gebhart/patrepeval huggingface dataset:
Identification of the von Willebrand Factor Binding Site in Collagen Using Triple Helical Peptides. (2005)

Abstract The interaction of the plasma protein von Willebrand factor (VWF) with subendothelial collagen initiates adhesion of blood platelets to the damaged vessel wall or ruptured atherosclerotic plaque. A detailed molecular description of the VWF-collagen interaction may facilitate development of a novel class of antithrombotic drugs that inhibits this vital step in platelet thrombus formation. We have previously used site-directed mutagenesis to map the collagen-binding site in the VWF A3 domain. Here, we report the identification of a 9-aminoacid sequence in collagen type III which mediates VWF binding. We have synthesized a set of 57 peptides, each containing 27 amino acids of native collagen sequence flanked at each end by five GPP (standard amino acid nomenclature) triplets which support the triple helical structure that is essential for ligand recognition by collagen. The sequence of each peptide overlaps by 9 amino acids with that of each adjacent peptide. A single peptide from this set (#23) was shown to bind VWF in a solid-phase binding assay. The affinity of peptide #23 for VWF was comparable to that of native collagen type III. The peptide #23-VWF interaction was abolished by a monoclonal antibody directed against the collagen-binding site on the VWF A3 domain. Furthermore, recombinant VWF variants that were previously shown to lack collagen-binding capacity (delta A3, His1023Ala) were not able to bind to the peptide. Using surface plasmon resonance, we showed that the peptide bound strongly to the isolated VWF A3 domain (Kd 300 nM). Immobilized peptide #23 also supported platelet adhesion from whole blood under flow conditions and washed platelet adhesion under static conditions. Platelet adhesion to peptide #23 could be abrogated by a monoclonal antibody directed against the VWF A3 domain, which inhibits the interaction of VWF with full-length collagen. We subsequently synthesized a set of truncated and alanine-modified triple helical peptides based on the sequence of #23, which were all tested for VWF and platelet binding from whole blood under flow conditions. Modified peptides either strongly interacted with both VWF and platelets, or lacked both VWF and platelet binding. Based on these experiments, we identified the sequence RGQOGVMGF (O is hydroxyproline) as the minimal VWF binding sequence in collagen type III. Mutation of either Q or M to alanine (A) did not affect VWF binding, whereas replacement of R, O, V, and F by A completely abolished VWF binding. Glycine residues were not replaced, as they are essential for triple helix formation. A model of the VWF A3 domain with this nonapeptide collagen sequence was constructed to give detailed insight into the VWF-collagen interaction. In conclusion, we have identified a 9 amino acid sequence in collagen type III that is entirely responsible for high affinity binding to VWF. The detailed molecular description of the VWF-collagen interaction described here may facilitate development of agents disrupting this interaction, which may have potential as antithrombotic drugs.
Copolymers of Ethylene Imine and <i>N</i>-(2-Hydroxyethyl)-ethylene Imine as Tools To Study Effects of Polymer Structure on Physicochemical and Biological Properties of DNA Complexes (2002)

A series of five poly[(ethylene imine)-co-N-(2-hydroxyethyl-ethylene imine)] copolymers with similar molecular weights and different degrees of branching was established to study structure-function relationship with regard to physicochemical and biological properties as gene delivery systems. Copolymers were synthesized by acid-catalyzed ring-opening copolymerization of aziridine and N-(2-hydroxyethyl)-aziridine in aqueous solution and characterized by GPC-MALLS, (1)H- and (13)C NMR, IR, potentiometric titration, and ion exchange chromatography. Complexation of DNA was determined by agarose gel electrophoresis, and complex sizes were quantitated by PCS. Cytotoxicity of the copolymers in fibroblasts was assessed by MTT-assay, LDH-assay, and hemolysis. The transfection efficiency was determined using the reporter plasmid pGL3 in 3T3 mouse fibroblasts. The copolymers obtained by solution polymerization had relatively low molecular weights of about 2000 Da, and the degree of branching increased with increasing ethylene imine ratio. The pK(a) as well as the buffer capacity increased proportional to the number of primary and secondary amines. Higher branched polymers showed stronger complexation and condensation of DNA, formed smaller polymer/DNA complexes, and induced the expression of plasmids to a higher extent than less branched polymers. In vitro cytotoxic effects and the hemolysis of erythrocytes decreased with decreased branching. Our results indicate that the basicity and degree of protonation of the polymers depending on their amount of primary and secondary amines seem to be important factors both for their transfection efficiency and for their cytotoxicity in gene transfer.
A VLSI architecture for a universal high-speed multirate FIR digital filter with selectable power-of-two decimation/interpolation ratios (1991)

A universal architecture for decimation/interpolation digital filtering applications is proposed for custom VLSI implementation to accommodate real-time signal processing at throughput rates in excess of 100 MHz. The main innovation of this architecture is that it allows a single chip to selectively perform decimation or interpolation filtering with selectable conversion ratios of 2/sup 1/,2/sup 2/,. . .2/sup N/. The key feature of the proposed architecture is that a single decimate/interpolate-by-two half-band digital filter is used as the computational engine, and the output samples are simply recycled through the same filter after each decimation/interpolation stage for further filtering. A delicate timing allocation scheme for this half-band filter to be shared among each decimation/interpolation stage plays a critical role in allowing the filter to have selectable conversion ratios and still accommodate throughput rates in excess of 100 MHz.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone–Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation (2012)

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
A sequential multi-assay protocol for the preclinical assessment of natural product complex carbohydrate immunomodulators. (1992)

A major barrier to the understanding, development and utilization of natural product complex carbohydrate immunomodulators has been the lack of standardization during pre-clinical efficacy and safety testing. In addition, it has been our experience that no single assay system or model is adequate for assessing preclinical efficacy and safety of these agents. To address these important issues, our laboratory group has developed a sequential multi-assay protocol for the preclinical evaluation of natural product complex carbohydrate immunomodulators. This sequential multi-assay screening protocol is divided into four phases: 1) physiochemical characterization of the carbohydrate polymer; 2) evaluation of immune stimulatory activity; 3) assessing in vivo anti-microbial activity and anti-tumor efficacy and 4) preclinical safety evaluation. This sequential protocol provides an effective, reproducible and rational approach to the preclinical assessment of complex carbohydrate immunomodulators that, in our experience, is predictive of clinical safety and efficacy.
Subunit arrangement in the human 20S proteasome (1997)

In human 20S proteasomes two copies of each of seven different alpha-type and seven different beta-type subunits are assembled to form a stack of four seven-membered rings, giving the general structure alpha(1-7), beta(1-7), beta(1-7), alpha(1-7). By means of immunoelectron microscopy and chemical crosslinking of neighboring subunits, we have determined the positions of the individual subunits in the proteasome. The topography shows that for the trypsin-like, the chymotrypsin-like, and the postglutamyl cleaving activities, the pairs of beta type subunits, which are thought to form active sites, are nearest neighbors.
Mechanisms of mercury bioremediation (2002)

Mercury is one of the most toxic heavy metals, and has significant industrial and agricultural uses. These uses have led to severe localized mercury pollution. Mercury volatilization after its reduction to the metallic form by mercury-resistant bacteria has been reported as a mechanism for mercury bioremediation [Brunke, Deckwer, Frischmuth, Horn, Lunsdorf, Rhode, Rohricht, Timmis and Weppen (1993) FEMS Microbiol. Rev. 11, 145-152; von Canstein, Timmis, Deckwer and Wagner-Dobler (1999) Appl. Environ. Microbiol. 65, 5279-5284]. The reduction/volatilization system requires to be studied further, in order to eliminate the escape of the metallic mercury into the environment. Recently we have demonstrated three different mechanisms for mercury detoxification in one organism, Klebsiella pneumoniae M426, which may increase the capture efficiency of mercury.
Activation of fibroblast metabolism in a dermal and skin equivalent model: a screening test for activity of peptides (1998)

Skin firmness, elasticity and tone are gradually lost with age. These changes originate in the dermis and correspond to a decrease in the ability of cells, particularly the fibroblasts, to regenerate the molecules which make up the extracellular matrix. Skin ageing is also characterized by a reduction of the epidermal thickness and by a flattening of the basal membrane. The recent development of two 3-dimensional culture systems, in which the cells develop within a porous structure reproducing the extracellular matrix of the human dermis, is a way of reproducing in vivo conditions and demonstrating the biological effects of anti-ageing compounds. The dermal equivalent model used in this study is composed of a dermal matrix made of collagen-chitosan-glycosaminoglycans populated by normal human fibroblasts which synthesized their own extracellular matrix. A skin equivalent model is obtained by the cell culture of normal human keratinocytes onto a dermal equivalent elevated at the air-liquid interface. Such models were used to prove anti-ageing activity of promising compounds. Cosmetic Science has used many protein hydrolysates in order to fight skin ageing, but up to now, these natural peptides were poorly studied, and their efficacy poorly demonstrated. Eight protein hydrolysates were screened in a proliferation study in monolayered cultures giving two selected polypeptides. A soya derived peptide was used for an efficiency study in 3-dimensional models. In the dermal equivalent model, this peptide increased fibroblast proliferation by 40% and led to a stimulation of collagen formation (165%) and elastin (116%) synthesis. The effect of this soya peptide on glycosaminoglycan synthesis was also significant, with increases of 36% for chondroitin-4-sulfate and 68% for hyaluronic acid. These results were confirmed using a skin equivalent model. In this model, the soya peptide increased the thickness of the epidermis.
Intestinal flora in breast- and bottle-fed infants (1998)

We verified whether an adapted formula, which presents poly-oligosaccharides containing maltose, promotes intestinal implantation of bacterial microflora to the extent that breast milk does, as an epidemiological link exists between newborn feeding methods and infant health. Stool specimens were taken and cultured at the fourth day of life from vaginally born neonates. Twenty-two were breast-fed and 20 were fed with formula. In breast-fed infants, the Bifidobacterium was significantly prevalent expressed in percentage (47.6% vs 15%) and in mean bacterial fecal counts/g (7.1 +/- 0.8 vs 5.3 +/- 0.6). Enterococci prevailed in formula-fed infants (mean counts 6.7 +/- 0.9 vs 7.4 +/- 0.5). Of interest is the significant and simultaneous presence of Bifidobacteria and Bacteroides in breast-fed infants. Our study indicates that flora with a diet-dependent pattern is present from the fourth day of life. These results support a preference for breast feeding over formula feeding, even though renewed.
Template-free 3D titanium carbide (Ti<sub>3</sub>C<sub>2</sub>T<sub>x</sub>) MXene particles crumpled by capillary forces (2016)

Ti<sub>3</sub>C<sub>2</sub>T<sub>x</sub> and other types of MXene nanosheets are an exciting new class of 2D materials. However, little has been reported on manipulating the shape of MXene nanosheets. Here, we demonstrate that flat Ti<sub>3</sub>C<sub>2</sub>T<sub>x</sub> nanosheets encapsulated within spray-dried droplets can be scrolled, bent, and folded into 3D crumpled structures. This morphological change was observed to be reversible upon rehydration.
Anti-Interference Performance Analysis in Bluetooth Frequency Hopping System (2007)

The main goal of this paper is to evaluate the anti-interference performance of a Bluetooth piconet in a multi-Bluetooth piconets environment. An overview of the frequency hop selection mechanism is presented and the basic design based on 79-hop is described. We study correlation characteristics of the hopping sequences in typical scenarios and the simulation results show that the interference caused by the neighboring Bluetooth piconet is sensitive both to the address offset and the frequency offset between the victim and the inbreaker.
Natural Fiber Welding: Ionic Liquid Facilitated Biopolymer Mobilization and Reorganization (2012)

In this report, we discuss “natural fiber welding” - an ionic liquid-based methodology that enables the generation of complex, functionalized composites from natural fibrous materials. A unique feature of fiber welding is the ability to selectively open and mobilize biopolymer structures while simultaneously preserving a portion of the biopolymer (micro and meso structures) in the native state. By precisely regulating process variables such as the purity, type, amount, and placement of ionic liquid solvent as well as the duration and temperature of treatment, controlled reorganization of natural material hydrogen bonding networks is achieved. The end result is often dramatic enhancement and modification of physical and chemical properties without disruption to many desirable properties intrinsic to natural materials.
Multi-bond fragmentation of tert-butyl 2-methyl-2-tert-butylperoxyperpropanoate (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMulti-bond fragmentation of tert-butyl 2-methyl-2-tert-butylperoxyperpropanoateWilliam H. Richardson and William C. KoskinenCite this: J. Org. Chem. 1976, 41, 19, 3182–3187Publication Date (Print):September 1, 1976Publication History Published online1 May 2002Published inissue 1 September 1976https://pubs.acs.org/doi/10.1021/jo00881a026https://doi.org/10.1021/jo00881a026research-articleACS PublicationsRequest reuse permissionsArticle Views52Altmetric-Citations4LEARN 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
Effect of heparin bonding on catheter-induced fibrin formation and platelet activation. (1984)

Pathologic and experimental evidence indicates that platelet activation and fibrin formation contribute to the pathogenesis of angina pectoris, coronary vasospasm and myocardial infarction. Detection of localized intravascular platelet activation and fibrin formation in vivo by selective blood sampling requires catheters that do not induce coagulation ex vivo. We studied the effect of heparin bonding of catheter surfaces on activation of the coagulation system by cardiovascular catheters. Woven Dacron, polyvinylchloride, and polyurethane catheters were tested and compared with identical catheters with heparin-bonded surfaces in 47 patients undergoing percutaneous cardiac catheterization. Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), beta-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels. In blood samples collected through conventional catheters, FPA, PF4, BTG, and TXB2 levels were markedly elevated; blood sampling through heparin-bonded catheters had no significant effect on FPA, PF4, BTG, or TXB2 levels. Scanning electron microscopy disclosed extensive platelet aggregates and fibrin strands adherent to the surface of conventional catheters but not to heparin-bonded catheter surfaces. This study demonstrates that (1) collection of blood samples through cardiovascular catheters causes artifactual elevation of FPA, PF4, BTG, and TXB2 levels, and (2) heparin-bonded catheter surfaces effectively prevent catheter-induced platelet alpha-granule release and fibrin formation on catheter surfaces. Heparin-bonded catheters will facilitate investigation of the role of intravascular coagulation in coronary artery disease by eliminating catheter-induced fibrin formation and platelet activation.
Engineering Polymer‐Enhanced Bimetallic Cooperative Interactions in the Hydrolytic Kinetic Resolution of Epoxides (2008)

Abstract Through systematic variations of the length of oligo(ethylene glycol)‐based linkers and the catalyst density of poly(styrene)‐supported cobalt‐salen catalysts, we have elucidated an optimal catalyst flexibility and density of polymeric Co‐salen catalysts for the hydrolytic kinetic resolution (HKR) of racemic terminal epoxides that follows a bimetallic cooperative pathway. The optimized polymeric catalyst brings the two cooperative Co‐salen units to a favorable proximity efficiently and hence displays significantly improved catalytic performance in the HKR compared with its monomeric small molecule analogue. Complex Co(5b) , representing the most active poly(styrene)‐supported HKR catalyst known so far, can effect the resolution of a variety of epoxides to reach ≥98 % ee in 6–24 h with a low cobalt loading of 0.01–0.1 mol %.
Stem Cell Therapy for Neurologic Disorders: Therapeutic Potential of Adipose-Derived Stem Cells (2005)

There is growing evidence to suggest that reservoirs of stem cells may reside in several types of adult tissue. These cells may retain the potential to transdifferentiate from one phenotype to another, presenting exciting possibilities for cellular therapies. Recent discoveries in the area of neural differentiation are particularly exciting given the limited capacity of neural tissue for intrinsic repair and regeneration. Adult adipose tissue is a rich source of mesenchymal stem cells, providing an abundant and accessible source of adult stem cells. These cells have been termed adipose derived stem cells (ASC). The characterization of these ASCs has defined a population similar to marrow-derived and skeletal muscle-derived stem cells. The success seen in differentiating ASC into various mesenchymal lineages has generated interest in using ASC for neuronal differentiation. Initial in vitro studies characterized the morphology and protein expression of ASC after exposure to neural induction agents. Additional in vitro data suggests the possibility that ASCs are capable of neuronal activity. Progress in the in vitro characterization of ASCs has led to in vivo modeling to determine the survival, migration, and engraftment of transplanted ASCs. While work to define the mechanisms behind the transdifferentiation of ASCs continues, their application to neurological diseases and injuries should also progress. The subject of this review is the capacity of adipose derived stem cells (ASC) for neural transdifferentiation and their application to the treatment of various neurologic disorders.
Discriminative vs informative learning (1997)

The goal of pattern classification can be approached from two points of view: informative- where the classifier learns the class densities, or discriminative- where the focus is on learning the class boundaries without regard to the underlying class densities. We review and synthesize the tradeoffs between these two approaches for simple classifiers, and extend the results to modern techniques such as Naive Bayes and Generalized Additive Models. Data mining applications often operate in the domain of high dimensional features where the tradeoffs between informative and discriminative classifiers are especially relevant. Experimental results are provided for simulated and real data.