gebhart/patrepeval huggingface dataset:
<title>Optimization of quantitative sonographic diagnostic analysis of breast lesions</title> (1994)

The purpose of this study was to enhance the ability of quantitative sonography to distinguish between B-scan images of malignant and benign lesions of the breast. Several second-order pixel gray level statistics have been used to achieve a good but not acceptable diagnostic accuracy in characterizing breast lesions. Therefore, this study sought to optimize the diagnostic accuracy of second order statistics. The co-occurrence matrix is the most useful second-order statistic so far studied. It is an estimate of the joint probability distribution of gray levels of two pixels separated by a given distance and orientation. Several distances and orientations have been tried previously, but no systematic attempt had been made to find the optimum parameters for diagnosis. In this study, co-occurrence statistics of malignant and benign lesion images were determined as a function of distance and orientation. In particular, the correlation function was modeled as a separable, exponential function, first order for increments in both the x and y directions. Model parameters were used as features for discriminating benign from cancer lesions. An attempt was made to optimize the features by excluding the noisy data from the fit and again using the model parameters.
Insulin Potentiating Action of Synthetic Peptides Relating to the Amino Terminal Sequence of Human Growth Hormone (1974)

Various synthetic fragments of the amino terminal sequence of human growth hormone (HGH) have been studied with respect to their in vitro action on glucose uptake and in vivo insulin potentiating effects. The results show that the biologic activities so far investigated are confined to sequences containing the octapeptide, Leu-Ser-Arg- Leu-Phe-Asp- Asn-Ala. There is also a correlation between the in vitro reversal of somantin induced inhibition of glyceraldehyde-3-phosphate dehy-drogenase by the active peptides and their insulin potentiating effect in vivo. The GAPD system provides a convenient and rapid means for monitoring such peptides, but its physiologic significance is at present in doubt. Large doses (10 mg./kg. body weight) of the active peptide HGH 1-15 do not increase the degree of lowering of blood glucose, but prolong the effect of the peptide and depress plasma immunoreac-tive insulin (IRI) in rabbits. The mechanism of action of the active sequence has not been established at present, and the physiological significance is not yet known.
An Efficient Intermolecular Palladium-Catalyzed Synthesis of Aryl Ethers (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAn Efficient Intermolecular Palladium-Catalyzed Synthesis of Aryl EthersKaren E. Torraca, Xiaohua Huang, Cynthia A. Parrish, and Stephen L. BuchwaldView Author Information Department of Chemistry Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 2001, 123, 43, 10770–10771Publication Date (Web):October 4, 2001Publication History Received16 August 2001Published online4 October 2001Published inissue 31 October 2001https://pubs.acs.org/doi/10.1021/ja016863phttps://doi.org/10.1021/ja016863prapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views11333Altmetric-Citations241LEARN 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 SUBJECTS:Anions,Aromatic compounds,Hydrocarbons,Ligands,Substituents Get e-Alerts
Synthesis, secretion, and perception of abscisic acid regulates stress responses in Chlorella sorokiniana (2017)

Abstract Abscisic acid (ABA) is a phytohormone that has been extensively characterized in higher plants for its roles in seed and bud dormancy, leaf abscission, and stress responses. Genomic studies have identified orthologs for ABA-related genes throughout the Viridiplantae , including in unicellular algae; however, the role of ABA in algal physiology has not been characterized, and the existence of such a role has been a matter of dispute. In this study, we demonstrate that ABA is involved in regulating algal stress responses. Chlorella sorokiniana strain UTEX 1230 contains genes orthologous to those of higher plants which are essential for ABA biosynthesis, sensing, and degradation. RNAseq-based transcriptomic studies reveal that treatment with ABA induces dramatic changes in gene expression profiles, including the induction of a subset of genes involved in DNA replication and repair, a phenomenon which has been demonstrated in higher plants. Pretreatment of C. sorokiniana cultures with ABA exerts a protective effect on cell viability in response to ultraviolet radiation. Additionally, C. sorokiniana produces and secretes biologically relevant amounts of both ABA and the oxylipin 12-oxo-phytodienoic acid (OPDA) into the growth medium in response to abiotic stressors. Taken together, these phenomena suggest that ABA signaling evolved as an intercellular stress response signaling molecule in eukaryotic microalgae prior to the evolution of multicellularity and colonization of land.
Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate (1986)

The essential catalytic base at the active site of the glycolytic enzyme triosephosphate isomerase is the carboxylate group of Glu-165, which directly abstracts either the 1-pro-R proton of dihydroxyacetone phosphate or the 2-proton of (R)-glyceraldehyde 3-phosphate to yield the cis-enediol intermediate. Using the methods of site-directed mutagenesis, we have replaced Glu-165 by Asp. The three enzymes chicken isomerase from chicken muscle, wild-type chicken isomerase expressed in Escherichia coli, and mutant (Glu-165 to Asp) chicken isomerase expressed in E. coli have each been purified to homogeneity. The specific catalytic activities of the two wild-type isomerases are identical, while the specific activity of the mutant enzyme is reduced by a factor of about 1000. The observed kinetic differences do not derive from a change in mechanism in which the aspartate of the mutant enzyme acts as a general base through an intervening water molecule, because the D2O solvent isotope effects and the stoichiometries of inactivation with bromohydroxyacetone phosphate are identical for the wild-type and mutant enzymes. Using the range of isotopic experiments that were used to delineate the free-energy profile of the wild-type chicken enzyme, we here derive the complete energetics of the reaction catalyzed by the mutant protein. Comparison of the reaction energetics for the wild-type and mutant isomerases shows that only the free energies of the transition states for the two enolization steps have been seriously affected. Each of the proton abstraction steps is about 1000-fold slower in the mutant enzyme. Evidently, the excision of a methylene group from the side chain of the essential glutamate has little effect on the free energies of the intermediate states but dramatically reduces the stabilities of the transition states for the chemical steps in the catalyzed reaction.
Abstract 389: Amino Terminal Region of Cardiac Myosin Binding Protein-C is Necessary for Cardiac Function (2016)

Rationale: Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that has been suggested to regulate cardiac contraction via its amino terminal (N’) region. However, the necessity of the N’-C0-C1f region (domains C0 through C1 and the first 17 residues of the M-domain) of cMyBP-C in regulating cardiac function in vivo has not been elucidated. Hypothesis: The N’-C0-C1f region of cMyBP-C is critical for normal cardiac function in vivo . Methods and Results: Transgenic mice with 80±4% expression of a truncated cMyBP-C missing the N’-C0-C1f region (cMyBP-C 110kDa ) were generated and characterized at 3-months of age. cMyBP-C 110kDa animals exhibited cardiac hypertrophy as suggested by an increased heart weight to body weight ratio (5.0±0.1 mg/g NTG vs. 6.9±0.1 mg/g cMyBP-C 110kDa , p&lt;0.0001) and an elevation in pathological hypertrophy markers determined by real-time PCR. Histopathological analysis showed increased cardiac fibrosis in cMyBP-C 110kDa hearts compared to hearts from non-transgenic (NTG) littermates. Intriguingly, increased phosphorylation of cMyBP-C at Ser-282 and Ser-302, sites important for cMyBP-C’s regulation of actomyosin interactions, was observed in cMyBP-C 110kDa hearts compared to controls. Electron microscopy revealed normal sarcomere structure in cMyBP-C 110kDa hearts but with apparently weaker cMyBP-C stripes. Furthermore, the ability of cMyBP-C to slow actin-filament sliding within the C-zone of native thick filaments isolated from NTG hearts was lost on thick filaments from cMyBP-C 110kDa hearts. Short-axis M-mode echocardiography indicated a significant elevation in left ventricular internal diameter and a significant reduction in fractional shortening (31±5% NTG vs. 16±3% cMyBP-C 110kDa , p=0.0003) in cMyBP-C 110kDa hearts compared to controls. Finally, global longitudinal strain analysis revealed abnormal wall motion in cMyBP-C 110kDa hearts. Based upon these data, we propose that the N’-region of cMyBP-C is a critical regulator of actomyosin interactions and controls aberrant contraction kinetics within the cardiac sarcomere. Conclusion: The N’-C0-C1f region of cMyBP-C regulates cardiac contractility and is necessary for maintaining normal cardiac function in vivo .
CROSS-GENRE FEATURE COMPARISONS FOR SPOKEN SENTENCE SEGMENTATION (2007)

Automatic sentence segmentation of spoken language is an important precursor to downstream natural language processing. Previous studies combine lexical and prosodic features, but can impose significant computational challenges because of the large size of feature sets. Little is understood about which features most benefit performance, particularly for speech data from different speaking styles. We compare sentence segmentation for speech from broadcast news versus natural multi-party meetings, using identical lexical and prosodic feature sets across genres. Results based on boosting and forward selection for this task show that (1) features sets can be reduced with little or no loss in performance, and (2) the contribution of different feature types differs significantly by genre. We conclude that more efficient approaches to sentence segmentation and similar tasks can be achieved, especially if genre differences are taken into account.
Solution-processed flexible transparent conductors based on carbon nanotubes and silver grid hybrid films (2014)

In a simple, cost-effective, and solution-based process, a thin-film of single-walled carbon nanotubes is hybridized on a PET film which has been patterned with solution self-assembled Ag nanoparticles. Such a flexible and transparent electrode exhibits a sheet resistance down to ∼5.8 Ω sq(-1) at ∼83.7% optical transmittance. The hybrid films are stable under ambient conditions and offer excellent bendability.
Metachromatic leukodystrophy: Identification of the first deletion in exon 1 and nine novel point mutations in the arylsulfatase A gene (1997)

Metachromatic leukodystrophy (MLD), a lysosomal storage disease caused by the deficiency of arylsulfatase A (ASA), is inherited as an autosomal recessive trait, and its frequency is estimated to be 1 in 40,000 live births. Genomic DNA from 21 MLD patients (14 late-infantile and 7 juvenile cases) was amplified in four overlapping PCR fragments and tested by allele-specific oligonucleotide (ASO) for the two common mutations 459+1G→A and P426L. These mutations were found in only 28.6% of the alleles studied. The remaining alleles were analyzed by chemical mismatch cleavage (CMC) and automatic sequencing. In addition to five previously reported mutations (459+1G→a, A212V, R244C, R390W, P426L), 10 novel mutations were identified: 9 missense mutations (S95N, G119R, D152Y, R244H, S250Y, A314T, R384C, R496H, K367N) and one 8 bp deletion in exon 1, the first mutation reported in this exon. These methods allowed us to identify 76% of the alleles tested. Genotype-phenotype correlations could be established for some of these mutations. These results confirm the heterogeneity of mutations causing MLD and suggest that CMC is a reliable and informative screening method for point mutation detection in the arylsulfatase A gene. Hum Mutat 9:234–242, 1997. © 1997 Wiley-Liss, Inc.
13C NMR studies on dibenz[b,f]azepines (1983)

Abstract The assignment of the 13 C nmr resonances of six dibenz[ b,f ]azepines ( 1‐6 ) in dimethylsulfoxide‐d 6 was made using chemical shift arguments, coupling to a fluorine substituent, selective proton decoupling, and fully coupled spectra. Exchange of the heterocyclic N‐H with deuterium simplified and clarified the coupled spectrum of 1 .
Discovery and Characterization of SY-1365, a Selective, Covalent Inhibitor of CDK7 (2019)

Recent studies suggest that targeting transcriptional machinery can lead to potent and selective anticancer effects in cancers dependent on high and constant expression of certain transcription factors for growth and survival. Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of the CDK-activating kinase complex. Its function is required for both cell-cycle regulation and transcriptional control of gene expression. CDK7 has recently emerged as an attractive cancer target because its inhibition leads to decreased transcript levels of oncogenic transcription factors, especially those associated with super-enhancers. Here, we describe a selective CDK7 inhibitor SY-1365, which is currently in clinical trials in populations of patients with ovarian and breast cancer (NCT03134638). <i>In vitro</i>, SY-1365 inhibited cell growth of many different cancer types at nanomolar concentrations. SY-1365 treatment decreased MCL1 protein levels, and cancer cells with low BCL2L1 (BCL-XL) expression were found to be more sensitive to SY-1365. Transcriptional changes in acute myeloid leukemia (AML) cell lines were distinct from those following treatment with other transcriptional inhibitors. SY-1365 demonstrated substantial antitumor effects in multiple AML xenograft models as a single agent; SY-1365-induced growth inhibition was enhanced in combination with the BCL2 inhibitor venetoclax. Antitumor activity was also observed in xenograft models of ovarian cancer, suggesting the potential for exploring SY-1365 in the clinic in both hematologic and solid tumors. Our findings support targeting CDK7 as a new approach for treating transcriptionally addicted cancers. SIGNIFICANCE: These findings demonstrate the molecular mechanism of action and potent antitumor activity of SY-1365, the first selective CDK7 inhibitor to enter clinical investigation.
Chemoselectivity and enantiocontrol in catalytic intramolecular metal carbene reactions of diazo acetates linked to reactive functional groups by naphthalene-1,8-dimethanol (1999)

The use of chiral dirhodium(II) carboxamidate catalysts for metal carbene transformations of diazo acetates linked to a reactive functionality through naphthalene-1,8-dimethanol produces chemoselective and enantioselective reaction either at the remote functionality or by addition to the 1,2-position of the naphthalene ring; enantioselectivities up to 84% ee have been obtained for the Büchner reaction.
A novel application of machine learning techniques for activity-based load disaggregation in rural off-grid, isolated solar systems (2016)

In power systems and electricity markets, accurate monitoring and prediction of electricity demand is important in order to manage real-time load balancing and for distribution and transmission planning. In the context of rural electrification, the uncertainty of both supply - often with 100% renewables - and demand is large and the central reason that solar-based micro-grids and home systems can be expensive. Oversizing battery storage and solar panel size or limiting the electricity available to each user can alleviate this uncertainty but increases system costs. Historical data for solar irradiance is available and allows quantification of the uncertainty associated with supply. However, electricity demand in rural households is not well characterized in developing world contexts. In an ideal scenario, the data should be captured on a per-household level and must be measured on a sufficiently fine time resolution to translate the demand onto individual, user activities. This massive quantity of household demand data requires automatic tools to convert time series power usage data into data on the use of individual appliances. This paper presents a methodology, based on data acquired in individual, isolated solar home systems in Jharkhand, India, on utilizing classification and clustering algorithms to create activity-based models that can be used to conduct load forecasts. Additional statistical data analysis can yield insights on users' power consumption behavior in relation to exogenous variables such as time of day and conditioned on ambient air temperature.
Integrin αIIbβ3 (2013)

From the initial description of platelets in 1882, their propensity to aggregate and to contribute to thrombosis was apparent. Indeed, excessive platelet aggregation is associated with myocardial infarction and other thrombotic diseases whereas Glanzmann thrombasthenia, in which platelet aggregation is reduced, is a bleeding syndrome. Over the last half of the 20th century, many investigators have provided insights into the cellular and molecular basis for platelet aggregation. The major membrane protein on platelets, integrin αIIbβ3, mediates this response by rapidly transiting from its resting to an activated state in which it serves as a receptor for ligands that can bridge platelets together. Monoclonal antibodies, natural products, and small peptides were all shown to inhibit αIIbβ3 dependent platelet aggregation, and these inhibitors became the forerunners of antagonists that proceeded through preclinical testing and into large patient trials to treat acute coronary syndromes, particularly in the context of percutaneous coronary interventions. Three such αIIbβ3 antagonists, abciximab, eptifibatide, and tirofiban, received Food and Drug Administration approval. Over the past 15 years, millions of patients have been treated with these αIIbβ3 antagonists and many lives have been saved by their administration. With the side effect of increased bleeding and the development of new antithrombotic drugs, the use of αIIbβ3 antagonists is waning. Nevertheless, they are still widely used for the prevention of periprocedural thrombosis during percutaneous coronary interventions. This review focuses on the biology of αIIbβ3, the development of its antagonists, and some of the triumphs and shortcomings of αIIbβ3 antagonism.
Structure of an HIV-1 IN-allosteric inhibitor complex at 2.93 Å resolution: routes to inhibitor optimization (2022)

HIV integrase (IN) inserts viral DNA into the host genome and is the target of the strand transfer inhibitors (STIs), a class of small molecules currently in clinical use. Another potent class of antivirals is the allosteric inhibitors of integrase, or ALLINIs. ALLINIs promote IN aggregation by stabilizing an interaction between the catalytic core domain (CCD) and carboxy-terminal domain (CTD) that undermines viral particle formation in late replication. Ongoing challenges with inhibitor potency, toxicity, and viral resistance motivate research to understand their mechanism. Here, we present a 2.93 resolution structure of a minimal ternary complex formed by the IN CCD, CTD, and the preclinical lead ALLINI BI-224436. The structure reveals side chain orientations and a more precise view of the molecular interactions that underlie ALLINI-induced aggregation of HIV IN. The complex has a pronounced asymmetry, with non-identical ALLINI binding interfaces that depend on the nature of the proximal CTD dimers formed in the crystal lattice. We identify several new interactions including a network of cation- and - interactions at the protein-protein and protein-drug interfaces. An accessible pocket adjacent to the bound ALLINI is occupied by ethylene glycol, suggesting specific directions for drug design. The minimal CCDALLINICTD assembly, like the full-length protein complex, favors the formation of drug-induced polymers in solution via two modes of CTD dimerization, providing orthogonal evidence supporting a branched polymer mechanism of aggregation. From this improved atomic model, we can generalize the mode of action for firstgeneration molecules and current clinical leads, facilitating routes for improvement of existing ALLINI scaffolds. We have further extended these studies by determining the structure of another ALLINI, BI-D, and two additional ALLINI-resistant forms of intact IN that are found in replication-competent viruses (INW1C and INN222K), at 4.5 . These data reveal structural perturbations that would undermine the branched polymer network promoted by ALLINI binding. Together, these results provide important insights to help optimize ALLINI design.
Combined Compression and Classificationwith Learning Vector Quantization (1999)

Combined compression and classification problems are becoming increasingly important in many applications with large amounts of sensory data and large sets of classes. These applications range from automatic target recognition (ATR) to medical diagnosis, speech recognition, and fault detection and identification in manufacturing systems. In this paper, we develop and analyze a learning vector quantization (LVQ) based algorithm for combined compression and classification. We show convergence of the algorithm using the ODE method from stochastic approximation. We illustrate the performance of the algorithm with some examples.
Substituent Effect in Sensitization Mechanisms of Pyrromethene Dyes in Solution. (2000)

The sensitization mechanisms for photo-initiations comprised a sensitizer dyes such as 2, 8-diethyl-1, 3, 5, 7, 9-pentamethylbipyrromethene difluoroborate (EBP), 1, 3, 5, 7, 9-pentamethyl-bipyrromethene difluoroborate (HBP), and 2, 8-diethyl-1, 3, 5, 7-teramethyl-9-phenylbipyrromethene difluoroborate (PBP), and a radical generating reagent 3, 3′, 4, 4′-tetrakis(t-butylperoxycarbonyl) benzophenone (BTTB) in acetonitrile have been investigated by singe photon counting.