gebhart/patrepeval huggingface dataset:
Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein (2011)

Dengue virus (DENV) causes the major arboviral disease of the tropics, characterized in its severe forms by signs of hemorrhage and plasma leakage. DENV encodes a nonstructural glycoprotein, NS1, that associates with intracellular membranes and the cell surface. NS1 is eventually secreted as a soluble hexamer from DENV-infected cells and circulates in the bloodstream of infected patients. Extracellular NS1 has been shown to modulate the complement system and to enhance DENV infection, yet its structure and function remain essentially unknown. By combining cryoelectron microscopy analysis with a characterization of NS1 amphipathic properties, we show that the secreted NS1 hexamer forms a lipoprotein particle with an open-barrel protein shell and a prominent central channel rich in lipids. Biochemical and NMR analyses of the NS1 lipid cargo reveal the presence of triglycerides, bound at an equimolar ratio to the NS1 protomer, as well as cholesteryl esters and phospholipids, a composition evocative of the plasma lipoproteins involved in vascular homeostasis. This study suggests that DENV NS1, by mimicking or hijacking lipid metabolic pathways, contributes to endothelium dysfunction, a key feature of severe dengue disease.
A distortion-based metric for location privacy (2009)

We propose a novel framework for measuring and evaluating location privacy preserving mechanisms in mobile wireless networks. Within this framework, we first present a formal model of the system, which provides an efficient representation of the network users, the adversaries, the location privacy preserving mechanisms and the resulting location privacy of the users. This model is general enough to accurately express and analyze a variety of location privacy metrics that were proposed earlier. We provide formal representations of four among the most relevant categories of location privacy metrics, by using the proposed model. We also present a detailed comparative analysis of these metrics based on a set of criteria for location privacy measurement. Finally, we propose a novel and effective metric for measuring location privacy, called distortion-based metric, which satisfies these criteria for privacy measurement and is capable of capturing the mobile users' location privacy more precisely than the existing metrics. Our metric measures location privacy as the expected level of distortion of the adversary's hypothesized trajectories of the users, considering the adversary's knowledge and also the observed parts of the users' trajectories.
Chemistry and Pharmacological Characterization of Novel Nitrogen Analogues of AMOP-H-OH (Sazetidine-A, 6-[5-(Azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) as α4β2-Nicotinic Acetylcholine Receptor-Selective Partial Agonists (2010)

In order to advance therapeutic applications of nicotinic ligands, continuing research efforts are being directed toward the identification and characterization of novel nicotinic acetylcholine receptor (nAChR) ligands that are both potent and subtype selective. Herein we report the synthesis and pharmacological evaluation of members of a new series of 3-alkoxy-5-aminopyridine derivatives that display good selectivity for the α4β2-nAChR subtype based on ligand binding and functional evaluations. The most potent ligand in this series, compound 64, showed high radioligand binding affinity and selectivity for rat α4β2-nAChR with a K(i) value of 1.2 nM and 4700-fold selectivity for α4β2- over α3β4-nAChR, and ∼100-fold selectivity for functional, high-sensitivity, human α4β2-nAChR over α3β4*-nAChR. In the mouse forced swim test, compound 64 exhibited antidepressant-like effects. Structure-activity relationship (SAR) analyses suggest that the introduction of additional substituents to the amino group present on the pyridine ring of the N-demethylated analogue of compound 17 can provide potent α4β2-nAChR-selective ligands for possible use in treatment of neurological and psychiatric disorders including depression.
Budding Yeast Centrosome Duplication Requires Stabilization of Spc29 via Mps1-mediated Phosphorylation (2009)

Protein phosphorylation plays an important role in the regulation of centrosome duplication. In budding yeast, numerous lines of evidence suggest a requirement for multiple phosphorylation events on individual components of the centrosome to ensure their proper assembly and function. Here, we report the first example of a single phosphorylation event on a component of the yeast centrosome, or spindle pole body (SPB), that is required for SPB duplication and cell viability. This phosphorylation event is on the essential SPB component Spc29 at a conserved Thr residue, Thr(240). Mutation of Thr(240) to Ala is lethal at normal gene dosage, but an increased copy number of this mutant allele results in a conditional phenotype. Phosphorylation of Thr(240) was found to promote the stability of the protein in vivo and is catalyzed in vitro by the Mps1 kinase. Furthermore, the stability of newly synthesized Spc29 is reduced in a mutant strain with reduced Mps1 kinase activity. These results demonstrate the first evidence for a single phosphorylation event on an SPB component that is absolutely required for SPB duplication and suggest that the Mps1 kinase is responsible for this protein-stabilizing phosphorylation.
Over Kennett (Correctly Over Kellet), Lancashire (1914)

Journal Article Over Kennett (Correctly Over Kellet), Lancashire Get access Henry Taylor, F.S.A. Henry Taylor, F.S.A. 1Birklands, Birkdale, Lancashire Search for other works by this author on: Oxford Academic Google Scholar Notes and Queries, Volume s11-IX, Issue 214, 31 January 1914, Page 91, https://doi.org/10.1093/nq/s11-IX.214.91b Published: 31 January 1914
Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator (2023)

The NTSR1 neurotensin receptor (NTSR1) is a G protein-coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS modulates dopamine neuronal activity, induces opioid-independent analgesia, and regulates food intake. Recent studies indicate that biasing NTSR1 toward β-arrestin signaling can attenuate the actions of psychostimulants and other drugs of abuse. Here, we provide the cryoEM structures of NTSR1 ternary complexes with heterotrimeric Gq and GoA with and without the brain-penetrant small-molecule SBI-553. In functional studies, we discovered that SBI-553 displays complex allosteric actions exemplified by negative allosteric modulation for G proteins that are Gα subunit selective and positive allosteric modulation and agonism for β-arrestin translocation at NTSR1. Detailed structural analysis of the allosteric binding site illuminated the structural determinants for biased allosteric modulation of SBI-553 on NTSR1.
Energy-efficient spectrum sensing for cognitive sensor networks (2009)

We consider a combined sleeping and censoring scheme for energy-efficient spectrum sensing in cognitive sensor networks. We analyze the detection performance of this scheme by theoretically deriving the global probabilities of detection and false-alarm. Our goal is to minimize the energy consumption incurred in distributed sensing, given constraints on the global probabilities of detection and false-alarm, by optimally designing the sleeping rate and the censoring thresholds. Using specific transceiver models for sensors based on IEEE 802.15.4/ZigBee, we show the energy savings achieved under an optimum choice of the design parameters.
Earth Abundant Metal Corroles As Catalysts for Energy Relevant Processes (2017)

We have recently introduced corrole metal complexes (metallocorroles) as catalysts for various energy-relevant reactions. This includes those that are of prime importance for water splitting into its elements, the hydrogen and oxygen evolution reactions, and also the oxygen reduction reaction for fuel cells. A careful choice of substituents on the corrole ligand and the kind of metal ion (all earth abundant) chelated by them allows for lowering of the electrocatalytic overpotential, increasing reactivity, and controlling selectivity. An arsenal of electrochemical and spectroscopic methodologies, which in the case of metallocorroles is very rich, was applied for acquiring highly valuable information about the mechanisms of action such as characterization of a cobalt-dioxgen intermediate. REFERENCES “Cobalt Corrole Catalyst for Efficient Hydrogen Evolution Reaction from H 2 O under Ambient Conditions: Reactivity, Spectroscopy and DFT Calculations”, Inorg. Chem. 2013 , 52 , 3381-3387. "The Cobalt Corrole Catalyzed Hydrogen Evolution Reaction: Surprising Electronic Effects and Characterization of Key Reaction Intermediates" Chem. Commun. 2014 , 50 , 2725-2727. "Metallocorroles as photocatalysts for driving endergonic reactions, exemplified by bromide to bromine conversion", Angew. Chem. 2015 , 54 , 12370 –12373. "Metallocorroles as Non-Precious Metal Catalysts for Oxygen Reduction", Angew. Chem. 2015 , 54, 14080 –14084. “Metallocorroles as Non-Precious Metal Electrocatalysts for Highly Efficient Oxygen Reduction in Alkaline Media" ChemCatChem 2016 , 8 , 2832-2837. “Metallocorroles as Electrocatalysts for the Oxygen Reduction Reaction (ORR)", Israel J. Chem. 2016 , 56 , 756– 762. “Dioxygen bound Cobalt Corroles”, Chem. Commun. 2017 , in press.
Digital Computer Simulation of a Reciprocating Compressor-A Simplified Analysis (1972)

Cellular signaling pathways involving mTOR, PI3K and ERK have dominated recent studies of breast cancer biology, and inhibitors of these pathways have formed a focus of numerous clinical trials. We have chosen trametinib, a drug targeting MEK in the ERK pathway, to address two questions. Firstly, does inhibition of a signaling pathway, as measured by protein phosphorylation, predict the antiproliferative activity of trametinib? Secondly, do inhibitors of the mTOR and PI3K pathways synergize with trametinib in their effects on cell proliferation? A panel of 30 human breast cancer cell lines was chosen to include lines that could be classified according to whether they were ER and PR positive, HER2 over-expressing, and "triple negative". Everolimus (targeting mTOR), NVP-BEZ235 and GSK2126458 (both targeting PI3K/mTOR) were chosen for combination experiments. Inhibition of cell proliferation was measured by IC50 values and pathway utilization was measured by phosphorylation of signaling kinases. Overall, no correlation was found between trametinib IC50 values and inhibition of ERK signaling. Inhibition of ERK phosphorylation was observed at trametinib concentrations not affecting proliferation, and sensitivity of cell proliferation to trametinib was found in cell lines with low ERK phosphorylation. Evidence was found for synergy between trametinib and either everolimus, NVP-BEZ235 or GSK2126458, but this was cell line specific. The results have implications for the clinical application of PI3K/mTOR and MEK inhibitors.
Linking Open Drug Data to Cheminformatics and Proteochemometrics (2009)

My talk at SWAT4LS 2009 in Amsterdam.
Distinct life histories impact dikaryotic genome evolution in the rust fungus Puccinia striiformis causing stripe rust in wheat (2019)

Abstract Stripe rust of wheat, caused by the obligate biotrophic fungus Puccinia striiformis f. sp. tritici , is a major threat to wheat production world-wide with an estimated yearly loss of US $1 billion. The recent advances in long-read sequencing technologies and tailored-assembly algorithms enabled us to disentangle the two haploid genomes of Pst . This provides us with haplotype-specific information at a whole-genome level. Exploiting this novel information, we perform whole genome comparative genomics of two P . striiformis f. sp . tritici isolates with contrasting life histories. We compare one isolate of the old European lineage (PstS0), which has been asexual for over 50 years, and a Warrior isolate (PstS7 lineage) from a novel incursion into Europe in 2011 from a sexual population in the Himalayan region. This comparison provides evidence that long-term asexual evolution leads to genome expansion, accumulation of transposable elements, and increased heterozygosity at the single nucleotide, structural and allele levels. At the whole genome level, candidate effectors are not compartmentalized and do not exhibit reduced levels of synteny. Yet we were able to identify two subsets of candidate effector populations. About 70% of candidate effectors are invariant between the two isolates while 30% are hypervariable. The latter might be involved in host adaptation on wheat and explain the different phenotypes of the two isolates. Overall this detailed comparative analysis of two haplotype-aware assemblies of P . striiformis f. sp . tritici are the first steps in understanding the evolution of dikaryotic rust fungi at a whole genome level.
PLOC++ (2022)

We propose a novel version of the GPU-oriented massively parallel locally-ordered clustering (PLOC) algorithm for constructing bounding volume hierarchies (BVHs). Our method focuses on removing the weaknesses of the original approach by simplifying and fusing different phases, while replacing most performance critical parts by novel and more efficient algorithms. This combination allows for outperforming the original approach by a factor of 1.9 - 2.3x.
Application of a Submerged Impinging Jet to Investigate the Influence of Temperature, Dissolved CO2, and Fluid Velocity on Corrosion of Pipeline-Grade Steel in Brine (2001)

Abstract Experimental results and analyses are reported on the electrochemical behavior of pipeline-grade steel in high-shear environments of brine saturated in CO2 at 1 atm at temperatures of 30 and 60° C. The environments studied represents well waters encountered in many typical oil and gas fields. A submerged axisymmetric impinging jet was used to study the influence of large fluid velocities on corrosion and video microscopy, corrosion potential monitoring, and impedance spectroscopy were used to investigate the state of the system and the reactivity of the electrode surface. Flow-induced removal of protective films was observed by video microscopy at the open-circuit potential in CO2-saturated brine, and such removal of protective films caused an increase in reactivity as determined by impedance measurements.
Indium Tin Oxide Electrode with an Ultrathin Al Buffer Layer for Flexible Organic Light Emitting Diode (2010)

This paper reports that the mechanical and electrical stability of indium tin oxide (ITO) film deposited on flexible plastic substrate can be much enhanced with a thin Al buffer layer while maintaining a visible transmittance over 75%. The improved stability is attributed to the effective elastic mismatch between the film and the substrate reduced by a ductile interlayer. A polymer light emitting diode fabricated using an ITO/Al anode exhibited a luminance of 13,000 cd/m 2 with a current efficiency of 16 cd/A. Bending-induced degradation of the device performance was also alleviated when a mechanical buffer layer was inserted.
Biological phenotypes of HIV‐1 subtypes A and B strains of diverse origins (1995)

The identification of specific biologic phenotypic traits that can be correlated with different HIV-1 genetic subtypes was sought. The genetic subtypes were determined by either sequencing (Cameroonian strains, n = 18) or by the heteroduplex mobility assay (HMA) (Belgian strains, n = 21 and Ivorian strains, n = 25). Seventeen (81%) of the 21 Belgian isolates belonged to subtype B and 4 (17%) were subtype A strains. Subtype A variants were predominant in the two African countries studied; 11 (61%) of 18 strains from Cameroon and 23 (92%) of 25 strains from the Ivory Coast. Of the 64 isolates, 38 (58%) and 19 (29%) belonged to subtypes A and B, respectively. No significant difference was observed for biological phenotypes (slow/low and rapid/high) of both genetic subtypes. In symptomatic individuals, however, a significantly higher number of subtype B isolates were of rapid/high phenotype, compared with subtype A (5 of 10; 50%) vs. 2 of 22; 9%), respectively; X2 = 6.7, P = 0.02). The findings suggest that overall HIV-1 isolates belonging to genetic subtype B are not distinguishable from subtype A variants on the basis of their biological phenotypes. Syncytium-inducing variants were less prevalent regardless of the geographic origin of the isolates.
Funktionsmuster eines haptischen Bedienelements für INKOMAN (2007)

Zusammenfassung: Diese Diplomarbeit beschreibt die Entwicklung eines Bedienelementes zur Steuerung eines Operationswerkzeuges mit haptischer Ruckmeldung fur die minimalinvasive Leber-Chirurgie. Die Entwicklung des Bedienkonzeptes erfolgt nach der Analyse ergonomischer Anforderungen, angepasst an den Arbeitsablauf der laparoskopischen Operation: Der Chirurg steuert eine intrakorporale Kinematik. Dazu halt er das Bedienelement mit einem Pistolengriff. Mit dem Daumen steuert er einen Joystick in drei kartesischen Freiheitsgraden und positioniert so den Endeffektor des Instrumentes im Operationsfeld. Der Joystick stellt gleichzeitig die an der Spitze des Instrumentes gemessenen Krafte in drei Raumrichtungen bis 5 N dar. Krafte werden in Abhangigkeit von ihrer Frequenz wahrgenommenen. Daher werden in einem Versuch am haptischen Leberphantom die bei der Operation auftretenden Krafte gemessen und im Frequenzbereich mit einer Wahrnehmungsfunktion gewichtet. Ergebnis des Versuchs ist, dass aus rein physiologischer Sicht Krafte bis in einen Bereich von f = 1...2 kHz haptisch darzustellen sind. Um den Krafteindruck dynamisch an den Nutzer zu ubertragen, ist der Joystick als parallelkinematischer Tripod realisiert. Die antreibenden Aktoren sind am Griff befestigt, so dass ihre Masse nicht beschleunigt werden muss. Eine Ausrichtung bestimmter Gelenkachsen erzeugt einen Mechanismus, fur den - im Gegensatz zu allgemeinen Parallelkinematiken - das Ubertragungsverhalten in geschlossener Form gelost werden kann. Das Weg- und Kraftubertragungsverhalten des Tripods wird in dieser Arbeit hergeleitet. Der Tripod besitzt einen zylindrischen Arbeitsaum von 30 mm Hohe und einem Durchmesser von 50 mm. Als Aktoren kommen elektronisch kommutierte DC-Antriebe zum Einsatz, um haptisch wahrnehmbare Effekte durch eine mechanische Kommutierung zu verhindern. Zur Kommutierung wird eine Schaltung entwickelt und in Betrieb genommen, die eine spannungsgesteuerte Stromquelle realisiert. Bei einer Eingangsspannung von ±1 V sind lastunabhangige Strome bis ±10 A moglich. Das Ergebnis ist die Erzeugung eines haptischen Feedbacks proportional einer Steuerspannung. In die Motoren integrierte Hall-Sensoren dienen zur Positionserfassung. Die Steuerung des Systems uber die hergeleiteten Ubertragungsfunktionen erfolgt unter LabView mit einen Steuerrechner.
Tandem Diels−Alder Cycloadditions in Organic Synthesis (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTandem Diels−Alder Cycloadditions in Organic SynthesisJeffrey D. WinklerView Author Information Department of Chemistry, The University of Pennsylvania, Philadelphia, Pennsylvania 19104 Cite this: Chem. Rev. 1996, 96, 1, 167–176Publication Date (Web):February 1, 1996Publication History Received22 September 1995Revised6 November 1995Published online1 February 1996Published inissue 1 January 1996https://doi.org/10.1021/cr950029zCopyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views5360Altmetric-Citations331LEARN 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 InReddit Read OnlinePDF (567 KB) Get e-AlertscloseSUBJECTS:Addition reactions,Adducts,Chemical reactions,Cyclization,Hydrocarbons Get e-Alerts
Side Channels of Cyber-Physical Systems: Case Study in Additive Manufacturing (2017)

As 3-D printers are becoming increasingly relevant in various domains, including critical infrastructure, cyber-security questions naturally arise. This article investigates how to leverage analog emissions (vibration, acoustic, magnetic, and power) of 3-D printers in order to identify the printed object and compromise confidentiality.
QRICH1 is a CARD11 interactor that negatively regulates T cell activation (2022)

Abstract Precise regulation of lymphocyte activation is crucial for fighting off pathogens while preventing autoimmunity and lymphoma. CARD11 is a scaffold protein and signaling hub that links antigen receptor engagement to activation of the NF-κB, JNK, and mTOR pathways. We identified QRICH1 as a previously unrecognized binding partner of CARD11 that binds CARD11 in a signal-dependent manner during T cell receptor (TCR) signaling. To identify the function of QRICH1 in TCR signaling, we used CRISPR/Cas9 genomic editing to disrupt QRICH1 expression in Jurkat T cells. QRICH1 knockout resulted in enhanced TCR-induced NF-κB activation and IL-2 secretion, while QRICH1 overexpression in HEK293T and Jurkat T cells dose-dependently inhibited NF-κB activation by wild-type CARD11 and by constitutively active and oncogenic CARD11 mutants. Domain deletion experiments revealed that the inhibitory activity of QRICH1 resides in the N-terminal half of the protein, while the C-terminus contains an autoinhibitory domain that participates in intramolecular interactions and modulates the ability of QRICH1 to inhibit CARD11 signaling to NF-κB. To study the function of QRICH1 in vivo, we generated mice with a conditional QRICH1 allele. We found that QRICH1-deficient CD4+ and CD8+ T cells produced higher levels of IL-2 and IFN-ɣ, respectively, following stimulation by anti-CD3/CD28. Our findings identify QRICH1 as a negative regulator of T cell activation that modulates the signaling output of CARD11. This work was supported by NIH grants F31CA254167, RO1AI148143, and T32GM007445.