gebhart/patrepeval huggingface dataset:
Pyrazolo[1,5-a]pyrimidines:  Estrogen Receptor Ligands Possessing Estrogen Receptor β Antagonist Activity (2004)

In our search for novel subtype-selective estrogen receptor (ER) ligands, we have examined various heterocyclic units as core structural elements. Here, we have investigated the fused, bicyclic pyrazolo[1,5-a]pyrimidine core, which is a system that allows for analogues to be readily assembled in a library-like fashion. This series of pyrazolo[1,5-a]pyrimidine ER ligands provided us with a new pharmacological profile for an ER ligand: compounds that are passive on both ERs, with a distinct potency selectivity in favor of ERbeta. The most distinctive ligand in this series, 2-phenyl-3-(4-hydroxyphenyl)-5,7-bis(trifluoromethyl)-pyrazolo[1,5-a]pyrimidine, was 36-fold selective for ERbeta in binding. Curiously, on the basis of molecular modeling, the ERbeta binding selectivity of compounds in this series appears to be derived from differing orientations that they adapt in the ligand binding pockets of ERalpha vs ERbeta. In transcription assays this pyrazolopyrimidine was fully effective as an ERbeta antagonist while exhibiting no significant activity on ERalpha. Thus, this ligand functions as a potency- and efficacy-selective ERbeta antagonist that would abrogate estrogen action through ERbeta with minimal effects on its activity through ERalpha; as such, it could be used to study the biological function of ERbeta.
Scalable instruction-level parallelism through tree-instructions (1997)

In this approach, a prvgram is represented as a sequence oftree-
Dissection of a carboxy-terminal region of the yeast regulatory protein RAP1 with effects on both transcriptional activation and silencing. (1992)

RAP1 is an essential sequence-specific DNA-binding protein in Saccharomyces cerevisiae whose binding sites are found in a large number of promoters, where they function as upstream activation sites, and at the silencer elements of the HMR and HML mating-type loci, where they are important for repression. We have examined the involvement of specific regions of the RAP1 protein in both repression and activation of transcription by studying the properties of a series of hybrid proteins containing RAP1 sequences fused to the DNA-binding domain of the yeast protein GAL4 (amino acids 1 to 147). GAL4 DNA-binding domain/RAP1 hybrids containing only the carboxy-terminal third of the RAP1 protein (which lacks the RAP1 DNA-binding domain) function as transcriptional activators of a reporter gene containing upstream GAL4 binding sites. Expression of some hybrids from the strong ADH1 promoter on multicopy plasmids has a dominant negative effect on silencers, leading to either partial or complete derepression of normally silenced genes. The GAL4/RAP1 hybrids have different effects on wild-type and several mutated but functional silencers. Silencers lacking either an autonomously replicating sequence consensus element or the RAP1 binding site are strongly derepressed, whereas the wild-type silencer or a silencer containing a deletion of the binding site for another silencer-binding protein, ABF1, are only weakly affected by hybrid expression. By examining a series of GAL4 DNA-binding domain/RAP1 hybrids, we have mapped the transcriptional activation and derepression functions to specific parts of the RAP1 carboxy terminus.(ABSTRACT TRUNCATED AT 250 WORDS)
Current Protocols in Cytometry (2001)

Current Protocols in Cytometry (CPC), published in affiliation with the International Society for Analytical Cytology, features carefully edited flow and image cytometry methods provided by leading laboratories from around the world. All methods included in the one-volume looseleaf manual are rigorously tested and proven before being selected for CPC. Carefully edited, step-by-step protocols replete with material lists, expert commentaries, and safety and troubleshooting tips ensure that you can duplicate the experimental results in your own laboratory. This publication also includes extensive coverage of cytometry instrumentation, safety and quality control, and data processing and analysis. Quarterly updates, which are filed into the looseleaf, keep the set current with the latest developments in cytometry methods. The initial purchase includes one year of updates and then subscribers may renew their annual subscriptions. Current Protocols publishes a family of laboratory manuals for bioscientists, including Molecular Biology, Immunology, Human Genetics, Protein Science, Cell Biology, Neuroscience, Pharmacology, and Toxicology.
Stem Cells in Skeletal Muscle (2004)

Skeletal muscle is responsible for movement in animals. Pathologies of muscle tissue have serious consequences for the patient, such as decreased mobility, paralysis, and, in extreme cases, death. Often, those conditions are refractory to conventional medical treatments. This explains why much effort in fundamental research is directed toward understanding the complex physiology of skeletal muscle, particularly the means of maintenance and repair of this tissue.
Resolution and Synthesis of Optically Active Alcohols with Immobilized Water-soluble Proteins from Green Pea, Soybean and Buckwheat as New Bio-catalysts (2000)

Kinetic resolution of racemic alcohols, (+/-)-1-(4-substituted phenyl)ethanol and (+/-)-1-(2-naphthyl)ethanol, was done with immobilized green pea, soybean, or buckwheat proteins. The resolution was done stereoselectively by oxidizing only one enantiomer of a racemic alcohol to leave an optically active alcohol with a high purity. In addition, each protein could be reused consecutively at least three times without any decrease of yield or optical purity.
5-(N-Oxyaza)-7-substituted-1,4-dihydroquinoxaline-2,3-diones:  Novel, Systemically Active and Broad Spectrum Antagonists for NMDA/glycine, AMPA, and Kainate Receptors (1997)

A group of 5-aza-7-substituted-1,4-dihydroquinoxaline-2,3-diones (QXs) and the corresponding 5-(N-oxyaza)-7-substituted QXs were prepared and evaluated as antagonists of ionotropic glutamate receptors. The in vitro potency of these QXs was determined by inhibition of [3H]-5,7-dichlorokynurenic acid ([3H]DCKA) binding to N-methyl-D-aspartate (NMDA)/glycine receptors, [3H]-(S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding to AMPA receptors, and [3H]kainate ([3H]KA) binding to KA receptors in rat brain membranes. 5-(N-Oxyaza)-QXs 12a-e all have low micromolar or submicromolar potency for NMDA/glycine receptors and low micromolar potencies for AMPA and KA receptors. QXs 12a-e display 2-12-fold selectivity for NMDA/glycine receptors compared to AMPA receptors, and approximately 2-fold difference between AMPA and KA potency. In contrast to other QXs that either show high selectivity for NMDA (such as ACEA 1021) or AMPA (such as NBQX) receptors, these molecules are broad spectrum antagonists of ionotropic glutamate receptors. 7-Nitro-5-(N-oxyaza)-QX (12e) is the most potent inhibitor among 12a-e, having IC50 values of 0.69, 1.3, and 2.4 microM at NMDA, AMPA, and KA receptors, respectively. In functional assays on glutamate receptors expressed in oocytes by rat cerebral cortex poly(A+) RNA, 7-chloro-5-(N-oxyaza)-QX (12a) and 7-nitro-5-(N-oxyaza)-QX (12e) have Kb values of 0.63 and 0.31 microM for NMDA/glycine receptors, and are 6- and 4-fold selective for NMDA over AMPA receptors, respectively. 5-(N-Oxyaza)-7-substituted-QXs 12a-e all have surprisingly high in vivo potency as anticonvulsants in a mouse maximal electroshock-induced seizure (MES) model. 7-Chloro-5-(N-oxyaza)-QX (12a), 7-bromo-5-(N-oxyaza)-QX (12b), and 7-methyl-5-(N-oxyaza)-QX (12c) have ED50 values of 0.82, 0.87, and 0.97 mg/kg i.v., respectively. The high in vivo potency of QXs 12a-e is particularly surprising given their low log P values (approximately -2.7). Separate studies indicate that QXs 12a and 12e are also active in vivo as neuroprotectants and also have antinociceptive activity in animal pain models. In terms of in vivo activity, these 5-(N-oxyaza)-7-substituted-QXs are among the most potent broad spectrum ionotropic glutamate antagonists reported.
Treatment of cutaneous T cell lymphoma with low doses of interferon alpha-2b. (1996)

This study had demonstrated that the overall response rate in treatment of patients with CTCL was 81.25% and higher (85.7%-87.5%) in the subgroups at early stages I and II of the disease. The dosage (mean dose of 6 x 10(6) IU/week) adopted by us is optimal for the Chinese patients with CTCL. Intralesional injection of INF could be recommended.
On vocabulary-independent speech modeling (2002)

The use of vocabulary-independent (VI) models to improve the usability of speech recognizers is described. Initial results using generalized triphones as VI models show that with more training data and more detailed modeling, the error rate of VI models can be reduced substantially. For example, the error rates for VI models with 5000, 10000, and 15000 training sentences, are 23.9%, 15.2%, and 13.3%, respectively. Moreover, if task-specific training data are available, one can interpolate them with VI models. This task adaptation can reduce the error rate by 18% over task-specifying models.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Inhibition of Myeloperoxidase Activity in Cystic Fibrosis Sputum by Peptide Inhibitor of Complement C1 (PIC1) (2017)

Myeloperoxidase is the major peroxidase enzyme in neutrophil granules and implicated in contributing to inflammatory lung damage in cystic fibrosis. Free myeloperoxidase is present in cystic fibrosis lung fluid and generates hypochlorous acid. Here we report a new inhibitor of myeloperoxidase activity, Peptide Inhibitor of Complement C1 (PIC1). Using TMB as the oxidizing substrate, PIC1 inhibited myeloperoxidase activity in cystic fibrosis sputum soluble fractions by an average of a 3.4-fold decrease (P = 0.02). PIC1 also dose-dependently inhibited myeloperoxidase activity in a neutrophil lysate or purified myeloperoxidase by up to 28-fold (P < 0.001). PIC1 inhibited myeloperoxidase activity similarly, on a molar basis, as the specific myeloperoxidase inhibitor 4-Aminobenzoic acid hydrazide (ABAH) for various oxidizing substrates. PIC1 was able to protect the heme ring of myeloperoxidase from destruction by NaOCl, assayed by spectral analysis. PIC1 incubated with oxidized TMB reversed the oxidation state of TMB, as measured by absorbance at 450 nm, with a 20-fold reduction in oxidized TMB (P = 0.02). This result was consistent with an antioxidant mechanism for PIC1. In summary, PIC1 inhibits the peroxidase activity of myeloperoxidase in CF sputum likely via an antioxidant mechanism.
Milk and Dairy Products (2007)

Abstract The article contains sections titled: 1. Introduction 2. Historical Aspects 3. Composition of Milk 3.1. Milk Fat 3.1.1. Composition 3.1.2. Properties of Fat Globules 3.2. Milk Proteins 3.2.1. Major Nitrogen Fractions in Milk 3.2.2. Nomenclature and Properties of Cow's Milk Proteins 3.2.3. Caseins 3.2.4. Whey Proteins 3.2.5. Nonprotein Nitrogen (NPN) 3.3. Lactose 3.4. Minerals 3.5. Vitamins 3.6. Contaminants 4. Physical and Physicochemical Properties of Milk 5. Microbiology of Milk 6. Nutritional Value of Milk 6.1. Milk as a Nutrient Source for Humans 6.2. Health Aspects of Milk Consumption 7. Dairy Technology 7.1. Milk Production and Transport 7.2. Pretreatment in Dairies 7.3. Thermal Treatment 7.3.1. Thermal Processes 7.3.2. Effects of Heat on Milk 7.3.2.1. Effect on Microorganisms 7.3.2.2. Inactivation of Milk Enzymes 7.3.2.3. Heat‐Induced Destruction of Nutrients 7.4. Homogenization 7.5. Separation Processes 7.5.1. Microfiltration 7.5.2. Ultrafiltration 7.5.3. Nanofiltration and Reverse Osmosis 7.5.4. Ion Exchange Processes 7.5.5. Electrodialysis 7.6. Cleaning and Disinfection 7.7. Water Treatment 8. Fluid Milk 8.1. Consumer's Milk 8.1.1. Legal Classes of Consumer's Milk 8.1.2. Characterization According to Heat Treatment 8.1.3. Modified Consumer's Milks 8.1.4. Packaging of Fluid Milks and Milk Products 8.2. Reconstituted and Recombined Milk 9. Milk Products 9.1. Flavored Milk and Milk Beverages 9.2. Evaporated (Condensed) Milk 9.2.1. Technology of Concentration by Evaporation 9.2.2. Unsweetened Condensed Milk 9.2.3. Sweetened Condensed Milk 9.3. Dry Milk Products 9.3.1. Drying Processes 9.3.2. Whole and Skim Milk Powders 9.3.3. Butter and Buttermilk Powders 9.3.4. Whey Powders and Permeates 9.3.5. </jats
γ-AApeptides bind to RNA by mimicking RNA-binding proteins (2011)

The interactions between proteins and RNAs are of vital importance for many cellular processes, including transcription and processing of RNA, translation, and viral infections. Here we report an γ-AApeptide that can mimic HIV-1 Tat protein and bind to TAR RNAs of HIV and BIV with nanomolar affinity, comparable to that of the RNA-binding fragment of Tat (amino acids 49-58). The interaction is resistant to the presence of a large excess of tRNA. With resistance to proteolytic hydrolysis and limitless potential for diversification, γ-AApeptides may emerge as a new class of peptidomimetics to modulate RNA-protein interactions.
Therapeutic potential of curcumin in non-alcoholic steatohepatitis (2005)

Non-alcoholic steatohepatitis (NASH) may be associated with a number of clinical conditions, but it occurs most commonly in patients with insulin resistance. There is as yet no established disease-modifying treatment, and a safe and broadly available agent that targets hepatic steatosis, insulin resistance, inflammation and fibrosis is necessary. The polyphenolic compound curcumin exhibits antioxidant and anti-inflammatory properties, inhibits NF-kappaB and activates PPAR-gamma. In rodents, curcumin prevents dietary-induced hepatic steatosis, hepatic stellate cell activation and production of fibrotic proteins, and ameliorates steatohepatitis induced by the intake of alcohol or a methionine-choline-deficient diet. Indirect evidence suggests that curcumin may improve insulin sensitivity in diabetes and inflammatory states. The present paper reviews the numerous cellular and animal studies indicating that curcumin attenuates many of the pathophysiological processes involved in the development and progression of NASH. It is suggested that basic and clinical studies on curcumin in the development and progression of NASH are indicated.
Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA.(II). (2002)

We investigated the estrogenic activities of isoflavone derivatives in competition binding assays with human estrogen receptor (hER) alpha or hER beta protein, and in a gene expression assay using a yeast system. Coumestrol binds as strongly as 17beta-estradiol to both hERs. Biochanin A, 5-OMe-genistein, formononetin, and tectorigenin bind well to hER beta, but significant binding to hER alpha is only observed with 5-OMe-genistein, formononetin and tectorigenin. The binding of 7-OMe-genistein and irisolidone is poor to both receptors. Among the glucosides, sissotorin binds both receptors and the binding is stronger than genistin. Coumestrol induces transcription as strongly as genistein. Tectorigenin also induces transcription with both hERs. Though biochanin A, 5-OMe-genistein, 7-OMe-genistein, irisolidone and formononetin slightly induce transcription with hER beta, they act as antagonists in the induction of transcription by 17beta-estradiol. The results show that methylation or glucosidation of isoflavones generally inhibits their phytoestrogenic activities.
WIN 64821, a new competitive antagonist to substance P, isolated from an Aspergillus species: structure determination and solution conformation (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTWIN 64821, a new competitive antagonist to substance P, isolated from an Aspergillus species: structure determination and solution conformationColin J. Barrow, Ping Cai, John K. Snyder, David M. Sedlock, Hao H. Sun, and Raymond CooperCite this: J. Org. Chem. 1993, 58, 22, 6016–6021Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/jo00074a031https://doi.org/10.1021/jo00074a031research-articleACS PublicationsRequest reuse permissionsArticle Views590Altmetric-Citations82LEARN 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
Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9 (2014)

Genome engineering using programmable nucleases enables homologous recombination (HR)-mediated gene knock-in. However, the labour used to construct targeting vectors containing homology arms and difficulties in inducing HR in some cell type and organisms represent technical hurdles for the application of HR-mediated knock-in technology. Here, we introduce an alternative strategy for gene knock-in using transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) mediated by microhomology-mediated end-joining, termed the PITCh (Precise Integration into Target Chromosome) system. TALEN-mediated PITCh, termed TAL-PITCh, enables efficient integration of exogenous donor DNA in human cells and animals, including silkworms and frogs. We further demonstrate that CRISPR/Cas9-mediated PITCh, termed CRIS-PITCh, can be applied in human cells without carrying the plasmid backbone sequence. Thus, our PITCh-ing strategies will be useful for a variety of applications, not only in cultured cells, but also in various organisms, including invertebrates and vertebrates.
The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cellGunter Fischer and Franz X. SchmidCite this: Biochemistry 1990, 29, 9, 2205–2212Publication Date (Print):March 6, 1990Publication History Published online1 May 2002Published inissue 6 March 1990https://pubs.acs.org/doi/10.1021/bi00461a001https://doi.org/10.1021/bi00461a001research-articleACS PublicationsRequest reuse permissionsArticle Views1442Altmetric-Citations272LEARN 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
Near-optimal character animation with continuous control (2007)

We present a new approach to realtime character animation with interactive control. Given a corpus of motion capture data and a desired task, we automatically compute near-optimal controllers using a low-dimensional basis representation. We show that these controllers produce motion that fluidly responds to several dimensions of user control and environmental constraints in realtime. Our results indicate that very few basis functions are required to create high-fidelity character controllers which permit complex user navigation and obstacle-avoidance tasks.
Synthesis, Purification, and Tumor Cell Uptake of 67Ga-Deferoxamine−Folate, a Potential Radiopharmaceutical for Tumor Imaging (1996)

The vitamin folic acid was covalently linked to the chelating agent deferoxamine (DF) via an amide bond using a simple carbodiimide coupling reaction. A mixture of two isomers, DF--folate(alpha) and DF--folate(gamma), was produced involving the alpha- and gamma-carboxyl group of folic acid, respectively. These two isomers were separated by anion-exchange chromatography using a NH4HCO3 gradient. Competitive binding studies revealed that only the DF-folate(gamma) is recognized by the folate receptor on KB cells, interacting with an affinity comparable to unconjugated folic acid. The DF--folate conjugates were radiolabeled with the gamma-emitting radionuclide 67Ga3+ and tested for uptake by cultured KB cells overexpressing the folate receptor. The cellular accumulation of 67Ga-DF-folate(gamma) tracer exhibited rapid uptake kinetics in cell culture with a t1/2 of approximately 3 min. The KB cell association of 67Ga-DF--folate(gamma) was competitively blocked by free folic acid, indicating that uptake of the 67Ga-DF--folate(gamma) was specifically mediated by the folate receptor. Since the folate receptor is overexpressed on the surfaces of many neoplastic cells, these results suggest that 67Ga-DF--folate(gamma) complex might be useful as a diagnostic agent for noninvasive imaging of folate receptor-positing tumors.
Increased Malonyl Coenzyme A Biosynthesis by Tuning the Escherichia coli Metabolic Network and Its Application to Flavanone Production (2009)

Identification of genetic targets able to bring about changes to the metabolite profiles of microorganisms continues to be a challenging task. We have independently developed a cipher of evolutionary design (CiED) to identify genetic perturbations, such as gene deletions and other network modifications, that result in optimal phenotypes for the production of end products, such as recombinant natural products. Coupled to an evolutionary search, our method demonstrates the utility of a purely stoichiometric network to predict improved Escherichia coli genotypes that more effectively channel carbon flux toward malonyl coenzyme A (CoA) and other cofactors in an effort to generate recombinant strains with enhanced flavonoid production capacity. The engineered E. coli strains were constructed first by the targeted deletion of native genes predicted by CiED and then second by incorporating selected overexpressions, including those of genes required for the coexpression of the plant-derived flavanones, acetate assimilation, acetyl-CoA carboxylase, and the biosynthesis of coenzyme A. As a result, the specific flavanone production from our optimally engineered strains was increased by over 660% for naringenin (15 to 100 mg/liter/optical density unit [OD]) and by over 420% for eriodictyol (13 to 55 mg/liter/OD).