gebhart/patrepeval huggingface dataset:
The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats (2016)

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.
Accelerated Refolding of Subtilisin BPN' by Tertiary-Structure-Forming Mutants of Its Propeptide (2001)

The propeptide of subtilisin BPN', which functions as an intramolecular chaperone and a temporary inhibitor of subtilisin, is unique in that it acquires its three-dimensional structure by formation of a complex with the cognate protease. We previously showed that the successive amino acid replacements Ala47-->Phe, Gly13-->Ile, and Val65-->Ile in the propeptide to increase its hydrophobicity resulted in formation of a tertiary structure, accompanied by increased ability to bind to the protease and increased resistance to proteolysis. In this study, we examined the effects of these tertiary-structure-forming mutations on the intramolecular chaperone activity of the propeptide. The successive amino acid replacements mentioned above were introduced into pro-subtilisin*, possessing a Ser221-->Ala mutation in the catalytic residue. Refolding experiments were started by rapid dilution of the denatured pro-subtilisin*, and formation of tertiary structure in subtilisin was monitored kinetically by increase in tryptophan fluorescence. The wild-type pro-subtilisin* was found to refold with a rate constant of 4.8 x 10(-3) s(-1) in the equation describing an intramolecular process. The Ala47-->Phe replacement in the propeptide resulted in a 1.2-fold increase in the rate constant of subtilisin refolding. When the additional replacement Gly13-->Ile was introduced, refolding of subtilisin was substantially accelerated, and its kinetics could be fitted to a double exponential process composed of a fast phase with a rate constant of 2.1 x 10(-2) s(-1) and a slow phase with a rate constant of 4.5 x 10(-3) s(-1). The rate constant of the fast phase was increased slightly by a further replacement, Val65-->Ile. Since the slow phase is considered to correspond to proline isomerization, we concluded that tertiary-structure-forming mutations in the propeptide produce positive effects on its intramolecular chaperone activity through acceleration of the propeptide-induced formation of the tertiary structure of subtilisin BPN'.
Volumetric Determination of Sulfate IonUsing Barium Ion and A Standard Disodium Dihydrogen Ethylenediamine Tetraacetate Solution (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVolumetric Determination of Sulfate IonUsing Barium Ion and A Standard Disodium Dihydrogen Ethylenediamine Tetraacetate SolutionJ. R. Munger, R. W. Nippler, and R. S. IngolsCite this: Anal. Chem. 1950, 22, 11, 1455–1457Publication Date (Print):November 14, 1950Publication History Published online1 May 2002Published inissue 14 November 1950https://pubs.acs.org/doi/10.1021/ac60047a034https://doi.org/10.1021/ac60047a034research-articleACS PublicationsRequest reuse permissionsArticle Views166Altmetric-Citations20LEARN 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
Antihypertensive combination therapy (1998)

The rationale behind employing combination antihypertensive therapy stems from growing evidence that there is a greater need for more aggressive control of systemic arterial pressure to levels below what we have traditionally accepted (140/90 mmHg), and that we have had historically poor control rates with existing approaches to antihypertensive therapeutics. Single agent therapeutic approaches result in only a 40-50% control rate after 6 months of therapy, illustrating that there is a dramatically high rate of discontinuation of antihypertensive drugs in clinical practice. These poor results suggest that there are issues about inadequate education, insufficient efficacy or poor tolerability for which we need to be concerned. Consequently, efforts are under way to reapproach antihypertensive care by focusing on the need for improved education, as well as to reevaluate the traditional teaching of starting with one drug and titrating it upward until an adequate clinical response is achieved. The problem with the latter approach is that it frequently results in an increased incidence of adverse events which interfere with patient tolerability and compliance. Utilization of lower doses of two or more agents may provide satisfactory reduction of blood pressure without the increased risk of adverse events with higher doses of the individual monotherapies. Moreover, there may be complimentary, additive, or even synergistic effects of two drugs working together by different mechanisms. Therefore, a low-dose therapeutic combination may represent an optimal approach, not only for patients unresponsive to higher doses of individual monotherapies, but perhaps also to initiate treatment.
1-(2-Pyrimidinyl)-Piperazine as Active Metabolite of Buspirone in Man and Rat (1986)

Buspirone (BP), a newly developed antianxiety agent, forms 1-(2-pyrimidinyl)-piperazine (PmP) during its biotransformation in rats and man. After oral administration of pharmacologically effective doses of BP-hydrochloride to rats (1 and 10 mg/kg), the metabolite appears in significant amounts in body fluids and tissues; it is highly concentrated in the central nervous system, the brain-to-plasma concentration ratios being approximately 5 at the time of the maximum concentrations (Cmax). In man given the anxiolytic dose (20 mg) of BP the metabolite reaches higher plasma Cmax values than its parent drug. Its plasma elimination t1/2 is more than double that for BP. These results, together with the fact that PmP is biochemically and pharmacologically active, suggest that the metabolite may contribute significantly to the central effects of the parent drug.
Learning to Attend, Copy, and Generate for Session-Based Query Suggestion (2017)

Users try to articulate their complex information needs during search sessions by reformulating their queries. To make this process more effective, search engines provide related queries to help users in specifying the information need in their search process. In this paper, we propose a customized sequence-to-sequence model for session-based query suggestion. In our model, we employ a query-aware attention mechanism to capture the structure of the session context. is enables us to control the scope of the session from which we infer the suggested next query, which helps not only handle the noisy data but also automatically detect session boundaries. Furthermore, we observe that, based on the user query reformulation behavior, within a single session a large portion of query terms is retained from the previously submitted queries and consists of mostly infrequent or unseen terms that are usually not included in the vocabulary. We therefore empower the decoder of our model to access the source words from the session context during decoding by incorporating a copy mechanism. Moreover, we propose evaluation metrics to assess the quality of the generative models for query suggestion. We conduct an extensive set of experiments and analysis. e results suggest that our model outperforms the baselines both in terms of the generating queries and scoring candidate queries for the task of query suggestion.
A Novel Dietary Supplement Containing Multiple Phytochemicals and Vitamins Elevates Hepatorenal and Cardiac Antioxidant Enzymes in the Absence of Significant Serum Chemistry and Genomic Changes (2010)

A novel dietary supplement composed of three well-known phytochemicals, namely, Salvia officinalis (sage) extract, Camellia sinensis (oolong tea) extract, and Paullinia cupana (guarana) extract, and two prominent vitamins (thiamine and niacin) was designed to provide nutritional support by enhancing metabolism and maintaining healthy weight and energy. The present study evaluated the safety of this dietary supplement (STG; S=sage; T=tea; G=guarana) and assessed changes in target organ antioxidant enzymes (liver, kidneys and heart), serum chemistry profiles and organ histopathology in Fisher 344 rats. Adult male and female Fisher 344 rats were fed control (no STG) or STG containing (1X and 7X, 1X=daily human dose) diets and sacrificed after 2 and 4 months. Serum chemistry analysis and histopathological examination of three vital target organs disclosed no adverse influence on protein, lipid and carbohydrate profiles, genomic integrity of the liver and/or the tissue architecture. However, analysis of the most important antioxidant components in the liver, kidney and heart homogenates revealed a dramatic increase in total glutathione concentrations, glutathione peroxidase and superoxide dismutase enzyme activities. Concomitantly, oxidative stress levels (malondialdehyde accumulation) in these three organs were less than control. Organ specific serum markers (ALT/AST for the liver; CPK/AST for the heart; BUN/creatinine for kidneys) and the genomic integrity disclosed no STG-induced alteration. Some of the serum components (lipid and protein) showed insignificant changes. Overall, STG-exposed rats were more active, and the results suggest that STG exposure produces normal serum chemistry coupled with elevated antioxidant capacity in rats fed up to seven times the normal human dose and does not adversely influence any of the vital target organs. Additionally, this study reiterates the potential benefits of exposure to a pharmacologically relevant combination of phytochemicals compared to a single phytochemical entity.
Actin Filament Guidance on a Chip:  Toward High-Throughput Assays and Lab-on-a-Chip Applications (2006)

Biological molecular motors that are constrained so that function is effectively limited to predefined nanosized tracks may be used as molecular shuttles in nanotechnological applications. For these applications and in high-throughput functional assays (e.g., drug screening), it is important that the motors propel their cytoskeletal filaments unidirectionally along the tracks with a minimal number of escape events. We here analyze the requirements for achieving this for actin filaments that are propelled by myosin II motor fragments (heavy meromyosin; HMM). First, we tested the guidance of HMM-propelled actin filaments along chemically defined borders. Here, trimethylchlorosilane (TMCS)-derivatized areas with high-quality HMM function were surrounded by SiO(2) domains where HMM did not bind actin. Guidance along the TMCS-SiO(2) border was almost 100% for filament approach angles between 0 and 20 degrees but only about 10% at approach angles near 90 degrees . A model (Clemmens, J.; Hess, H.; Lipscomb, R.; Hanein, Y.; Bohringer, K. F.; Matzke, C. M.; Bachand, G. D.; Bunker, B. C.; Vogel, V. Langmuir 2003, 19, 10967-10974) accounted for essential aspects of the data and also correctly predicted a more efficient guidance of actin filaments than previously shown for kinesin-propelled microtubules. Despite the efficient guidance at low approach angles, nanosized (<700 nm wide) TMCS tracks surrounded by SiO(2) were not effective in guiding actin filaments. Neither was there complete guidance along nanosized tracks that were surrounded by topographical barriers (walls and roof partially covering the track) unless there was also chemically based selectivity between the tracks and surroundings. In the latter case, with dually defined tracks, there was close to 100% guidance. A combined experimental and theoretical analysis, using tracks of the latter type, suggested that a track width of less than about 200-300 nm is sufficient at a high HMM surface density to achieve unidirectional sliding of actin filaments. In accord with these results, we demonstrate the long-term trapping of actin filaments on a closed-loop track (width < 250 nm). The results are discussed in relation to lab-on-a-chip applications and nanotechnology-assisted assays of actomyosin function.
Unequally Spaced Waveguide Arrays for Silicon Nanomembrane-Based Efficient Large Angle Optical Beam Steering (2009)

In this paper, we present a design methodology for silicon nanomembrane-based phased array structures with unequally spaced elements for large angle optical beam steering. By optimizing a dielectric waveguide structure for transverse-magnetic-polarized single-mode operation at wavelength of 1.55 mum, we show that a one-stage optical phased array allows 2-D plusmn60deg and plusmn45deg optical beam scanning with minimal degradation in sidelobe level and power efficiency. The number of array elements necessary to realize the desired array performance depends on the fabrication technique, which is formulated in the presented design methodology.
[Severe dysplasia in Barrett's esophagus]. (2000)

Two patients with Barret's esophagus developed severe dysplasia diagnosed during endoscopic surveillance. Both patients underwent esophagectomy. The surgical specimen revealed adenocarcinoma in situ in the first patient and invasive adenocarcinoma to the submucosa in the second one. The life expectancy in these patients is at least 75% at 5 years, much better than the 5% five year survival of the patients diagnosed when they present with dysphagia. The natural history, pathogenesis, diagnosis, treatment and prevention are discussed.
Notes- Phosphonic Acids and Esters. I. Radical Initiated Addition of Phospherous Acid to Olefins (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNotes- Phosphonic Acids and Esters. I. Radical Initiated Addition of Phospherous Acid to OlefinsClaibourne Griffin and Henry WellsCite this: J. Org. Chem. 1959, 24, 12, 2049–2051Publication Date (Print):December 1, 1959Publication History Published online18 July 2003Published inissue 1 December 1959https://doi.org/10.1021/jo01094a624Request reuse permissionsArticle Views210Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (411 KB) Get e-Alertsclose Get e-Alerts
Preparation and reactions of 3,4‐dihydro‐2<i>H</i>‐pyran‐2‐ones (1982)

Abstract The Michael reaction of ethyl cinnamates with deoxybenzoin gave ethyl 3,4,5‐triaryl‐5‐oxopentanoates which were hydrolysed to the corresponding acids. The latter could be cyclized to the respective 3,4‐dihydro‐2 H ‐pyran‐2‐ones which underwent ring opening with several nucleophiles to the corresponding acid derivatives. However, their reaction with ammonium acetate led to the formation of 3,4‐dihydro‐2‐pyridones. The 3,4‐dihydro‐2‐pyrones and pyridones were dehydrogenated to the corresponding 2‐pyrones and 2‐pyridones by fusion with sulfur.
Laboratory observation of elastic waves in solids (1990)

Compressional, torsional, and bending waves in bars and plates can be studied with simple apparatus in the laboratory. Although compressional and torsional waves show little or no dispersion, bending waves propagate at a speed proportional to (f)1/2. Reflections at boundaries lead to standing waves that determine the vibrational mode shapes and mode frequencies. Boundary conditions include free edges, simply supported edges, and clamped edges. Typical mode shapes and mode frequencies for rectangular bars, circular plates, and square plates are described.
<i>In Vitro</i> Antibacterial Activity of AZD0914, a New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-Positive, Fastidious Gram-Negative, and Atypical Bacteria (2014)

AZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potent in vitro antibacterial activity against key Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzae and Neisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance in S. aureus, and if mutants were obtained, the mutations mapped to gyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration and in vitro time-kill studies. In in vitro checkerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potent in vitro antibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.
Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution (2016)

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.
Molecular Sieving on the Surface of a Protein Provides Protection Without Loss of Activity (2012)

Abstract Tethering polymers to surfaces represents the cornerstone of a wide range of applications, including the stabilization of colloids/biomolecules and the preparation of functional coatings. Unfortunately, despite the prevalence of protein‐tethered polymers in the pharmaceutical sector, the analysis of such polymer monolayers on a molecular level is difficult. In this work, simple 1 H NMR spectroscopy and the catalytic properties of α‐chymotrypsin are used to analyze the conformational/permeability properties of protein‐bound monolayers of poly(oligoethyleneglycol monomethylether methacrylate) (pOEGMA), a biocompatible comb‐polymer of interest in the biomedical field. By analyzing >100 distinct conjugates of α‐chymotrypsin and pOEGMA, a detailed picture of the behavior of pOEGMA on the surface of a protein was obtained. Remarkably, control of polymer conformation and inter‐penetration produced a thus far overlooked molecular sieving effect. The application of this effect for the “smart” PEGylation of proteins is portrayed, from which insight is provided for the design of other therapeutic bioconjugates and functional coatings with selective permeability properties.