gebhart/patrepeval huggingface dataset:
Decorin Modulates Fibrin Assembly and Structure (2006)

Emerging evidence indicates that fibrin clotting is regulated by different external factors. We demonstrated recently that decorin, a regulator of collagen fibrillogenesis and transforming growth factor-beta activity, binds to the D regions of fibrinogen (Dugan, T.A., Yang, V. W.-C., McQuillan, D.J., and Höök, M. (2003) J. Biol. Chem. 278, 13655-13662). We now report that the decorin-fibrinogen interaction alters the assembly, structure, and clearance of fibrin fibers. Relative to fibrinogen, substoichiometric amounts of decorin core protein modulated clotting, whereas an excess of an active decorin peptide was necessary for similar activity. These concentration-dependent effects suggest that decorin bound to the D regions sterically modulates fibrin assembly. Scanning electron microscopy images of fibrin clotted in the presence of increasing concentrations of decorin core protein showed progressively decreasing fiber diameter. The sequestration of Zn(2+) ions from the N-terminal fibrinogen-binding region abrogated decorin incorporation into the fibrin network. Compared with linear thicker fibrin fibers, the curving thin fibers formed with decorin underwent accelerated tissue-type plasminogen activator-dependent fibrinolysis. Collectively, these data demonstrate that decorin can regulate fibrin organization and reveal a novel mechanism by which extracellular matrix components can participate in hemostasis, thrombosis, and wound repair.
Parallel free-text search on the connection machine system (1986)

A new implementation of free-text search using a new parallel computer—the Connection Machine®—makes possible the application of exhaustive methods not previously feasible for large databases.
Selective degradation of early-response-gene mRNAs: functional analyses of sequence features of the AU-rich elements. (1994)

The metabolic lifetime of mRNA can be specified by specific cis-acting elements within mRNA. One type of element is an adenylate- and uridylate-rich element (ARE) found in the 3' untranslated region of many highly unstable mRNAs for mammalian early-response genes (ERGs). Among the better-characterized members of the ERG family are certain genes encoding nuclear transcription factors. Of particular significance was the finding that their mRNAs decay rapidly with kinetics similar to those of c-fos mRNA. Our previous studies of the c-fos ARE-directed mRNA decay have revealed the existence in this ARE of two structurally distinct and functionally interdependent domains, termed domain I and domain II. We proposed that the c-fos ARE-directed decay is a two-step mechanism in which rapid shortening of the poly(A) tail leads to the decay of the mRNA body and further hypothesized that this is a general mechanism by which the ERG AREs mediate rapid mRNA degradation. To test this hypothesis and to further address the generality of the critical structural characteristics within the c-fos ARE, the RNA-destabilizing functions of more than 10 different AU-rich sequences from various nuclear transcription factor mRNAs have been tested. Consistent with the above-mentioned hypothesis is the observation that mRNAs carrying the functional AREs display a biphasic decay, which is characteristic of the proposed two-step mechanism. Our results indicated that the presence of AUUUA pentanucleotides in an AU-rich region does not always guarantee an RNA-destabilizing function for this region. Our results also led to the identification of a novel class of AU-rich destabilizing elements which contains no AUUUA pentanucleotide. The results of sequence comparison and functional tests revealed that a continuous U-rich sequence is a unique feature among the functional AREs. Finally, our experiments further showed that the c-fos ARE domain II has an RNA decay-enhancing ability upon its fusion to heterologous AU-rich regions and defined for the first time an RNA decay-enhancing element, which we termed the RDE element.
Adenovirus-Mediated Gene Transfer of Ciliary Neurotrophic Factor Can Prevent Photoreceptor Degeneration in the Retinal Degeneration ( rd ) Mouse (1997)

Mutations in the beta-subunit of the cGMP phosphodiesterase gene (betaPDE) can cause photoreceptor degeneration leading to blindness in humans, dogs, and mice. Since intravitreal administration of trophic factors has been shown to reduce photoreceptor death in the Royal College of Surgeons rat and the light overexposure models of photoreceptor degeneration, we have tested the possibility of rescuing photoreceptors in the rd mouse using ciliary neurotrophic factor (CNTF). Following intravitreal injection of an adenoviral vector encoding a ngf/cntf fusion gene into one eye of rd/rd mice, many strong CNTF-immunoreactive profiles are detected in various cell types of the injected eyes. Semiquantitative analysis of the corresponding retinae reveals that the photoreceptor-containing layer (outer nuclear layer, or ONL) retains significantly more rows of photoreceptor nuclei than that of eyes treated with a control (LacZ) vector, or untreated, for at least 18 days after vector administration (the longest survival time analyzed). A smaller, but significant, protective effect was also seen 9 days after intravitreal injection of recombinant CNTF. Because apoptotic cell death has been shown to be the common terminal fate of photoreceptors in the rd mouse and many other animal models of retinitis pigmentosa, these results suggest the possibility that administration of neurotrophic factors may prove beneficial in reducing photoreceptor loss in multiple forms of retinitis pigmentosa.
Structural and Functional Analyses of Benzamidine-Based Inhibitors in Complex with Trypsin:  Implications for the Inhibition of Factor Xa, tPA, and Urokinase (1998)

The trypsin-like serine proteinase superfamily contains a number of potential therapeutic targets, many of which are unsuitable for routine X-ray crystallographic studies. We have cocrystallized a selection of benzamidine-based inhibitors with bovine trypsin and solved their structures to a resolution of up to 1.7 A. Despite similar chemical formulas, the inhibitors exhibit a range of diverse binding modes that reflect their inhibitory spectra against the serine proteinases trypsin, thrombin, factor Xa, tissue-type plasminogen activator (tPA) and urokinase (uPA). In contrast to the compact folded conformations of thrombin inhibitors which allow optimal binding in the well-defined hydrophobic S2/S4 pocket of thrombin, those effective against factor Xa exhibit an extended conformation that allows occupation of the S3/S4 region, where hydrophobic and electrostatic interactions can stabilize the conformation. One group of inhibitors containing an N-terminal 2,4, 6-triisopropylphenylsulfonyl (TIPPS) moiety show little or no penetration into the S3/S4 subsites of trypsin. These latter sites are occluded in uPA, explaining why this class of compounds is effective against uPA. Despite presenting an extensive hydrophobic surface toward the solvent, the Ki values for TIPPS-containing compounds against trypsin is in the range 10(-7) to 10(-8) M. Comparison of the binding of a bis-benzamidine inhibitor in trypsin and tPA indicate that a shift in potency can be induced by relatively minor changes in binding mode. Implications for the inhibition of these proteinases are discussed.
Thermal, electrical and morphological properties of DGEBA/DDM and TGDDM/DDM epoxies modified by a flexible diepoxide and octaphenylamine-POSS (2013)

Polyhedral oligomeric silsesquioxane (POSS) nanocrosslinker namely octaaminophenyl silsesquioxane reinforced with 1,1-bis(3-methyl-4-glycidyloxyphenyl)cyclohexane (diepoxide) modified diglycidyl ether of bisphenol-A (DGEBA) and tetraglycidyl diamino diphenyl methane (TGDDM) epoxy resins and cured with 4,4′-diaminodiphenylmethane (DDM). The chemical reactions that occurred between epoxy resins and DDM with POSS were confirmed by Fourier transform infrared spectroscopy. POSS-reinforced hybrid diepoxide-epoxy resin nanocomposites were characterised for their thermal, electrical and morphological properties. T g and heat distortion temperature of hybrid epoxy increases with increased incorporation of POSS. The data obtained from thermal studies indicated that the incorporation of nano-POSS into diepoxide-modified hybrid systems possess improved thermal stability. Dielectric properties decreased with increasing percentage of POSS in both systems. The nanolevel dispersion of octaaminophenyl silsesquioxane (POSS) was confirmed by X-ray diffraction analysis and transmission electron microscope studies.
Molecular haplotyping of genetic markers 10 kb apart by allele-specific long-range PCR (1996)

Haplotypes, combinations of polymorphic markers in a chromosome, are critical for genome diversity research. However, their utility in population samplings is compromised by uncertain linkage phase determinations from unrelated individuals. Molecular haplotyping accomplishes direct phase determination by generation of hemizygous templates from diploid genomic samples. We report molecular haplotyping by allele-specific long-range PCR of two markers 9.5 kb apart at the CD4 locus: a bi-allelic Alu deletion and a multi-allelic repeat. We verified CD4 molecular haplotypes by classical Mendelian analysis. Molecular haplotyping should prove useful in mapping disease genes and in establishing founder effects.
A New Genetic Method for Isolating Functionally Interacting Genes: High plo1+-Dependent Mutants and Their Suppressors Define Genes in Mitotic and Septation Pathways in Fission Yeast (2000)

We describe a general genetic method to identify genes encoding proteins that functionally interact with and/or are good candidates for downstream targets of a particular gene product. The screen identifies mutants whose growth depends on high levels of expression of that gene. We apply this to the plo1(+) gene that encodes a fission yeast homologue of the polo-like kinases. plo1(+) regulates both spindle formation and septation. We have isolated 17 high plo1(+)-dependent (pld) mutants that show defects in mitosis or septation. Three mutants show a mitotic arrest phenotype. Among the 14 pld mutants with septation defects, 12 mapped to known loci: cdc7, cdc15, cdc11 spg1, and sid2. One of the pld mutants, cdc7-PD1, was selected for suppressor analysis. As multicopy suppressors, we isolated four known genes involved in septation in fission yeast: spg1(+), sce3(+), cdc8(+), and rho1(+), and two previously uncharacterized genes, mpd1(+) and mpd2(+). mpd1(+) exhibits high homology to phosphatidylinositol 4-phosphate 5-kinase, while mpd2(+) resembles Saccharomyces cerevisiae SMY2; both proteins are involved in the regulation of actin-mediated processes. As chromosomal suppressors of cdc7-PD1, we isolated mutations of cdc16 that resulted in multiseptation without nuclear division. cdc16(+), dma1(+), byr3(+), byr4(+) and a truncated form of the cdc7 gene were isolated by complementation of one of these cdc16 mutations. These results demonstrate that screening for high dose-dependent mutants and their suppressors is an effective approach to identify functionally interacting genes.
Synergistic Induction of Oxidative Injury and Apoptosis in Human Multiple Myeloma Cells by the Proteasome Inhibitor Bortezomib and Histone Deacetylase Inhibitors (2004)

Sequential exposure to bortezomib in conjunction with clinically relevant HDAC inhibitors potently induces mitochondrial dysfunction and apoptosis in human MM cells through a ROS-dependent mechanism, suggesting that a strategy combining these agents warrants further investigation in MM.
Inhibition of Versican Synthesis by Antisense Alters Smooth Muscle Cell Phenotype and Induces Elastic Fiber Formation In Vitro and in Neointima After Vessel Injury (2005)

The proteoglycan versican is implicated in several atherogenic events, including stimulation of vascular smooth muscle cell (VSMC) growth and migration, retention of lipoproteins, and promotion of thrombogenesis. A high content of intimal versican also correlates with a low content of elastin, suggesting an inhibitory role for versican in elastogenesis. To determine whether reduced production of versican can be used to enhance elastogenesis, we transduced Fischer rat VSMC (FRSMC) with a versican antisense sequence using the retroviral vector LXSN. Stable expression of versican antisense (LVaSN) significantly reduced versican production, induced a flattened morphology, reduced cell proliferation and migration, increased tropoelastin synthesis, increased elastin binding protein (S-Gal/EBP), and increased deposition of elastic fibers in long-term cultures. Add-back of chondroitin sulfate chains, or versican, decreased S-Gal/EBP and elastic fiber formation. LVaSN cells seeded into balloon catheter-injured rat carotid arteries formed neointimae containing low levels versican, increased amounts of S-Gal/EBP, and increased elastin deposits 7 days postinjury. At 4 weeks, neointimae formed from LVaSN cells were highly structured and contained multiple layers of elastic fibers and lamellae. These results indicate a central role for versican and its constituent chondroitin sulfate chains in controlling cell phenotype, elastogenesis, and intimal structure.
A new distribution network based on controlled switching elements and its applications (1995)

The paper presents a new distribution network which is capable of concentrating and shifting the incoming active packets simultaneously, without requiring dummy destination address generation and extraction processes. It has the structure of a reverse banyan network (RBN) and consists of controlled switching elements (CSEs) which is obtained by extending the passive iterative-cells introduced by Narasimha [1994]. The CSE-based RBN has a set of external control inputs (ECIs) in addition to the data input and output lines and can generate different output patterns according to the ECI values. It is shown through four properties that the CSE-based RBN can perform the distribution function of the conventional distributor. In addition, it is rigorously described in the properties how to determine the set of ECI values to achieve the desired distribution function, which includes the distribution in the normal mode, in the reversed mode, and in alternation of these two modes. The proposed CSE-based distributor can be applied to a variety of occasions by modifying the use of the counter, the numbers to write on the registers, and the table to store the ECI values. Some of useful examples are demonstrated through applications to shift-sequence permutation, N/spl times/R concentration, nonblocking point-to-point switching, and virtual FIFO queueing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Variable extent of clopidogrel responsiveness in patients after coronary stenting (2004)

Clopidogrel is an effective and specific inhibitor of ADP-induced platelet aggregation. After metabolic activation, the active clopidogrel metabolite irreversibly impairs the human platelet P2Y12 ADP receptor. Gialpha-protein activation and inhibition of vasodilator-stimulated phosphoprotein (VASP) phosphorylation are two key elements of the P2Y12 receptor pathway suitable for quantitation of clopidogrel effects. So far, only limited data exist about a diminished responsiveness to clopidogrel and underlying possible mechanisms. We investigated clopidogrel effects in 57 patients after percutaneous coronary intervention and stent implantation by flow cytometry for the analysis of intracellular VASP phosphorylation. Patients were treated with a 300 mg clopidogrel loading dose, followed by 75 mg/day clopidogrel in combination with 100 mg/day aspirin. Samples were drawn after a median of 5 days of clopidogrel treatment. Considerable differences in the responsiveness to clopidogrel could be observed and it was shown that 17.5% (10/57) of the patients revealed an inadequate responsiveness to clopidogrel despite continuation of clopidogrel intake. Comparable amounts of Gialpha and VASP were found in two clopidogrel low-responding patients as well as in two responding patients. To exclude a molecular defect of P2Y12 ADP receptor, the P2Y12 receptor gene of eight clopidogrel treated patients (seven patients with inadequate responsiveness, one responder) was sequenced. We only found a single silent mutation in exon 2 at position 1828 (GA). We suggest that individual differences in clopidogrel metabolization could cause relevant variations in clopidogrel responsiveness despite the use of a 300 mg clopidogrel loading dose.
Dermal fillers: ever-expanding options for esthetic use. (2007)

Aesthetic volume rejuvenation with dermal fillers continues to be a very popular procedure that is sought by a growing number of patients who seek the rounder softer contours attributable to a more youthful appearance, including fuller curves of the cheeks, lips, and temples. Not only are fillers easier to use, but the outcomes that equal or exceed more invasive surgical options make volume restoration an increasingly popular procedure. Continued patient demand has fueled the introduction of a wider variety of injectable fillers, which include dermal and subdermal fillers with varying degrees of viscosity and duration of benefit. There are also several dermal implants that have stood the test of time or offer innovative technologies and approaches. This article will focus on the most popular, time-tested, and innovative fillers available today.
Lentiviral vectors: basic to translational (2012)

More than two decades have passed since genetically modified HIV was used for gene delivery. Through continuous improvements these early marker gene-carrying HIVs have evolved into safer and more effective lentiviral vectors. Lentiviral vectors offer several attractive properties as gene-delivery vehicles, including: (i) sustained gene delivery through stable vector integration into host genome; (ii) the capability of infecting both dividing and non-dividing cells; (iii) broad tissue tropisms, including important gene- and cell-therapy-target cell types; (iv) no expression of viral proteins after vector transduction; (v) the ability to deliver complex genetic elements, such as polycistronic or intron-containing sequences; (vi) potentially safer integration site profile; and (vii) a relatively easy system for vector manipulation and production. Accordingly, lentivector technologies now have widespread use in basic biology and translational studies for stable transgene overexpression, persistent gene silencing, immunization, in vivo imaging, generating transgenic animals, induction of pluripotent cells, stem cell modification and lineage tracking, or site-directed gene editing. Moreover, in the present high-throughput '-omics' era, the commercial availability of premade lentiviral vectors, which are engineered to express or silence genome-wide genes, accelerates the rapid expansion of this vector technology. In the present review, we assess the advances in lentiviral vector technology, including basic lentivirology, vector designs for improved efficiency and biosafety, protocols for vector production and infection, targeted gene delivery, advanced lentiviral applications and issues associated with the vector system.
Building and exploiting ad hoc concept hierarchies for web log analysis (2002)

Abstract. Web usage mining aims at the discovery of interesting usage patterns from Web server log files. “Interestingness ” relates to the business goals of the site owner. However, business goals refer to business objects rather than the page hits and script invocations recorded by the site server. Hence, Web usage analysis requires a preparatory mechanism that incorporates the business goals, the concepts reflecting them and the expert’s background knowledge on them into the mining process. To this purpose, we present a methodology and a mechanism for the establishment and exploitation of application-oriented concept hierarchies in Web usage analysis. We demonstrate our approach on a real data set and show how it can substantially improve both the search for interesting patterns by the mining algorithm and the interpretation of the mining results by the analyst.
Angular strain estimation method for elastography (2007)

In the conventional cross-correlation-based strain estimation, there is a trade-off between the interpolation accuracy and the computational requirement. On the other hand, the autocorrelation-based method does not need interpolation, but it cannot estimate the wide range of displacements for elastography. We have developed a new strain estimator, called the angular strain estimation method, which does not need any interpolation and can estimate strain without restricting the range of displacements. The new method estimates strain utilizing complex correlation between correlated ultrasound signals from pre-and post-compression frames. From simulation and experiments, we found that the angular strain estimation method improves the accuracy and strain image quality compared to the conventional strain estimator using cross correlation with interpolation. Furthermore, it is computationally efficient and can be readily incorporated in ultrasound machines for rea -time elastography.
Adherence to a Low-Risk, Healthy Lifestyle and Risk of Sudden Cardiac Death Among Women (2011)

Adherence to a low-risk lifestyle is associated with a low risk of SCD.
GABAAReceptor γ2 Subunit Mutations Linked to Human Epileptic Syndromes Differentially Affect Phasic and Tonic Inhibition (2007)

GABA acts on GABA(A) receptors to evoke both phasic inhibitory synaptic events and persistent, tonic currents. The gamma2 subunit of the GABA(A) receptor is involved in both phasic and tonic signaling in the hippocampus. Several mutations of this subunit are linked to human epileptic syndromes with febrile seizures, yet it is not clear how they perturb neuronal activity. Here, we examined the expression and functional impact of recombinant gamma2 in hippocampal neurons. We show that the K289M mutation has no effect on membrane trafficking and synaptic aggregation of recombinant gamma2, but accelerates the decay of synaptic currents. In contrast, the R43Q mutation primarily reduces surface expression of recombinant gamma2. However, it has no dominant effect on synaptic currents but instead reduces tonic GABA currents, at least in part by reducing surface expression of the alpha5 subunit. Our data suggests that the phenotypic specificity of mutations affecting the GABA(A) receptor gamma2 gene may result from different actions specific to distinct modes of GABAergic signaling.
Reduction of the Ring Size of Radiolabeled Lactam Bridge–Cyclized α-MSH Peptide, Resulting in Enhanced Melanoma Uptake (2010)

The reduction of the peptide ring size dramatically increased the melanoma uptake and decreased the renal uptake of (111)In-DOTA-Nle-CycMSH(hex), providing a new insight into the design of a novel radiolabeled lactam bridge-cyclized alpha-MSH peptide for melanoma imaging and treatment.
Fast Decoupled Load Flow (1974)

This paper describes a simple, very reliable and extremely fast load-flow solution method with a wide range of practical application. It is attractive for accurate or approximate off-and on-line routine and contingency calculations for networks of any size, and can be implemented efficiently on computers with restrictive core-store capacities. The method is a development on other recent work employing the MW-Θ/ MVAR-V decoupling principle, and its precise algorithmic form has been determined by extensive numerical studies. The paper gives details of the method's performance on a series of practical problems of up to 1080 buses. A solution to within 0.01 MW/MVAR maximum bus mismatches is normally obtained in 4 to 7 iterations, each iteration being equal in speed to 1½ Gauss-Seidel iterations or 1/5th of a Newton iteration. Correlations of general interest between the power-mismatch convergence criterion and actual solution accuracy are obtained.