gebhart/patrepeval huggingface dataset:
Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H) (2019)

Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure-activity relationship studies assisted by X-ray crystallographic analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) with good aqueous solubility, liver microsomal stability, and oral bioavailability.
Re: Infiltrating Macrophages Increase RCC Epithelial Mesenchymal Transition (EMT) and Stem Cell-Like Populations via AKT and mTOR Signaling (2016)

No AccessJournal of UrologyAdult Urology1 Jan 2017Re: Infiltrating Macrophages Increase RCC Epithelial Mesenchymal Transition (EMT) and Stem Cell-Like Populations via AKT and mTOR Signaling Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.10.008AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Infiltrating Macrophages Increase RCC Epithelial Mesenchymal Transition (EMT) and Stem Cell-Like Populations via AKT and mTOR Signaling." The Journal of Urology, 197(1), pp. 51–52 © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 197Issue 1January 2017Page: 51-52 Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
The long tail of significantly mutated genes in prostate cancer. (2017)

131 Background: The mutational landscapes of primary and metastatic PCa have been robustly analyzed in multiple whole exome sequencing (WES) studies. We hypothesized that an aggregate, uniform analysis of all data generated to date would enable discovery of new significantly mutated genes and pathways not previously associated with PCa, and shed more light onto the genetic differences between primary and metastatic PCa. Methods: We assembled and uniformly analyzed a cohort of 1,021 tumor and matched germline primary and metastatic PCa whole exomes (686 primary, 335 metastatic), and performed mutational significance analysis using statistical and biological approaches to determine which genes and pathways are recurrently altered. Results: We identified 117 significantly mutated genes (Mutsig q&lt;0.1) in PCa, which included many novel genes and pathways. These include epigenetic modifiers [KMT2C (6%), KMT2D (6%), and KDM6A (2.7%)], regulators of the SWI/SNF complex [SMARCA1 (1.1%), ARID1A (1.5%), ARID1B (1.3%), ARID2 (1.3%), and PBRM1 (0.7%)], and the splicing pathway [SF3B1 (1.1%) and U2AF1 (0.5%)]. In addition, we identified mutations in FUBP1 (0.4%), a splicing regulator involved in the regulation of MDM2 splicing. We also found truncating mutations in SPEN, a hormone inducible transcriptional repressor, in 2.8% of samples, similar to the frequency observed in breast tumors. Finally, a comparison of primary and metastatic samples enabled discovery of a genetic profile associated with metastatic disease, including AR amplifications and mutations, and loss of TP53, PTEN, and RB1. At lower frequency, metastatic tumors showed enrichment in mutations in MLLs (KMT2C/D), APC, CDK12, BRCA2, CTNNB1, and amplifications of MYC and CCND1. Conclusions: Through aggregation and uniform genomic analysis, we refined the map of somatic mutations in PCa and identified cancer genes and pathways not previously associated with this disease. Our findings may inform patient stratification and translational investigation.
Fracture of epoxies subjected to uniaxial and triaxial stress fields (1994)

The uniaxial fracture properties of dogbone specimens are often used to estimate the performance of polymers in other loading situations, e.g. composite matrices. Although triaxial stress states ar ...
Tirer ou ne pas tirer ? Passage à l’acte à la lumière du biais du tireur (2008)

Certaines bavures policières ont été étudiées en psychologie sociale expérimentale sous l’intitulé du « biais du tireur ». Ainsi, si la victime est noire, serait-ce que les policiers sont racistes ?Les travaux montrent que la réalité est plus complexe et que pour comprendre un comportement violent, il importe de prendre en compte les facteurs socioculturels, psychologiques et liés au contexte.
Novel Epoxy Particulate Composites for Mitigation of Insect Residue Adhesion on Future Aircraft Surfaces (2014)

Drag is reduced significantly for airflow over surfaces when laminar flow can be maintained over greater chord lengths, the distance from the leading edge of an airfoil.1 However, surface imperfections, such as chipped paint, scratches, and events that change topography on a microscopic scale can introduce airflow instabilities resulting in premature transition to turbulent flow.1 Although many of these surface imperfections can be avoided with proper maintenance, advanced materials, and advanced manufacturing practices, topographical surface anomalies arising during flight from insect impacts cannot be controlled and can influence laminar flow stability. Practical solutions to this operational challenge need to be developed for future aircraft to have full advantage of laminar flow designs that improve fuel efficiency.2 Researchers have investigated various methods to mitigate insect residue adhesion for decades.3 Although several techniques have demonstrated efficacy including mechanical scrapers, active liquid discharge systems, and sacrificial paper coatings, they have not been commercially implemented due to increased manufacturing and operational complexity, environmental impact, and weight penalties. Coatings offer a simple route for passive insect residue adhesion prevention without many of the challenges associated with maintenance of laminar flow.4 In our previous work, we determined that most commercially available materials were not effective at insect residue adhesion.5 We also identified improvements when both surface energy could be controlled by surface modifying agents and the topography could be altered through the use of micron-sized and nanometer-sized filler materials.6 In this work, these general principles were applied to an epoxy system to evaluate the behavior of the surface modifying agent, a fluorinated alkyl ether oligomer, on surface energy and insect residue adhesion properties.
The β-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is Believing (2012)

ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTThe β-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is BelievingHank F. Kung*View Author Information Departments of Radiology and Pharmacology, University of Pennsylvania, 3700 Market Street, Room 305, Philadelphia, Pennsylvania 19104, United States*Tel: 215-662-3096. Fax: 215-349-5035. E-mail: [email protected]Cite this: ACS Med. Chem. Lett. 2012, 3, 4, 265–267Publication Date (Web):March 12, 2012Publication History Published online12 March 2012Published inissue 12 April 2012https://pubs.acs.org/doi/10.1021/ml300058mhttps://doi.org/10.1021/ml300058meditorialACS PublicationsCopyright © 2012 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views8939Altmetric-Citations89LEARN 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 PDF (5 MB) Get e-AlertscloseSUBJECTS:Biological imaging,Central nervous system,Peptides and proteins,Pharmaceuticals,Positron emission tomography Get e-Alerts
CONCORDANT SEGREGATION OF THE EXPRESSION OF SV40 T ANTIGEN AND HUMAN CHROMOSOME 7 IN MOUSE-HUMAN HYBRID SUBCLONES (1974)

Subcloning of Simian virus 40 (SV40) T antigen-positive mouse-human hybrids, derived from the fusion of mouse cells deficient in thymidine kinase with SV40-transformed Lesch Nyhan fibroblasts, resulted in their segregation into T antigen-positive and negative subclones. Positive correlation between the presence of human chromosome 7 and the expression of SV40 T antigen was established in the subclones examined. These results negate the possibility of a transfer of the SV40 genome to a mouse chromosome.
Bioluminescent Monitoring of NIS-Mediated 131I Ablative Effects in MCF-7 Xenografts (2006)

Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with (131)I is predicated on the expression of the Na(+)/I- symporter (NIS) in many tumors and uptake of I- in some. The pattern of (131)I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of (131)I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in (131)I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in (131)I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less (99m)TcO(4)(-) than untreated tumors. NIS immunoreactivity was present in <50% of (131)I-treated cells compared to 85-90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after (131)I administration was observed in NIS-expressing breast cancer xenografts.
Can a noisy encoder be used to communicate reliably? (2014)

In this paper the problem of reliable communication with a noisy encoder is examined. We explicitly provided the construction of the encoder and show that even when all logic gates that constitute the encoder are noisy, reliable communication with a positive rate is still possible. The encoding complexity is shown to be O(log 1/p <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">tar</sub> /log1/ε) per bit to achieve a target bit error rate p <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">tar</sub> , where ε denotes the error probability of each noisy gate. This complexity upper bound is shown to coincide with a lower bound in order sense, and is hence tight. The key technique in the proposed construction is to embed noisy decoders inside the noisy encoder, which are utilized repeatedly to prevent the bit error rate from escalating. The proposed noisy encoder has a direct application in noisy computing of a linear transform.
Mitsunobu Reaction Using Triphenylphosphine Linked to Non-Cross-Linked Polystyrene (2001)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTMitsunobu Reaction Using Triphenylphosphine Linked to Non-Cross-Linked PolystyreneAndré B. Charette, Marc K. Janes, and Alessandro A. BoezioView Author Information Département de Chimie, Université de Montréal, P.O. Box 6128, Station Downtown, Montréal (Québec) Canada, H3C 3J7 [email protected]Cite this: J. Org. Chem. 2001, 66, 6, 2178–2180Publication Date (Web):February 22, 2001Publication History Received8 November 2000Published online22 February 2001Published inissue 1 March 2001https://pubs.acs.org/doi/10.1021/jo005727khttps://doi.org/10.1021/jo005727kbrief-reportACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1363Altmetric-Citations45LEARN 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 SUBJECTS:Alcohols,Chemical reactions,Group 15 compounds,Polymers,Substitution reactions Get e-Alerts
Metal transfer and double acyl formation in the reaction of ((trimethylsilyl)ethynyl)(Fischer carbene)metal complexes with dicobalt octacarbonyl (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal transfer and double acyl formation in the reaction of ((trimethylsilyl)ethynyl)(Fischer carbene)metal complexes with dicobalt octacarbonylLurdes Jordi, Josep M. Moreto, Susagna Ricart, Josep M. Vinas, Milagros Mejias, and Elies MolinsCite this: Organometallics 1992, 11, 11, 3507–3510Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/om00059a011https://doi.org/10.1021/om00059a011research-articleACS PublicationsRequest reuse permissionsArticle Views144Altmetric-Citations28LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential (2016)

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in a broad range of inflammatory and oncologic diseases. MIF is unique among cytokines in terms of its release profile and inflammatory role, notably as an endogenous counter-regulator of the anti-inflammatory effects of glucocorticoids. In addition, it exhibits a catalytic tautomerase activity amenable to the design of high affinity small molecule inhibitors. Although several classes of these compounds have been identified, biologic characterization of these molecules remains a topic of active investigation. In this study, we used in vitro LPS-driven assays to characterize representative molecules from several classes of MIF inhibitors. We determined that MIF inhibitors exhibit distinct profiles of anti-inflammatory activity, especially with regard to TNFα. We further investigated a molecule with relatively low anti-inflammatory activity, compound T-614 (also known as the anti-rheumatic drug iguratimod), and found that, in addition to exhibiting selective MIF inhibition in vitro and in vivo, iguratimod also has additive effects with glucocorticoids. Furthermore, we found that iguratimod synergizes with glucocorticoids in attenuating experimental autoimmune encephalitis, a model of multiple sclerosis. Our work identifies iguratimod as a valuable new candidate for drug repurposing to MIF-relevant diseases, including multiple sclerosis.
A Decentralized Variance-Reduced Method for Stochastic Optimization Over Directed Graphs (2021)

In this paper, we propose a decentralized first-order stochastic optimization method Push-SAGA for finite-sum minimization over a strongly connected directed graph. This method features local variance reduction to remove the uncertainty caused by random sampling of the local gradients, global gradient tracking to address the distributed nature of the data, and push-sum consensus to handle the imbalance caused by the directed nature of the underlying graph. We show that, for a sufficiently small step-size, Push-SAGA linearly converges to the optimal solution for smooth and strongly convex problems, making it the first linearly-convergent stochastic algorithm over arbitrary strongly-connected directed graphs. We illustrate the behavior and convergence properties of Push-SAGA with the help of numerical experiments for strongly convex and non-convex problems.
Secure Distributed Membership Tests via Secret Sharing: How to Hide Your\n Hostile Hosts Harnessing Shamir Secret Sharing (2015)

Data security and availability for operational use are frequently seen as\nconflicting goals. Research on searchable encryption and homomorphic encryption\nare a start, but they typically build from encryption methods that, at best,\nprovide protections based on problems assumed to be computationally hard. By\ncontrast, data encoding methods such as secret sharing provide\ninformation-theoretic data protections. Archives that distribute data using\nsecret sharing can provide data protections that are resilient to malicious\ninsiders, compromised systems, and untrusted components.\n In this paper, we create the Serial Interpolation Filter, a method for\nstoring and interacting with sets of data that are secured and distributed\nusing secret sharing. We provide the ability to operate over set-oriented data\ndistributed across multiple repositories without exposing the original data.\nFurthermore, we demonstrate the security of our method under various attacker\nmodels and provide protocol extensions to handle colluding attackers. The\nSerial Interpolation Filter provides information-theoretic protections from a\nsingle attacker and computationally hard protections from colluding attackers.\n
Measurement of the inclusive isolated prompt photons cross section inppcollisions ats=7  TeVwith the ATLAS detector using4.6  fb−1 (2014)

Measurement of the inclusive isolated prompt photons cross section in pp collisions at ffiffi s p 7 TeV with the ATLAS detector using 4.6 fb -1
Vortex Unsteadiness in the Endwall Region of a High-Lift Low-Pressure Turbine Passage (2022)

Abstract Three-dimensional vortical structures within the endwall region of turbine passages directly affect the aerodynamic efficiency and heat transfer characteristics of the turbine. Interactions between the vortical endwall structures and the suction surface flow have been shown to be a significant source of loss generation through passages. One dominant vortex extends from the leading edge junction region of the blade across the passage, where it interacts with the flow along the suction surface of the adjacent blade. In high-lift low-pressure turbine cascade passages, the vortical structure intermittently loses coherence and exhibits unsteady variations of strength and position as it extends across the passage. The present paper details the temporal behavior through high-speed measurements in a low speed linear cascade of high-lift low-pressure turbine blades. Stereoscopic particle image velocimetry measurements in the passage are used to evaluate the unsteady behavior of the vortex. Space-time iso-surface plots of Q-criterion clearly show the evolution of the vortex over time. Analysis of the data reveals the various time scales of fluctuations in strength and position. Comparisons of the temporal fluctuations in the high-lift turbine passage are made with similar phenomena found in canonical junction flow papers in the literature. Key findings support the hypothesis that in-passage vortex unsteady characteristics near the endwall are influenced by leading edge junction flow dynamics, and provide additional insight into the unsteady endwall flow physics that are necessary to further the development of endwall loss reduction techniques.
Transient Exposure to Transforming Growth Factor Beta 3 Improves the Mechanical Properties of Mesenchymal Stem Cell–Laden Cartilage Constructs in a Density-Dependent Manner (2009)

Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering and regenerative medicine. However, the use of these cells has been limited by their reduced ability to form functional tissue compared to chondrocytes when placed in three-dimensional culture systems. To optimize MSC functional chondrogenesis, we examined the effects of increasing seeding density and transient application of transforming growth factor beta 3 (TGF-beta3), two factors previously shown to improve growth of chondrocyte-based constructs. Chondrocytes seeded in agarose at 20 million cells/mL and MSCs seeded at 20 or 60 million cells/mL agarose were cultured for 7 weeks under continuous or transient application of TGF-beta3. In the transient group, cell-laden constructs were exposed to TGF-beta3 for the initial 3 weeks, followed by 4 weeks of culture in medium without TGF-beta3. Compressive properties, biochemical content, and gene expression were assessed at 3, 5, and 7 weeks. Matrix distribution and collagen type was determined using histology and immunohistochemistry, and chondrogenic and osteogenic markers were assessed using real-time polymerase chain reaction. When maintained continuously with TGF-beta3, chondrocyte-seeded constructs achieved a higher equilibrium compressive modulus than MSCs similarly maintained. Although properties of both groups increased with respect to starting values, there was no difference in bulk mechanical or biochemical properties with higher seeding density when MSCs were cultured with constant TGF-beta3. Findings also showed that while transient application of TGF-beta3 elicited robust growth from chondrocyte-laden gels, MSCs seeded at the same density failed to respond, although constructs maintained their previously accrued properties and continued to express cartilaginous genes after TGF-beta3 removal. Conversely, MSCs seeded at 60 million cells/mL exhibited a strong anabolic response with transient TGF-beta3 exposure, achieving an equilibrium modulus of approximately 200 kPa. Although this represents the highest modulus we have been able to achieve with MSC-seeded constructs using our culture system, further work remains to optimize MSC chondrogenesis for cartilage tissue engineering, particularly in terms of collagen content and dynamic mechanical properties.