gebhart/patrepeval huggingface dataset:
C7L Family of Poxvirus Host Range Genes Inhibits Antiviral Activities Induced by Type I Interferons and Interferon Regulatory Factor 1 (2012)

Vaccinia virus (VACV) K1L and C7L function equivalently in many mammalian cells to support VACV replication and antagonize antiviral activities induced by type I interferons (IFNs). While K1L is limited to orthopoxviruses, genes that are homologous to C7L are found in diverse mammalian poxviruses. In this study, we showed that the C7L homologues from sheeppox virus and swinepox virus could rescue the replication defect of a VACV mutant deleted of both K1L and C7L (vK1L(-)C7L(-)). Interestingly, the sheeppox virus C7L homologue could rescue the replication of vK1L(-)C7L(-) in human HeLa cells but not in murine 3T3 and LA-4 cells, in contrast to all other C7L homologues. Replacing amino acids 134 and 135 of the sheeppox virus C7L homologue, however, made it functional in the two murine cell lines, suggesting that these two residues are critical for antagonizing a putative host restriction factor which has some subtle sequence variation in human and murine cells. Furthermore, the C7L family of host range genes from diverse mammalian poxviruses were all capable of antagonizing type I IFN-induced antiviral activities against VACV. Screening of a library of more than 350 IFN-stimulated genes (ISGs) identified interferon-regulated factor 1 (IRF1) as an inhibitor of vK1L(-)C7L(-) but not wild-type VACV. Expression of either K1L or C7L, however, rendered vK1L(-)C7L(-) resistant to IRF1-induced antiviral activities. Altogether, our data show that K1L and C7L antagonize IRF1-induced antiviral activities and that the host modulation function of C7L is evolutionally conserved in all poxviruses that can readily replicate in tissue-cultured mammalian cells.
Immunosuppressive agents in organ transplantation: past, present, and future. (2000)

The development of immunosuppressive agents reflects the progress in understanding the cellular and molecular mechanisms which mediate allograft rejection. Six paradigms represent the evolution of immunosuppressive strategies for organ transplantation. The proliferation paradigm advances agents which interrupt lymphocyte cell division (azathioprine, cyclophosphamide, mycophenolic acid). The depletion paradigm conscripts drugs that bind to lymphocyte cell surface markers, thereby producing cell lysis and/or inactivation (polyclonal ATGAM and thymoglobulin, and monoclonal OKT3 antilymphocyte antibodies). The cytokine paradigm uses agents that interrupt lymphocyte maturational events; eg, synthesis (calcineurin inhibitors: cyclosporine/tacrolimus), binding to surface receptors (anti-CD25 mAbs), or signal transduction phases of cytokine stimulation (sirolimus). The introduction of calcineurin inhibitors markedly reduces the rate of acute rejection episodes and increases short-term graft survival rates; nephrotoxicity and chronic allograft attrition remain as unanswered challenges. The cyclosporine A (CsA) sparing property of sirolimus permits the use of lower exposure to calcineurin agents, allows for early withdrawal of steroid therapy, and may delay allograft senescence. Furthermore, the combination of SRL with anti-IL-2R mAbs proffers an induction approach which allows prolonged periods of holiday from calcineurin inhibitors. To address the tissue nonselectivity of the calcineurin and mTOR inhibitors, which presumably causes the drug toxicities, new agents are being developed to selectively inhibit the T cell target Janus Kinase 3. In the costimulation paradigm, the accessory signals generated by antigen-presenting cells are interrupted by distinct agents: the receptor conjugate CTLA4-immunoglobulin and anti-B7 or anti-CD40 ligand mAbs. Another set of drugs (selectin blocking agents, anti-ICAM-1 antisense deoxy oligonucleotides, and the lymphocyte homing inhibitor FTY720) seeks to modulate the ischemia-reperfusion injury, which exacerbates cytokine-mediated events in the donor and the subsequent procurement injury and may also accelerate the progression of transplant senescence. Finally, the transplantation tolerance paradigm is based on the development of strategies which distort alloimmune recognition by antigen reactive cells (MHC peptides or proteins), produce anergy (costimulation blockers), functional inactivation, or deletion of antigen-reactive cells (donor bone marrow infusions and gene therapy). Presently, the optimal immunosuppressive strategy uses combinations of agents that act in synergistic fashion to provide the potency, freedom from toxic reactions, convenience of administration, and cost appropriate for the individual patient.
PA-1, a human cell model for multistage carcinogenesis: oncogenes and other factors. (1988)

We have developed a cell system which utilizes the human teratocarcinoma cell line PA-1, from which we have characterized four stages of tumor progression. Soon after establishment in culture PA-1 cells revert and are no longer tumorigenic in athymic nude mice. Later, PA-1 cells as they are passaged in culture, become tumorigenic at passage 100. The transition from nontumorigenic to tumorigenic is the result of the biological effects of an activated N-ras oncogene and can be reproduced by transfection of the cloned oncogene into preneoplastic PA-1 cells. Certain preneoplastic cells (prior to passage 100) in this series are susceptible to transformation by single oncogenes while others are not. In studying the basis of this susceptibility to single oncogene induced transformation we have found that somatic cell hybrids between preneoplastic cells which can suppress ras-induced transformation and ras-transformed cells are non-tumorigenic. Therefore, we believe that the progression from ras suppressing to ras susceptibility may be due to the inactivation of a trans-dominant suppressor gene. Our system has identified at least three steps which lead to tumorigenicity; establishment of growth past senesence, activation of a ras oncogene, and inactivation of an oncogene suppressor function. Further genetic alterations are necessary for tumor dissemination and metastasis.
Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression (2011)

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis.
Molecular genetic research into carbamoyl‐phosphate synthase I: Molecular defects and linkage markers (1998)

Deficiency of the hepatic enzyme carbamoyl-phosphate synthase I (CPSI), results in lethal or near-lethal hyperammonaemia. As part of our work on CPSI deficiency we have explored the development of markers for prenatal diagnosis, and the determination of molecular defects resulting in CPSI deficiency. We have determined a set of highly informative microsatellite markers flanking the CPSI gene. We have found 14 mutations in individuals with CPSI deficiency. During our mutation studies, we have made extensive use of cell lines not normally expressing CPSI through amplification of 'illegitimate' transcripts. We summarize these findings and review our current understanding of this important enzyme.
Rhodothermus obamensis sp. nov., a Modern Lineage of Extremely Thermophilic Marine Bacteria (1996)

A novel extremely thermophilic bacterium was isolated from a shallow marine hydrothermal vent environment (depth, 22 m) in Tachibana Bay, Nagasaki Prefecture, Japan. The cells of this organism were gram-negative rods. Growth occurred at temperatures between 50 and 85 degrees C (optimum temperature, 80 degrees C; doubling time at optimum temperature, 90 min), at pH 5.5 and 9.0 (optimum pH, 7.0), and in the presence of 1 and 5% NaCl (optimum NaCl concentration, 3%). The new isolate was an aerobic heterotroph which utilized the following compounds as sole energy and carbon sources: yeast extract, peptone, starch, casein, Casamino Acids, a variety of sugars, some carboxylic acids, and amino acids. As determined by a sequence analysis of the 16S rRNA, the new isolate belongs to the genus Rhodothermus and represents a modern lineage of extreme thermophiles within the domain Bacteria. On the basis of the physiological and molecular properties of the new isolate, we describe a new species, Rhodothermus obamensis. The type strain of R. obamensis is strain OKD7 (= JCM 9785).
IMPROVED OUTCOME WITH HYPOTENSIVE RESUSCITATION OF UNCONTROLLED HEMORRHAGIC SHOCK IN A SWINE MODEL (1992)

Recent animal studies have shown that aggressive saline infusion may produce significant mortality in models of moderately severe (20–30 mL/kg) uncontrolled hemorrhage. The postulated mechanism is an increase in hemorrhage that accompanies restoration of normal blood pressure. Although aggressive saline infusion and restoration of blood pressure appear indicated when hemorrhage is potentially lethal (40–45 mL/kg), we hypothesized that the attempt to restore blood pressure with aggressive saline infusion would not improve survival. This study used a swine model of severe uncontrolled hemorrhagic shock to compare the effects of resuscitation to mean pressures of 40 and 80 mm Hg. Twenty-four immature swine, each with a surgical steel aortotomy wire in place, were bled rapidly from a femoral artery catheter to a mean arterial pressure (MAP) of 30 mm Hg. The aortotomy wire was then pulled, producing a 4-mm aortic tear and free intraperitoneal hemorrhage. When the pulse pressure decreased to 5 mm Hg, saline infusion was begun at 6 mL/ kg/minute and continued as needed to maintain the following endpoints: group I (MAP = 40 mm Hg), group II (MAP = 80 mm Hg), and group III (no resuscitation). After a maximum saline infusion of 90 mL/kg, the infusate was changed to shed blood at 2 mL/kg/minute. Data were compared using analysis of variance and Fisher's exact test. One-hour survival was 87.5%, 37.5%, and 12.5% for groups I, II, and III, respectively. Intraperitoneal hemorrhage for the three groups was 8.2 mL/kg, 39.9 mL/kg, and 6.7 mL/kg. The amount of saline infused was 55.8 mL/kg in group I and 90 mL/kg in group II. We conclude that the attempt to restore normotension with aggressive saline infusion markedly increases hemorrhage volumes and fails to improve survival in the setting of severe uncontrolled hemorrhage. Maintenance of the hypotensive state with judicious saline administration causes less blood loss and may be preferable before definitive surgical repair of the bleeding site.
Dialkylformamldines: depurination resistant N6-protecting group for deoxyadenosine (1983)

Sterically hindered N6-dialkylformamidine protected deoxyadenosine is more stable to acidic depurination than N6-benzoyldeoxyadenosine and is potentially a valuable protecting group in the synthesis of deoxyoligonucleotides.
Physical properties of hyaluronic acid and hydroxypropylmethylcellulose in solution: Evaluation of coating ability (1994)

Abstract Hyaluronic acid (HA) and hydroxypropylmethylcellulose (HPMC) in buffered saline are “viscoelastics” used in ophthalmic surgery to prevent mechanical damage to delicate eye structures and to form a protective coating over corneal endothelium. HA is a high molecular weight polysaccharide that exhibits decreasing viscosity at increased shear rates. HPMC is a cellulose derivative that exhibits low surface tension. This study examines the physical properties of HA and HPMC solutions and attempts to correlate these properties with the ability of those macromolecules to coat and protect ocular structures. Results presented in this article suggest mixtures of HA and HPMC exhibit low surface tension and ease of aspiration characteristics that are desired in viscoelastic materials. For this reason a blend of these two macromoleculars offers handling advantages over each of these individual macromolecules. © 1994 John Wiley &amp; Sons, Inc.
Biological and Immunological Relations among Human Parvovirus B19 Genotypes 1 to 3 (2007)

The human parvovirus B19 is now divided into three genotypes: type 1 (prototype), type 2 (A6- and LaLi-like), and type 3 (V9-like). In overall DNA sequence, the three virus types differ by approximately 10%. The most striking DNA dissimilarity, of >20%, is observed within the p6 promoter region. Because of the scarcity of data on the biological activities and pathogenetic potentials of virus types 2 and 3, we examined the functional characteristics of these virus types. We found the activities of the three p6 promoters to be of equal strength and to be most active in B19-permissive cells. Virus type 2 capsid protein VP2, alone or together with VP1, was expressed with the baculovirus system and was shown to assemble into icosahedral parvovirus-like particles, which were reactive in the hemagglutination assay. Furthermore, sera containing DNA of any of the three B19 types were shown to hemagglutinate. The infectivities of these sera were examined in two B19-permissive cell lines. Reverse transcription-PCR revealed synthesis of spliced B19 mRNAs, and immunofluorescence verified the production of NS and VP proteins in the infected cells. All three genotypes showed similar functional characteristics in all experiments performed, showing that the three virus types indeed belong to the same species, i.e., human parvovirus B19. Additionally, the antibody activity in sera from B19 type 1- or type 2-infected subjects (long-term immunity) was examined with homo- and heterologous virus-like particles. Cross-reactivity of 100% was observed, indicating that the two B19 genotypes comprise a single serotype.
Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism (2004)

Glycoprotein D (gD) determines which cells can be infected by herpes simplex virus (HSV) by binding to one of the several cell surface receptors that can mediate HSV entry or cell fusion. These receptors include the herpesvirus entry mediator (HVEM), nectin-1, nectin-2, and sites in heparan sulfate generated by specific 3-O-sulfotransferases. The objective of the present study was to identify residues in gD that are critical for physical and functional interactions with nectin-1 and nectin-2. We found that double or triple amino acid substitutions at positions 215, 222, and 223 in gD caused marked reduction in gD binding to nectin-1 and a corresponding inability to function in cell fusion or entry of HSV via nectin-1 or nectin-2. These substitutions either enhanced or did not significantly inhibit functional interactions with HVEM and modified heparan sulfate. These and other results demonstrate that different domains of gD, with some overlap, are critical for functional interactions with each class of entry receptor. Viral entry assays, using gD mutants described here and previously, revealed that nectins are the principal entry receptors for selected human cell lines of neuronal and epithelial origin, whereas HVEM or nectins could be used to mediate entry into a T lymphocyte line. Because T cells and fibroblasts can be infected via HVEM, HSV strains carrying gD mutations that prevent entry via nectins may establish transient infections in humans, but perhaps not latent infections of neurons, and are therefore candidates for development of safe live virus vaccines and vaccine vectors.
Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements (2001)

PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been annotated by human experts, and a popular measure of retrieval accuracy (ROC) that can be normalized to take on values between 0 (worst) and 1 (best). The modifications we consider novel improve the ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the benefits from four modifications we included in the 'baseline' version, even though they were not implemented in PSI-BLAST version 2.0. The improvement in accuracy was confirmed on a small second test set. This test involved analyzing three protein families with curated lists of true positives from the non-redundant protein database. The modification that accounts for the majority of the improvement is the use, for each database sequence, of a position-specific scoring system tuned to that sequence's amino acid composition. The use of composition-based statistics is particularly beneficial for large-scale automated applications of PSI-BLAST.
Bone and joint diseases in inflammatory bowel disease (1998)

The intestinal and articular systems are closely linked in inflammatory bowel disease. Clinical and immunological studies support an important aetio-pathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This paper will focus on the prevalence, aetio-pathogenesis and treatment of arthritis (peripheral, sacroiliitis and spondylitis) and osteoporosis in inflammatory bowel disease.
The − 11391G/APolymorphism of the Adiponectin Gene Promoter is Associated with Metabolic Syndrome Traits and the Outcome of an Energy-restricted Diet in Obese Subjects (2008)

Adiponectin is an adipose tissue-specific hormone that is commonly decreased in obese subjects. Furthermore, single-nucleotide polymorphisms (SNPs) of the adiponectin gene have been associated with metabolic phenotypes. The present study investigated whether the adiponectin gene promoter variant -11391 G/A (rs17300539) could predict the risk of developing traits characterizing the metabolic syndrome (MetS) and the impact of weight management. The -11391 G/A SNP was genotyped in 180 Spanish volunteers (BMI: 31.4+/-3.2 kg/m (2); age: 35+/-5 years). Clinical measurements were determined at baseline, following an 8-week low-calorie diet (LCD), and at 32 and 60 weeks. At baseline, the GG genotype was associated with higher HOMA-IR, insulin and triacylglyceride concentrations than other genotypes (p<0.05) and was also related with a higher risk of insulin resistance (OR: 2.437, p=0.025) and MetS clinical manifestations (OR: 3.236, p=0.003). Following the LCD, the increased risk in GG subjects compared with others disappeared (p>0.05). By 32 weeks after dietary therapy (n=84), GG carriers had recovered the risk of metabolic comorbidities (OR: 2.420, p=0.043). This risk was even more evident after 60 weeks (OR: 2.875, p=0.014). These data show an increased risk of insulin resistance and MetS complications in obese subjects of the -11391 GG genotype. The risk was markedly reduced during an energy-restricted diet, but was not sustained. Carriage of the A allele therefore confers protection from weight regain, and the effect is particularly evident 32-60 weeks after the dietary intervention, when improvement in GG subjects had disappeared.
Direct observation of DNA chain orientation and relaxation by electric birefringence: Implications for the mechanism of separation during pulsed-field gel electrophoresis (1989)

Electric birefringence studies on DNA's of lengths N trapped in an agarose gel show a dynamic behavior which is more complex than predicted by the biased reptation theory: An ${\mathrm{N}}^{3}$ dependence of the two longest relaxation times is observed as expected, but a third short time, of large amplitude, varies as ${\mathrm{N}}^{1.5}$, suggesting that it is due to the Zimm-Rouse time of the chains. Moreover, the orientation under low electric field E varies as ${\mathrm{E}}^{\mathrm{\ensuremath{-}}1}$. Thus, successive elongations and retractions of the primitive path may play a major role in the separation of large DNA's by pulsed-field gel electrophoresis.
Power Distribution Engineering: Fundamentals and Applications (1994)

PREFACE UTILITY DISTRIBUTION SYSTEM DESIGN AND CHARACTERISTICS 1 Introduction Design Overhead vs. Underground Grounding Load and Fault Characteristics Questions TRANSFORMERS AND REGULATORS Transformers Distribution Transformer Connections Regulators Questions APPLICATION OF CAPACITORS FOR DISTRIBUTION SYSTEMS 64 Fundamentals Voltage Rise and Voltage Drop Losses Questions DISTRIBUTION OVERCURRENT PROTECTION Introduction Characteristics of Devices Coordination of Devices Questions SURGE ARRESTERS CharaC't:eristics of Lightning System Overvoltage Silicon Carbide vs. MOV Arresters Classes of Arresters Arrester Selection Insulation Coordination Traveling Waves Line Protection Induced Strikes Reference Questions DISTRIBUTION RELIABILITY Introduction Fundamentals Power Quality Factors Affecting Reliability Reference Questions POWER QUALITY FUNDAMENTALS Introduction Definitions Voltage Quality Sensitive Loads Power Line Conditioning Electromagnetic Fields Stray Voltage Reference Questions DISTRIBUTION ECONOMICS Introduction Time Value of Money Annual Carrying Charge Definition of Terms Economic Evaluations Reference- Questions INDEX
Microchip technology in mass spectrometry (2009)

Microfabrication of analytical devices is currently of growing interest and many microfabricated instruments have also entered the field of mass spectrometry (MS). Various (atmospheric pressure) ion sources as well as mass analyzers have been developed exploiting microfabrication techniques. The most common approach thus far has been the miniaturization of the electrospray ion source and its integration with various separation and sampling units. Other ionization techniques, mainly atmospheric pressure chemical ionization and photoionization, have also been subject to miniaturization, though they have not attracted as much attention. Likewise, all common types of mass analyzers have been realized by microfabrication and, in most cases, successfully applied to MS analysis in conjunction with on-chip ionization. This review summarizes the latest achievements in the field of microfabricated ion sources and mass analyzers. Representative applications are reviewed focusing on the development of fully microfabricated systems where ion sources or analyzers are integrated with microfluidic separation devices or microfabricated pums and detectors, respectively. Also the main microfabrication methods, with their possibilities and constraints, are briefly discussed together with the most commonly used materials.