gebhart/patrepeval huggingface dataset:
Myeloperoxidase Impairs ABCA1-dependent Cholesterol Efflux through Methionine Oxidation and Site-specific Tyrosine Chlorination of Apolipoprotein A-I (2006)

High density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-chlorotyrosine. Myeloperoxidase (MPO) is the only known source of 3-chlorotyrosine in vivo, indicating that MPO oxidizes HDL in humans. We previously reported that Tyr-192 is the major site that is chlorinated in apolipoprotein A-I (apoA-I), the chief protein in HDL, and that chlorinated apoA-I loses its ability to promote cholesterol efflux from cells by the ATP-binding cassette transporter A1 (ABCA1) pathway. However, the pathways that promote the chlorination of specific Tyr residues in apoA-I are controversial, and the mechanism for MPO-mediated loss of ABCA1-dependent cholesterol efflux of apoA-I is unclear. Using site-directed mutagenesis, we now demonstrate that lysine residues direct tyrosine chlorination in apoA-I. Importantly, methionine residues inhibit chlorination, indicating that they can act as local, protein-bound antioxidants. Moreover, we observed near normal cholesterol efflux activity when Tyr-192 of apoA-I was mutated to Phe and the oxidized protein was incubated with methionine sulfoxide reductase. Thus, a combination of Tyr-192 chlorination and methionine oxidation is necessary for depriving apoA-I of its ABCA1-dependent cholesterol transport activity. Our observations suggest that biologically significant oxidative damage of apoA-I involves modification of a limited number of specific amino acids, raising the feasibility of producing oxidation-resistant forms of apoA-I that have enhanced anti-atherogenic activity in vivo.
Escherichia coli heat-stable enterotoxin receptors (1996)

Functional ST receptors are expressed in normal colonic tissue and primary and metastatic colorectal tumors but not by extraintestinal tissues in humans. Expression of ST receptors does not vary as a function of the metastatic site or grade of these tumors. Receptors expressed by colorectal tumors retain their characteristic function, with binding of ST coupled to activation of guanylyl cyclase. These studies support the suggestion that ST receptors represent a specific marker for human colorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.
Epstein-Barr virus genome may encode a protein showing significant amino acid and predicted secondary structure homology with glycoprotein B of herpes simplex virus 1 (1985)

We report significant sequence and predicted secondary structure homology between the herpes simplex virus 1 glycoprotein B (gB) and a protein predicted to be encoded by the BALF4 reading frame of Epstein-Barr virus (EBV). Homology was detectable at the DNA level and was highly significant at the protein level and when evolutionary substitution frequencies of amino acids in related proteins were taken into account. Hydropathic analyses predicted that the two proteins possess conserved N-terminal and C-terminal hydrophobic domains. The N-terminal hydrophobic domains share features in common with known cleavable membrane insertion signal sequences. The amino acid sequences of the C-terminal hydrophobic domains predict three adjacent membrane-spanning segments as had been previously predicted for gB. In an alignment of the two amino acid sequences, 247 of 903 gB residues had a matched pair in the BALF4 sequence, and 247 of 854 BALF4 residues were found to have a matched pair in the gB sequence. In addition, all 10 cysteine residues located outside the predicted signal sequence of both proteins were conserved, as were four predicted N-linked glycosylation sites. In all, 43% of the residues in the aligned sequences are predicted to possess equivalent secondary structures. gB is a virion envelope glycoprotein required for virus entry into cells. The domain of gB determining the rate of entry into cells has been mapped; the predicted structure of this domain in gB and the predicted EBV protein are almost identical. Similarly, the cytoplasmic domain of gB postulated to interact with submembrane proteins was also nearly identical in predicted structure to that of the EBV protein. These results suggest that EBV encodes a protein similar in structure and function to the herpes simplex virus 1 gB.
Engineering resistance to ‘aging’ of phosphylated human acetylcholinesterase Role of hydrogen bond network in the active center (1993)

Recombinant human acetylcholinesterase (HuAChE) and selected mutants (E202Q, Y337A, E450A) were studied with respect to catalytic activity towards charged and noncharged substrates, phosphylation with organophosphorus (OP) inhibitors and subsequent aging of the OP-conjugates. Amino acid E450, unlike residues E202 and Y337, is not within interaction distance from the active center. Yet, the bimolecular rates of catalysis and phosphylation are 30-100 fold lower for both E450A and E202Q compared to Y337A or the wild type and in both mutants the resulting OP-conjugates show striking resistance to aging. It is proposed that a hydrogen bond network, that maintains the functional architecture of the active center, involving water molecules and residues E202 and E450, is responsible for the observed behaviour.
Inequality of Asian-type neighborhood environmental quality in communities with different urbanization levels (2013)

Inequality of neighborhood environmental quality (NEQ) is an important pathway through which social inequality results in health disparity. It is critical to assess NEQ which is related to the urbanization level (UL) of the residents’ domiciles and socio-economic status (SES). This study evaluates the major determinants and inequality of Asian-type NEQ, considering both UL and SES. Data from a representative country-wide survey in Taiwan were adopted to assess the chemical, disturbance, and social aspects of NEQ, with 1.906 subjects aged 18 years or above from 88 communities. The results showed that 30% and 24% of subjects living within 15 m from busy roads and smoky/greasy restaurants, respectively, demonstrating widespread traffic pollution and spot pollution sources within communities. ULs of communities, education, age, and SES are statistically significant determinants of various NEQ indicators. More importantly, NEQ inequality does exist and shows opposite patterns across different spatial scales, revealing spatial heterogeneity. Subjects in communities of higher ULs, consisted of larger percentages of residents with better SES, have higher odds of chemical exposure (2.2–21.2), disturbance (3.5–4.3), and social stress (1.9–4.3) than those in rural communities. On the other hand, within communities of the same ULs, subjects of poorer SES have higher odds of pollution exposure (2.6–2.7) and social stress (4.8). Furthermore, this work demonstrates an objective assessment of NEQ with survey methods which can be applied to assess important neighborhood environmental issues in all countries. Spatial heterogeneity of environmental inequality is identified by this study for the first time. It may be a common phenomenon shared by other countries; it has significant implications for environmental health policies and studies.
Comparison of rizatriptan and other triptans on stringent measures of efficacy (2001)

Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response.
The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway (2010)

Double-strand DNA breaks are common events in eukaryotic cells, and there are two major pathways for repairing them: homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). The various causes of double-strand breaks (DSBs) result in a diverse chemistry of DNA ends that must be repaired. Across NHEJ evolution, the enzymes of the NHEJ pathway exhibit a remarkable degree of structural tolerance in the range of DNA end substrate configurations upon which they can act. In vertebrate cells, the nuclease, DNA polymerases, and ligase of NHEJ are the most mechanistically flexible and multifunctional enzymes in each of their classes. Unlike repair pathways for more defined lesions, NHEJ repair enzymes act iteratively, act in any order, and can function independently of one another at each of the two DNA ends being joined. NHEJ is critical not only for the repair of pathologic DSBs as in chromosomal translocations, but also for the repair of physiologic DSBs created during variable (diversity) joining [V(D)J] recombination and class switch recombination (CSR). Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient.
Migraine Pathophysiology (2005)

A combination of basic science and human physiology, particularly functional neuroimaging, has radically altered our understanding of migraine with a focus on brain mechanisms for this common and disabling disorder. Genetic studies have begun to provide plausible targets for the basic molecular defect in terms of ion channels, albeit thus far in the rare condition of familial hemiplegic migraine (FHM). Migraine pathophysiology involves the trigeminovascular system and central nervous system modulation of the pain-producing structures of the cranium. The degree to which head pain results from the activation of the nociceptors of pain-producing intracranial structures, or to the facilitation or lack of inhibition of afferent signals, is not clear at this time. An understanding of the pain mechanism is likely to provide insights into the mechanisms underlying the more generalized sensory dysfunction that is so typical of migraine.
Saturation Distribution in a Linear System During Oil Displacement (1956)

Abstract Displacement studies were performed on a Berea sandstone core in which a residual brine saturation was initially present. The oil saturation was determined as a function of time and distance by measuring the electrical resistance of segments of the core. Relative permeability was measured by a modified Penn State method for the same porous medium used in the displacement studies and static capillary pressures were determined for adjacent samples. The shape of the stabilized zone and recovery at water breakthrough were calculated using both measured and computed relative permeability data and these agreed with the experimental. The fraction of brine flowing at a given oil saturation was determined from saturation distribution data at various times and distances during the displacement runs by calculations based on the continuity equation. As the stabilized zone is formed, the shape of the fw vs So curve approaches a straight line for a certain range of saturations. Introduction A wide variety of experimental work on fluid displacement in porous media has appeared in the petroleum engineering literature during the last two decades. Along with this has appeared the theoretical treatment which forms the basis of our present concepts in this field. One of the first papers of background interest for this particular study was that of Leverett in which was developed the fractional-flow formula. A short time later Buckley and Leverett presented a form of the continuity equation as well as a method of using it and a simplified version of the fractional-flow formula (gravity and capillary-pressure terms neglected) to calculate the distance which any saturation has traveled in a given time interval. Terwilliger et al observed that after their water gas interfaced advanced a certain distance from the inlet of the system, all gas saturations over a certain interval beginning at the extreme flood front advanced at the same velocity. On the basis of the continuity equation they concluded that the change of fractional flow (gas) with saturation must be constant and this zone wherein all saturations moved at the same rate was named the "stabilized zone." They presented a method of calculating the saturation distribution in the stabilized and non-stabilized zones and obtained reasonable agreement between calculated and experimental values.
The vascular endothelial growth factor family of polypeptides (1991)

Vascular endothelial growth factor (VEGF) was identified as a heparin-binding polypeptide mitogen with a target cell specificity restricted to vascular endothelial cells. Molecular cloning reveals the existence of four species of VEGF having 121, 165, 189, and 206 amino acids. These have strikingly different secretion patterns, which suggests multiple physiological roles for this family of polypeptides. The two shorter forms are efficiently secreted, while the longer ones are mostly cell-associated. Alternative splicing of mRNA, rather that transcription from different genes, is the mechanism for their generation. In situ hybridization reveals that the VEGF mRNA is widely distributed in most tissues and organs and expressed at particularly high levels in areas of active vascular proliferation, like the ovarian corpus luteum. Ligand autoradiography on rat tissue sections demonstrates that VEGF binding sites are associated with vascular endothelial cells of both fenestrated and non-fenestrated capillaries and with the endothelium of large vessels, while no displaceable binding is evident on non-endothelial cell types. These findings support the hypothesis that VEGF plays a highly specific role in the maintenance and in the induction of growth of vascular endothelial cells.
The design and implementation of an intelligent interface for information retrieval (1989)

Commercial information (text) retrieval systems have been available since the early 1960's. While they have provided a service allowing individuals to find useful documents out of the millions of documents contained in online databases, there are, a number of problems that prevent the user from being more effective. The primary problems are an inadequate means for specifying information needs, a single way of responding to all users and their information needs, and an inadequate user interface. This thesis describes the design and implementation of I$\\sp3$R, an intelligent interface for information retrieval the purpose of which is to overcome the limitations of current information retrieval systems by providing multiple ways of assisting the user to precisely specify his information need and to search for information. The system organization is based on a blackboard architecture and consists of a number of "experts" that work cooperatively to assist the user. The operation of the experts is coordinated by a control expert that makes its decisions based on a plan derived from the analysis of human search intermediaries, end user dialogues, and user model. The experts provide multiple formal search strategies, the use and collection of domain knowledge, and browsing assistance. The operation of the system is demonstrated by four scenarios.
Nucleotide sequences of the 26S mRNAs of the viruses defining the Venezuelan equine encephalitis antigenic complex. (1998)

Genetic relationships among viruses defining the Venezuelan equine encephalitis (VEE) virus antigenic complex were determined by analyzing the 3'-terminal 561 nucleotides of the nonstructural protein 4 gene and the entire 26S RNA region of the genome. New sequence information is reported for VEE 78V-3531 (VEE subtype-variety IF), Mucambo (IIIA), Tonate (IIIB), 71D-1252 (IIIC), Pixuna (IV), Cabassou (V), and AG80-663 (VI) viruses. The results reported here and by previous investigators largely support the current classification scheme of these viruses, while clearly identifying Everglades (II) as a subtype I virus. A genetic relationship between 78V-3531 (IF) and AG80-663 (VI) viruses contradicted previous serologic results. Mutations near the amino terminus of the E2 envelope proteins of Pixuna and AG80-663 viruses probably account for the previously reported low reactivity of the protective monoclonal antibody 1A2B-10 with these two viruses. Variations in the distribution of potential glycosylation sites in the E2 glycoprotein are discussed.
Recombinant Adeno-Associated Virus for the Generation of Autologous, Gene-Modified Tumor Vaccines: Evidence for a High Transduction Efficiency into Primary Epithelial Cancer Cells (1998)

To explore the potential of recombinant vectors based on recombinant adeno-associated virus (rAAV) for cancer vaccination, we investigated the transduction efficiency of rAAV into cancer cells ex vivo. Infection of human epithelial cancer cell lines with rAAV carrying reporter genes encoding beta-galactosidase (rAAV/LacZ) or luciferase (rAAV/Luc) resulted in high levels of reporter gene expression (>90% positive cells). In marked contrast, rAAV poorly transduced all murine tumor cell lines, as well as human hematopoietic cell lines. Either irradiation or adenovirus infection of tumor cells prior to rAAV infection induced a 10- to 100-fold increase of reporter gene expression. To determine the transduction efficiency of rAAV into primary cancer cells, freshly isolated, irradiated tumor cells from malignant melanoma and ovarian carcinoma patients were infected with rAAV/Luc, resulting in up to 6.9-fold higher levels of gene expression than in a HeLa tumor cell line. Time course experiments with freshly isolated tumor cells infected with rAAV/Luc showed maximal levels of luciferase expression between days 3 and 9 posttransduction. Simultaneous infection of primary tumor cells with up to three rAAV vectors containing genes encoding the immunostimulatory proteins B7-2 (CD86), p35 subunit of IL-12, and p40 subunit of IL-12 resulted in high expression of B7-2 in more than 90% of the tumor cells and in the secretion of high levels of IL-12. Taken together, our results demonstrate that rAAV efficiently transduces freshly isolated human, epithelial tumor cells and might therefore be a potent tool to produce improved, gene-modified cancer vaccines.
Sequential Treatment of Anemia in Ulcerative Colitis with Intravenous Iron and Erythropoietin (1999)

Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.
Prebiopsy localization of non-palpable breast cancer. (1990)

Mammographic screening results in the detection of non-palpable breast lesions which demand surgical excision after careful marking by the radiologist. The main localization procedures are described as well as their preferential indications. Stereotaxic localization and harpoon technique are analysed more in detail and so are their advantages and inconvenients. Continuous research for the best compromise patient tolerance/efficiency/costs of the method remains an absolute necessity. To this regard the use of a carbon material suspension described in 1983 by Svane appears to be a really interesting and promising preoperative tracer.
Chemokine (C-C Motif) Ligand 20, a Potential Biomarker for Graves' Disease, Is Regulated by Osteopontin (2013)

These results demonstrated that CCL20 might serve as a biomarker for GD and suggested the possible role of OPN in induction of CCL20 expression.
Protective Effects of Specific Immunity to Viral Neuraminidase on Influenza Virus Infection of Mice (1968)

Antibody specific for viral neuraminidase can be demonstrated in mice following (i) pulmonary infection with influenza virus, (ii) immunization with ultraviolet-in-activated influenza virus, (iii) immunization with isolated neuraminidase of influenza A(2) virus, and (iv) passive immunization with sera of rabbits immunized with isolated A(2) neuraminidase. Neuraminidase antibody produced by any of these methods exerts a profound inhibiting effect on virus replication in the lungs of mice challenged with strains of virus having homologous neuraminidase protein, even in the absence of hemagglutinating inhibiting antibody to the challenge virus, and results in markedly decreased pulmonary virus titers and diminished lung lesions. These observations suggest that antineuraminidase immunity may play a significant role in the protection against influenza virus challenge observed in mice after infection or artificial immunization.
Immunotoxins: A New Approach to Cancer Therapy (1983)

Conjugates of tumor-reactive antibody and toxins (immunotoxins) have been used to eradicate tumor cells in vitro and in vivo. Such immunotoxins are highly effective in killing murine leukemic cells in infiltrated bone marrow and should be useful in the bone marrow rescue approach for the treatment of cancer. Similar immunotoxins injected parentally can help to induce prolonged remissions in leukemic mice, and antigen-containing immunotoxins can induce immunologic unresponsiveness in vitro in normal murine splenocytes. Thus, long-range goals for the parental use of immunotoxins include the killing of cancer cells in vivo and the modulation of the immune response for therapeutic purposes.
Identification of a noncatalytic cGMP-binding domain conserved in both the cGMP-stimulated and photoreceptor cyclic nucleotide phosphodiesterases. (1990)

Partial amino acid sequence has been determined for the cone, alpha' subunit of the bovine photoreceptor cyclic nucleotide phosphodiesterase (PDE) and deduced from nucleotide sequences of a partial cDNA clone. These sequences identify the alpha' subunit as the product of a gene that is distinct from those encoding the alpha or beta subunits of the membrane-associated rod photoreceptor PDE. Comparisons between the recently determined cGMP-stimulated-PDE sequence and those of the alpha and alpha' photoreceptor PDE subunits reveal an unexpected sequence similarity. In addition to the catalytic domain conserved in eukaryotic PDEs, all three PDEs possess a second conserved segment of approximately 340 residues that contains two internally homologous repeats. Limited proteolysis and direct photolabeling studies indicate that the noncatalytic, cGMP-binding site(s) in the cGMP-stimulated PDE is located within this conserved domain, suggesting that it also may serve this function in the photoreceptor PDEs. Moreover, other PDEs that do not bind cGMP at noncatalytic sites do not contain this conserved domain. The function of the conserved segment in the photoreceptor PDEs is not known, but the homology to allosteric sites of the cGMP-stimulated PDE suggests a role in cGMP binding and modulation of enzyme activity.
Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate (2002)

Heterochromatin in the model plant Arabidopsis thaliana is confined to small pericentromeric regions of all five chromosomes and to the nucleolus organizing regions. This clear differentiation makes it possible to study spatial arrangement and functional properties of individual chromatin domains in interphase nuclei. Here, we present the organization of Arabidopsis chromosomes in young parenchyma cells. Heterochromatin segments are organized as condensed chromocenters (CCs), which contain heavily methylated, mostly repetitive DNA sequences. In contrast, euchromatin contains less methylated DNA and emanates from CCs as loops spanning 0.2-2 Mbp. These loops are rich in acetylated histones, whereas CCs contain less acetylated histones. We identified individual CCs and loops by fluorescence in situ hybridization by using rDNA clones and 131 bacterial artificial chromosome DNA clones from chromosome 4. CC and loops together form a chromosome territory. Homologous CCs and territories were associated frequently. Moreover, a considerable number of nuclei displayed perfect alignment of homologous subregions, suggesting physical transinteractions between the homologs. The arrangement of interphase chromosomes in Arabidopsis provides a well defined system to investigate chromatin organization and its role in epigenetic processes.