gebhart/patrepeval huggingface dataset:
Transcriptional and posttranscriptional regulation of alpha 1,3- galactosyltransferase in activated endothelial cells results in decreased expression of Gal alpha 1,3Gal (1998)

Gal alpha 1,3Gal carbohydrate residues are present in the glycoproteins and glycolipids of lower mammals, and appear to be involved in the binding specificity of several membrane receptors. We report here that endothelial cells stimulated with lipopolysaccharide or inflammatory cytokines modulate their expression of UPD-Gal: beta-D-Gal alpha 1,3-galactosyltransferase (alpha 1,3GT), the Golgi enzyme that attaches a galactose in alpha 1,3 configuration to an N-acetyllactosamine acceptor. Upon activation, the steady state level of mRNA is transiently increased, the modifications being paralleled by a transcriptional regulation of the gene. Cell-associated enzyme activity, on the other hand, falls rapidly after activation, before being up- and downregulated with kinetics that parallel those of the mRNA, and after 3 days reaches a level representing 40-60% of the activity in cells before activation. Overall Gal alpha 1,3Gal expression at the cell surface follows enzyme activity, except that it is insensitive to the rapid and transient reduction of activity occurring shortly after activation. This reduced alpha 1,3GT activity in stimulated EC is correlated with lower stability of the protein, and with a switch in the expression of the isoform pattern, isoform 1 being predominant in resting cells whereas after activation it is isoform 2 that predominates. The two isoforms, however, appear to have similar intrinsic stability, so that the reduced stability of the enzyme in activated EC probably results from an induced proteolytic degradation pathway.
Pharmacodynamics of (−)-β-2′,3′-Dideoxy-3′-Thiacytidine in Chronically Virus-Infected Woodchucks Compared to Its Pharmacodynamics in Humans (1998)

The pharmacodynamics of (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) was studied in chronically woodchuck hepatitis virus-infected woodchucks and compared to that in previous studies in hepatitis B virus (HBV)-infected humans. Net depletion rates of serum virus DNA in woodchucks receiving 3TC were modeled as a sum of an exponentially declining virus input and a first-order elimination. Preceding shoulders and pseudo-first-order virus half-lives in serum ranged from 1 to 7 days and were dose dependent. Higher plasma 3TC concentrations were needed in woodchucks for virus depletion similar to that attained in humans. Human HBV depletion curves from a previous clinical study with 3TC (>/=100 mg per day) were described by a biexponential relationship. The average half-life value in humans, normalized to fraction of area under the serum virus load-time curve, was similar to the average half-life value observed in woodchucks given the highest 3TC dose (2.4 and 2.0 days, respectively). On cessation of therapy, virus load rebounds in woodchucks were dose dependent and resembled posttherapy virus "flares" reported to occur in humans. The estimates of drug exposures that could lead to optimal antiviral effects presented indicate that 3TC should not be underdosed and compliance should be monitored. The study of chronically infected woodchucks may prove useful for optimizing drug regimens for hepadnavirus infections.
Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum. (1989)

The antibody response to the Plasmodium falciparum major merozoite surface antigen (gp195) of congenic mouse strains differing in H-2 haplotype has been examined. All seven strains of mice were capable of producing gp195-specific antibodies. Generalized immune recognition of gp195 by mice of diverse H-2 haplotypes distinguished gp195 from the P. falciparum circumsporozoite protein and the 230-kDa and 48/45-kDa gamete surface antigens. However, the H-2 genetic locus appeared to influence the specificity of gp195-specific antibodies. Immunoblot patterns of mouse sera with parasite antigens revealed a complex pattern of reactivity with terminal and intermediate processing fragments of gp195. The majority of immunoblot bands observed were similar for all of the mouse strains; however, there were several strains that additionally recognized a few unique fragments or displayed more intense reactivities with specific processing fragments. These results suggest that while individuals of diverse major histocompatibility complex makeup are capable of recognizing the gp195 antigen, the recognition of specific gp195 B-cell and T-cell epitopes may be under control of the major histocompatibility complex.
Transient Dominant Selection for the Modification and Generation of Recombinant Infectious Bronchitis Coronaviruses (2008)

We have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV genome is inserted into the vaccinia virus genome under the control of a T7 promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has the advantage that modifications can be introduced into the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. Here we describe the use of transient dominant selection as a method for introducing modifications into the IBV cDNA. We have used it successfully for the substitution of specific nucleotides, deletion of genomic regions, and the exchange of complete genes. Infectious recombinant IBVs are generated in situ following the transfection of vaccinia virus DNA containing the modified IBV cDNA into cells infected with a recombinant fowlpox virus expressing T7 DNA-dependent RNA polymerase.
A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen (2003)

Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen, occur in 24-60% of all patients with systemic lupus erythematosus. Anti-Ro antibodies are correlated with photosensitivity and cutaneous lesions in these patients and with neonatal lupus, a syndrome in which mothers with anti-Ro antibodies give birth to children with complete congenital heart block and photosensitive skin lesions. In higher eukaryotes, the Ro protein binds small RNAs of unknown function known as Y RNAs. Because the Ro protein also binds misfolded 5S rRNA precursors, it is proposed to function in a quality-control pathway for ribosome biogenesis. Consistent with a role in the recognition or repair of intracellular damage, an orthologue of Ro in the radiation-resistant eubacterium Deinococcus radiodurans contributes to survival of this bacterium after UV irradiation. Here, we show that mice lacking the Ro protein develop an autoimmune syndrome characterized by anti-ribosome antibodies, anti-chromatin antibodies, and glomerulonephritis. Moreover, in one strain background, Ro-/- mice display increased sensitivity to irradiation with UV light. Thus, one function of this major human autoantigen may be to protect against autoantibody development, possibly by sequestering defective ribonucleoproteins from immune surveillance. Furthermore, the finding that mice lacking the Ro protein are photosensitive suggests that loss of Ro function could contribute to the photosensitivity associated with anti-Ro antibodies in humans.
Power system bidding tournaments for a deregulated environment (2002)

We describe certain tools for understanding and operating power systems in a deregulated environment. Many of the current models for this competitive market that employ an independent system operator (ISO) for controlling transmission, ensuring fair access and security, and providing a spot market for power are studied. This centrally dispatched power pool also ensures that generation meets demand based on bids submitted daily from independent generators (and from customers offering interruptible loads). Currently, most ISO bidding models allow only a single bid per day. We present an asynchronous bidding scheme as a possible alternative. In particular, we examine the effects of including a feedback mechanism such that upon receiving generation levels from the ISO, independent generators (IGs) be allowed to modify their bid if they so desire. This competitive or 'sequential' bidding process should be allowed to take place each day for a predetermined period of time; in this way, IGs will have a chance to compete and hopefully optimize their profit margins. The paper also discusses the development tools necessary for examining the effects of different bidding processes on the ISO model and evaluating their capability of driving the market to an efficient state of operation.
Physical and biological mechanisms of direct plasma interaction with living tissue (2009)

Mechanisms of plasma interaction with living tissues and cells can be quite complex, owing to the complexity of both the plasma and the tissue. Thus, unification of all the mechanisms under one umbrella might not be possible. However, the authors are attempting to make first steps in this direction. In this paper, analysis of interaction of floating electrode dielectric barrier discharge (FE-DBD) with living tissues and cells is presented and biological and physical mechanisms are discussed. In physical mechanisms, charged species are identified as the major contributors to the desired effect and a mechanism of this interaction is proposed. Biological mechanisms are also addressed and a hypothesis of plasma selectivity and its effects is offered.
Selection of Virus Variants and Emergence of Virus Escape Mutants after Immunization with an Epitope Vaccine (1998)

In this report, we assessed the evolution of the cytotoxic T-lymphocyte (CTL) response induced by an epitope vaccine. In two macaques immunized with a mixture of lipopeptides derived from simian immunodeficiency virus (SIV) Nef and Gag proteins, CTL responses were directed against the same, single epitope of the Nef protein (amino acids 128 to 137) presenting an alanine at position 136 (Nef 128-137/136A). However, after 5 months of SIV infection, peripheral blood mononuclear cells from both macaques lost their ability to be stimulated by autologous SIV-infected cells while still retaining their capacity to generate cytotoxic responses after specific Nef 128-137/136A peptide stimulation. The sequences of the pathogenic viral isolate used for the challenge showed a mixture of several variants. Within the Nef epitopic sequence from amino acids 128 to 137, 82% of viral variants expressed the epitopic peptide Nef 128-137/136A; the remaining variants presented a threonine at position 136 (Nef 128-137/136T). In contrast, sequence analysis of cloned proviral DNA obtained from both macaques 5 months after SIV challenge showed a different pattern of quasi-species variants; 100% of clones presented a threonine at position 136 (Nef 128-137/136T), suggesting the disappearance of viral variants with an alanine at this position under antiviral pressure exerted by Nef 128-137/136A-specific CTLs. In addition, 12 months after SIV challenge, six of eight clones from one macaque presented a glutamic acid at position 131 (Nef 128-137/131E+136T), which was not found in the infecting isolate. Furthermore, CTLs generated very early after SIV challenge were able to lyse cells sensitized with the Nef 128-137/136A epitope. In contrast, lysis was significantly less effective or even did not occur when either the selected peptide Nef 128-137/136T or the escape variant peptide Nef 128-137/131E+136T was used in a target cell sensitization assay. Dose analysis of peptides used to sensitize target cells as well as a major histocompatibility complex (MHC)-peptide stability assay suggested that the selected peptide Nef 128-137/136T has an altered capacity to bind to the MHC. These data suggest that CTL pressure leads to the selection of viral variants and to the emergence of escape mutants and supports the fact that immunization should elicit broad CTL responses.
The design of the MasPar MP-1: a cost effective massively parallel computer (2002)

The design and implementation of the MasPar MP-1 are described. It is a general-purpose massively parallel computer system that achieves peak computation rates beyond a billion floating point operations per second yet is priced like a minicomputer. The architecture of the MP-1 is scalable in a way that permits its computational power to be increased along two axes: the performance of each processor and the number of processors. This feasibility is well matched to VLSI technology where circuit densities continue to increase at a rapid rate. The scalable nature of massively parallel systems protects the customers' software investment while providing an increasing performance in successive products. The array control unit, processor array, processor elements, memory, X-Net mesh interconnect, and multistage crossbar interconnect are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A mannose receptor mediates mannosyl-rich glycoprotein-induced mitogenesis in bovine airway smooth muscle cells. (1994)

The putative mannose receptor (MR), previously implicated in mannosyl-rich glycoprotein-induced mitogenesis in bovine airway smooth muscle (ASM) cells, was studied to determine its properties. Specific binding of the mitogenic neoglycoprotein, mannosylated bovine serum albumin (Man-BSA) to ASM cells was saturable, with an apparent Kd = 5.0 x 10(-8) M. Cell-bound ManBSA-colloidal gold conjugate was localized by electron microscopy to clathrin-coated pits on the cell surface, and was found to undergo internalization to endosomes; this was inhibitable by weak bases and swainsonine, that also inhibited ligand-induced mitogenesis. The ASM-MR, isolated by mannose-affinity chromatography, had the same apparent molecular mass as the macrophage (Mø) MR (M(r) = 175 kD), and was immunoprecipitated by an anti-MøMR immune serum. This antiserum blocked 125I-labeled-ManBSA binding to intact ASM cells, stimulated mitogenesis, and immunolocalized the ASM-MR in cytoplasmic vesicles compatible with endosomes. A monoclonal antibody directed against the MøMR also reacted with the ASM-MR; like the polyclonal antibodies, it stimulated mitogenesis as effectively as beta-hexosaminidases. These data indicate that the ASM-MR shares a number of functional and structural properties with the MøMR and suggest that similar receptors may have different main functions in different cells.
Kinetic properties of the glucose‐6‐phosphate and 6 phosphogluconate dehydrogenases from Corynebacterium glutamicum and their application for predicting pentose phosphate pathway flux in vivo (2000)

The glucose-6-phosphate (Glc6P) and 6-phosphogluconate (6PG) dehydrogenases of the amino-acid-producing bacterium Corynebacterium glutamicum were purified to homogeneity and kinetically characterized. The Glc6P dehydrogenase was a heteromultimeric complex, which consists of Zwf and OpcA subunits. The product inhibition pattern of the Glc6P dehydrogenase was consistent with an ordered bi-bi mechanism. The 6PG dehydrogenase was found to operate according to a Theorell-Chance ordered bi-ter mechanism. Both enzymes were inhibited by NADPH and the 6PG dehydrogenase additionally by ATP, fructose 1,6-bisphosphate (Fru1,6P2), D-glyceraldehyde 3-phosphate (Gra3P), erythrose 4-phosphate and ribulose 5-phosphate (Rib5P). The inhibition by NADPH was considered to be most important, with inhibition constants of around 25 microM for both enzymes. Intracellular metabolite concentrations were determined in two isogenic strains of C. glutamicum with plasmid-encoded NAD- and NADP-dependent glutamate dehydrogenases. NADP+ and NADPH levels were between 130 microM and 290 microM, which is very much higher than the respective Km and Ki values. The Glc6P concentration was around 500 microM in both strains. The in vivo fluxes through the oxidative part of the pentose phosphate pathway calculated on the basis of intracellular metabolite concentrations and the kinetic constants of the purified enzymes determined in vitro were in agreement with the same fluxes determined by NMR after 13C-labelling. From the derived kinetic model thus validated, it is concluded that the oxidative pentose phosphate pathway in C. glutamicum is mainly regulated by the ratio of NADPH and NADP+ concentrations and the specific enzyme activities of both dehydrogenases.
White Matter Reduction in the Parahippocampal Gyrus of Patients With Schizophrenia (1987)

<h3>To the Editor.—</h3> A recent postmortem study by Brown et al<sup>1</sup>compared morphometric measurements obtained from photographs of coronal brain slices of patients with schizophrenia and affective disorder. In the schizophrenic group, the lateral ventricles were larger, with the difference between the groups being most marked in the temporal lobe, where the temporal horn cross-sectional area was 97% larger. This difference was associated with a significantly lower average thickness of the nearby parahippocampal cortex (by 11%). The findings further emphasize the temporal lobe as a possible focus of the disease process in schizophrenia. <h3>Patients and Methods.—</h3> Histologic material stained with phosphotungstic acidhematoxylin at this anatomical level was also available from some of the same brains. Five areas of the medial temporal lobe were demarcated by specific criteria (Figure) and measured (with the diagnosis unknown) at x 10 magnification by computerized image analysis. The sample was selected as previously described
Why do farmers have so little interest in futures markets? (2002)

Abstract A farm financial model with leverage and investment in two farm enterprises is specified. The model is extended to incorporate futures hedging and the Separation Theorem is used to show that optimal hedging is zero. The assumption of a risk‐free asset is relaxed and, while this leads to a violation of the Separation Theorem, the result that optimal hedging is zero is maintained providing that futures markets are efficient. It is concluded that if capital markets are efficient then farmers will have little interest in futures markets except to speculate.
Identification of Homologous Biologically Active Sites on the N-Terminal Domain of Laminin Alpha Chains (2001)

Laminin, a multifunctional glycoprotein of the basement membrane, consists of three different subunits, alpha, beta, and gamma chains. To date, five different alpha chains have been identified. N-terminal domain VI in the alpha1 chain has various biological activities. Here we screened biologically active sequences on domain VI of the laminin alpha2, alpha3, and alpha5 chains using a large number of overlapping peptides. HT-1080 human fibrosarcoma cell attachment to the peptides was evaluated using peptide-coated plastic plates and peptide-conjugated Sepharose beads. We identified four cell adhesive sequences from laminin alpha2 chain domain VI, two sequences from the alpha3 chain, and two sequences from the laminin alpha5 chain. Sequences homologous to A13 (RQVFQVAYIIIKA, alpha1 chain 121-133) on all the alpha chains (FQIAYVIVKA, alpha2 chain 130-139; GQLFHVAYILIKF, alpha3 chain 96-108; FHVAYVLIKA, alpha5 chain 74-83) showed strong cell attachment activity. A5-16 (LENGEIVVSLVNGR, alpha5 chain 147-160) showed the strongest cell attachment activity in the plate assay, and the homologous peptide in the alpha3 chain promoted similar strong cell attachment activity. A5-16 and its homologous peptide in the alpha2 chain promoted moderate cell attachment, while the homologous peptide to A5-16 in the alpha1 chain did not show activity. A2-7 (SPSIKNGVEYHYV, alpha2 chain 108-120) showed cell attachment activity only in the plate assay, but homologous sequences in the alpha1, alpha3, and alpha5 chains did not promote activity. A2-7 promoted endothelial cell sprouting from aortic rings in vitro and melanoma colonization to murine lungs in vivo. However, none of the homologous peptides of A2-7 promoted experimental pulmonary metastasis by B16-BL6 melanoma cells. These results indicate that there are chain-specific active sites in domain VI of the laminin alpha chains, some of which contain conserved activities.
Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease (2011)

Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn's disease.
Heat shock protein-90, IL-6 and IL-10 in bladder cancer. (2001)

The progression of transitional-cell carcinomas of the bladder is associated with changes in general and local immune status. To understand the factors involved in the progression of transitional cell carcinoma and in the maintenance of an efficient anti-tumoural response, in this study we investigated by immunohistochemistry expression of HSP-90, IL-6 and IL-10 proteins in 56 surgical specimens obtained from superficial and deeply invasive bladder carcinomas. Of the 56 bladder carcinoma 52 (92.9%) expressed HSP-90, 48 (85.7%) IL-6 and 45 (80.3%) IL-10. High-grade and muscle-invasive tumours contained significantly higher levels of HSP-90 and IL-6 antibodies than low-grade and superficial tumours (p < 0.05). Linear regression showed a significant correlation between HSP-90 and IL-10 (p = 0.022) but not between HSP-90 and IL-6, or IL-6 and IL-10 expression. The variable quantities of HSP-90, IL-6 and IL-10 in the high-grade bladder carcinomas studied suggest that these proteins have independent functional roles and may be the immunogenic targets for an anti-tumoural response.
Histone deacetylase inhibitors: a survey of recent patents (2005)

Histone deacetylase (HDAC) inhibitors have been the subject of an intense drug discovery effort in the pharmaceutical industry and in some academic institutions over the last few years. Although, at present, only a small number of compounds have progressed to human clinical trials, the prospect of finding safe compounds useful in therapy, particularly in cancer and inflammatory processes, is still a strong motivating factor for further research efforts. A patent literature review of small organic molecules as HDAC inhibitors is presented here, as many of the major pharmaceutical companies have shown a continued effort in the field [1]. This paper provides an update on the patenting activity in 2004 – 2005 related to HDAC inhibitors.
Squamous Cell Carcinoma Arising in a Mature Cystic Teratoma (2012)

Introduction. Malignant transformation in a mature cystic teratoma of the ovary is a rare complication. Squamous cell carcinoma is the most common transformation. We describe a new case of squamous cell carcinoma arising in a mature cystic teratoma. Case Report. A premenopausal 52-year-old female patient is diagnosed with vaginal bleeding. According to examination made on the women and the pelvic scanning, 7 cm mass is found on the right adnexa of the patient. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic lymph node dissection, and debulking were the treatments completed on the patient. According to histopathological diagnosis, squamous cell carcinoma arising in a mature cystic teratoma is diagnosed as a reason for the mass in the right adnexa of the patient. Conclusion. The prognosis of the malign transformation of MCT depends on surgery stage; however it is extremely poor. The patient should receive chemotherapy regardless of stage. We have decided to administer second cycle carboplatin and paclitaxel treatments on the patient.