gebhart/patrepeval huggingface dataset:
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent (2015)

We discovered and developed a novel series of tetrahydropyridophthlazinones as poly(ADP-ribose) polymerase (PARP) 1 and 2 inhibitors. Lead optimization led to the identification of (8S,9R)-47 (talazoparib; BMN 673; (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one). The novel stereospecific dual chiral-center-embedded structure of this compound has enabled extensive and unique binding interactions with PARP1/2 proteins. (8S,9R)-47 demonstrates excellent potency, inhibiting PARP1 and PARP2 enzyme activity with Ki = 1.2 and 0.87 nM, respectively. It inhibits PARP-mediated PARylation in a whole-cell assay with an EC50 of 2.51 nM and prevents proliferation of cancer cells carrying mutant BRCA1/2, with EC50 = 0.3 nM (MX-1) and 5 nM (Capan-1), respectively. (8S,9R)-47 is orally available, displaying favorable pharmacokinetic (PK) properties and remarkable antitumor efficacy in the BRCA1 mutant MX-1 breast cancer xenograft model following oral administration as a single-agent or in combination with chemotherapy agents such as temozolomide and cisplatin. (8S,9R)-47 has completed phase 1 clinical trial and is currently being studied in phase 2 and 3 clinical trials for the treatment of locally advanced and/or metastatic breast cancer with germline BRCA1/2 deleterious mutations.
A modular time-domain model of single-phase photovoltaic inverters enabling realistic harmonic large-scale simulations in low voltage networks (2022)

This paper presents the use of a modular time domain model to study the interaction of single-phase photovoltaic inverters in public low voltage networks. Currently, specific time domain implementations of individual inverters are designed and studied from a power electronics perspective. If circuit and controller are unknown, e.g. for commercially available photovoltaic inverters, time domain modelling is not possible and measurement-based black-box models in frequency domain have to be used. This paper proposes a modular modelling approach for generating a large and realistic set of different inverter implementations for general and probabilistic system-level studies of their interaction in public low voltage networks. The modular model can be used for time domain studies but also enables to derive frequency domain models as required in case of large-scale studies. It is shown in frequency domain that the modular model represents adequately commercially available devices, which have been characterized by black-box measurements in the laboratory.
Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss (2017)

Volumetric muscle loss (VML) is associated with loss of skeletal muscle function, and current treatments show limited efficacy. Here we show that bioconstructs suffused with genetically-labelled muscle stem cells (MuSCs) and other muscle resident cells (MRCs) are effective to treat VML injuries in mice. Imaging of bioconstructs implanted in damaged muscles indicates MuSCs survival and growth, and ex vivo analyses show force restoration of treated muscles. Histological analysis highlights myofibre formation, neovascularisation, but insufficient innervation. Both innervation and in vivo force production are enhanced when implantation of bioconstructs is followed by an exercise regimen. Significant improvements are also observed when bioconstructs are used to treat chronic VML injury models. Finally, we demonstrate that bioconstructs made with human MuSCs and MRCs can generate functional muscle tissue in our VML model. These data suggest that stem cell-based therapies aimed to engineer tissue in vivo may be effective to treat acute and chronic VML.
A Simplified Model for Portfolio Analysis (1963)

This paper describes the advantages of using a particular model of the relationships among securities for practical applications of the Markowitz portfolio analysis technique. A computer program has been developed to take full advantage of the model: 2,000 securities can be analyzed at an extremely low cost—as little as 2% of that associated with standard quadratic programming codes. Moreover, preliminary evidence suggests that the relatively few parameters used by the model can lead to very nearly the same results obtained with much larger sets of relationships among securities. The possibility of low-cost analysis, coupled with a likelihood that a relatively small amount of information need be sacrificed make the model an attractive candidate for initial practical applications of the Markowitz technique.
Simultaneous Screening of Multiple Mutations by Invader Assay Improves Molecular Diagnosis of Hereditary Hearing Loss: A Multicenter Study (2012)

Although etiological studies have shown genetic disorders to be a common cause of congenital/early-onset sensorineural hearing loss, there have been no detailed multicenter studies based on genetic testing. In the present report, 264 Japanese patients with bilateral sensorineural hearing loss from 33 ENT departments nationwide participated. For these patients, we first applied the Invader assay for screening 47 known mutations of 13 known deafness genes, followed by direct sequencing as necessary. A total of 78 (29.5%) subjects had at least one deafness gene mutation. Mutations were more frequently found in the patients with congenital or early-onset hearing loss, i.e., in those with an awareness age of 0-6 years, mutations were significantly higher (41.8%) than in patients with an older age of awareness (16.0%). Among the 13 genes, mutations in GJB2 and SLC26A4 were mainly found in congenital or early-onset patients, in contrast with mitochondrial mutations (12S rRNA m.1555A.G, tRNA(Leu(UUR)) m.3243A.G), which were predominantly found in olderonset patients. The present method of simultaneous screening of multiple deafness mutations by Invader assay followed by direct sequencing will enable us to detect deafness mutations in an efficient and practical manner for clinical use.
Synthese und Anwendung von Alkalimetallantimoniden – ein neuer Ansatz in der Antimonchemie (2022)

Abstract Alkalimetalldihydrogenantimonide [M(L) x SbH 2 ], kurz: Alkalimetallantimonide (M=Li, Na, K, Rb, Cs; 1 : L=pmdta; 2 : L=Kronenether), wurden aus Stiban und n ‐Butyllithium, M(hmds) (hmds=Hexamethyldisilazan) bzw. MO t Bu hergestellt. Wir haben einen allgemein anwendbaren Syntheseweg für diese Verbindungen entwickelt und die erhaltenen Verbindungen auf ihre Stabilität in Abhängigkeit vom verwendeten Alkalimetall und stabilisierenden Additiv untersucht, wobei die Verwendung geeigneter Kronenether ihre Isolierung und Charakterisierung bei Raumtemperatur ermöglichte. Darüber hinaus war das 1,4‐Dioxan‐Addukt [Na(dioxan) x SbH 2 ] die geeignete Ausgangsverbindung für die Synthese des ersten primären Silylstibans (Me 3 Si) 3 SiSbH 2 ( 3 ), welches NMR‐ und IR‐spektroskopisch charakterisiert wurde. Die Reaktion von 3 mit (Dipp 2 NacNac)Ga (Dipp 2 NacNac=HC{C(Me)N(Dipp)} 2 ; Dipp=2,6‐ i Pr 2 C 6 H 3 ) führte zur Bildung von (Dipp 2 NacNac)GaH(SbHSi(SiMe 3 ) 3 ) ( 4 ), das durch Röntgenbeugung am Einkristall charakterisiert werden konnte.
On-Line Monitoring of Mechanical Faults in Variable-Speed Induction Motor Drives Using the Wigner Distribution (2008)

This paper deals with the detection of mechanical load faults in induction motors during speed transients. The detection strategy is based on stator current analysis. Mechanical load faults generally lead to load torque oscillations at specific frequencies related to the mechanical rotor speed. The torque oscillations produce a characteristic sinusoidal phase modulation of the stator current. Speed transients result in time-varying supply frequencies that prevent the use of classical, Fourier transform-based spectral estimation. This paper proposes the use of a time-frequency distribution, the Wigner Distribution, for stator current analysis. Fault indicators are extracted from the distribution for on-line condition monitoring. The proposed methods are implemented on a low-cost digital signal processor. Experimental results in a steady-state and during transients with load torque oscillations and load imbalance are presented.
Dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine–dichlorophenylborane (2009)

In the crystal structure of the title compound, C(39)H(54)BCl(2)P, the phospho-rus atom is coordinated by a dichloro-phenyl-borane unit. The substituted biphenyl group and the two cyclo-hexyl groups at the phospho-rus atom are arranged in such a way to avoid steric crowding in the mol-ecule as far as possible.
Nueva Alternativa para el Control de Compactación de Tranques de Relave. El Penetrómetro PANDA (2007)

"La minería del cobre es uno los pilares fundamentales de la economía en Chile y representa del orden del 36% de la producción mundial. La producción de concentrados de sulfuros de cobre genera millones de toneladas de residuos al año, siendo uno de los principales los denominados relaves. Entre los diversos depósitos utilizados para su disposición, los tranques de arenas de relave son los más empleados. Sin embargo, debido al método constructivo, condiciones de saturación y la actividad sísmica de Chile, estos presentan importantes problemas de licuefacción e inestabilidad de taludes. Por lo tanto, el control durante la fase operacional, particularmente el de la compactación, tiene especial relevancia. El artículo presenta los resultados de las investigaciones realizadas sobre la aplicación del penetrómetro PANDA para el control de compactación en diferentes tranques de arenas de relave de la mediana minería del cobre en Chile. Las ventajas económicas y la rapidez de ejecución del ensayo abren nuevas perspectivas para estudiar la variabilidad de las propiedades geotécnicas de este tipo de materiales, y estimar de manera más precisa el riesgo de licuefacción y la estabilidad mecánica. Los resultados obtenidos confirmarían al equipo PANDA como alternativa eficiente e innovadora para el control de compactación en estos depósitos."
Local Active Content Fingerprint: Solutions for general linear feature maps (2016)

This paper presents solutions to the local patch based Active Content Fingerprint (aCFP) with linear modulation, general linear feature map and convex constraints on the properties of the local feature descriptor. A direct approximation of the linear feature map such that the image distortion is as small as possible and the approximate linear feature map is as close as possible to the original map is proposed. Then an explicit regularization of the trade-off between the modulation distortion and the robustness of the local feature is introduced trough a novel problem formulation. A computer simulation using local image patches, extracted from publicly available data set is provided, demonstrating the advantages under: additive white Gaussian noise (AWGN), lossy JPEG compression and projective geometrical transform distortions.
Lower influenza-specific cell-mediated immune responses in individuals with atopic dermatitis compared with healthy controls (2020)

In a sub-study of a clinical trial (NCT01737710) investigating the immunogenicity of trivalent inactivated influenza vaccine (IIV3) administered intradermally or intramuscularly to individuals with atopic dermatitis (AD), we assessed T cell and antigen-presenting cell (APC) responses to influenza B in AD and Non-AD controls. The comparison of IFN-γ ELISpot in 58 AD and 31 Non-AD showed lower responses in AD pre-vaccination. Pre-vaccination, AD also had lower Th2 responses and less inflammatory cytokine production by APC measured by flow cytometry and cytokine levels in culture supernatants. AD also had lower Th1 and Th2 responses to nonspecific anti-CD3/anti-CD28-stimulation, but these were not significantly correlated with the influenza-specific responses, suggesting a primary role for the APC in the decreased influenza-specific T cell responses. Multivariate modeling of influenza-specific responses pre-vaccination with influenza-specific antibody titers and IFN-γ ELISpot as outcome measures identified several T cell and APC subsets that negatively or positively predicted protective responses to the vaccine. However, none of the functional differences between AD and Non-AD had high predictive value on adaptive responses to influenza vaccine, which was in agreement with the overall similar responses to the vaccine in the parent clinical trial.
Review: a meta‐analysis of GWAS and age‐associated diseases (2012)

Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age-associated diseases (i.e., 'wellness'), we performed a meta-analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb 'bins' and mapping the 1775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease-associated SNPs. In contrast, 10 bins (0.06%) were significantly (P < 0.05) enriched for susceptibility to multiple diseases, 5 of which formed two highly significant peaks of disease association (P < .0001). These peaks mapped to the Major Histocompatibility (MHC) locus on 6p21 and the INK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g., cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human healthspan.
Résonateurs à ondes acoustiques guidées sur miroir de Bragg pour communications radio-fréquences (2010)

Les résonateurs à ondes acoustiques de volumes (appelés résonateurs BAW pour Bulk Acoustic Wave) sont des composants particulièrement attractifs pour les communications radio-fréquences (f &gt; 1 GHz). Ils permettent de réaliser des filtres aux performances accrues et aux encombrements et coûts réduits, ou d'intégrer des oscillateurs de référence à faible consommation. Les résonateurs BAW classiques possèdent une fréquence de fonctionnement fixe déterminée principalement par l'épaisseur de la couche piézoélectrique. Cette contrainte est une limitation importante si l'on considère l'évolution actuelle des communications mobiles vers les circuits multi-standards et reconfigurables. Le travail présenté vise à développer un nouveau type de résonateur acoustique en technologie SMR (résonateur isolé du substrat par un miroir de Bragg), qui permette la co-intégration de résonateurs de fréquences différentes. Il repose sur l'utilisation de la résonance latérale d'ondes acoustiques guidées dont la fréquence est déterminée par une étape de gravure. Les principaux résultats présentés concernent la conception d'un miroir de Bragg assurant une isolation efficace de l'onde guidée vis à vis du substrat, la conception du peigne d'électrodes inter-digitées qui optimise le couplage de l'onde acoustique recherchée et minimise les modes parasites, et la technologie de fabrication mise en œuvre pour réaliser ces résonateurs sur substrat silicium. Les caractéristiques mesurées de ces résonateurs sont comparées aux résultats publiés pour des résonateurs à ondes de Lamb réalisés en technologie FBAR (résonateur sur membrane).
Signaling by a New Anti-Thy 1 Monoclonal Antibody Inhibits T Cell Proliferation and Interferes with T-Cell-Mediated Induction of Costimulatory Molecule B7-2 (1995)

Costimulatory activity on antigen-presenting cells is a critical determinant of the fate T cells when the T cell receptors are engaged by MHC:peptide complexes. Therefore, control of the expression of the costimulatory molecules regulates T cell responses. While several types of interactions between T cells and B cells up-regulate costimulatory molecules on antigen-presenting cell, no T cell surface molecules have been implicated in inhibiting the induction of the costimulatory molecules on B cells. Here we characterize a new anti-Thy1 mAb, 21F10, which inhibits T cell proliferation to selective stimuli. T cells stimulated by anti-CD3 together with anti-Thy1 mAb are anergic to further stimulation through the CD3, which suggests that the anti-Thy1 mAb interferes with the delivery of the costimulatory activity to T cells. Consistent with this notion, anti-Thy1 mAb 21F10 completely inhibits the induction of B7-2 on B cells. Induction of several T cell surface molecules such as CD69 and CD40 ligand was largely unaffected. As this inhibition requires a bivalent anti-Thy1 mAb and does not require binding of more than 50% of Thy1 molecules on T cell surface, we suggest that Thy1 may mediate a negative signaling pathway which inhibits the T-cell-mediated induction of costimulatory activity, including expression of co-stimulatory molecule B7-2.
Optimal backup interval of database by incremental backup method (2009)

Some media faults occur at random. To lessen the overhead of backup processing, the operation of a incremental backup with small overhead is adopted between the operations of a full backup. The mean time to full backup and the expected cost of these schemes are derived, using the theory of stochastic processes. The total expected cost of backup operation is obtained and an optimal full backup interval is easily determined.
Interaction between a dimethylamino group and an electron-deficient alkene in ethyl (E)-2-cyano-3-(8-dimethylamino-1-naphthyl)propenoate (2000)

The interaction between the peri substituents in the title compound, C18H18N2O2, measured at 150 K, represents an early stage in the addition reaction of an amino group to an electron-deficient alkene, and has an N⋯Csp2 separation of 2.531 (2) Å; comparison with related structures indicates that the nitrile group activates an alkene to nucleophilic attack more than a coplanar carboxyl­ic ester group.
Pancreatic Beta Cell Differentiation From Human Pluripotent Stem Cells (2018)

Insulin-expressing beta cells are crucial for the maintenance of systemic glucose homeostasis. Elucidation of the molecular and cellular mechanisms of beta cell development, expansion, survival, and function are required for full understanding of the molecular pathogenesis of diabetes. However, access to human beta cells for such studies is limited by virtue of the logistics of acquisition, prior medical status of donor, and imperfect culture systems for maintaining beta cell identity and function after isolation from human pancreas. Here, a technique for generation of beta cells from human pluripotent stem cells (hPSCs) by modification of key signaling pathways during islet development is described. Up to 70% C-peptide-positive beta cells can be obtained from endodermal anlagen after 27 days of differentiation with specific growth factors and small molecules. Although 50% of them are monohormonal C-peptide-positive cells and have molecular and cellular characteristics consistent with human beta cells in the Islets of Langerhans, a sub-population co-expressing other endocrine markers are also generated, indicating the immaturity of these cells. © 2018 by John Wiley & Sons, Inc.
The Trifluoroacetic Acid Catalyzed Chlorination of Aromatic Hydrocarbons in Carbon Tetrachloride. Inhibition by Acetic Acid (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Trifluoroacetic Acid Catalyzed Chlorination of Aromatic Hydrocarbons in Carbon Tetrachloride. Inhibition by Acetic AcidR. M. Keefer and L. J. AndrewsCite this: J. Am. Chem. Soc. 1960, 82, 17, 4547–4553Publication Date (Print):September 1, 1960Publication History Published online1 May 2002Published inissue 1 September 1960https://pubs.acs.org/doi/10.1021/ja01502a026https://doi.org/10.1021/ja01502a026research-articleACS PublicationsRequest reuse permissionsArticle Views136Altmetric-Citations3LEARN 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
Biological and Clinical Significance of Cathepsin D in Breast Cancer (1992)

AbstractCathepsin D, an aspartyl protease of lysosomes, is overproduced and hypersecreted by breast cancer cells. The prognostic value of its immunoassay in breast cancer cytosol is reviewed from the first retrospective clinical studies available, which show a strong correlation between high concentrations of cathepsin D in the cytosol of primary tumor and further occurrence of metastasis. This new prognostic factor is induced by estrogen in hormone dependent breast cancer but expressed at a high level in hormone independent breast cancer and appears to be independent of other more classical factors. Its value in node negative patients varies according to the studies. In nude mice, transfection of cathepsin D cDNA into tumor cells increases their metastatic potential, suggesting that overexpression of this protease may be one of the factors responsible for metastasis in human breast cancer. The mechanism by which this protease might facilitate metastasis in vivo is still unknown, even though cathepsin D has the potential to initiate a proteolytic cascade, to degrade extracellular matrix and to liberate FGFs like growth factors from the matrix. These studies should stimulate the search for new therapeutical agents in order to inhibit cathepsin D action.Key Words: Breast cancerproteasesmetastasislysosomesestrogensprognostic markerman-nose-6-phosphate receptorimmunoassay.
A perspective on possible manifestations of entanglement in biological systems (2014)

In this chapter, we will focus on the phenomenon of quantum entanglement. Entanglement is a special property that some states of two or more quantum particles may possess. When particles are in an entangled state they are correlated. But entanglement is far more than mere correlation. Entanglement is a type of correlation that macroscopic objects cannot have, even in principle; it is what we call a 'non-local' correlation.