gebhart/patrepeval huggingface dataset:
Acute Cerebrovascular Disease in Women (2001)

In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings.
Engineering altered protein–DNA recognition specificity (2018)

Protein engineering is used to generate novel protein folds and assemblages, to impart new properties and functions onto existing proteins, and to enhance our understanding of principles that govern protein structure. While such approaches can be employed to reprogram protein-protein interactions, modifying protein-DNA interactions is more difficult. This may be related to the structural features of protein-DNA interfaces, which display more charged groups, directional hydrogen bonds, ordered solvent molecules and counterions than comparable protein interfaces. Nevertheless, progress has been made in the redesign of protein-DNA specificity, much of it driven by the development of engineered enzymes for genome modification. Here, we summarize the creation of novel DNA specificities for zinc finger proteins, meganucleases, TAL effectors, recombinases and restriction endonucleases. The ease of re-engineering each system is related both to the modularity of the protein and the extent to which the proteins have evolved to be capable of readily modifying their recognition specificities in response to natural selection. The development of engineered DNA binding proteins that display an ideal combination of activity, specificity, deliverability, and outcomes is not a fully solved problem, however each of the current platforms offers unique advantages, offset by behaviors and properties requiring further study and development.
Eliminating inter-speaker variability prior to discriminant transforms (2005)

This paper shows the impact of speaker normalization techniques, such as vocal tract length normalization (VTLN) and speaker-adaptive training (SAT), prior to discriminant feature space transforms, such as LDA (linear discriminant analysis). We demonstrate that removing the inter-speaker variability by using speaker compensation methods results in improved discrimination as measured by the LDA eigenvalues and also in improved classification accuracy (as measured by the word error rate). Experimental results on the SPINE (speech in noisy environments) database indicate an improvement of up to 5% relative over the standard case where speaker adaptation (during testing and training) is applied after the LDA transform which is trained in a speaker independent manner. We conjecture that performing linear discriminant analysis in a canonical feature space (or speaker normalized space) is more effective than LDA in a speaker independent space because the eigenvectors carve a subspace of maximum intra-speaker phonetic separability whereas in the latter case this subspace is also defined by the inter-speaker variability. Indeed, we show that the more normalization is performed (first VTLN, then SAT), the higher the LDA eigenvalues become.
Nonlinear adaptive prediction of nonstationary signals (1995)

We describe a computationally efficient scheme for the nonlinear adaptive prediction of nonstationary signals whose generation is governed by a nonlinear dynamical mechanism. The complete predictor consists of two subsections. One performs a nonlinear mapping from the input space to an intermediate space with the aim of linearizing the input signal, and the other performs a linear mapping from the new space to the output space. The nonlinear subsection consists of a pipelined recurrent neural network (PRNN), and the linear section consists of a conventional tapped-delay-line (TDL) filter. The nonlinear adaptive predictor described is of general application. The dynamic behavior of the predictor is demonstrated for the case of a speech signal; for this application, it is shown that the nonlinear adaptive predictor outperforms the traditional linear adaptive scheme in a significant way.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Supplemental advance warning devices (1993)

This synthesis will be of interest to traffic engineers, highway design engineers, and others concerned with the operation, safety, and design of the roadway environment. Information is presented on a variety of advance warning devices that are used by state and local agencies to advise motorists of unusual or dangerous road conditions. This synthesis describes the state of the art with respect to these devices. This report of the Transportation Research Board describes more than 340 such devices that have been applied and are in keeping with accepted traffic engineering principles, but are not presently included in the Manual on Uniform Traffic Control Devices (MUTCD). Both active and passive warning devices are presented in the following general categories: environmental conditions (e.g., snow and ice), heavy vehicles, school zones, pedestrian crossings, rail-highway grade crossings, roadway cross sections, congestion and queues, and others. The purpose and characteristics of each device are described, including any information available on their effectiveness, cost, or other features. A drawing of each device is shown to aid the reader in visualizing the device.
Time‐discretized variational formulation of non‐smooth frictional contact (2001)

Abstract The present work extends the non‐smooth contact class of algorithms introduced by Kane et al. to the case of friction. The formulation specifically addresses contact geometries, e.g. involving multiple collisions between tightly packed non‐smooth bodies, for which neither normals nor gap functions can be properly defined. A key aspect of the approach is that the incremental displacements follow from a minimum principle. The objective function comprises terms which account for inertia, strain energy, contact, friction and external forcing. The Euler–Lagrange equations corresponding to this extended variational principle are shown to be consistent with the equations of motion of solids in frictional contact. In addition to its value as a basis for formulating numerical algorithms, the variational framework offers theoretical advantages as regards the selection of trajectories in cases of non‐uniqueness. We present numerical and analytical examples which demonstrate the good momentum and energy conservation characteristics of the numerical algorithms, as well as the ability of the approach to account for stick and slip conditions. Copyright © 2001 John Wiley &amp; Sons, Ltd.
Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus (1993)

Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non-Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV-encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR "silent" CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.
Characterization of the ternary Usher syndrome SANS/ush2a/whirlin protein complex (2017)

The Usher syndrome (USH) is the most common form of inherited deaf-blindness, accompanied by vestibular dysfunction. Due to the heterogeneous manifestation of the clinical symptoms, three USH types (USH1-3) and additional atypical forms are distinguished. USH1 and USH2 proteins have been shown to function together in multiprotein networks in photoreceptor cells and hair cells. Mutations in USH proteins are considered to disrupt distinct USH protein networks and finally lead to the development of USH.To get novel insights into the molecular pathomechanisms underlying USH, we further characterize the periciliary USH protein network in photoreceptor cells. We show the direct interaction between the scaffold protein SANS (USH1G) and the transmembrane adhesion protein ush2a and that both assemble into a ternary USH1/USH2 complex together with the PDZ-domain protein whirlin (USH2D) via mutual interactions. Immunohistochemistry and proximity ligation assays demonstrate co-localization of complex partners and complex formation, respectively, in the periciliary region, the inner segment and at the synapses of rodent and human photoreceptor cells. Protein-protein interaction assays and co-expression of complex partners reveal that pathogenic mutations in USH1G severely affect formation of the SANS/ush2a/whirlin complex. Translational read-through drug treatment, targeting the c.728C > A (p.S243X) nonsense mutation, restored SANS scaffold function. We conclude that USH1 and USH2 proteins function together in higher order protein complexes. The maintenance of USH1/USH2 protein complexes depends on multiple USH1/USH2 protein interactions, which are disrupted by pathogenic mutations in USH1G protein SANS.
CRH Defects in Alzheimer's and Other Neurologic Diseases (1988)

The demonstration of an upregulation of CRH receptors in the cerebral cortex after a decrease in cortical CRH content in Alzheimer's disease indicates the physiologic relevance of the receptor site. It is consistent with the concept that CRH acts as a neurotransmitter in normal cortical functions and that disease of this peptidergic system may be important in certain manifestations of dementia.
Reassortment of Human Rotavirus Possessing Genome Rearrangements with Bovine Rotavirus: Evidence for Host Cell Selection (1987)

Mixed infections of secondary rhesus monkey kidney cells with human rotaviruses carrying rearranged genomes and with bovine rotavirus yielded a high percentage of reassortants. The genotypes of 511 plaque-purified clones raised in either MA104 or BSC-1 cells have been determined and the frequencies of different genotypes have been calculated. It was found that reassortants did not emerge at random; there was non-random association of certain genes; the cell line used to isolate reassortants influenced the result, i.e. host cell factors had a selective effect on a recombinational mixture.
C. Elegans II (1998)

Why should one study a worm? This simple creature is one of several “model” organisms that together have provided tremendous insight into how all organisms are put together. It has become increasingly clear over the past two decades that knowledge from one organism, even one so simple as a worm, can provide tremendous power when connected with knowledge from other organisms. And because of the experimental accessibility of nematodes, knowledge about worms can come more quickly and cheaply than knowledge about higher organisms.
Therapeutic aerosols 1--physical and practical considerations. (1983)

The inhaled route is a logical means of treating respiratory disorders since drugs may be delivered directly to the large surface area of the tracheobron- chial tree and alveoli. The value of inhalation treatment was recognised by ancient civilisations in India, China, and the Middle East, as well as by Hippocrates and Galen.' Since those times, and par- ticularly recently, inhalation treatment has increased greatly in sophistication, and the advantages of this route for the delivery of specific drugs have become well recognised. The drugs often begin to act very rapidly, and as a smaller dose can be used than with oral or intravenous delivery there is generally a reduction in the incidence of systemic side effects.
Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals (2012)

Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of flanking residues. These in vitro findings were supported by in vivo population-level analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV-infected individuals: HLA-associated mutations immune pressures drove the selection of residues that are less cleavable by aminopeptidases predominantly at N-flanking sites, leading to reduced epitope production and immune recognition. These results underscore an important and widespread role of Ag processing mutations in HIV immune escape and identify molecular mechanisms underlying impaired epitope presentation.
Evaluation of Periostat for patient management. (1999)

The cause of adult periodontitis involves complex bacteria-host interactions, with modifying influences exerted by genetic and environmental factors. Current thinking indicates that successful, long-term management of adult periodontitis requires a treatment approach that takes into account the various etiologic components of the disease. Recently, a formulation containing a subantimicrobial dose of doxycycline (Periostat) was approved for use as an adjunct to scaling and root planing (SRP) in the treatment of adult periodontitis. As an inhibitor of matrix metalloproteinases that have been implicated in the pathologic degradation of connective tissue collagen in periodontal support structures, Periostat in conjunction with SRP was shown to significantly improve clinical attachment and reduce probing depth compared with placebo in conjunction with SRP. This article reviews the clinical trial results leading to US Food and Drug Administration approved of Periostat and discusses the potential use of this host-modulatory agent as a complementary systemic pharmacotherapy in periodontal management programs.
The Binary Interacting Network of the Conserved Oligomeric Golgi Tethering Complex (2004)

Several recent studies have revealed the existence of a conserved oligomeric Golgi (COG) complex consisting of several novel proteins as well as known Golgi proteins that were identified by independent approaches. The mammalian COG complex contains eight subunits: COG1/LdlBp, COG2/LdlCp, COG3/Sec34, COG4/Cod1, COG5/GTC-90/Cod4, COG6/Cod2, COG7, and COG8/Dor1. COG1, COG2, and COG7 seem structurally unique to mammalian cells, whereas the other five subunits are structurally conserved in yeast, which also contains three other unique proteins (COG1/Sec36p/Cod3p, COG2/Sec35p, and COG7/Cod5p). We report here the network of intermolecular interactions of the COG complex, revealed by in vitro translation and co-immunoprecipitation approaches. Our results suggest that COG4 serves as a core component of the complex by interacting directly with COG1, COG2, COG5, and COG7. COG3 is incorporated by its direct interaction with COG1 and COG2, whereas COG6 and COG8 do not interact with any individual subunit. Incorporation of COG6 into the complex depends on the concerted interaction of both COG5 and COG7, whereas optimal incorporation of COG8 depends on the concerted interaction of COG5, COG6, and COG7. Because COG4 (together with COG1, COG2, and COG3) is among the four essential genes of the COG complex in yeast, this molecular network highlights the structural basis for a crucial role of COG4 in the assembly/function of the complex. A model for the assembly of the COG complex is presented.
Amphiphilic derivatives of sodium alginate and hyaluronate for cartilage repair: Rheological properties (2000)

Various amphiphilic derivatives of sodium alginate and hyaluronate were prepared by covalent fixation of long alkyl chains (dodecyl and octadecyl) with various ratios on the polysaccharide backbones via ester functions. In the semidilute regime, aqueous solutions of the resulting compounds exhibited the typical rheological properties of hydrophobically associating polymers: tremendous enhancement of zero shear rate Newtonian viscosity, steep shear-thinning behavior, and formation of physically cross-linked gel-like networks. The influence of the alkyl chain length, its content on the polysaccharide and of the polymer concentration in the solution was well identified. All obtained results are discussed with respect to the schedule of conditions related to materials, which could be used for cartilage repair, such as in synovial fluid viscosupplementation as well as in cartilage replacement. In particular, it is seen that HA-C(12)-5 (hyaluronate substituted with 5% of dodecyl chains) and HA-C(18)-1 (hyaluronate substituted with 1% of octadecyl chains) in a 0.15N NaCl solution at 8 g/L have rheological properties quite similar to those of healthy synovial fluid. On the other hand, the rheological parameters of solutions at 8 g/L in 0.15N NaCl of some of derivatives, such as, for example, AA-C(12)-8 (alginate substituted with 8% of dodecyl chains) or HA-C(18)-2, are well fitted for a use in cartilage repair.
Side Chain Chemistry Mediates Backbone Fragmentation in Hydrogen Deficient Peptide Radicals (2008)

A crown ether based, photolabile radical precursor which forms noncovalent complexes with peptides has been prepared. The peptide/precursor complexes can be electrosprayed, isolated in an ion trap, and then subjected to laser photolysis and collision induced dissociation to generate hydrogen deficient peptide radicals. It is demonstrated that these peptide radicals behave very differently from the hydrogen rich peptide radicals generated by electron capture methods. In fact, it is shown that side chain chemistry dictates both the occurrence and relative abundance of backbone fragments that are observed. Fragmentation at aromatic residues occurs preferentially over most other amino acids. The origin of this selectivity relates to the mechanism by which backbone dissociation is initiated. The first step is abstraction of a beta-hydrogen from the side chain, followed by beta-elimination to yield primarily a-type fragment ions. Calculations reveal that those side chains which can easily lose a beta-hydrogen correlate well with experimentally favored sites for backbone fragmentation. In addition, radical mediated side chain losses from the parent peptide are frequently observed. Eleven amino acids exhibit unique mass losses from side chains which positively identify that particular amino acid as part of the parent peptide. Therefore, side chain losses allow one to unambiguously narrow the possible sequences for a parent peptide, which when combined with predictable backbone fragmentation should lead to greatly increased confidence in peptide identification.
Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. (2001)

We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3'-kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increasing VEGF expression. The importance of the VEGF receptor neuropilin was indicated by the ability of a neuropilin-binding VEGF isoform to enhance breast carcinoma survival. Moreover, the expression of neuropilin in neuropilin-deficient breast carcinoma cells protected them from apoptosis. The identification of this VEGF autocrine signaling pathway has important implications for tumor metastasis and therapeutic intervention.