gebhart/patrepeval huggingface dataset:
Emerging therapies in multiple sclerosis (2005)

Multiple sclerosis (MS) is the most common neurological cause of disability in young people. The disease-modifying treatments, IFN-beta and glatiramer acetate, have been widely available over the last decade and have shown a beneficial effect on relapse rate and magnetic resonance imaging parameters of disease activity; however, their effect on disease progression and disability is modest. Therefore, the search for alternative treatment strategies continues. As understanding of the heterogeneous pathophysiology of MS has increased, emphasis has shifted to more selective therapy that targets components of the inflammatory cascade and the promotion of remyelination and neuroprotection. These agents target the blood-brain barrier, systemic immune dysfunction, local inflammation and neurodegeneration. Combination therapies are being investigated for patients who fail first-line treatments. Many new drugs are being developed and tested that address these issues with the aim of finding a more effective and convenient therapy. These include humanized monoclonal antibodies such as daclizumab (IL-2 antagonist), oral immunomodulators such as sirolimus and statins and neuroprotective agents such as NMDA antagonists and Na+-channel blockers. Many of the treatments discussed in this review are still at early stages of development, but provide exciting potential treatment options; others have proved disappointing in larger extended-phase studies.
Improvement of SAXS measurements on Kratky slit systems by Göbel mirrors and imaging-plate detectors (2000)

Laboratory X-ray sources emit a highly divergent beam. The Kratky compact camera is constructed to maximize the intensity in the sample using a slit collimation system. The performance of this camera can be further increased if the primary beam is collimated from a divergent into a parallel beam. A recently developed device for this purpose is the so-called `Göbel mirror'. This mirror is made of parabolically bent multilayers, designed to collimate divergent X-rays from laboratory X-ray sources into a parallel and monochromatic beam of high brilliance. Modification of the block collimation system in combination with a Göbel mirror leads to a different beam geometry, resulting in an intensity increase by a factor of about 10. The gain in intensity implicates the use of imaging-plate detectors, which have a wide linear range in intensity and allow the full use of the increased intensity. Hence the quality of the SAXS data is improved by the higher intensity primary beam, the much lower background due to the exclusive use of Cu K α radiation, and a detection unit which is linear in the measured intensity regime. All these advantages, such as intensity gain, lower background, better quality of the data, are demonstrated with some selected experimental results.
Detection of Mycobacterium leprae antigens in the sera of leprosy patients by sandwich immunoradiometric assay using monoclonal antibodies (1990)

An immunological technique for demonstration of Mycobacterium leprae antigen in sera was developed by using specific as well as cross-reactive monoclonal antibodies. The sandwich immunoradiometric assay which we developed is a simple, robust assay that is sensitive to the nanogram level. Sera from 72 leprosy patients were screened for the presence of antigen by this assay. A total of 69% of untreated tuberculoid leprosy patients showed 35-kDa antigen positivity, and 45% of these patients showed anti-35-kDa antibody positivity. Consistently higher antigen positivity rates for the 35-, 12-, and 30- to 40-kDa components of M. leprae were observed in lepromatous leprosy patients than in tuberculoid leprosy patients. During the course of therapy the antigen positivity rate gradually declined, and the antigen could not be detected in any of the 15 patients with subsided cases of leprosy. As antigen is presumably in excess before the antibody response is evoked, our experimental approach for antigen detection is likely to be useful by itself or along with antibody detection for diagnosis of early leprosy.
Activation of the Wnt signaling pathway in chronic lymphocytic leukemia (2004)

B cell chronic lymphocytic leukemia (CLL) is characterized by an accumulation of mature, functionally incompetent B cells. Wnts are a large family of secreted glycoproteins involved in cell proliferation, differentiation, and oncogenesis. The classical Wnt signaling cascade inhibits the activity of the enzyme glycogen synthase kinase-3beta, augmenting beta-catenin translocation to the nucleus, and the transcription of target genes. Little is known about the potential roles of Wnt signaling in CLL. In this study, we quantified the gene expression profiles of the Wnt family, and their cognate frizzled (Fzd) receptors in primary CLL cells, and determined the role of Wnt signaling in promoting CLL cell survival. Wnt3, Wnt5b, Wnt6, Wnt10a, Wnt14, and Wnt16, as well as the Wnt receptor Fzd3, were highly expressed in CLL, compared with normal B cells. Three lines of evidence suggested that the Wnt signaling pathway was active in CLL. First, the Wnt/beta-catenin-regulated transcription factor lymphoid-enhancing factor-1, and its downstream target cyclin D1, were overexpressed in CLL. Second, a pharmacological inhibitor of glycogen synthase kinase-3 beta, SB-216763, activated beta-catenin-mediated transcription, and enhanced the survival of CLL lymphocytes. Third, Wnt/beta-catenin signaling was diminished by an analog of a nonsteroidal antiinflammatory drug (R-etodolac), at concentrations that increased apoptosis of CLL cells. Taken together, these results indicate that Wnt signaling genes are overexpressed and are active in CLL. Uncontrolled Wnt signaling may contribute to the defect in apoptosis that characterizes this malignancy.
The fabrication of thin films with nanopores and nanogrooves from block copolymer thin films on the neutral surface of self-assembled monolayers (2007)

A simple and well-ordered fabrication procedure for polymeric thin films with nanopores and nanogrooves is described. By utilizing the neutral surface of self-assembled monolayers (SAMs) of commercially available 3-(p-methoxyphenyl)propyltrichlorosilane (MPTS), the cylindrical microdomains of PMMA of the asymmetric polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) block copolymer were oriented perpendicular to the surface due to the balanced interfacial interactions of the blocks with the surface. Thin films with perpendicularly oriented lamellae without mixed lamellae could also be fabricated by simply using a binary blend of the same asymmetric PS-b-PMMA diblock copolymer and PMMA homopolymer in the wet-brush regime up to 50% of the total PMMA weight fraction on the same neutral surface. Nanotemplates with arrays of nanopores and nanogrooves were fabricated by selective removal of PMMA domains via ultraviolet (UV) irradiation and sequential washing. SAMs of MPTS on a substrate with aluminium oxide surface were also fabricated and were used to fabricate nanoporous thin film. A thin film of PS-b-PEO with perpendicularly oriented poly(ethylene oxide) (PEO) domains on the SAMs of MPTS is also demonstrated.
Purification and characterization of a 14-kilodalton protein that is bound to the surface of polyhydroxyalkanoic acid granules in Rhodococcus ruber (1994)

The N-terminal amino acid sequence of the polyhydroxyalkanoic acid (PHA) granule-associated M(r)-15,500 protein of Rhodococcus ruber (the GA14 protein) was analyzed. The sequence revealed that the corresponding structural gene is represented by open reading frame 3, encoding a protein with a calculated M(r) of 14,175 which was recently localized downstream of the PHA synthase gene (U. Pieper and A. Steinbüchel, FEMS Microbiol. Lett. 96:73-80, 1992). A recombinant strain of Escherichia coli XL1-Blue carrying the hybrid plasmid (pSKXA10*) with open reading frame 3 overexpressed the GA14 protein. The GA14 protein was subsequently purified in a three-step procedure including chromatography on DEAE-Sephacel, phenyl-Sepharose CL-4B, and Superose 12. Determination of the molecular weight by gel filtration as well as electron microscopic studies indicates that a tetrameric structure of the recombinant, native GA14 protein is most likely. Immunoelectron microscopy demonstrated a localization of the GA14 protein at the periphery of PHA granules as well as close to the cell membrane in R. ruber. Investigations of PHA-leaky and PHA-negative mutants of R. ruber indicated that expression of the GA14 protein depended strongly on PHA synthesis.
Molecular basis of osmotic regulation (1995)

Cells almost universally respond to the stress of long-term hyperosmolality by accumulating compatible organic osmolytes. This allows them to maintain normal cell volume without a deleterious increase in intracellular inorganic ion concentration. Cells in the renal inner medulla are exposed to variable concentrations of salt and urea that may reach molal levels. The organic osmolytes that they accumulate include sorbitol, betaine, inositol, taurine, and glycerophosphocholine (GPC). This review considers recent advances in understanding osmotic regulation of these substances. Sorbitol is synthesized from glucose catalyzed by aldose reductase. Hypertonicity elevates the abundance of this enzyme by increasing transcription of its gene. Betaine is taken up via a specialized transporter. Hypertonicity raises the number of transporters by increasing their transcription. Current studies demonstrate that the 5' regions flanking the aldose reductase and betaine transporter genes contain osmotic response elements that increase transcription in response to hypertonicity. Osmotic regulation of inositol and taurine uptake also involves increased expression of specific transporter genes. GPC is unique in that its level rises in response to high urea, as well as hypertonicity. GPC accumulation is mainly regulated by changes in its degradation to choline, catalyzed by GPC:choline phosphodiesterase. Numerous other genes, including those for heat shock proteins, are also induced by hypertonicity. Their regulation and their role in osmotic regulation are the subject of considerable ongoing research.
From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy (2018)

Nanopore sequencing is a rapidly maturing technology delivering long reads in real time on a portable instrument at low cost. Not surprisingly, the community has rapidly taken up this new way of sequencing and has used it successfully for a variety of research applications. A major limitation of nanopore sequencing is its high error rate, which despite recent improvements to the nanopore chemistry and computational tools still ranges between 5% and 15%. Here, we review computational approaches determining the nanopore sequencing error rate. Furthermore, we outline strategies for translation of raw sequencing data into base calls for detection of base modifications and for obtaining consensus sequences.
Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity (2013)

There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase-topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K(+) channel block. On the other hand, analog 49e displayed lower hERG K(+) channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.
Spatial modulation of critical current density in niobium based Josephson junctions induced by selective heating (2013)

Results about induced spatial modulation of critical current density in niobium based Josephson devices by a selective radiation heating are presented. The localized heating inside a single circuit element with a good spatial resolution (less than 1 μm) is made possible by depositing a carbon film on the desired region exploiting the larger absorbance coefficient of carbon (close to 1) with respect to niobium (about 0.2). Measurements of critical current as a function of the external magnetic field on high quality Josephson junctions at T = 4.2 K evidenced that the critical current density was changed only in the absorber covered region, leaving unchanged the critical current density outside that region and ensuring the capability to locally modify the Josephson critical current density. The experimental data have been compared with theoretical predictions obtained by using a suitable junction barrier model based on step-like barrier shape. Such results are very interesting in view of applications in quantum computing, Majorana fermions detection, and superconducting magnetic sensors.
Premenstrual asthma: the effect of estrogen on symptoms, pulmonary function, and beta 2-receptors. (1997)

To characterize asthma symptoms, pulmonary function, and responsiveness to beta 2-agonist stimulation, and in vitro beta 2-receptor density and cyclic adenosine 3',5'-monophosphate (cAMP) response throughout the menstrual cycle in women with premenstrual asthma (PMA); and to examine the effect of exogenous estradiol administration on asthma symptoms, pulmonary function and responsiveness, and beta 2-receptor density and function in these women.Open-label, longitudinal, 9-week study.A university clinical research center.Seventeen women with mild to moderate asthma, of whom 14 completed the study.Every morning on awakening during the entire 9-week study, each subject completed visual analog scales for asthma symptomatology (cough, wheezing, breathlessness, chest tightness) and measured and recorded her peak expiratory flow rate (PEFR) with a peak flow meter. Also measured at various times throughout the menstrual cycle were dyspnea index scores, pulmonary function (PEFR, forced expiratory volume in 1 sec [FEV1]), pulmonary response to subcutaneous terbutaline, T lymphocyte beta 2-receptor density (Bmax) and function (cAMP), and estradiol, progesterone, and catecholamine concentrations, both with and without exogenous estradiol administration.At the time of enrollment, only 5 subjects reported premenstrual worsening of asthma symptoms, but all 14 had greater than 20% decrease in PEFR and/or increase in symptoms premenstrually during the study. Significant differences (p < 0.05) existed in asthma symptoms and PEFR between day 13 (highest estradiol concentrations) and day 26 (lowest estradiol concentrations) of the menstrual cycle. Asthma symptoms and dyspnea index scores were significantly improved (p < 0.05) after estradiol administration compared with baseline (premenstrual period without exogenous estrogen). Pulmonary response to terbutaline, beta 2-receptor density and function, and catecholamine concentrations were not significantly altered after estradiol administration, but the trend was toward significant differences (0.05 < p < 0.2) in pulmonary function tests (PEFR, FEV1).Even asthmatics not previously aware of PMA may experience premenstrual worsening of asthma symptoms and/or PEFR. Estradiol is associated with a significant improvement in asthma symptoms and dyspnea index scores. This ameliorating effect does not appear to be related to beta 2-receptors.
Antibacterial activity of copper-amino acid complexes. (1990)

Copper complexes of L-alanine, L-arginine, L-histidine, L-lysine, L-proline and L-threonine were studied for their antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes and Escherichia Coli. The complexes of 1-alanine, 1-proline and 1-threonine were nearly as active as ampicillin against Strep. Pyogenes. Mixed complexes of these amino acids showed similar effect. Other complexes were also active to a significant extent against all the three strains studied.
47 (1998)

Institute of Pathophysiology, Department of Surgery and Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Changes in Serum Interleukin-8 and Interleukin-12 Levels in Patients with Ischemic Heart Disease in a Chinese Population (2001)

Increasing evidence has indicated the important roles of inflammation and immune response in the development of atherosclerosis and ischemic heart disease (IHD). We measured the serum interleukin (IL)-8 and IL-12 levels of patients with unstable angina pectoris (UAP) and patients with acute myocardial infarction (AMI), and compared findings with those of normal subjects. The results showed that the serum level of IL-8 was significantly higher in patients with UAP and patients with AMI than in healthy control subjects. To our knowledge, this is the first report that serum IL-12 level was elevated in patients with AMI but not in patients with UAP. These findings suggest that IL-8 and IL-12 are involved in the process of IHD, and serum IL-12 may be a marker for differentiating AMI from UAP.
Stem Cell Cardiomyoplasty: State-of-the-Art (2004)

Congestive heart failure (CHF) remains the most common diagnosis made in cardiology wards today. No long-term therapeutic option for end-stage CHF is available except for orthotopic heart transplant. Cellular-based therapy has emerged as a potential new therapy for patients with advanced heart failure. Different cell types are being explored in preclinical and clinical studies with encouraging results. Critical issues, such as types of cells, ideal number of cells, route of delivery, timing and targets of delivery, remain to be optimised to maximise the benefits of the cell therapy. In this review, we seek to summarise the latest data and postulate future directions in this potentially exciting field.
Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip (1993)

Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.
Control of GL2 expression in Arabidopsis leaves and trichomes (1998)

ABSTRACT More than twenty genes are required for the correct initiation, spacing, and morphogenesis of trichomes in Arabidopsis. The initial selection of trichome precursors requires the activity of both the GLABROUS1 (GL1) and TRANSPARENT TESTA GLABROUS (TTG) genes. The GLABRA2 (GL2) gene is required for subsequent phases of trichome morphogenesis such as cell expansion, branching, and maturation of the trichome cell wall. Previous studies have shown that GL2 is a member of the homeodomain class of transcription factors. Here we report a detailed analysis of GL2 expression in the shoot using anti-GL2 antibodies and the GUS reporter gene fused to the GL2 promoter. The GL2 expression profile in the shoot is complex, and involves spatial and temporal variation in developing leaves and trichomes. Two separate promoter domains that are expressed in trichomes were identified. GL2, like GL1, is expressed in developing trichomes and in cells surrounding trichomes during early stages of trichome development. Unlike GL1, GL2 expression persists in mature trichomes. It was found that while GL1 and TTG were not required for the initiation of GL2 expression in the non-trichome cells, the presence of a functional GL1 or TTG gene was able to increase GL2 expression in these cells compared to ttg gl1 plants. The hypothesis that GL1 regulates aspects of GL2 expression is consistent with epistatic analysis of gl1 and gl2 and the expression patterns of GL1 and GL2. In support of this hypothesis, it was found that ectopic expression of GL1 in the presence of ectopic expression of the maize R gene, which can bypass the requirement for TTG, can ectopically activate GL2 transcription.
Activation of JNK and p38 in rat hippocampus after kainic acid induced seizure (2000)

Kainic acid, an analogue of glutamate, causes limbic seizures and induces cell death in the rat brain. We examined the activation of MAPK family kinases; ERKs, JNKs and p38 kinase in rat hippocampus after KA treatment. Activation of all three kinases were observed at 30 min after the treatment, but, in contrary to ERK phosphorylation, which lasted up to 3 h, the phosphorylation of JNK and p38 returned to the basal level by 2 h. The phosphorylation of' upstream kinases for the MAPK family was distinct. The phosphorylation of MEK1 clearly increased at 30 min but diminished rapidly thereafter. The phosphorylation of MKK6 was also increased but reached peak at 2 h after KA treatment. However, the phosphorylation of other upstream kinases, SEK1 and MKK3, gradually decreased to 3 h after KA treatment. These results indicate that the KA activates all of the three MAPK family kinases with different time patterns and suggest the possibility that MKK3 and MKK6, and SEK1 may not be the upstream kinases for p38 and JNK in rat hippocampus.
Effects of alkyl and aryl substitution on the myocardial specificity of radioiodinated phosphonium, arsonium, and ammonium cations (1985)

Several radioiodinated iodopentenyl-trisubstituted phosphonium, arsonium, and ammonium iodides have been prepared and evaluated in rats to determine the effects of structural variations of the cations on myocardial uptake and retention. The synthesis of (E)-(1-iodo-1-penten-5-yl)-trisubstituted phosphonium, arsonium, and ammonium iodides via the condensation of trisubstituted phosphine, arsine, and amine precursors, respectively, with (E)-1,5-diiodopentene is described. In some cases a second route involved condensation with (E)-1-borono-5-iodo-1-pentene followed by iodination. In the phosphonium series, the compounds triphenyl 1, dicyclohexylphenyl 5, tricyclohexyl 6, and dimethyl-n-octyl 8 were prepared. The triphenylarsonium 10 and triethylammonium 11 compounds were also prepared. The corresponding radioiodinated analogues were prepared and tissue distribution studies performed in rats. The results (percent dose/gram, 30 min) demonstrate that replacement of phosphorus with arsenic (1, 3.99%; 10, 3.17%) or the replacement of the phenyl ring with the cyclohexyl ring system (6, 2.67%) has no apparent effect on heart uptake. In the series of compounds studied, replacement of the cyclic ring system with alkyl groups, however, significantly decreased heart uptake with both the phosphorus (8, 1.95%) and nitrogen agents (11, 1.11%). Gamma camera imaging studies with [123I]-5 and [123I]-8 further substantiated the decreased heart uptake with alkyl substitution and the apparent hepatobiliary clearance of 8.