gebhart/patrepeval huggingface dataset:
0646 THE PREVALENCE OF HYPERSOMNOLENCE, ITS CORRELATES AND ASSOCIATED ROLE IMPAIRMENT IN THE NATIONAL COMORBIDITY SURVEY REPLICATION (NCS-R) (2017)

The prevalence of hypersomnolence in the U.S. and associated socio-demographic characteristics are not well studied. Its comorbidity with insomnia and relationship with psychiatric, alcohol and drug use disorders, use of prescription medications and impact on functional impairment is poorly delineated. The National Comorbidity Survey Replication (NCS-R) is a nationally representative community household survey of individuals ≥18 years. As part of this survey, subjects (n=5,962) were queried about their sleep in the NCS-R Part II questionnaire. Socio-demographic characteristics and prescription medication use were assessed. Subjects were administered the WHO Composite International Diagnostic Interview (WHO-CIDI) to determine various DSM-IV diagnoses and the WHO Disability Assessment Schedule 2.0 (WHO-DAS II) to evaluate for functional impairment. The prevalence of 12-month hypersomnolence, defined per DSM-5 as a subjective sense of sleepiness during the daytime associated with lapses into sleep, not feeling rested despite getting adequate sleep, or having difficulty waking in the morning, was determined. Odds ratios were used to assess associations with various socio-demographic characteristics, insomnia, DSM-IV diagnoses, prescription medication use, alcohol and drug abuse/dependence as well as functional impairment. The prevalence of hypersomnolence in U.S. adults was 23.34% (SE=0.88). Tetrachoric correlations among constituent symptoms were high (0.56 to 0.97; all p<0.05). Among socio-demographic characteristics, being female (OR=1.41; CI:1.20–1.61), ≤45 years (OR=1.35; CI:1.10–1.66), having a low/low-average family income (OR=1.36; CI:1.13–1.65) and being unemployed (OR=1.38; CI:1.11–1.70) were associated with a higher risk of hypersomnolence. Insomnia (OR=5.65; CI:4.55–7.02), DSM-IV anxiety disorders (OR=2.78; CI:2.34–3.31), mood disorders (OR=2.72; CI:2.18–3.39), conduct and oppositional disorders (OR=2.11; CI:1.52–2.93), and substance use disorders (OR=1.56; CI:1.27–1.91) were significantly comorbid with hypersomnolence after accounting for socio-demographic characteristics and other DSM-IV diagnoses. Hypersomnolence was significantly associated with functional impairment (OR=2.01; CI:1.30–3.12). Among medication classes, antidepressants (OR=1.77; CI:1.43–2.19), benzodiazepines (OR=1.50; CI:1.15–1.95) and buspirone (OR=2.78; CI:1.46–5.27) were associated with increased rates of hypersomnolence. Hypersomnolence is common in the general population, especially in younger, female, lower income and unemployed subgroups. Hypersomnolence is comorbid with multiple psychiatric and substance abuse disorders, particularly insomnia, anxiety and depression, as well as antidepressant and benzodiazepine use. Finally, hypersomnolence is associated with significant functional impairment. N/A.
The association of sequence variants in DNA repair and cell cycle genes with cancers of the upper aerodigestive tract (2006)

Cancers of the upper aerodigestive tract (UADT), comprising the oral cavity, pharynx, larynx and oesophagus, account for 5.2% of all cancers cases worldwide. The major risk factors, tobacco and alcohol can directly or indirectly generate DNA damage, which if unrepaired can give rise to mutations, unregulated cell growth and apoptosis induction. To clarify the role of DNA repair and cell cycle control proteins in UADT cancer susceptibility, we studied the risk in relation to 28 SNPs in 18 DNA repair enzymes and 9 SNPs in 7 cell cycle control genes. A case-control study was conducted from 2000 to 2002 in six centers from Romania, Poland, Russia, Slovakia and the Czech Republic. Patients diagnosed with squamous cell carcinoma of the UADT (n=811) and controls with a recent diagnosis of diseases unrelated to tobacco and alcohol (n=1083) were recruited. For UADT cancer risk, associations were observed for the homozygous carriers of the variant alleles of MGMT L84F [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.32-4.20], MGMT 171C > T (OR 2.24, 95% CI 1.20-4.17) and OGG1 S326C (OR 2.07, 95% CI 1.15-3.73) whilst three variants were associated with a protective effect (XPA 23G > A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron 9-200T > C, P for trend 0.009). Several other sequence variants showed associations with specific cancers without an overall association with UADT cancer. While some of these associations are consistent with previous studies, we cannot rule out the possibility of false-positive associations. The positive findings should be explored in another large-scale study on UADT cancers.
HPMA Copolymer Conjugates of Paclitaxel and Docetaxel with pH-Controlled Drug Release (2010)

In this paper we describe the synthesis, physicochemical characteristics and data on the biological activity of polymer prodrugs based on the anticancer drugs paclitaxel (PTX) and docetaxel (DTX) conjugated with a water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer drug carrier. The drugs were derivatized and then attached to the polymer backbone via a spacer that is stable under physiological conditions (pH 7.4) and hydrolytically degradable in mild acidic environments (e.g., endosomes, pH approximately 5). Polymer-drug conjugates were designed to achieve prolonged blood circulation and release of the active compound in target cells. Six types of conjugates differing in the structure of the keto acid (levulic, 3-(acetyl)acrylic acid) and 4-(2-oxopropyl)benzoic acid-containing spacer or in the amount of drug bound to the HPMA copolymer were synthesized. In all the conjugates, the linkage susceptible to hydrolytic cleavage was formed by the reaction of the carbonyl group of a drug derivative with the hydrazide group-terminated side chains of the polymer. In vitro incubation of the conjugates in buffers resulted in much faster release of drugs or their derivatives from the polymer at pH 5 than at pH 7.4 with the rate depending on the detailed structure of the spacer. Conjugates containing drugs acylated with levulic acid were tested for their anticancer activity in vivo using two murine models. The PTX-containing conjugate showed better antitumor efficacy in the 4T1 model of mammary carcinoma than the parent drug and its derivative. The DTX-containing conjugate demonstrated high activity in treating EL4 T cell lymphoma. The treatment with the polymer conjugates was devoid of side toxicity. In both models, we achieved complete regression of established tumors accompanied by a durable tumor resistance in most of the cured animals.
Signal Architecture for a Distributed Magnetic Local Positioning System (2004)

This paper presents a sensing system which can be used by a mobile robot to measure absolute position and attitude, even in the cluttered environment of an office building or warehouse. The system is based on extremely-low frequency magnetic fields, which have excellent characteristics for penetrating line-of-sight obstructions. Multiple beacons distributed throughout a building are used to generate the magnetic signals, which are based on sets of pseudorandom codes. This signal architecture results in low overall frequency content, reducing eddy field noise and enabling the system to have a large number of beacons and extended coverage volume.
DEEPre: sequence-based enzyme EC number prediction by deep learning (2017)

Abstract Motivation Annotation of enzyme function has a broad range of applications, such as metagenomics, industrial biotechnology, and diagnosis of enzyme deficiency-caused diseases. However, the time and resource required make it prohibitively expensive to experimentally determine the function of every enzyme. Therefore, computational enzyme function prediction has become increasingly important. In this paper, we develop such an approach, determining the enzyme function by predicting the Enzyme Commission number. Results We propose an end-to-end feature selection and classification model training approach, as well as an automatic and robust feature dimensionality uniformization method, DEEPre, in the field of enzyme function prediction. Instead of extracting manually crafted features from enzyme sequences, our model takes the raw sequence encoding as inputs, extracting convolutional and sequential features from the raw encoding based on the classification result to directly improve the prediction performance. The thorough cross-fold validation experiments conducted on two large-scale datasets show that DEEPre improves the prediction performance over the previous state-of-the-art methods. In addition, our server outperforms five other servers in determining the main class of enzymes on a separate low-homology dataset. Two case studies demonstrate DEEPre’s ability to capture the functional difference of enzyme isoforms. Availability and implementation The server could be accessed freely at http://www.cbrc.kaust.edu.sa/DEEPre. Supplementary information Supplementary data are available at Bioinformatics online.
Differential activation of nerve fibers with magnetic stimulation in humans (2006)

A differential evocation of motor and sensory fibers was demonstrated and indicates that it may be possible to induce unidirectional action potentials in myelinated peripheral nerve fibers with magnetic stimulation.
Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem cells and B cells (1996)

Abstract A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains immunoglobulin-like loops and epidermal growth factor [EGF] homology domains), is expressed in vascular endothelial and hematopoietic cells. We generated monoclonal antibodies (MoAbs) against the extracellular domain of TIE and a polyclonal antibody against the TIE carboxyterminus and used them to analyze expression of TIE in hematopoietic cells. Western blotting detected two forms of TIE protein with a molecular mass of 135 and 130 kD in hematopoietic and endothelial cells. Northern blotting analysis revealed that TIE was expressed preferentially in undifferentiated cell lines, especially when megakaryocytic, but not erythroid differentiation was induced. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that TIE was predominantly expressed in the human hematopoietic progenitor fraction, CD34+ cells. Fluorescence- activated cell sorting (FACS) showed that 42% of CD34+ and 17% of KIT- positive (KIT+) cells were TIE-positive (TIE+). The majority (81%) of the primitive hematopoietic stem cells, CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term culture-initiating cells (LTC- IC) showed that the TIE+ fraction contained more primitive cells than the TIE- fraction. Some TIE+ cells were in the CD34- fraction, which were CD19+ and CD20+ (B cells). These findings indicate that TIE has a unique spectrum of expression in primitive hematopoietic stem cells and B cells. Although its ligand has not been identified, TIE and its ligand may establish a novel regulatory pathway not only in early hematopoiesis, but also in the differentiation and/or proliferation of B cells.
Phenolic Extraction from Apple Peel by Cellulases from Thermobifida fusca (2005)

With the optimization of the pretreatment conditions for the crude Thermobifida fusca cellulase activity and phenolic release from apple peel, we focused on the activity of individual purified cellulase related to the antioxidant activity. The overall phenolic release was significantly increased in a synergistic manner with combined pretreatment, not with individual pretreatment such as boiling, acid, and pectinase treatment. Approximately 60 mg of reducing sugar equivalent were produced per g of apple peel by treatment with T. fusca crude extract, and up to 3 times more reducing sugars were released when the apple peel was boiled and then treated with acid and pectinase. There was good correlation between the release of phenolics and reducing sugar by cellulase treatment and also between the amount of total phenolics and antioxidant capacity by each enzyme treatment (r2> 0.95). Among the tested enzymes purified from T. fusca cell extract, cellulase activity on apple peel was the highest with cellulase 6A (Cel 6A; 43% digestion), and the highest antioxidant capacity was obtained by incubation with Cel 6B (16 mg vitamin C equiv/g). Synergism in the activity was found from the combined treatment with Cel 6A and 6B in both cellulase activity and antioxidant capacity after 20 h of incubation. Cel 9A (progressive endocellulase) exhibited greater cellulase activity and antioxidant capacity than Cel 9A cd which lacks in cellulose-binding module, indicating that the cellulose-binding domain might play important roles in cellulolysis of apple peel. This study could provide some insights into the action mechanism of various cellulases on the digestion of cellulose-containing byproducts and expand the opportunity for cellulase utilization in the extraction of functional ingredients from the plant-derived byproducts.
Fmoc-Based Synthesis of Peptide-αThioesters:  Application to the Total Chemical Synthesis of a Glycoprotein by Native Chemical Ligation (1999)

The technique of native chemical ligation has enabled the total chemical synthesis of proteins with molecular weights far in excess of those achievable by conventional stepwise solid-phase peptide synthesis. The method involves the condensation of two unprotected peptide segments, one bearing a C-terminal αthioester and the other an N-terminal cysteine residue, to afford a protein with a native amide linkage at the site of ligation. Here we report an extension of the native chemical ligation method to the total synthesis of a glycosylated protein, the antimicrobial O-linked glycoprotein diptericin. The major challenge in our synthesis was preparation of a 24-residue glycopeptide-αthioester segment, which was complicated by the incompatibility of glycosidic linkages with Boc chemistry and by the incompatibility of thioesters with Fmoc chemistry. The use of an alkanesulfonamide “safety-catch” linker circumvented this problem and permitted the solid-phase synthesis of the glycopeptide-αthioester using standard Fmoc chemistry protocols. Ligation of this thioester with a 58-residue glycopeptide bearing an N-terminal cysteine residue yielded the full-length glycoprotein with two sites of glycosylation. The fully deprotected diptericin glycoform was active in antimicrobial assays.
The kinetic properties of phosphoenolpyruvate carboxykinase of Escherichia coli (1980)

Initial rate kinetic studies on phosphoenolpyruvate carboxykinase of Escherichia coli are consistent with either of two sequential kinetic mechanisms: rapid equilibrium random, or partially ordered. However, the kinetics of isotope exchange at chemical equilibrium allows clear discrimination in favor of a random mechanism containing a preferred pathway of substrate addition and product release. All plots of exchange rates vs. reactant concentrations leveled off at constant rates at saturating levels of substrates; since complete inhibition of any exchange was not observed, a compulsory sequence may be eliminated. High concentrations of phosphoenolpyruvate and (or) ATP repressed the oxaloacetate in equilibrium bicarbonate exchange, however, indicating that the latter pair of substrates add most favorably to the free enzyme. Exchange rates between various substrate-product pairs were not identical, ruling out a formally rapid equilibrium random mechanism with rate-limiting interconversion of the central complex. A comparison of the relative rates of the overall reaction and the ATP-dependent oxaloacetate in equilibrium bicarbonate exchange showed the latter to be much faster than net formation of oxaloacetate. The requirement for ATP in promoting this exchange may be rationalized in terms of substrate synergism, with occupation of the ATP binding site a requisite for its catalysis.
A Spreadsheet Approach to Automated Protein Crystallization (1996)

To design and analyse a large number of protein crystallization experiments, a set of macros running in Excel 4.0 has been developed. The macros are designed to work in a multiuser environment. An interface for a crystallization robot based on two Gilson autosamplers is included.
Xylitol Production by an Enterobacter Species (1973)

A xylose-utilizing bacterial strain was isolated from soil.
Endpoint forces obtained during intraspinal microstimulation of the cat lumbar spinal cord - experimental and biomechanical model results (2003)

We studied the structure of endpoint forces produced by microstimulation of the cat spinal cord, and from combinations of muscles using a biomechanical model of the cat hindlimb. The forces evoked by microstimulation were of four types. At some stimulation sites, the force patterns exhibited a point of convergence where the active endpoint force was zero. The endpoint forces produced by activating combinations of muscles in the biomechanical model were of types similar to the experimental ones, although they demonstrated points of convergence in locations not observed experimentally. These results suggest that the spinal circuitry uses a subset of the possible muscular combinations.
Basic and acidic fibroblast growth factors interact with the same cell surface receptors. (1986)

Despite quantitative differences, the activity of basic and acidic fibroblast growth factors (FGF) on a wide variety of normal diploid cells derived from neuroectoderm and mesoderm is intrinsically similar. This suggests that they bind to the same cell surface receptors. This was investigated using a baby hamster kidney cell line (BHK-21) as a model. BHK-21 cell membrane components that interact with basic and acidic FGF have been identified by covalent cross-linking to their respective 125I-labeled ligands. Under appropriate conditions, basic and acidic 125I-FGF were cross-linked, using disuccinimidyl suberate, to two receptor species with apparent molecular masses of 145,000 and 125,000 daltons, respectively. The labeling of those receptors is inhibited when either native basic or acidic FGF are present in excess during incubation of cells with either acidic or basic 125I-FGF. Competition of basic 125I-FGF with increasing concentrations of native acidic FGF results in a preferential decrease in the labeling of the 125,000-dalton species, whereas competition of acidic 125I-FGF with increasing concentrations of native basic FGF leads to a preferential decrease in the labeling of the 145,000-dalton species. The data suggest that qualitatively both mitogens interact with the same 145,000- and 125,000-dalton receptor species. The different affinities displayed by acidic and basic FGF toward their common receptor molecules could explain why acidic FGF, depending on the cell type considered, is 20-100-fold less potent than basic FGF.
Th1 and Th2 cytokine induction in pulmonary T cells during infection with respiratory syncytial virus (1996)

Helper T (Th) cells can be classified functionally into two main types. Broadly, Th1 cells play a major role in eliminating viral pathogens, while Th2 cells mediate anti-parasite immunity and allergic responses. These functions are thought to depend on characteristic and distinct patterns of cytokine production. Infection with human respiratory syncytial virus, an important common cold virus, causes transient lymphocytic bronchiolitis in mice. Activated T cells are partly responsible for this disease, but also eliminate the virus. To show whether polarized cytokine production occurs in individual cells during viral bronchiolitis, we sampled murine bronchoalveolar lavage and mediastinal lymph node cells before and after infection. RT-PCR of cellular mRNA and flow cytometric analysis of intracellular cytokine production showed a rapid IFN-gamma response at both sites, which persisted for more than 3 weeks in the lung. Most IFN-gamma-producing cells were CD8+. Some early CD4+ IFN-gamma-producing cells also made IL-10. Only low levels of IL-2, IL-4 and IL-5 mRNA or protein expression were detected at any time at either site. No cytokines were detected in B cell populations at either site. These novel techniques show the true complexity of cytokine production patterns on a cell-by-cell basis, allowing T cells to be reclassified according to function.
Reversal of peptide backbone direction may result in the mirroring of protein structure (1992)

In linear polypeptides, inversion of amino acid chirality (all-L to all-D) achieves a mirroring of side chain positions and interactions in conformational space. A similar mirroring of side chain positions is independently achieved by a reversal of the direction of the peptide backbone (retro modification). Thus, while an all-D chain could be expected to adopt a perfect 'mirror image' of the three-dimensional structure of its parent all-L protein, the retro-all-L chain could be expected to adopt a topological equivalent of such a mirror image, through the symmetry transformations of side chain interactions. These notions, supported by sequence analyses, modelling studies, and evidence relating to the activity of 'retro-inverso' peptides, are extended towards the proposal, that the backbone reversed chain of a large globular protein might recognize the chiral opposite of the parent protein's substrate(s).
Uniform Evaluation of Hardware Implementations of the Round-Two SHA-3 Candidates (2010)

Abstract. We describe our high-speed hardware modules for the 14 candidates of the second evaluation round of the SHA-3 hash function competition. Emphasis has been put on bringing as many aspects of design and implementation as possible into agreement in order to receive consistent and comparable evaluation results. For most candidates we have tested a range of different design and implementation options. The evaluation involved a large number of synthesis runs in a uniform setup and under the use of a simple optimization heuristic. In addition to identifying good hardware-design options, this approach has yielded data on numerous possible area-performance tradeoffs for the different hardware modules. The best configurations then underwent place &amp;amp; route in order to reach the highest degree of accuracy of performance metrics short of actual implementation in silicon.
Visualization of Protein‐Specific Glycosylation inside Living Cells (2016)

Protein glycosylation is a ubiquitous post-translational modification that is involved in the regulation of many aspects of protein function. In order to uncover the biological roles of this modification, imaging the glycosylation state of specific proteins within living cells would be of fundamental importance. To date, however, this has not been achieved. Herein, we demonstrate protein-specific detection of the glycosylation of the intracellular proteins OGT, Foxo1, p53, and Akt1 in living cells. Our generally applicable approach relies on Diels-Alder chemistry to fluorescently label intracellular carbohydrates through metabolic engineering. The target proteins are tagged with enhanced green fluorescent protein (EGFP). Förster resonance energy transfer (FRET) between the EGFP and the glycan-anchored fluorophore is detected with high contrast even in presence of a large excess of acceptor fluorophores by fluorescence lifetime imaging microscopy (FLIM).