gebhart/patrepeval huggingface dataset:
Effect of Exogenous Creatine Supplementation on Muscle PCr Metabolism (2000)

31P NMR was used to assess the influence of two weeks creatine supplementation (21g x d(-1)) on resting muscle PCr concentration, on the rate of PCr repletion (R(depl)), and on the half-time of PCr repletion (t 1/2). Body mass (BM) and volume of body water compartments were also estimated by impedance spectroscopy. Fourteen healthy male subjects (20.8+/-1.9 y) participated in this double-blind study. PCr was measured using a surface coil placed under the calf muscle, at rest and during two exercise bout the duration of which was 1 min. They were interspaced by a recovery of 10 min. The exercises comprised of 50 plantar flexions-extensions against weights corresponding to 40% and 70% of maximal voluntary contraction (MVC), respectively. Creatine supplementation increased resting muscle PCr content by approximately 20% (P= 0.002). R(depl) was also increased by approximately 15% (P< 0.001) and approximately 10% (P = 0.026) during 40% and 70% MVC exercises, respectively. No change was observed in R(repl) and t1/2. BM and body water compartments were not influenced. These results indicate that during a standardized exercise more ATP is synthesized by the CK reaction when the pre-exercise level in PCr is higher, giving some support to the positive effects recorded on muscle performance.
Magnetically enhanced insulin release in diabetic rats (1987)

Polymer matrices containing insulin and embedded magnets were implanted subcutaneously in diabetic rats for 51 days. Passive release of insulin from the polymer resulted in a decrease in the blood glucose level. When the diabetic rats were exposed to an oscillating magnetic field, the blood glucose levels were additionally lowered by nearly 30%. No statistically significant effect in blood glucose decrease was observed in four different sets of control animals subjected to the magnetic field. Because of the very small size of the implants, they may, with additional study, provide an alternative to current modes of therapy using programmable implantable infusion pumps.
Effect of polyamines on the carbamoyl-phosphate synthase activity of CAD protein. (1989)

The effects of polyamines were studied on carbamoyl-phosphate synthase II (EC 6.3.5.5.) which is the first and rate limiting enzyme in mammalian pyrimidine synthesis. Polyamines in physiological concentrations (0.1-1 mM) strongly inhibited the carbamoyl-phosphate synthesis. Of the polyamines tested spermine was the most effective followed by spermidine and putrescine. Spermine increased the KM for ATP and the requirement for Mg++ of carbamoyl-phosphate synthase reaction. UTP, an inhibitor, had similar, while phosphoribosyl-pyrophosphate, an activator of the enzyme had an opposite effect. Increasing concentrations of phosphoribosyl-pyrophosphate completely reversed the inhibition caused by spermine, while did not influence the degree of inhibition caused by UTP. A possible physiological role of polyamines in synchronizing the substrate and activator functions of phosphoribosyl-pyrophosphate in pyrimidine synthesis is suggested.
New Substrate Analogue Inhibitors of Factor Xa Containing 4-Amidinobenzylamide as P1 Residue: Part 1 (2006)

The trypsin-like serine protease factor Xa (fXa) is located at the convergence point of the intrinsic and extrinsic coagulation cascade, and therefore has emerged as an attractive target for the design of novel anticoagulants. During the development of substrate-analogue urokinase inhibitors we have found that the protection of the P3-dSer side chain leads to a scaffold of potent fXa inhibitors with the general structure R1-SO2-dSer(R2)-Gly-4-amidinobenzylamide. The first lead (3) with an N-terminal benzylsulfonyl group and dSer(tBu) as P3 residue inhibits human fXa with a Ki of 14 nM. A variety of derivatives with modified P4, P3, and P2 residues have been investigated in terms of inhibition of fXa and related proteases and for their anticoagulant potency and elimination behaviour. Most inhibitors were rapidly cleared from the circulation of rats. However, compound 48 (Ki= 3.5 nM), one of the most potent and selective inhibitors containing a dArg as P3 residue was relatively slowly eliminated (t1/2 approximately 1 h). Inhibitor 48 doubled clotting times in human plasma at 0.32 microM (aPTT) and 0.28 microM (PT), and is approximately 10-fold more potent than the reference fXa inhibitor DX-9065a in the inhibition of the prothrombinase complex. The structures of two inhibitors in complex with human fXa were solved by X-ray crystallography.
A survey on Learning to Rank (LETOR) approaches in information retrieval (2011)

In Recent years, the application of machine learning approaches to conventional IR system evolve a new dimension in the field. The emphasis is now shifted from simply retrieving a set of documents to rank them also for a given query in terms of user's need. The researcher's task is not only to retrieve the documents from the corpus but also to rank them in order of their relevance to the user's requirement. To improve the system's performance is now the hot area of research. In this paper, an attempt has been made to put some of most commonly used algorithms in the community. It presents a survey on the approaches used to rank the retrieved documents and their evaluation strategies.
High resolution structure and sequence of T. aurantiacus Xylanase I: Implications for the evolution of thermostability in family 10 xylanases and enzymes with βα‐barrel architecture (1999)

Xylanase I is a thermostable xylanase from the fungus Thermoascus aurantiacus, which belongs to family 10 in the current classification of glycosyl hydrolases. We have determined the three-dimensional X-ray structure of this enzyme to near atomic resolution (1.14 Å) by molecular replacement, and thereby corrected the chemically determined sequence previously published. Among the five members of family 10 enzymes for which the structure has been determined, Xylanase I from T. aurantiacus and Xylanase Z from C. thermocellum are from thermophilic organisms. A comparison with the three other available structures of the family 10 xylanases from mesophilic organisms suggests that thermostability is effected mainly by improvement of the hydrophobic packing, favorable interactions of charged side chains with the helix dipoles and introduction of prolines at the N-terminus of helices. In contrast to other classes of proteins, there is very little evidence for a contribution of salt bridges to thermostability in the family 10 xylanases from thermophiles. Further analysis of the structures of other proteins from thermophiles with eight-fold βα-barrel architecture suggests that favorable interactions of charged side chains with the helix dipoles may be a common way in which thermophilic proteins with this fold are stabilized. As this is the most common type of protein architecture, this finding may provide a useful guide for site-directed mutagenesis aimed to improve the thermostability of βα-barrel proteins. Proteins 1999;36:295–306. © 1999 Wiley-Liss, Inc.
A Simplified Immune Suppression Scheme Leads to Persistent Micro-dystrophin Expression in Duchenne Muscular Dystrophy Dogs (2011)

Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×10(12) vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model.
Assessment of acid producing mine soils in the Northern Plains (1984)

In the Northern Plains both coal overburden and hardrock mine waste materials tend to contain most of the unoxidized sulfur in the organic form rather than as sulfides. Little is known about acid generation from organic sulfur when these materials are uncovered and oxidized during mining. Stoichiometrical analysis indicates one mole of organic sulfur can yield two moles of H/sup +/ which is similar to the yield of a mole of pyrite sulfur upon complete oxidation. However, not all soil organic sulfur compounds decompose upon weathering. Uncertainties associated with the yield of acid from organic sulfur make laboratory weathering methods a desirable alternative for lime requirement determination compared to existing analytical laboratory approaches.
Effects of film morphology and gate dielectric surface preparation on the electrical characteristics of organic-vapor-phase-deposited pentacene thin-film transistors (2002)

Organic vapor phase deposition was used to grow polycrystalline pentacene channel thin-film transistors. Substrate temperature, chamber pressure during film deposition, and growth rate were used to vary the crystalline grain size of pentacene films on O2-plasma treated SiO2 from 0.2 to 5 μm, leading to room-temperature saturation regime field-effect hole mobilities (μeff) from 0.05±0.02 to 0.5±0.1 cm2/V s, respectively. Surface treatment of SiO2 with octadecyltrichlorosilane (OTS) prior to pentacene deposition resulted in μeff⩽1.6 cm2/V s, and drain current on/off ratios of ⩽108 at room temperature, while dramatically reducing the average grain size. X-ray diffraction studies indicate that the OTS treatment decreases the order of the molecular stacks. This suggests an increased density of flat-lying molecules, accompanying the improvement of the hole mobility at the pentacene/OTS interface.
Photoincorporation of tetracycline into Escherichia coli ribosomes. Identification of the major proteins photolabeled by native tetracycline and tetracycline photoproducts and implications for the inhibitory action of tetracycline on protein synthesis (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotoincorporation of tetracycline into Escherichia coli ribosomes. Identification of the major proteins photolabeled by native tetracycline and tetracycline photoproducts and implications for the inhibitory action of tetracycline on protein synthesisRobert A. Goldman, Tayyaba Hasan, Clifford C. Hall, William A. Strycharz, and Barry S. CoopermanCite this: Biochemistry 1983, 22, 2, 359–368Publication Date (Print):January 18, 1983Publication History Published online1 May 2002Published inissue 18 January 1983https://pubs.acs.org/doi/10.1021/bi00271a020https://doi.org/10.1021/bi00271a020research-articleACS PublicationsRequest reuse permissionsArticle Views348Altmetric-Citations97LEARN 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
Expression of chromosomal proteins HMG-14 and HMG-17 in transformed human cells. (1990)

The relation between cellular phenotype and expression of chromosomal high mobility group proteins 14 and 17 (HMG-14 and HMG-17) has been examined in human cell lineages. Quantitation of HMG-14 and HMG-17 mRNA in several human cell lines revealed differences in both the steady state mRNA level and in the ratio of HMG-14 to HMG-17 mRNA. Analysis of phenotypically distinct derivatives of human bronchial epithelial cells revealed small differences between both the steady state mRNA levels and the relative amount of these proteins among the clonal variants. The effect of myeloid differentiation on the mRNA level of HMG-14 and HMG-17 was examined in the human promyelocytic leukemia cell line HL-60 following treatment with several granulocytic and monocytic differentiating agents. The ratio of HMG-17 mRNA to either HMG-14 or histone H4 mRNA varied among the cell phenotypes suggesting that phenotype switching may result in detectable alterations in the expression of the HMG-14 and HMG-17 genes. The data suggest that, although the ratio of HMG-14 to HMG-17 mRNA varies among human cell lines, these variations are relatively small.
Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute‐phase response (2007)

TNF-alpha has proved to be a successful target in the treatment of many peripheral inflammatory diseases, but the same interventions worsen immune-mediated CNS disease. However, anti-TNF-alpha strategies may offer promise as therapy for non-immune CNS injury. In this study, we have microinjected IL-1beta or lipopolysaccharide (LPS) into the rat brain as a simple model of brain injury and have systemically administered the TNF-alpha antagonist etanercept to discover whether hepatic TNF-alpha, produced as part of the acute-phase response to CNS injury, modulates the inflammatory response in the brain. We report a significant reduction in neutrophil numbers recruited to the IL-1beta- or LPS-challenged brain as a result of TNF-alpha inhibition. We also show an attenuation in the levels of hepatic mRNA including TNF-alpha mRNA and of TNF-alpha-induced genes, such as the chemokines CCL-2, CXCL-5, and CXCL-10, although other chemokines elevated by the injury were not significantly changed. The reduction in hepatic chemokine synthesis results in reduced numbers of circulating neutrophils, and also a reduction in the numbers recruited to the liver as a consequence of brain injury. These findings suggest that TNF-alpha inhibitors may reduce CNS inflammatory responses by targeting the hepatic acute-phase response, and thus therapies for brain injury need not cross the blood-brain barrier to be effective.
Bacillus Calmette–Guérin treatment of non‐muscle invasive bladder cancer (2010)

Bacillus Calmette-Guérin (BCG) has been used in the intravesical treatment of non-muscle invasive bladder cancer (NMIBC) for nearly 35 years; however, its use is still subject to controversy. The objective of this paper is to review the role of BCG in the treatment of patients with NMIBC. Clinical trials, meta-analyses and guidelines related to the administration, safety and efficacy of intravesical BCG were reviewed. Intravesical BCG is more effective than intravesical chemotherapy in decreasing the risk of recurrence and progression to muscle invasive disease; however, it is associated with more local and systemic side-effects. It is the gold standard in patients at high risk of progression. Maintenance BCG is required in order to achieve the best therapeutic results; however, the optimal dose, induction and maintenance schedules, and duration of treatment are unknown and might be different for each patient. Patients failing BCG treatment have a poor prognosis, and cystectomy is then the recommended treatment. Patients at low risk of recurrence and progression should not receive BCG, because of its side effects. Intermediate-risk patients might be treated with either intravesical chemotherapy or BCG; however, for patients at high risk of progression, BCG is recognized as the treatment of choice. Further research is urgently needed to identify markers associated with BCG failure and to develop effective alternatives to cystectomy in patients failing BCG.
Principle of the Bark of<i>Phellodendron amurense</i>to Suppress the Cellular Immune Response (1994)

We previously reported that Wen-Qing-Yin (Unsei-in), a traditional Chinese blended medicine, inhibited the induction phase of various kinds of delayed type hypersensitivity (DTH) and local graft-versus-host (GvH) reactions, but did not affect humoral immune responses or the effector phase of DTH in experimental animals. In another report, we demonstrated that Phellodendri Cortex (bark of Phellodendron amurense Rupr. Rutaceae) was a component having the most potent suppressive effect on the cellular immune response among the 8 medical plants composing Unsei-in. In the present study, we isolated OB-1 and OB-5 from Phellodendri Cortex as the biologically active principles to suppress local GvH reactions in mice. OB-1 and OB-5 are quaternary base alkaloids known as magnoflorine and phellodendrine, respectively. They suppressed the local GvH reaction, when given i.p. to the host mice at 5-20 mg/kg for 8 consecutive days from the day of spleen cell transfer to cause the reaction. Both OB-1 and OB-5 suppressed picryl chloride-induced delayed type hypersensitivity (PC-DTH) when given i.p. to mice at 10 and 20 mg/kg for 5 consecutive days from the day of the sensitization, but did not suppress it when given at the time of the challenge. These results suggest that OB-1 and OB-5 suppress the induction phase but not the effector phase of the cellular immune response. They are expected to have a value as a new type of immunosuppressor.
Optimization of Protein Kinase CK2 Inhibitors Derived from 4,5,6,7-Tetrabromobenzimidazole (2004)

Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and infective diseases. Thus, CK2 inhibitors designed to dissect the signaling pathways affected by this kinase, in perspective, may give rise to pharmacological tools. One of the most successful CK2 inhibitors is TBB (4,5,6,7-tetrabromobenzotriazole). Here we show that its inhibitory properties can be markedly improved by generating adducts in which N(2) is replaced by a carbon atom bound to a variety of polar functions. The most efficient inhibitor is 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (2c) followed by the methylsulfanyl (8), isopropylamino (2e), and amino (2a) congeners. All these compounds display K(i) values <100 nM (40 nM in the case of 2c). 2c induces apoptosis of Jurkat cells more readily than TBB (DC(50) value 2.7 vs 17 microM) and, unlike TBB, it does not display any side effect on mitochondria polarization up to 10 microM concentration. Molecular modeling of the CK2-2c complex, based on the crystal structure of the CK2-TBB complex suggests that a number of additional apolar contacts between its two methyl groups and hydrophobic residues nearby could account for its superior inhibitory properties. Consequently, 2c is even more susceptible than TBB to mutations of the unique hydrophobic residues V66 and/or I174 to alanine. We propose to adopt 2c as first choice CK2 inhibitor instead of TBB, especially for in cell studies.
Boosting Virtual Screening Enrichments with Data Fusion: Coalescing Hits from Two-Dimensional Fingerprints, Shape, and Docking (2013)

Virtual screening is an effective way to find hits in drug discovery, with approaches ranging from fast information-based similarity methods to more computationally intensive physics-based docking methods. However, the best approach to use for a given project is not clear in advance of the screen. In this work, we show that combining results from multiple methods using a standard score (Z-score) can significantly improve virtual screening enrichments over any of the single screening methods. We show that an augmented Z-score, which considers the best two out of three scores for a given compound, outperforms previously published data fusion algorithms. We use three different virtual screening methods (two-dimensional (2D) fingerprint similarity, shape-based similarity, and docking) and study two different databases (DUD and MDDR). The average enrichment in the top 1% was improved by 9% for DUD and 25% for the MDDR, compared with the top individual method. Improvements of 22% for DUD and 43% for MDDR are seen over the average of the three individual methods. Statistics are presented that show a high significance associated with the findings in this work.
The molecular environment of intracellular sodium: <sup>23</sup>Na NMR relaxation (1991)

The comprehensive approach described in the accompanying paper is illustrated here with the 23Na signal of a concentrated solution of bovine serum albumin (BSA) in saline and the intracellular (Nai) 23Na resonance of a dense suspension of Na(+)-loaded yeast cells. We use frequency shift reagents to discriminate the latter from the extracellular resonance. We find that the Nai signal corresponds to that of an effective single population of Na+ ions exhibiting a single type c spectrum. This is true despite the fact that the yeast protoplasm is too large and too compartmentalized for a given Na+ ion to sample its entirety on the relevant NMR timescale. Our results show clearly that, in addition to the decay of transverse magnetization, the recovery of longitudinal magnetization is biexponential. This is required for a type c spectrum but has not often been detected. The temperature dependence of the relaxation rate constants of the Nai resonance is not consistent with either a simple Debye process or a discrete exchange mechanism connecting two sites in the fast limit. We have fitted the data using an asymmetric continuous distribution of correlation times for the fluctuations of electric field gradients sensed by the Nai nuclei. The analogous distribution function for the Na+ in a 44% (w/w) BSA solution is quite similar to that of the Nai at the same temperature. This suggests that while the macromolecular environment of the Nai ions is quite congested, it is also isotropic on quite a small spatial scale. Also, one can use the correlation time distribution function, obtained from fitting the relaxation data, to calculate a relaxometry curve. This is useful because experimental 23Na relaxometry is difficult. The calculated curve may be a reasonable model for the mostly extracellular 23Na resonance encountered in vivo.