gebhart/patrepeval huggingface dataset:
From Homology Models to a Set of Predictive Binding Pockets–a 5-HT<sub>1A</sub> Receptor Case Study (2017)

Despite its remarkable importance in the arena of drug design, serotonin 1A receptor (5-HT<sub>1A</sub>) has been elusive to the X-ray crystallography community. This lack of direct structural information not only hampers our knowledge regarding the binding modes of many popular ligands (including the endogenous neurotransmitter-serotonin), but also limits the search for more potent compounds. In this paper we shed new light on the 3D pharmacological properties of the 5-HT<sub>1A</sub> receptor by using a ligand-guided approach (ALiBERO) grounded in the Internal Coordinate Mechanics (ICM) docking platform. Starting from a homology template and set of known actives, the method introduces receptor flexibility via Normal Mode Analysis and Monte Carlo sampling, to generate a subset of pockets that display enriched discrimination of actives from inactives in retrospective docking. Here, we thoroughly investigated the repercussions of using different protein templates and the effect of compound selection on screening performance. Finally, the best resulting protein models were applied prospectively in a large virtual screening campaign, in which two new active compounds were identified that were chemically distinct from those described in the literature.
Conformationally Locked Carbocyclic Nucleosides Built on a 4′-Hydroxymethyl-3′-hydroxybicyclo[4.1.0]heptane Template. Stereoselective Synthesis and Antiviral Activity (2022)

Two new families of enantiomerically pure carbocyclic nucleoside analogues based on a cyclohexane moiety with five chiral centers and a fused cyclopropyl ring have been synthesized. A highly regio- and stereoselective synthetic approach for the modular construction of the functionalized bicyclo[4.1.0]heptyl azide intermediate <b>6</b> has been established. Key steps to achieve this asymmetric synthesis involved highly diastereoselective allylic oxidation and hydroboration reactions. The first family of compounds, <b>1a</b>,<b>b</b> and <b>2</b>, presents different natural nucleobases, whereas the second one <b>3a</b>-<b>e</b> bears functionalized 1,2,3-triazoles. These derivatives have been tested as antiviral agents, and compound <b>3d</b> has shown to display moderate activity against coxsackie B4 virus.
Short and Long-Term Effects of Telaprevir on Kidney Function in Patients with Hepatitis C Virus Infection: A Retrospective Cohort Study (2015)

Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m2 as previously reported.
Lyn sustains oncogenic signaling in chronic lymphocytic leukemia by strengthening SET-mediated inhibition of PP2A (2015)

Aberrant protein kinase activities, and the consequent dramatic increase of Ser/Thr and -Tyr phosphorylation, promote the deregulation of the survival pathways in chronic lymphocytic leukemia (CLL), which is crucial to the pathogenesis and progression of the disease. In this study, we show that the tumor suppressor protein phosphatase 2A (PP2A), one of the major Ser/Thr phosphatases, is in an inhibited form because of the synergistic contribution of 2 events, the interaction with its physiologic inhibitor SET and the phosphorylation of Y307 of the catalytic subunit of PP2A. The latter event is mediated by Lyn, a Src family kinase previously found to be overexpressed, delocalized, and constitutively active in CLL cells. This Lyn/PP2A axis accounts for the persistent high level of phosphorylation of the phosphatase's targets and represents a key connection linking phosphotyrosine- and phosphoserine/threonine-mediated oncogenic signals. The data herein presented show that the disruption of the SET/PP2A complex by a novel FTY720-analog (MP07-66) devoid of immunosuppressive effects leads to the reactivation of PP2A, which in turn triggers apoptosis of CLL cells. When used in combination with SFK inhibitors, the action of MP07-66 is synergistically amplified, providing a new option in the therapeutic strategy for CLL patients.
More Accurate Modeling of Core Loss in Self-Excited Reluctance Generator (2018)

Due to the environmental hazard caused by using fossil fuels, extensive works are being carried out to switch to green renewable energy sources such as wind. Self-excited reluctance generator (SERG) has gained acceptance for use to generate electricity from wind conversion systems. As a result, steady state, transient as well as dynamic analyses of SERG have received thorough investigations. In these investigations, core loss, either has been neglected or approximately represented. This paper proposes an accurate model of core loss in SERG. As shown in this paper, there is a perfect agreement between simulated and experimental outcomes. This demonstrates largely the nobility, feasibility and accuracy of the model presented in the paper. Effect of neglecting the core loss is also presented in this paper.
C-Nucleosides: synthesis of novel ribavirin analogs by cycloaddition reactions of D-allononitrile N-sulfide (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTC-Nucleosides: synthesis of novel ribavirin analogs by cycloaddition reactions of D-allononitrile N-sulfideDiederik K. Buffel, Berthold P. Simons, Johnny A. Deceuninck, and Georges J. HoornaertCite this: J. Org. Chem. 1984, 49, 12, 2165–2168Publication Date (Print):June 1, 1984Publication History Published online1 May 2002Published inissue 1 June 1984https://pubs.acs.org/doi/10.1021/jo00186a017https://doi.org/10.1021/jo00186a017research-articleACS PublicationsRequest reuse permissionsArticle Views163Altmetric-Citations10LEARN 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
Metastability and hysteresis in the low-frequency dielectric response of the charge-density wave in<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">K</mml:mi></mml:mrow><mml:mrow><mml:mn>0.3</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">MoO</mml:mi></mml:mrow><mml:mrow><mml:mn>3</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math> (1986)

We have investigated the dielectric response of the charge-density wave (CDW) in ${\mathrm{K}}_{0.3}$${\mathrm{MoO}}_{3}$ at temperatures between 30 and 90 K, a temperature regime where the effects of metastable CDW states become the dominant influence on the low-frequency CDW behavior. We observe temperature-quenched metastable CDW states at temperatures below 90 K which are erased by biasing above the threshold field for nonlinear conductivity. We have characterized the density of states for the metastable CDW configuration through measurements of \ensuremath{\epsilon}(\ensuremath{\omega}). Further, we observe in bias-dependent dielectric measurements the effects of long-lived metastable CDW states in the pinned regime over the whole temperature range, as well as very long relaxation times in the sliding state at low temperatures.
The Signaling Pathway Involved in Neutrophil Elastase–Stimulated <i>MUC1</i> Transcription (2007)

We previously reported that neutrophil elastase (NE) stimulated MUC1 gene expression in A549 lung epithelial cells through binding of Sp1 to the MUC1 promoter element. The current study was undertaken to elucidate the complete signaling pathway leading to Sp1 activation. Using a combination of pharmacologic inhibitors, dominant-negative mutant, RNA interference, and soluble receptor blocking techniques, we identified a protein kinase Cdelta (PKCdelta) --> dual oxidase 1 (Duox1) --> reactive oxygen species (ROS) --> TNF-alpha-converting enzyme (TACE) --> TNF-alpha --> TNF receptor (TNFR)1 --> extracellular signal-regulated kinase (ERK)1/2 --> Sp1 pathway as responsible for NE-activated MUC1 transcription. This cascade was identical up to the point of TACE with the signaling pathway previously reported for NE-stimulated MUC5AC production. However, unlike the MUC5AC pathway, TNF-alpha, TNFR1, ERK1/2, and Sp1 were unique components of the MUC1 pathway. Given the anti-inflammatory role of MUC1 during airway bacterial infection, up-regulation of MUC1 by inflammatory mediators such as NE and TNF-alpha suggests a crucial role for MUC1 in the control of excessive inflammation during airway bacterial infection.
Asymmetric Access to Peptidyl β<sup>3</sup>‐Aldehydes by Coupling of <i>N</i>‐Phthalyl α‐Amino Acids with a Synthetic Heterocyclic β‐Amino Aldehyde Precursor (2006)

Abstract Asymmetric access to novel N ‐protected (di)peptidyl β 3 ‐aldehydes (“β 3 ‐PAs”) has been achieved through direct coupling of a chiral non‐racemic 6‐alkoxytetrahydrooxazinone with N ‐phthalyl L ‐α‐amino acids. Kinetic resolution allows for the fruitful use of racemic amino acids in this process. Acidic hydrolysis of the diastereomerically pure, coupling products leads to the title N ‐phthalyl‐β 3 ‐PAs in high yields. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
N,N′-1,2-Phenylene-bis(3-tert-butylsalicylideneiminato)nickel (II) (2023)

A nickel complex with a Schiff base Ni(3-tert-butyl-salophen) was synthesized and structurally characterized by single-crystal X-ray diffraction, 1H, 13C{1H}, 1H–13C HMQC, 1H–13C HMBC, 1H-1H dqf-COSY and 1H-1H NOESY NMR spectroscopy, and IR and UV-vis spectroscopy.
&lt;title&gt;Experimental study of network-centric data fusion algorithms&lt;/title&gt; (2003)

Network-centric architectures are defined by the complete absence of a traditional central data fusion site and also, in general, a central communication facility. Instead, the data fusion is performed at each network node and these nodes communicate on a strictly point-to-point basis. The network topology, which may be dynamic, is assumed to be unknown. These governing constraints imply a fault-tolerant, scalable, and modular system. However, such systems are prone to possible inconsistent fused estimates as a consequence of the well-known rumor propagation problem. The algorithmic challenge is to combat this problem without sacrificing the aforementioned benefits. This has led to the formulation of a technique known as Covariance Intersection (CI). Most recently, CI has been integrated with the Kalman filter to produce the Split CI algorithm - a general solution to decentralised data fusion in arbitrary communication networks. These algorithms have not yet been evaluated outside of a limited simulation environment. The purpose of this paper is to present a study of their relative performance in a hardware-based decentralised sensor network system. The paper will describe a number of indoor experiments that involve tracking a ground target by means of multiple, networked, wall-mounted cameras. High precision ground truth target positions are available from a laser-tracking device. The experiments will evaluate Kalman, CI, and Split CI algorithm performance - measured in terms of consistency, convergence and accuracy - with respect to a range of static and dynamic network topologies.
The regeneration of sensory neurones in the reconstruction of the anterior cruciate ligament (1999)

We examined whether somatosensory evoked potentials (SEPs) were detectable after direct electrical stimulation of injured, reconstructed and normal anterior cruciate ligaments (ACL) during arthroscopy under general anaesthesia. We investigated the position sense of the knee before and after reconstruction and the correlation between the SEP and instability. We found detectable SEPs in all ligaments which had been reconstructed with autogenous semitendinosus and gracilis tendons over the past 18 months as well as in all cases of the normal group. The SEP was detectable in only 15 out of 32 cases in the injured group, although the voltages in the injured group were significantly lower than those of the controls. This was not the case in the reconstructed group. The postoperative position sense in 17 knees improved significantly, but there was no correlation between it and the voltage. The voltage of stable knees was significantly higher than that of the unstable joints. Our findings showed that sensory reinnervation occurred in the reconstructed human ACL and was closely related to the function of the knee.
Toward an Alternative Bio-Based SP Flooding Technology: I. Biosurfactant Evaluation (2015)

Abstract Surfactant-polymer (SP) flooding is one of the most promising methods in enhanced oil recovery (EOR), especially where an existing waterflooding infrastructure is in place. This work is part of a broader research theme in which our group is evaluating the potential of biochemicals for chemical enhanced oil recovery (CEOR). Biosurfactants belong to a diverse group of surface-active chemicals generated by microbial fermentation. Recently, the use of biosurfactants in a CEOR formulation has gained greater attention due to their biodegradability, low toxicity, and effectiveness at high temperature and salinity. In this work, we evaluate the potential of a particular biosurfactant for CEOR application in a carbonate reservoir that is characterized by high temperature and high salinity. We evaluate the biosurfactant compatibility, interfacial tension (IFT) reduction, stability, and adsorption. We benchmark its performance against a synthetic surfactant that had previously proved potent. Compatibility with the field brines (injected and connate) is investigated by observation of solution appearances. IFT reduction is measured using a spinning drop tensiometer. IFT, after prolonged heating, was also measured to investigate the stability of the biosurfactant. Finally, static adsorption tests were conducted using crushed rock samples where changes in biosurfactant concentration, and adsorption, was inferred using a total organic content analyzer. The biosurfactant showed excellent compatibility with field brines at reservoir temperature. It exhibited low static adsorption of 0.65 mg/g. Most importantly, at a concentration of 2000 ppm, the biosurfactant resulted in a very low IFT in the order of 10−2 mN/m. The biosurfactant resulted in an IFT reduction that is comparable to that achieved with the benchmark surfactant. A coreflood, where the biosurfactant was injected in a tertiary mode, demonstrated an additional production of around 6.5% OOIC (original oil in the core). The expected performance of this biosurfactant was further compared to the benchmark surfactant using numerical simulation. Core-scale simulation results suggest the biosurfactant can yield incremental recoveries that are comparable to those obtained using the benchmark surfactant. At the core-scale, a tertiary SP flood, in which a biochemical surfactant is used, can yield an additional production of around 17% OOIC. The results discussed in this paper constitute the first step toward developing an alternative bio-based SP flooding technology for carbonate reservoirs with harsh conditions.
Phase-stable source of polarization-entangled photons using a polarization Sagnac interferometer (2006)

We demonstrate a simple, robust, high-flux source of polarization-entangled photons based on a polarization Sagnac interferometer, measuring 5000 polarization-entangled pairs/s/mW of pump power in a 1-nm bandwidth with 96.8% quantum-interference visibility.
ARM: C-SAPR Surveillance scan (2011)

C-SAPR Surveillance scan
Progress of Advanced Fusion Energy Studies with Ultra-Intense Lasers. (2002)

Modern high-power lasers can generate extreme states of matter that are relevant to astrophysics, equation-of-state studies and fusion energy research. Laser-driven implosions of spherical polymer shells have, for example, achieved an increase in density of 1,000 times relative to the solid state. A new laser technology ‘ultra-intense’ laser is now opening a new ground of the laser fusion research, which is called as fast ignition. During the last several years, we have extensively studied elementary physics relevant to the fast ignitor. Based on these results, we have succeeded enforced heating of imploded plasmas with a 100 TW laser as the first demonstration of this new approach. The experimental result implies the future possibility of breakeven and ignition with significantly small laser energies. This new approach provides a route toefficientfusionenergy production.
Impact and Effectiveness of RotaTeq® Vaccine Based on 3 Years of Surveillance Following Introduction of a Rotavirus Immunization Program in Finland (2013)

Severe RVGE requiring hospitalization was virtually eliminated in vaccine-eligible children in the 3 years following implementation of universal RotaTeq vaccination in Finland.
Performance enhancement and resilience to short-lived failures via routing optimization (2008)

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Comparison of conventional and ultrasound-assisted methods for extraction of nutraceutical compounds from<i>Dendrobium candidum</i> (2014)

The present study was conducted with the objective of developing efficient method of extraction of nutraceutical compounds from protocorms of Dendrobium candidum for the food industry. Conventional heat reflux method was compared with ultrasonic-assisted method for extraction of polysaccharides, polyphenolics and flavonoids. Methanol, ethanol, acetone, acetonitrile and water were used as solvents for heat reflux extraction. Parameters tested for the optimization were methanol concentration (20, 40, 60, 80 and 100%) and duration of treatment (30 min, 1, 2, 4, 6 h). The treatment of samples with 80% methanol for 2-h period proved to be most suitable procedure for extraction of bioactive compounds. Heat reflux method was found superior to ultrasonic-assisted method since it yields higher amounts of bioactive compounds (463.0 mg g−1 DW polysaccharides, 10.75 mg g−1 DW polyphenolics and 5.30 mg g−1 DW flavonoids) and extracts obtained from heat reflux method also showed optimal antioxidant activity.
Data from Mutational and Functional Analysis Reveals &lt;i&gt;ADAMTS18&lt;/i&gt; Metalloproteinase as a Novel Driver in Melanoma (2023)

&lt;div&gt;Abstract&lt;p&gt;The disintegrin-metalloproteinases with thrombospondin domains (ADAMTS) genes have been suggested to function as tumor suppressors as several have been found to be epigenetically silenced in various cancers. We performed a mutational analysis of the &lt;i&gt;ADAMTS&lt;/i&gt; gene family in human melanoma and identified a large fraction of melanomas to harbor somatic mutations. To evaluate the functional consequences of the most commonly mutated gene, &lt;i&gt;ADAMTS18&lt;/i&gt;, six of its mutations were biologically examined. ADAMTS18 mutations had little effect on melanoma cell growth under standard conditions, but reduced cell dependence on growth factors. ADAMTS18 mutations also reduced adhesion to laminin and increased migration &lt;i&gt;in vitro&lt;/i&gt; and metastasis &lt;i&gt;in vivo&lt;/i&gt;. Melanoma cells expressing mutant &lt;i&gt;ADAMTS18&lt;/i&gt; had reduced cell migration after short hairpin RNA–mediated knockdown of ADAMTS18, suggesting that &lt;i&gt;ADAMTS18&lt;/i&gt; mutations promote growth, migration, and metastasis in melanoma. Mol Cancer Res; 8(11); 1513–25. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;
Hydrogen Exchange Measurements in Proteins (2006)

This chapter contains sections titled: Introduction Hydrogen Exchange in Unstructured Peptides Hydrogen Exchange in Native Proteins Hydrogen Exchange and Protein Motions Methods and Instrumentation Hydrogen Exchange Measured by Nuclear Magnetic Resonance (NMR) Spectroscopy Hydrogen Exchange Measured by Mass Spectrometry Hydrogen Exchange Measured by Fourier-transform Infrared (FT-IR) Spectroscopy Applications of Hydrogen Exchange to Study Protein Conformations and Dynamics Protein Folding Protein–Protein, Protein–DNA Interactions Macromolecular Complexes Protein–Ligand Interactions Allostery Protein Dynamics Future Developments References
One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo- and heterogeneous Lewis acids (2021)

Abstract Continuous flow chemistry holds great potential for the production of biologically relevant molecules. Herein, we present an approach for the continuous synthesis of cannabidiol and tetrahydrocannabinol in a one-flow system. The designed route consists of a reaction cascade involving Friedel-Crafts alkylation, subsequent ring opening and cyclisation in up to 45% yield. The reactions were successfully performed using both hetero- and homogeneous Lewis acids in continuous flow and provide yields that are similar to comparable batch processes. Graphical abstract
Characterization of human androgen receptor overexpressed in the baculovirus system. (1992)

An essential step in the process of understanding the structure and function of the human androgen receptor (hAR) involves the production of large quantities of the hAR. For this purpose, the full-length hAR has been overproduced in insect cells by using a baculovirus genetic expression system. The recombinant hAR is produced in Sf21 insect cells at approximately 7 pmol/mg of protein (1 x 10(6) AR molecules per cell), which is 70-150 times greater than levels detected in androgen target tissues. Androgen can bind to the baculovirus-expressed hAR with high affinity (Kd = 0.46 nM), and the specificity of hormone binding in baculovirus-expressed hAR is essentially identical to that of bona fide hAR. An anti-AR monoclonal antibody can recognize the baculovirus-expressed hAR at approximately 100 kDa upon Western blot analysis. Sucrose gradient analysis shows that baculovirus-expressed hAR complexes sediment at 4 S in a high salt medium and these complexes can interact with anti-AR monoclonal antibody to form complexes that sediment at 8-10 S. Therefore, production of recombinant hAR from the baculovirus expression system will provide an alternative source of biologically active hAR for studies on the molecular mechanisms of androgen action.
Supplemental Figure 2 from A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Non–Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial (2023)

&lt;p&gt;CD45-/Cytokeratin+ positive cell as seen in the left panel, with EGFR and MET FISH shown on the same cell in the right panel. This cell would be identified as a CTC based upon CD45/cytokeratin results even though neither EGFR nor MET amplification or polysomy are seen.&lt;/p&gt;