cell, 12 blastoid/large‐cell) by immunohistochemistry. Western blot analysis revealed the expected 37 kD protein product in both MCL cell lines and in five frozen tumours, with the blastoid case having the highest expression level. Using a cut‐off of >10% immunolabelled cells for Mcl‐1, it was found that 12 of 36 MCL tumours were positive. Mcl‐1‐positive tumours had a higher frequency of blastoid/large‐cell morphology (8/12 versus 4/24, p = 0.009), p53 overexpression (3/10 versus 1/23, p = 0.04), and higher Ki67 immuno‐labelling ( p = 0.002). It is concluded that expression of Mcl‐1 in MCL is heterogeneous. A relatively high level of Mcl‐1 expression correlates with high‐grade morphology, a high proliferative state, and p53 overexpression. Copyright © 2002 John Wiley & Sons, Ltd.
A Gain-Boosted Discrete-Time Charge-Domain FIR LPF with Double-Complementary MOS Parametric Amplifiers (2008)

Discrete-time charge-domain filters with FIR characteristics require the resetting of their sampling capacitors for every cycle.The gain boosting techniques presented in this paper are especially useful when applied to a high-order discrete-time charge-domain filter, where a multi-stage implementation is strongly preferred to obtain a large gain with appropriate circuit complexity. The chip is implemented in a 0.13 mum CMOS process. Implementation of the DCMPA for the discrete-time charge-domain filter is of practical significance as it easily provides the variable-gain capability. Triple wells are used to better isolate the DCMPAs from the clock pulse generator.
Masked Neural Style Transfer using Convolutional Neural Networks (2018)

In painting, humans can draw an interrelation between the style and the content of a given image in order to enhance visual experiences. Deep neural networks like convolutional neural networks are being used to draw a satisfying conclusion of this problem of neural style transfer due to their exceptional results in the key areas of visual perceptions such as object detection and face recognition.In this study, along with style transfer on whole image it is also outlined how transfer of style can be performed only on the specific parts of the content image which is accomplished by using masks. The style is transferred in a way that there is a least amount of loss to the content image i.e., semantics of the image is preserved.
Formal Certification and Compliance for Run-Time Service Environments (2012)

With the increased awareness of security and safety of services in on-demand distributed service provisioning (such as the recent adoption of Cloud infrastructures), certification and compliance checking of services is becoming a key element for service engineering. Existing certification techniques tend to support mainly design-time checking of service properties and tend not to support the run-time monitoring and progressive certification in the service execution environment. In this paper we discuss an approach which provides both design-time and runtime behavioural compliance checking for a services architecture, through enabling a progressive event-driven model-checking technique. Providing an integrated approach to certification and compliance is a challenge however using analysis and monitoring techniques we present such an approach for on-going compliance checking.
Disorders of Character (1956)

In a small but tightly packed volume, Dr. Michaels has compressed his medical career of research into the subject of persistent enuresis and has correlated this with a high incidence of the condition in juvenile delinquents, particularly those of a psychopathic type. He has elaborated his findings into a triad of maleness, persistent enuresis, and juvenile delinquency. This he has fitted into a rather deeply rooted character structure which he terms as having "bio-psycho-social" connotations.
A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy (2000)

We detected a point mutation in the transthyretin (TTR) gene associated with familial amyloidotic polyneuropathy (FAP) in a 57-year old male presenting with sensorimotor polyneuropathy, severe autonomic dysfunction and cardiomyopathy using a non-isotopic RNase cleavage assay (NIRCA). NIRCA suggested that the mutation site was near either amino acid position 58 of mature TTR or the 3′ end of exon 3. Direct DNA sequencing showed both a normal GA G (Glu) and a variantAAG (Lys) codon at amino acid position 89 of mature TTR, which has not been previously reported. The site of this mutation is near the 3′ end of exon 3, consistent with the result of NIRCA. This mutation was also confirmed by polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA).
Time-domain skin-effect model for transient analysis of lossy transmission lines (1982)

A skin-effect equivalent circuit consisting of resistors and inductors is derived from the skin-effect differential equations for simulating the loss of a transmission line. A numerical method is used to analyze the transmission-line differential equations and the skin-effect equivalent circuit, yielding a model which relates the new values of node voltages and line currents to their values at the previous time step. Based on this model, a very simple program was written on a desk-top computer for the transient analysis of lossy trammission lines. Two examples are presented. The first example is an analysis of the step and pulse responses of a 600-m RG-8/U coaxial cable. The computed results show excellent agreement with measured data. The second example studies the current at the end of a 12-in 7-Ω strip line under different loading conditions. Very good agreement has been obtained between the calculated steady-state solution and that obtained by the frequency-domain method.
ActiveOS: virtualizing intelligent memory (2003)

Current trends in DRAM memory chip fabrication have led many researchers to propose "intelligent memory" architectures that integrate microprocessors or logic with memory. Such architectures offer a potential solution, to the growing communication bottleneck between conventional microprocessors and memory. Previous studies, however, have focused upon single-chip systems and have largely neglected off-chip communication in larger systems. We introduce ActiveOS, an operating system which demonstrates multi-process execution on Active Pages, a page-based intelligent memory architecture. We present results from multiprogrammed workloads running on a prototype operating system implemented on top of the SimpleScalar processor simulator. Our results indicate that paging and inter-chip communication can be scheduled to achieve high performance for applications that use Active Pages with minimal adverse effects to applications that only use conventional pages. Overall, ActiveOS allows Active Pages to accelerate individual applications by up to 1000 percent and to accelerate total workloads from 20 to 60 percent as long as physical memory can contain the working set of each individual application.
A nucleoside kinase as a dual selector for genetic switches and circuits (2010)

The development of genetic switches and their integrated forms (genetic circuits) with desired specifications/functions is key for success in synthetic biology. Due to the difficulty in rational design, genetic switches and circuits with desirable specifications are mostly obtained by directed evolution. Based on a virus-derived nucleotide kinase as a single-gene dual selector, we constructed a robust, efficient and stringent selection system for genetic switches. This method exhibited unprecedented enrichment efficacy (>30,000-fold) of functional switches from non-functional ones in a single selection cycle. In addition, negative (OFF) selection was exceptionally stringent, allowing the rapid and efficient selection of non-leaky from leaky circuits.
Quasi 2D Ultrahigh Carrier Density in a Complex Oxide Broken‐Gap Heterojunction (2015)

Two‐dimensional (2D) ultra‐high carrier densities are of considerable current research interest for novel plasmonic and high charge‐gain devices. However, the highest 2D electron density obtained is thus far limited to 3 × 1014 cm–2 (½ electron/unit cell/interface) at GdTiO 3 /SrTiO 3 interfaces, and is typically an order of magnitude lower at LaAlO 3 /SrTiO 3 interfaces. We show from experiment and modeling that carrier densities much higher than expected based on resolution of the polar discontinuity at perovskite oxide heterojunctions can be achieved via band engineering. The SrTiO 3 (8 u.c.)/NdTiO 3 ( t u.c)/SrTiO 3 (8 u.c.)/LSAT(001) heterostructure shows the expected electronic reconstruction behavior starting at t = 2 u.c., but then exhibits a higher carrier density regime at t ≥ 6 u.c. due to additional charge transfer from band alignment.
Byrnes, Bevin and the Temporary Settlement, 1946 (2000)

It was clear from the London and Moscow Conferences that the success of Bevin's policy on the Italian colonies depended upon American support and whether an Anglo‐American policy could be fashioned to help avoid any undermining of Britain's position in the eastern Mediterranean and the Middle East, and thereby its standing as a great power. In the first quarter of 1946 this appeared possible in the wake of a general stiffening of the American stance towards the Soviet Union. It was the Iranian crisis which led the Truman Administration to pursue a more confrontational policy towards the Soviets in order, at this stage, to reach agreements satisfactory to US interests rather than as part of a Cold War strategy. This can be seen in the American attitude towards the Soviet claim to Tripolitania and the refashioning of American policy on the Italian colonies.
Joint Design of Communication and Sensing for Beyond 5G and 6G Systems (2021)

The 6G vision of creating authentic digital twin representations of the physical world calls for new sensing solutions to compose multi-layered maps of our environments. Radio sensing using the mobile communication network as a sensor has the potential to become an essential component of the solution. With the evolution of cellular systems to mmWave bands in 5G and potentially sub-THz bands in 6G, small cell deployments will begin to dominate. Large bandwidth systems deployed in small cell configurations provide an unprecedented opportunity to employ the mobile network for sensing. In this paper, we focus on the major design aspects of such a cellular joint communication and sensing (JCAS) system. We present an analysis of the choice of the waveform that points towards choosing the one that is best suited for communication also for radar sensing. We discuss several techniques for efficiently integrating the sensing capability into the JCAS system, some of which are applicable with NR air-interface for evolved 5G systems. Specifically, methods for reducing sensing overhead by appropriate sensing signal design or by configuring separate numerologies for communications and sensing are presented. Sophisticated use of the sensing signals is shown to reduce the signaling overhead by a factor of 2.67 for an exemplary road traffic monitoring use case. We then present a vision for future advanced JCAS systems building upon distributed massive MIMO and discuss various other research challenges for JCAS that need to be addressed in order to pave the way towards natively integrated JCAS in 6G.
Advantages of polypharmaceutical herbal Cannabis compared to single-ingredient, synthetic tetrahydrocannabinol (2000)

Introduction In the United States, marijuana (Cannabis sativa, possibly also Cannabis indica and Cannabis afghanica) is classified by the Drug Enforcement Administration (DEA) as a prohibited Schedule I drug (no currently accepted medical use). As a substitute for marijuana, the DEA approved dronabinol (Marinol®). Dronabinol is synthetic delta-9-tetrahydrocannabinol (∆-THC). It is formulated in a capsule, designed for oral administration. Because ∆-THC is the primary psychoactive ingredient in both Dronabinol and marijuana, the DEA considers Dronabinol equal to marijuana in effectiveness, for the treatment of nausea, vomiting, and anorexia. But Dronabinol and marijuana are not equal, according to many reports (Grinspoon & Bakalar 1997). Many patients report that marijuana has better therapeutic activity than Dronabinol, and that marijuana has less side effects than Dronabinol. Dronabinol often causes psychological “overdose” reactions, symptoms such as dysphoria, depersonalization, anxiety, panic reactions, and paranoia.
Aerodynamics And Optimization Of Airfoil Under Ground Effect (2009)

The Prediction of aerodynamic characteristics and shape optimization of airfoil under the ground effect have been carried out by integration of computational fluid dynamics and the multiobjective Pareto-based genetic algorithm. The main flow characteristics around an airfoil of WIG craft are lift force, lift-to-drag ratio and static height stability (H.S). However, they show a strong trade-off phenomenon so that it is not easy to satisfy the design requirements simultaneously. This difficulty can be resolved by the optimal design. The above mentioned three characteristics are chosen as the objective functions and NACA0015 airfoil is considered as a baseline model in the present study. The profile of airfoil is constructed by Bezier curves with fourteen control points and these control points are adopted as the design variables. For multi-objective optimization problems, the optimal solutions are not unique but a set of non-dominated optima and they are called Pareto frontiers or Pareto sets. As the results of optimization, forty numbers of non- dominated Pareto optima can be obtained at thirty evolutions.
<i>Clostridium perfringens</i> Enterotoxin Fragment Removes Specific Claudins from Tight Junction Strands (1999)

Claudins, comprising a multigene family, constitute tight junction (TJ) strands. Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half. We examined the effects of the COOH-terminal half fragment of CPE (C-CPE) on TJs in L transfectants expressing claudin-1 to -4 (C1L to C4L, respectively), and in MDCK I cells expressing claudin-1 and -4. C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2. In the presence of C-CPE, reconstituted TJ strands in C3L cells gradually disintegrated and disappeared from their cell surface. In MDCK I cells incubated with C-CPE, claudin-4 was selectively removed from TJs with its concomitant degradation. At 4 h after incubation with C-CPE, TJ strands were disintegrated, and the number of TJ strands and the complexity of their network were markedly decreased. In good agreement with the time course of these morphological changes, the TJ barrier (TER and paracellular flux) of MDCK I cells was downregulated by C-CPE in a dose-dependent manner. These findings provided evidence for the direct involvement of claudins in the barrier functions of TJs.
Lipopolysaccharide and interleukin 1 augment the effects of hypoxia and inflammation in human pulmonary arterial tissue. (1996)

The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor alpha on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1 beta, or tumor necrosis factor alpha augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.
Virtual Double-System Single-Box for Absolute Dissociation Free Energy Calculations in GROMACS (2021)

We describe a step-by-step protocol for the computation of absolute dissociation free energy with GROMACS code and PLUMED library, which exploits a combination of advanced sampling techniques and nonequilibrium alchemical methodologies. The computational protocol has been automated through an open source Python middleware (HPC_Drug) which allows one to set up the GROMACS/PLUMED input files for execution on high performing computing facilities. The proposed protocol, by exploiting its inherent parallelism and the power of the GROMACS code on graphical processing units, has the potential to afford accurate and precise estimates of the dissociation constants in drug-receptor systems described at the atomistic level. The procedure has been applied to the calculation of the absolute dissociation free energy of PF-07321332, an oral antiviral proposed by Pfizer, with the main protease (3CL<sup>pro</sup>) of SARS-CoV-2.