gebhart/patrepeval huggingface dataset:
Human pancreatic islet beta-cell destruction by cytokines involves oxygen free radicals and aldehyde production. (1996)

Cytokines produced by immune system cells infiltrating pancreatic islets are candidate mediators of islet beta-cell destruction in autoimmune insulin-dependent diabetes mellitus. Cytokine-induced islet beta-cell destruction may be mediated by reactive oxygen intermediates. To determine the possible roles of oxygen free radicals and nitric oxide (NO) as mediators of islet beta-cell destruction, we studied the relationships among cytokine-induced beta-cell destruction, production of malondialdehyde (MDA; an end product of lipid peroxidation), and production of nitrite (the stable end product of NO). The cytokine combination of interleukin-1 beta (50 U/mL), tumor necrosis factor-alpha (10(3) U/mL), and interferon-gamma (10(3) U/mL) induced significant increases in MDA and nitrite and significant decreases in insulin and DNA in islets after 60-h incubation. A novel antioxidant (lazaroid U78518E) significantly inhibited both a strong oxidant. t-butylhydroperoxide, and the combination of cytokines from inducing MDA production, but not from increasing nitrite production in the islets. Also, the lazaroid antioxidant significantly reversed the cytokine-induced decreases in insulin and DNA contents of the islet cultures. In contrast, L-NG-monomethyl arginine, an inhibitor of NO synthase, prevented cytokine-induced nitrite production, but did not prevent cytokine-induced increases in MDA and decreases in insulin and DNA in the islet cultures. In addition, the addition of MDA to the islets produced a dose-dependent decrease in their insulin and DNA contents, and this was only partially prevented by the lazaroid antioxidant. These results suggest that cytokines may be toxic to human islet beta-cells by inducing oxygen free radicals, lipid peroxidation, and aldehyde production in the islets, and that MDA is one of the cytotoxic mediators of cytokine-induced beta-cell destruction.
Development of the Expressed Ig CDR-H3 Repertoire Is Marked by Focusing of Constraints in Length, Amino Acid Use, and Charge That Are First Established in Early B Cell Progenitors (2005)

To gain insight into the mechanisms that regulate the development of the H chain CDR3 (CDR-H3), we used the scheme of Hardy to sort mouse bone marrow B lineage cells into progenitor, immature, and mature B cell fractions, and then performed sequence analysis on V(H)7183-containing Cmu transcripts. The essential architecture of the CDR-H3 repertoire observed in the mature B cell fraction F was already established in the early pre-B cell fraction C. These architectural features include V(H) gene segment use preference, D(H) family usage, J(H) rank order, predicted structures of the CDR-H3 base and loop, and the amino acid composition and average hydrophobicity of the CDR-H3 loop. With development, the repertoire was focused by eliminating outliers to what appears to be a preferred repertoire in terms of length, amino acid composition, and average hydrophobicity. Unlike humans, the average length of CDR-H3 increased during development. The majority of this increase came from enhanced preservation of J(H) sequence. This was associated with an increase in the prevalence of tyrosine. With an accompanying increase in glycine, a shift in hydrophobicity was observed in the CDR-H3 loop from near neutral in fraction C (-0.08 +/- 0.03) to mild hydrophilic in fraction F (-0.17 +/- 0.02). Fundamental constraints on the sequence and structure of CDR-H3 are thus established before surface IgM expression.
Safety considerations for deep brain stimulation: review and analysis (2005)

Deep brain stimulation has emerged rapidly as an effective therapy for movement disorders. Deep brain stimulation includes an implanted brain electrode and a pacemaker-like implanted pulse generator. The clinical application of deep brain stimulation proceeded in the absence of clear understandings of its mechanisms of action or extensive preclinical studies of safety and efficacy. Post mortem studies suggest that there is a loss of neurons in proximity to the active electrode, but the resulting lesions are not sufficient to treat the disorder and efficacy requires continued stimulation. Overall complication rates can exceed 25%, and permanent neurologic sequelae result in 4-6% of cases. As the application of deep brain stimulation expands, it is critical to understand the origin of adverse events and the delivery of nondamaging stimulation.
Induction of skewed Th1/Th2 T‐cell differentiation via subcutaneous immunization with Freund's adjuvant (2002)

CD4+ T cells differentiate into at least two distinct subsets, Th1 and Th2, that are characterized by their cytokine-producing profiles. In this study, we attempted to delineate whether and how CD4+ T-cell responses could be skewed in one direction or another. BALB/c mice were immunized with chicken ovalbumin (OVA) emulsified with either incomplete or complete Freund's adjuvant (IFA or CFA). When lymph node cells were assessed on day 7, antigen specific proliferation was similarly observed both in the mice immunized with IFA and CFA. In contrast, on day 28 there was a less significant response in the mice primed with IFA than in those primed with CFA. ELISA analyses revealed more Th1 predominant cytokine production by T cells immunized with OVA+CFA rather than in IFA, which resulted in balanced IFN-gamma and IL-4 production. Flow cytometric analyses of intracellular cytokines confirmed that T cells from mice primed with CFA produced Th1 cytokines more predominantly. When lymph node dendritic cells (DC) were compared for their co-stimulatory molecule expression, priming with CFA and IFA similarly upregulated CD80 and CD86 expression by lymph node DC, and no significant differences were observed in CD40, 54, 80 and 86 expression between the DC harvested from IFA and CFA immunized mice. In addition, both priming with IFA and CFA similarly induced IL-12 production by DC. Thus, although the reason(s) for the preferential induction of a Th1/Th2 response remains unknown, these results indicate that a relatively Th1/Th2 skewed response is differentially induced by different types of adjuvants, and induction of a Th1 skewed response may be responsible for long lasting cellular immunity.
Active Spinal Orthosis to Reduce Lumbar Postural Muscle Activity in Flexed Postures (2016)

ABSTRACT Introduction This article describes a prototype actively powered lumbar spinal orthosis that can be programmed to permit a gradual increase in range of motion. The hypothesis was that wearing the brace would reduce trunk extensor muscle activity in a range of flexed postures. Feasibility tests were performed in acute experiments on a single healthy subject. Methods The subject was asked to assume a quasi-static trunk flexion posture of 5°, 10°, 15°, or 20° repeated in a pseudorandomized order, both with and without use of the prototype orthosis. Muscle activity was measured from medial and lateral bipolar surface electrodes located bilaterally at the L3 level. Data were filtered and scaled to percent maximum voluntary contraction (%MVC). Results The results show that, for the range of postures studied, wearing the brace reduced mean observed %MVC values in every posture in both muscle groups studied, up to a maximum reduction of 9%. Discussion These pilot results suggest that this powered lumbar spinal orthosis has the potential to reduce postural muscle activity over a range of trunk flexion.
Elimination of cap structures generated by mRNA decay involves the new scavenger mRNA decapping enzyme Aph1/FHIT together with DcpS (2014)

Eukaryotic 5' mRNA cap structures participate to the post-transcriptional control of gene expression before being released by the two main mRNA decay pathways. In the 3'-5' pathway, the exosome generates free cap dinucleotides (m7GpppN) or capped oligoribonucleotides that are hydrolyzed by the Scavenger Decapping Enzyme (DcpS) forming m7GMP. In the 5'-3' pathway, the decapping enzyme Dcp2 generates m7GDP. We investigated the fate of m7GDP and m7GpppN produced by RNA decay in extracts and cells. This defined a pathway involving DcpS, NTPs and the nucleoside diphosphate kinase for m7GDP elimination. Interestingly, we identified and characterized in vitro and in vivo a new scavenger decapping enzyme involved in m7GpppN degradation. We show that activities mediating cap elimination identified in yeast are essentially conserved in human. Their alteration may contribute to pathologies, possibly through the interference of cap (di)nucleotide with cellular function.
Phase II Trial of Gemcitabine in Combination with Cisplatin in Inoperable or Advanced Hepatocellular Carcinoma (2008)

The progression-free survival and overall survival in our study were extremely short. Based on the results of our phase 2 study, we are unable to recommend further studies utilising gemcitabine and cisplatin combination in patients with advanced HCC.
Ductal carcinoma in situ: a proposal for a new classification. (1994)

Details of a proposed new classification for ductal carcinoma in situ (DCIS) are presented. This is based, primarily, on cytonuclear differentiation and, secondarily, on architectural differentiation (cellular polarisation). Three categories are defined. First is poorly differentiated DCIS composed of cells with very pleomorphic, irregularly spaced nuclei, with coarse, clumped chromatin, prominent nucleoli, and frequent mitoses. Architectural differentiation is absent or minimal. The growth pattern is solid or pseudo-cribriform and -micropapillary (without cellular polarisation). Necrosis is usually present. Calcification, when present, is amorphous. Second, at the other end of the spectrum is well-differentiated DCIS, composed of cells with monomorphic, regularly spaced nuclei containing fine chromatin, inconspicuous nucleoli, and few mitoses. The cells show pronounced polarisation with orientation of their apical border towards intercellular spaces usually resulting in cribriform, micropapillary and clinging patterns, although a solid pattern of well-differentiated DCIS also occurs. Necrosis is uncommon. Calcifications, when present, are usually psammomatous. The third category, intermediately differentiated DCIS, is composed of cells showing some pleomorphism but not so marked as in the poorly differentiated group. There is, however, always evidence of polarization around intercellular spaces, although this is not so pronounced as in the well-differentiated group. These two criteria, cytonuclear differentiation and architectural differentiation, have been found to be more consistent throughout a DCIS lesion than previously employed criteria of architectural pattern or the presence or absence of necrosis.
Absence of Clinical, Virological, and Immunological Signs of Progression in HIV-1-Infected Patients Receiving Active Anti-Interferon-α Immunization: A 30-Month Follow-Up Report (1996)

Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment, November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-alpha (IFN-alpha) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-alpha overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN-alpha levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-alpha immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 micrograms formalin-inactivated recombinant IFN-alpha-2b (iIFN-alpha) followed by intramuscular injections of 250 micrograms iIFN-alpha adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+ cell count decrease from pretreatment values was observed in IFN-alpha-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-alpha titers, while nonprogression of IFN-alpha-immunized patients was associated with decreased levels of circulating IFN-alpha.
Mutagenicity and genotoxicity of ethylvinyl ketone in bacterial tests (1990)

The mutagenic and genotoxic effects of ethylvinyl ketone were investigated. This alpha, beta-unsaturated carbonyl compound is widely distributed in the environment, in particular in food. Whereas ethylvinyl ketone shows only weak genotoxicity in the SOS Chromotest with Escherichia coli PQ37, it was distinctly mutagenic per se in the Salmonella preincubation assay with TA100. Using SKF 525 (an inhibitor of microsomal monooxygenase) and trichloropropene oxide (an inhibitor of epoxide hydrolase) we found indication for additional activation via epoxidation by S9 mix. The need for further investigation of the genotoxic, mutagenic and carcinogenic effects of this compound is strongly indicated.
Determination of the Resultant Dipole of the Heart from Measurements on the Body Surface (1954)

By means of the vector calculus, it is proved that the magnitude, orientation, and location of the resultant dipole of a system of sources and sinks inside a finite volume conductor is given by an integration over the bounding surface. The method is applied to finding the ``heart vector,'' or the resultant dipole moment of the human heart. The theory was checked in two- and three-dimensional electrolytic tank models of the human thorax.
Evaluation of four real-time PCR assays for detection of influenza A(H1N1)v viruses (2009)

The sensitivity and specificity of four real-time PCR assays (HPA A(H1)v, CDC A (H1)v, HPA A(N1)v and NVRL S-OIV assays) was evaluated for detection of influenza A(H1N1)v viruses. Nose and throat swab samples containing influenza A(H1N1)v viruses, seasonal influenza AH3N2, AH1N1, influenza B viruses, or negative for influenza viruses were tested by the four assays. Specificity was also analysed using influenza A viruses of different subtypes and non-related respiratory viruses. The sensitivities and specificities of the four assays were in a similar range and suitable for diagnostic use. The HPA (H1)v and the S-OIV assays were the most sensitive assays for use as a first line test, but the S-OIV assay was less specific, detecting all avian subtypes of influenza A viruses tested. The results of this study demonstrate that the concurrent use of primary diagnostic and confirmatory assays provides rapid and accurate assessment of confirmed cases, and allows appropriate management of patients.
Multiple Mechanisms Compensate to Enhance Tumor-Protective CD8+ T Cell Response in the Long-Term Despite Poor CD8+ T Cell Priming Initially: Comparison Between an Acute Versus a Chronic Intracellular Bacterium Expressing a Model Antigen (2002)

We evaluated CD8(+) T cell responses against the dominant CTL epitope, OVA(257-264), expressed by an acute (Listeria monocytogenes (LM) OVA) vs a chronic pathogen (Mycobacterium bovis bacillus Calmette-Guérin (BCG) OVA) to reveal the influence on CD8(+) T cell memory and consequent protection against a challenge with OVA-expressing tumor cells. Infection with lower doses of both pathogens resulted in stronger bacterial growth but weaker T cell memory indicating that memory correlates with pathogen dose but not with bacterial expansion. The CD8(+) T cell response induced by LM-OVA was helper T cell-independent and was characterized by a rapid effector response followed by a rapid, but massive, attrition. In contrast, BCG-OVA induced a delayed and weak response that was compensated for by a longer effector phase and reduced attrition. This response was partly dependent on CD4(+) T cells. CD8(+) T cell response induced by BCG-OVA, but not LM-OVA, was highly dependent on pathogen persistence to compensate for the weak initial CD8(+) T cell priming. Despite a stronger initial T cell response with LM-OVA, BCG-OVA provided more effective tumor (B16OVA) control at both local and distal sites due to the induction of a persistently activated acquired, and a more potent innate, immunity.
Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. (1991)

Genes in higher eukaryotes may span tens or hundreds of kilobases with the protein-coding regions accounting for only a few percent of the total sequence. Identifying genes within large regions of uncharacterized DNA is a difficult undertaking and is currently the focus of many research efforts. We describe a reliable computational approach for locating protein-coding portions of genes in anonymous DNA sequence. Using a concept suggested by robotic environmental sensing, our method combines a set of sensor algorithms and a neural network to localize the coding regions. Several algorithms that report local characteristics of the DNA sequence, and therefore act as sensors, are also described. In its current configuration the "coding recognition module" identifies 90% of coding exons of length 100 bases or greater with less than one false positive coding exon indicated per five coding exons indicated. This is a significantly lower false positive rate than any method of which we are aware. This module demonstrates a method with general applicability to sequence-pattern recognition problems and is available for current research efforts.
Dietary Ganglioside and Long-Chain Polyunsaturated Fatty Acids Increase Ganglioside GD3 Content and Alter the Phospholipid Profile in Neonatal Rat Retina (2005)

Animals fed dietary ganglioside increased in total retinal ganglioside and GD3 content during retinal development, with a concomitant alteration of phospholipid metabolism. Feeding animals dietary LCPs also affected ganglioside metabolism in the developing retina, suggesting a new mechanism by which these dietary lipids may promote maturation of photoreceptor cells.
Engineering for drought avoidance: expression of maize NADP‐malic enzyme in tobacco results in altered stomatal function (2002)

Water is a principal limitation to agricultural production during drought and in arid regions of the world. Mechanisms that plants use to cope with drought can be grouped into two different strategies: drought tolerance and drought avoidance. Previous efforts toward engineering plants for improved performance during drought have focused on drought tolerance, the ability to adjust to dry conditions. This report addresses the engineering of a drought-avoidance phenotype, which allows for the conservation of water during plant growth. The majority of water lost from plants occurs through stomata. When stomata are open, potassium, chloride and/or malate are present at high concentrations in guard cells. The accumulation of large numbers of ions during stomatal opening increases the turgor pressure of the guard cells, which results in increased pore size. Expression of a single gene from maize, NADP-malic enzyme (ME), which converts malate and NADP to pyruvate, NADPH, and CO(2), resulted in altered stomatal behaviour and water relations in tobacco. The ME-transformed plants had decreased stomatal conductance and gained more fresh mass per unit water consumed than did the wild type, but they were similar to the wild type in their growth and rate of development. Providing chloride via the transpiration stream partially reversed the effects of ME expression on stomatal aperture size, which is consistent with the interpretation that expression of ME altered malate metabolism in guard cells. These results suggest a role for malic enzyme in the mechanism of stomatal closure, as well as a potential mechanism for genetically altering plant water use.
Improvement of flow cytometry analysis and sorting of bull spermatozoa by optical monitoring of cell orientation as evaluated by DNA specific probing (1991)

Flow cytometry is a potential method for the separation of X and Y bearing spermatozoa, on the basis of their relative DNA content evaluated by the fluorescence emission intensity due to specific fluorochrome DNA staining. However, spermatozoa DNA is highly condensed and nuclei exhibit flat non spherical shape, which can produce artefacts impeding accurate analysis. In order to avoid these limitations, decondensation of DNA performed by enzymatic treatment and a modification of the flow cytometer that orients the spermatozoa relative to the laser beam are generally used. In this work, we describe alternative methods and materials for selection of 1) decondensed and thus dead spermatozoa without orientation, sorted on the basis of only the 10% spermatozoa containing the least DNA (expected Y) and the 10% spermatozoa containing the more DNA (expected X), or 2) native spermatozoa homogeneously oriented using a simultaneous measurement of Axial light loss (extinction) and Forward angle light scatter. For testing enrichment of each selected fraction we have worked out a molecular hybridization procedure using X and Y specific DNA probes. We analyse and sort bull spermatozoa on these basis: the purity obtained for these fractions is 80% without orientation after enzymatic treatment, and 70% on live spermatozoa "optically" oriented.
Compound Heterozygous Mutation of Rag1 Leading to Omenn Syndrome (2015)

Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility to infections and autoreactive T cells and resulting from defective genomic rearrangement of genes for the T cell and B cell receptors. The most frequent etiologies are hypomorphic mutations in "non-core" regions of the Rag1 or Rag2 genes, the protein products of which are critical members of the cellular apparatus for V(D)J recombination. In this report, we describe an infant with Omenn syndrome with a previously unreported termination mutation (p.R142*) in Rag1 on one allele and a partially characterized substitution mutation (p.V779M) in a "core" region of the other Rag1 allele. Using a cellular recombination assay, we found that while the p.R142* mutation completely abolished V(D)J recombination activity, the p.V779M mutation conferred a severe, but not total, loss of V(D)J recombination activity. The recombination defect of the V779 mutant was not due to overall misfolding of Rag1, however, as this mutant supported wild-type levels of V(D)J cleavage. These findings provide insight into the role of this poorly understood region of Rag1 and support the role of Rag1 in a post-cleavage stage of recombination.
Authentication of the Origin of Vanillin Using Quantitative Natural Abundance 13C NMR (2004)

The use of 13C isotopic distribution as an efficient means to determine the origin of vanillin has been substantiated. Using quantitative 13C NMR, the 13C/12C ratios at all eight carbon positions can be exploited. On a set of 21 samples of vanillin from five different origins, complete discrimination can be achieved. It is shown that, for many purposes, a rapid analysis in which only five sites are used is sufficient. However, improved discrimination using all eight sites is preferable to differentiate between different methods of production from natural ferulic acid or between natural and lignin-derived vanillin on the basis of the 13C/12C ratios characteristic of different origins. The C1 and C8 positions are demonstrated to be the most significant sites for discrimination using principle component analysis. However, aromatic carbon positions make an essential contribution, notably in differentiating between natural and lignin-derived vanillin.