gebhart/patrepeval huggingface dataset:
Modeling and Functional Analysis of the Interaction between von Willebrand Factor A1 Domain and Glycoprotein Ibα (2000)

Binding of the von Willebrand factor (vWF) A1 domain to the glycoprotein (GP) Ib-IX-V complex mediates platelet adhesion to reactive substrates under high shear stress conditions, a key event in hemostasis and thrombosis. We have now used the known three-dimensional structure of the A1 domain to model the interaction with the GP Ibalpha sequence 271-279, which has previously been implicated in ligand binding. Docking procedures suggested that A1 domain residues in strand beta3 and preceding loop (residues 559-566) as well as in helix alpha3 (residues 594-603) interact with Asp residues 272, 274, 277 and sulfated Tyr residues 278 and 279 in GP Ibalpha. To verify this model, 14 mutant A1 domain fragments containing single or multiple side chain substitutions were tested for their ability to mediate platelet adhesion under flow. Each of the vWF residues Tyr(565), Glu(596), and Lys(599) proved to be strictly required for A1 domain function, which, in agreement with previous findings, was also dependent on Gly(561). Moreover, an accessory functional role was apparent for a group of positively charged residues, including Arg at positions 629, 632, 636 and Lys at positions 643 and 645, possibly acting in concert. There was, however, no evidence from the model that these residues directly participate in forming the complex with GP Ibalpha. These results provide a partial model of the vWF-GP Ibalpha interaction linked to the manifestation of functional activity in platelet adhesion.
Compression of individual sequences via variable-rate coding (1978)

Compressibility of individual sequences by the class of generalized finite-state information-lossless encoders is investigated. These encoders can operate in a variable-rate mode as well as a fixed-rate one, and they allow for any finite-state scheme of variable-length-to-variable-length coding. For every individual infinite sequence <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</tex> a quantity <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\rho(x)</tex> is defined, called the compressibility of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</tex> , which is shown to be the asymptotically attainable lower bound on the compression ratio that can be achieved for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</tex> by any finite-state encoder. This is demonstrated by means of a constructive coding theorem and its converse that, apart from their asymptotic significance, also provide useful performance criteria for finite and practical data-compression tasks. The proposed concept of compressibility is also shown to play a role analogous to that of entropy in classical information theory where one deals with probabilistic ensembles of sequences rather than with individual sequences. While the definition of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\rho(x)</tex> allows a different machine for each different sequence to be compressed, the constructive coding theorem leads to a universal algorithm that is asymptotically optimal for all sequences.
Parametric Signal Processing (2011)

Recent advances in parametric signal processing are described. Parametric mixer role in processing of high-speed signals is recognized and illustrated in analog and digital domains. Rate-scalable signal replication in efficient, wideband mixer was used to redefine traditional analog-to-digital conversion and channelizer architectures. The limits and practical challenges of the parametric mixer technology are discussed.
Differential plasma protein binding to metal oxide nanoparticles (2009)

Nanoparticles rapidly interact with the proteins present in biological fluids, such as blood. The proteins that are adsorbed onto the surface potentially dictate the biokinetics of the nanomaterials and their fate in vivo. Using nanoparticles with different sizes and surface characteristics, studies have reported the effects of physicochemical properties on the composition of adsorbed plasma proteins. However, to date, few studies have been conducted focusing on the nanoparticles that are commonly exposed to the general public, such as the metal oxides. Using previously established ultracentrifugation approaches, two-dimensional gel electrophoresis and mass spectrometry, the current study investigated the binding of human plasma proteins to commercially available titanium dioxide, silicon dioxide and zinc oxide nanoparticles. We found that, despite these particles having similar surface charges in buffer, they bound different plasma proteins. For TiO2, the shape of the nanoparticles was also an important determinant of protein binding. Agglomeration in water was observed for all of the nanoparticles and both TiO2 and ZnO further agglomerated in biological media. This led to an increase in the amount and number of different proteins bound to these nanoparticles. Proteins with important biological functions were identified, including immunoglobulins, lipoproteins, acute-phase proteins and proteins involved in complement pathways and coagulation. These results provide important insights into which human plasma proteins bind to particular metal oxide nanoparticles. Because protein absorption to nanoparticles may determine their interaction with cells and tissues in vivo, understanding how and why plasma proteins are adsorbed to these particles may be important for understanding their biological responses.
The MafA transcription factor appears to be responsible for tissue-specific expression of insulin (2004)

Insulin gene expression is regulated by several islet-enriched transcription factors. However, MafA is the only beta cell-specific activator. Here, we show that MafA selectively induces endogenous insulin transcription in non-beta cells. MafA was also first detected in the insulin-producing cells formed during the second and predominant phase of beta cell differentiation, and absent in the few insulin-positive cells found in Nkx6.1(-/-) pancreata, which lack the majority of second-phase beta cells. These results demonstrate that MafA is a potent insulin activator that is likely to function downstream of Nkx6.1 during islet insulin-producing cell development.
Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain (2017)

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550.
STUDIES IN THE PYRIDINE SERIES. II. SYNTHESIS OF 2-METHYL-3-(β-HYDROXYETHYL)PYRIDINE AND OF THE PYRIDINE ANALOG OF THIAMINE (VITAMIN B1) (1941)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSTUDIES IN THE PYRIDINE SERIES. II. SYNTHESIS OF 2-METHYL-3-(β-HYDROXYETHYL)PYRIDINE AND OF THE PYRIDINE ANALOG OF THIAMINE (VITAMIN B1)ANN H. TRACY and ROBERT C. ELDERFIELDCite this: J. Org. Chem. 1941, 06, 1, 54–62Publication Date (Print):January 1, 1941Publication History Published online1 May 2002Published inissue 1 January 1941https://pubs.acs.org/doi/10.1021/jo01201a005https://doi.org/10.1021/jo01201a005research-articleACS PublicationsRequest reuse permissionsArticle Views220Altmetric-Citations38LEARN 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
Potent Natural Soluble Epoxide Hydrolase Inhibitors from Pentadiplandra brazzeana Baillon: Synthesis, Quantification, and Measurement of Biological Activities In Vitro and In Vivo (2015)

We describe here three urea-based soluble epoxide hydrolase (sEH) inhibitors from the root of the plant Pentadiplandra brazzeana. The concentration of these ureas in the root was quantified by LC-MS/MS, showing that 1, 3-bis (4-methoxybenzyl) urea (MMU) is the most abundant (42.3 μg/g dry root weight). All of the ureas were chemically synthesized, and their inhibitory activity toward recombinant human and recombinant rat sEH was measured. The most potent compound, MMU, showed an IC50 of 92 nM via fluorescent assay and a Ki of 54 nM via radioactivity-based assay on human sEH. MMU effectively reduced inflammatory pain in a rat nociceptive pain assay. These compounds are among the most potent sEH inhibitors derived from natural sources. Moreover, inhibition of sEH by these compounds may mechanistically explain some of the therapeutic effects of P. brazzeana.
Localized in situ amplification (LISA): a novel approach to in situ PCR (1994)

Amplification of specific gene target sequences has become a routine molecular procedure in a variety of laboratories. When coupled with either a direct or indirect method of detecting amplified product, in situ amplification offers an extremely powerful investigative tool. We describe a protocol for a localized in situ amplification (LISA) reaction that includes tissue-culture cloning rings and allows for the amplification of gene target sequences in specific regions of paraffin-embedded tissue sections. Digoxigenin-11-dUTP was added to the amplification reaction and thus incorporated into the amplified products, providing a mechanism by which direct nonisotopic detection could be performed. To demonstrate the approach, LISA was performed on known positive Pneumocystis carinii rat lung tissues, with primers specific for the P. carinii rRNA gene sequence.
Recombinant Expression and Characterization of Human Activin A (1988)

Activin, which stimulates the secretion of FSH from anterior pituitary cells, is a dimer of the beta-subunits of inhibin. Two species of activin (A and AB) have been purified from ovarian follicular fluid and characterized. We have been able to biosynthetically produce recombinant human activin A by constructing stable cell lines expressing the mRNA for the beta A subunit of human inhibin. These cell lines secreted a 24 kilodalton beta A dimer which stimulated FSH secretion in cultured pituitary cells. The ability of this protein to stimulate FSH secretion was sensitive to reduction of disulfide bonds, exhibited a slow onset of action, and was blocked by actinomycin D. In addition, recombinant activin A stimulated hemoglobin accumulation in K562 cells. These data show that recombinant activin A has the biochemical properties and biological activities that have been ascribed to native activin A. In addition, these results provide an independent confirmation, and thereby a final proof, of the structure and function of activin.
Cariogenicity of different types of milk: an experimental study using animal model. (2002)

This study evaluated the cariogenic potential of infant formulas and cow's milk, using a high cariogenic challenge in the animal model. Sixty female Wistar rats infected with Streptococcus sobrinus and desalivated were randomly divided into 6 groups, which received ad libitum: 1) sterilized deionized distilled water (SDW) with 5% sucrose; 2) cow's milk; 3) Nan 2; 4) Nestogeno 2; 5) Ninho growth supporting; 6) SDW. Groups 1 and 6 also received essential diet NCP#2 by gavage, twice a day. After 21 days, the animals were killed and evaluated according to recovered oral microbiota and caries score by using a modified Keyes method. The analysis of the carbohydrates in the milk samples was performed using HPLC. The results were analyzed by Shapiro-Wilk and Kruskal-Wallis tests. Cow's milk had the lowest cariogenic potential compared to the other test groups, but it was not statistically different from group 6. The percentage of S. sobrinus obtained from the oral cavity of the animals was not statistically different among the groups studied, except for the SDW group. It was concluded that cow's milk was not cariogenic and infant formulas showed some cariogenic potential.
Detection of Src homology 3-binding proteins, including paxillin, in normal and v-Src-transformed Balb/c 3T3 cells (1993)

The Src homology 3 (SH3) domain, located in the amino-terminal, noncatalytic half of pp60src, is highly conserved among members of the Src family of tyrosine kinases. SH3 domains have also been identified in a variety of proteins otherwise unrelated to protein-tyrosine kinases. The presence of SH3 domains in proteins with diverse functions suggests this domain may be important for directing protein-protein interactions necessary for protein function or cellular localization. To explore possible interactions between the SH3 domain and cellular proteins, we have established conditions for the isolation of proteins that bind in solution to the Src SH3 domain. A 67-amino acid fragment of c-Src containing either the entire glutathione S-transferase-SH3 domain (GST-SH3) or the SH3 domain from the neuronal form of c-Src (GST-SH3+) was expressed as a glutathione S-transferase fusion protein. The GST fusion proteins were incubated with lysates from [35S]methionine-labeled Balb/c 3T3 cells or v-Src-transformed Balb/c 3T3 cells. We found that GST-SH3, but not wild-type GST, specifically interacted with multiple cellular proteins, whereas GST-SH3+ only weakly associated with a small subset of these proteins. The majority of the SH3-binding proteins were found in particulate and detergent-insoluble cell fractions. Anti-phosphotyrosine immunoblots of the SH3-binding proteins revealed that several of the SH3-binding proteins are phosphorylated on tyrosine in v-Src-transformed cells. In addition, a number of the SH3-binding proteins were phosphorylated on serine and/or threonine in in vitro kinase assays, suggesting that one or more of the SH3-binding proteins has kinase activity. We identified paxillin, a vinculin-binding protein, as one of the Src SH3-binding proteins. This finding strongly supports the hypothesis that SH3 domains may be involved in subcellular localization of proteins to cytoskeleton and/or cellular membranes.
Transport and elimination of recombinant human NGF during long-term delivery to the brain (1996)

The gene for human nerve growth factor (NGF) has been cloned into a mammalian cell line and large quantities of recombinant human NGF (rhNGF) can now be produced for clinical use, but little is known about the fate of rhNGF following delivery to the brain. In this study, we implanted polymer matrices containing 125I-labeled rhNGF into the brains of adult rats and measured spatial distributions of the released protein for 8 weeks after implantation. NGF content in the tissue was determined by counting gamma radiation in thick (1 mm) sections and by autoradiography of thin (20 microns) sections. For the first several days, the rate of NGF release from the polymer matrix was high (approximately 100 ng/day); maximal NGF concentrations, measured at the polymer-tissue interface, were correspondingly high (> 20 micrograms/ml) though day 4. At later times, the release rate decreased (2-10 ng/day) and lower maximal concentrations were observed (1-10 micrograms/ml). NGF levels were always highest in the tissue sections closest to the polymer; during the 8 weeks of the experiment, NGF levels measured in thick sections decreased 100-fold, from 30 ng/section at day 2 to 0.3 ng/section at day 54. The first 10-fold decrease occurred during the first 10 days of the study; a further 6 weeks was required to achieve the second 10-fold decrease. Throughout the experiment, the majority of NGF remained within a restricted zone around the polymer at all times; the mass of NGF decreased to 10% of the maximal level within 2-3 mm of the polymer matrix. At early times (< 1 week), radiolabel corresponding to > 20 pg of NGF was also detected in regions of the brain further removed from the polymer. Comparison of local rhNGF concentration profiles with a simple mathematical model indicated that rhNGF diffuses through the brain interstitial space and is eliminated with a half-life of approximately 45 min, although elimination appears to be substantially slower in white matter regions. This limited ability of NGF to penetrate and be retained within the brain tissue indicates that NGF will need to be delivered almost directly to the target tissue for efficacy.
Jitter spectral extraction for multi-gigahertz signal (2004)

In this paper, we propose a method for extracting the spectral information of a multi-gigahertz jittery signal. This method may utilize existing on-chip single-shot period measurement techniques to measure the multi-gigahertz signal periods for spectral analysis. This method does not require an external sampling clock, nor any additional measurement beyond existing techniques. Experimental results show that this analysis method can accurately estimate the amount and frequencies of periodic and random jitter of a multi-gigahertz signal.
Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15 (1999)

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-gamma stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-alpha, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.
The Effect of Diabetes on B-Type Natriuretic Peptide Concentrations in Patients With Acute Dyspnea (2004)

History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure.
Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist (2004)

Disorders of sexual desire affect an estimated 30% of women in North America and Europe, with etiologies based on interpersonal, personal, and physiological factors. There are currently no pharmacological agents approved for use in the treatment of female sexual dysfunction. This is due, in part, to a focus on the effects of experimental drugs on reflexive components of sexual behavior, such as lordosis, in animal models. Here we report that PT-141, a peptide analogue of alpha-melanocyte-stimulating hormone that binds to central melanocortin receptors, selectively stimulates solicitational behaviors in the female rat. This occurs without affecting lordosis, pacing, or other sexual behaviors. PT-141 did not cause generalized motor activation, nor did it affect the perception of sexual reward. A selective pharmacological effect on appetitive sexual behavior in female rats has not been reported previously, and indicates that central melanocortin systems are important in the regulation of female sexual desire. Accordingly, PT-141 may be the first identified pharmacological agent with the capability to treat female sexual desire disorders.
Atomic structure of a thermostable subdomain of HIV-1 gp41 (1997)

Infection by HIV-1 involves the fusion of viral and cellular membranes with subsequent transfer of viral genetic material into the cell. The HIV-1 envelope glycoprotein that mediates fusion consists of the surface subunit gp120 and the transmembrane subunit gp41. gp120 directs virion attachment to the cell-surface receptors, and gp41 then promotes viral-cell membrane fusion. A soluble, alpha-helical, trimeric complex within gp41 composed of N-terminal and C-terminal extraviral segments has been proposed to represent the core of the fusion-active conformation of the HIV-1 envelope. A thermostable subdomain denoted N34(L6)C28 can be formed by the N-34 and C-28 peptides connected by a flexible linker in place of the disulfide-bonded loop region. Three-dimensional structure of N34(L6)C28 reveals that three molecules fold into a six-stranded helical bundle. Three N-terminal helices within the bundle form a central, parallel, trimeric coiled coil, whereas three C-terminal helices pack in the reverse direction into three hydrophobic grooves on the surface of the N-terminal trimer. This thermostable subdomain displays the salient features of the core structure of the isolated gp41 subunit and thus provides a possible target for therapeutics designed selectively to block HIV-1 entry.
Capillary electrochromatography: A review (1997)

Capillary electrochromatography (CEC) is a modern liquid chromatographic technique which has attracted renewed curiosity from the scientific community in recent years, despite having origins in the 1970s. The growing interest in this field is reflected in the increasing number of scientific publications and presentations dealing with the technique; the majority of work reviewed here is from the last five years. This review concerns itself primarily with both the development of capillary electrochromatography, from early experimentation to the present day, and its widespread application. The fundamental theory is discussed, as well as experimental aspects such as mode of operation (isocratic or gradient) and detection. Considerable attention is devoted to CEC columns; in particular, the preparation of frits and their associated problems. A large number of applications are summarised in tabular form, which provides an insight into the capabilities and scope of this technique. © 1997 John Wiley & Sons, Inc. J Micro Sep 9: 357–372, 1997