gebhart/patrepeval huggingface dataset:
A Novel Missense Mutation in the Spectrin Beta Nonerythrocytic 2 Gene Likely Associated with Spinocerebellar Ataxia Type 5 (2016)

To the Editor: Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal dominant spinocerebellar ataxia. Mutations in the spectrin beta nonerythrocytic 2 gene (SPTBN2) are known to cause SCA5, six of which have been reported, including three missense mutations and three deletion mutations.[1] The patient was a 19-year-old Chinese girl presenting with progressive unsteady gait while running from the age of 11 years. She was not concerned by the symptoms until a fever at the age of 18 years made her imbalance more evident. Downbeat nystagmus on bilateral gaze that was not suppressed by visual fixation was noted. Her gait was wide. The heel-knee-shin test was inaccurate and unsteady. Bilateral rebound tests were positive. Brain magnetic resonance imaging (MRI) showed marked atrophy of the cerebellar hemisphere and vermis with no evidence of abnormalities in supratentorial and brainstem structures [Figure 1].Figure 1: Brain MRIs: Atrophy of the cerebellar hemispheres sparing the brainstem and supratentorial structures is evident (a and c; arrows). Atrophy of the cerebellar vermis is apparent (b and d; arrows). MRI: Magnetic resonance imaging.Based on gene sequencing, one likely candidate mutation was found in the SPTBN2 gene, a heterozygous A > G transition at nucleotide position 833 (c. 833A > G) altering codon 278, substituting arginine for histidine (p.H278R). The p.H278R variant was not found in any database of normal sequence variation. Sorts intolerant from tolerant predicted that this mutation was damaging with a score of 0.001 where less than 0.05 is considered harmful.[2] Polymorphism phenotyping v2 predicted that it was possibly damaging with a score of 0.85. A value close to 1 is suggestive that the mutation is damaging.[3] We presented a case of SCA5 with a missense mutation in the SPTBN2 gene, which is a rare case reported worldwide. Her symptoms started at the age of eleven, which was earlier than the onset of symptoms in the German kindred, which ranged from 15 to 50 years (mean 32.8 ± 12.7 years, median 37.0 years).[4] The parents of our patient were normal clinically and based on genetic tests. Without further functional studies, we cannot confirm whether it is truly pathogenic. However, the patient experiences clinically supported spinocerebellar ataxia. In clinically appropriate patients lacking previously reported mutations, a novel missense mutation (p.H278R) in SPTBN2 should be considered. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Mechanisms controlling TCGF production by cloned sublines of EL-4 azgr in response to stimulation by anti-Thy-1 antibody. (1982)

The effect of xenogeneic anti-Thy-1 antibody on T cell growth factor (TCGF) production by T lymphoma cell lines has been examined as a model system for T cell activation. EL-4 G12 (a cloned subline of the producer EL-4 azgr cell line) produced TCGF when stimulated by a high concentration of anti-Thy-1, but none was induced by low concentrations of anti-Thy-1. Large amounts of TCGF were produced when these cells were cultured with Fc-receptor positive (FcR+) accessory cells. TCGF production by EL-4 G12 showed dose response kinetics similar to TCGF production by anti-Thy-1-stimulated, purified normal spleen T cells. Goat anti-rabbit IgG (GaRIG) and protein A substituted for this accessory helper effect, but neither FcR+ cells nor Protein A worked when (Fab')2 anti-Thy-1 was used instead of IgG anti-Thy-1. Anti-T-200 monoclonal antibody inhibited anti-Thy-1-induced TCGF production by EL-4 G12 and accessory cells. Phorbol myristic acetate and lymphocyte-activating factor also substituted in part for the accessory cell help. The data suggest there are at least 2 different accessory cell help mechanisms in anti-Thy-1-induced TCGF production, anti-Thy-1-bound membrane aggregation either by GaRIG, Protein A or FcR, and a LAF-dependent mechanism.
Traumatic brain injury: Affecting family recovery (1993)

Ongoing interest in how families adjust to traumatic events has encouraged much research, with varying results. Viewing the family process of adjustment from a systems perspective provides a workable model. The current article explores basic system tenets and provides data on varying adjustment issues for families. Results are consistent with current research trends and family data.
<title>Distributed optical fiber pressure sensor</title> (1998)

A new kind of distributed fiber optic sensor is described in the paper. On the basis of mode coupling between two orthogonal fundamental modes of HiBi polarization- maintaining fiber, a new method is developed to locate the mode coupling point caused by external pressure applied on the fiber.
Endothelin (2016)

The endothelins comprise three structurally similar 21-amino acid peptides. Endothelin-1 and -2 activate two G-protein coupled receptors, ETA and ETB, with equal affinity, whereas endothelin-3 has a lower affinity for the ETA subtype. Genes encoding the peptides are present only among vertebrates. The ligand-receptor signaling pathway is a vertebrate innovation and may reflect the evolution of endothelin-1 as the most potent vasoconstrictor in the human cardiovascular system with remarkably long lasting action. Highly selective peptide ETA and ETB antagonists and ETB agonists together with radiolabeled analogs have accurately delineated endothelin pharmacology in humans and animal models, although surprisingly no ETA agonist has been discovered. ET antagonists (bosentan, ambrisentan) have revolutionized the treatment of pulmonary arterial hypertension, with the next generation of antagonists exhibiting improved efficacy (macitentan). Clinical trials continue to explore new applications, particularly in renal failure and for reducing proteinuria in diabetic nephropathy. Translational studies suggest a potential benefit of ETB agonists in chemotherapy and neuroprotection. However, demonstrating clinical efficacy of combined inhibitors of the endothelin converting enzyme and neutral endopeptidase has proved elusive. Over 28 genetic modifications have been made to the ET system in mice through global or cell-specific knockouts, knock ins, or alterations in gene expression of endothelin ligands or their target receptors. These studies have identified key roles for the endothelin isoforms and new therapeutic targets in development, fluid-electrolyte homeostasis, and cardiovascular and neuronal function. For the future, novel pharmacological strategies are emerging via small molecule epigenetic modulators, biologicals such as ETB monoclonal antibodies and the potential of signaling pathway biased agonists and antagonists.
Mechanism of action of factor D of the alternative complement pathway. (1978)

Factor D (C3 proactivator convertase) of human serum has been shown to be absolutely necessary for alternative pathway function, for activation of the C3/C5 convertase of that pathway and not to be a subunit of this enzyme. Factor D was found to be present in human plasma in active form only, at a concentration of 2 microgram/ml, and not to be controlled by plasma protease inhibitors or by spontaneous decay. Unlike trypsin, factor D cleaves and activates factor B only when it is in Mg++-dependent complex with C3b, has no esterolytic activity, and is unable to cleave the B chain of insulin. The alleged functional and antigenic relationship of factor D to alpha-thrombin could not be verified. The results of this study led to the description of the mechanism of action of factor D in terms of the cryptic site hypothesis.
ChemInform Abstract: PREPARATION OF DEMETHOXYORIPAVINE AND ITS CONVERSION INTO N‐SUBSTITUTED N‐DEMETHYLAPOMORPHINE DERIVATIVES (1983)

Abstract Neomorphin (Ib), das Demethylierungsprodukt von Neopin (Ia), wird partiell acetyliert [‐ (Ic)] und nachfolgend mesyliert [‐ (Id)].
Room-temperature crystallization of hybrid-perovskite thin films via solvent–solvent extraction for high-performance solar cells (2015)

A simple one-step solvent-bathing process based on solvent–solvent extraction, is demonstrated for the controlled room-temperature crystallization of uniform, ultra-smooth hybrid-perovskite thin films for high-efficiency solar cells.
Rapid single-step method for flow cytometric detection of surface and intracellular antigens using whole blood (1996)

Fixation/permeabilization methods used for the detection of intracellular antigens by flow cytometry often result in the destruction of cellular morphology and surface immunoreactivity, properties useful in flow cytometry for the characterization of cells in heterogeneous populations. In addition, a majority of these methods are incompatible with whole blood and require that peripheral blood leukocytes (PBLs) be purified prior to fixation. This article describes a new technique for the rapid detection of both intracellular and cell surface antigens, while preserving cell morphology, through the use of a single-step fixation/permeabilization reagent, ORTHO PermeaFix (OPF). OPF is compatible with whole blood, allowing for the direct preparation of PBLs without prior cell separation. An additional red blood cell lysing reagent was not required because RBC lysis occurred upon resuspension of OPF-treated whole blood samples in isotonic solution. Discrimination of leukocyte populations by light scatter after OPF treatment was comparable to matched unfixed live cells. In addition, absolute lymphocyte and white blood cell (WBC) counts were not significantly affected when OPF-treated cells were compared with unfixed cells. Treatment of whole blood from 7 normal donors showed no significant difference in percentage of cells positive for CD2, CD3, CD4, CD8, CD16, or CD19 between fixed and unfixed samples when cells were stained before fixation, and no difference in CD3, CD4, CD8, CD16, or CD19 percentages when cells were stained following fixation. Monoclonal antibodies specific for intracellular antigens located at various sites within the cell were tested on fixed samples. OPF-treated peripheral blood lymphocytes showed greater than 95% reactivity for the inner mitochondrial membrane protein bcl-2, and the cytoskeletal cytoplasmic protein vimentin. TIA-1, a cytolytic granule-associated protein, showed differential reactivity within lymphocyte subsets, from a low of 8 +/- 2% in CD4+ cells to 89 +/- 6% in CD16+ cells, when whole blood from five normal donors was fixed and stained. Reh cells treated with OPF showed greater than 95% reactivity for the internuclear protein TdT. A comparison of OPF with two other fixation/permeabilization procedures, 1% paraformaldehyde followed by 45% ethanol and 0.25% paraformaldehyde followed by 0.2% Tween 20, showed that only OPF could be used both prior to or following cell surface staining with no effect on antigen detection while allowing optimal detection of all of the intracellular antigens tested.
Alcoholic liver disease and the potential role of plasminogen activator inhibitor-1 and fibrin metabolism (2012)

Plasminogen activator inhibitor-1 (PAI-1) is a major player in fibrinolysis due to its classical role of inhibiting plasminogen activators. Although increased fibrinolysis is common in alcoholic cirrhosis, decreased fibrinolysis (driven mostly by elevated levels of PAI-1) is common during the development of alcoholic liver disease (ALD). However, whether or not PAI-1 plays a causal role in the development of early ALD was unclear. Recent studies in experimental models have suggested that PAI-1 may contribute to the development of early (steatosis), intermediate (steatohepatitis) and late (fibrosis) stages of ALD. For example, fatty liver owing to both acute and chronic ethanol was blunted by the genetic inhibition of PAI-1. This effect of targeting PAI-1 appears to be mediated, at least in part, by an increase in very low-density lipoprotein (VLDL) synthesis in the genetic absence of this acute phase protein. Results from a two-hit model employing ethanol and lipopolysaccharide administration suggest that PAI-1 plays a critical role in hepatic inflammation, most likely due to its ability to cause fibrin accumulation, which subsequently sensitizes the liver to ensuing damaging insults. Lastly, the role of PAI-1 in hepatic fibrosis is less clear and appears that PAI-1 may serve a dual role in this pathological change, both protective (enhancing regeneration) and damaging (blocking matrix degradation). In summary, results from these studies suggest that PAI-1 may play multiple roles in the various stages of ALD, both protective and damaging. The latter effect is mediated by its influence on steatosis (i.e. decreasing VLDL synthesis), inflammation (i.e. impairing fibrinolysis) and fibrosis (i.e. blunting matrix degradation), whereas the former is mediated by maintaining hepatocyte division after an injury.
Conflict Cause Identification in Web-Based Concurrent Engineering Design System (2002)

Modern engineering design commonly involves the cooperative effort of design experts, who often come from different engineering backgrounds, have different geological locations, and communicate primarily via the web. Conflicts, which commonly exist in the design process, are exacerbated by this situation. This paper first presents a well-organized structure of conflict classes and causes. Based on an analysis of conflict nature and conflict-related human behavior in the concurrent engineering design, a new computational model for autonomously identifying the conflict cause in the web-based concurrent engineering design environment is developed and tested. The Plane World design simulation system is used as a test-bed to demonstrate and verify the conflict cause identification methods developed in this work.
High-sensitivity and no-crosstalk pixel technology for embedded CMOS image sensor (2001)

A high-photosensitivity and no-crosstalk pixel technology has been developed for an embedded active-pixel CMOS image sensor, by using a 0.35-/spl mu/m CMOS logic process. To increase the photosensitivity, we developed a deep p-well photodiode and an antireflective film, consisting of Si/sub 3/N/sub 4/ film, for the photodiode surface. To eliminate the high voltage required for the reset transistor in the pixel, we used a depletion-type transistor as the reset transistor. The reset transistor also operates as an overflow control gate, which enables antiblooming overflow when excess charge is generated in the photodiode by high-illumination conditions. To suppress pixel crosstalk caused by obliquely incident light, a double-metal photoshield was used, while crosstalk caused by electron diffusion in the substrate was suppressed by using the deep p-well photodiode. A 1/3-in 330-k-pixel active-pixel CMOS image sensor was fabricated using this technology. A sensitivity improvement of 110% for 550-nm incident light was obtained by using the deep p-well photodiode, while an improvement of 24% was obtained by using the antireflective film. The pixel crosstalk was suppressed to less than 1% throughout the range of visible light.
Insulinformulierungen: Herstellung schnell-wirkender Insuline und Verzögerungsinsuline — wie lässt sich diese Herausforderung technologisch lösen? (2001)

Schon bald nach der Entdeckung des Insulins im Jahre 1921 durch Banting und Best waren Herstellungsprozesse zur Gewinnung von Schweine-und Rinderinsulin etabliert [2]. Ebenso wurden in den zwanziger Jahren schon die unterschiedlichsten Applikationsformen getestet. Da Insulin als Peptid nach oraler Gabe durch proteolytische Enzyme sehr schnell im Magen/Darmtrakt abgebaut wird, hat sich bis heute die parenterale Applikation als Standard behauptet. Neben der überwiegend angewandten subkutanen Injektion ist eine intramuskuläre, intravenöse oder intraperitoneale Applikation möglich [1].
Infrared absorption by conical silicon microstructures made in a variety of background gases using femtosecond-laser pulses (2001)

Summary form only given. Previous work in our group has shown that novel conical microstructures are formed on the surface of silicon when it is irradiated with 100-fs laser pulses in the presence of halogen-containing gases. Structures are also formed using other background gases, such as N/sub 2/ or air, but they tend to be more blunt and irregular in shape. We have measured the optical,properties of microstructures formed in various gases. The structures are typically 1 /spl mu/m wide at the top and several /spl mu/m wide at the base, with a height in the range 1-20 /spl mu/m, depending on ambient gas pressure, and laser fluence.
Surface Engineering and Patterning Using Parylene for Biological Applications (2010)

Parylene is a family of chemically vapour deposited polymer with material properties that are attractive for biomedicine and nanobiotechnology. Chemically inert parylene “peel-off” stencils have been demonstrated for micropatterning biomolecular arrays with high uniformity, precise spatial control down to nanoscale resolution. Such micropatterned surfaces are beneficial in engineering biosensors and biological microenvironments. A variety of substituted precursors enables direct coating of functionalised parylenes onto biomedical implants and microfluidics, providing a convenient method for designing biocompatible and bioactive surfaces. This article will review the emerging role and applications of parylene as a biomaterial for surface chemical modification and provide a future outlook.
Efficacy and safety of desensitization to allopurinol following cutaneous reactions (2001)

The study confirms the long-term efficacy and safety of slow oral desensitization to allopurinol in patients with maculopapular eruptions, particularly in those with gout, who cannot be treated with uricosurics or other urate-lowering drugs. Although pruritic skin eruptions may recur both during and after desensitization, most of these cutaneous reactions can be managed by temporary withdrawal of allopurinol and dosage adjustment.
Minimal Nucleation State of α-Synuclein Is Stabilized by Dynamic Threonine–Water Networks (2017)

The first structures of α-synuclein (αSyn) fibrils have recently been solved. Here, we use a unique combination of molecular dynamics simulation strategies to address the minimal nucleation size of the 11-amino acid NAC protofibril solved by X-ray and to interrogate the dynamic behavior of unexpected crystal waters in the steric zipper. We found that protofibrils of >8 chains are thermodynamically stabilized due to protection of the fibril core from solvent influx and ordering of the end strands by the fibril core. In these stable oligomers, water molecules resolved in the crystal structure freely exchange with bulk solvent but are, on average, stably coordinated along the β-sheet by inward-facing Thr72 and Thr75. We confirm the persistence of this water coordination via simulations of the full-length Greek-key structure solved by NMR and speculate that these Thr–water networks are important in the context of enhanced fibril nucleation in the familial A53T mutation.
Quantitative Detection of Environmentally Important Dyes Using Diode Laser/Fiber-Optic Raman Spectroscopy (1995)

A compact diode laser/fiber-optic Raman spectrometer is used for quantitative detection of environmentally important dyes. This system is based on diode laser excitation at 782 nm, fiber-optic probe technology, an imaging spectrometer, and a state-of-the-art scientific CCD camera. The dyes studied include trypan blue, acid black 1, acid blue 40, and basic blue 7. Detection sensitivities (at rms S/N = 2) ranged from 0.2 ppm (3.24 × 10 −7 M) for acid black 1, to 25 ppm (4.86 × 10 −5 M) for basic blue 7.
Improved Immunoglobulin Production in Dialysis Patients Treated with Recombinant Erythropoietin (1992)

Improvements in B lymphocyte function have been reported in hemodialysis patients receiving erythropoietin. The present investigation studied whether erythropoietin interferes with B cell function and the mechanisms of this effect. Antibody production by cultured peripheral blood mononuclear cells (PBMC) (7 days) from 15 dialysis patients before and during erythropoietin treatment and from 14 healthy controls was followed. IgG and IgA were formed less in the uremic group than in healthy subjects. After 8 weeks of erythropoietin (hematocrit rose from 19 to 31%) basal IgG formation by PBMC rose from 304 +/- 83 to 566 +/- 49 ng/ml (p less than 0.02), while IgA production rose from 380 +/- 121 to 563 +/- 362 ng/ml (p less than 0.01). IgM production, which appeared to be normal in uremia, remained unchanged during erythropoietin treatment. Production of IgG and IgA stimulated by pokeweed-mitogen was subnormal in uremia, but improved under erythropoietin therapy. To establish whether erythropoietin acted by itself or through correction of the renal anemia, healthy PBMC were directly incubated with 2 U/ml of erythropoietin. Under these conditions production of IgG (+19%), IgA (+28%), and IgM (+32%) was enhanced. Taken together these data indicate a direct stimulant effect of erythropoietin on B lymphocytes in end-stage renal failure.
Malaria in southern Mozambique: Malariometric indicators and malaria casedefinition in Manhiça district (2003)

A total of 2057 children aged <10 years were selected at random from a demographic surveillance system and enrolled in 4 malariometric cross-sectional surveys in different seasons in Manhiça district in southern Mozambique. Plasmodium falciparum accounted for 90% of all malaria infections and the prevalence of asexual P. falciparum ranged from 13.7-21.7% at the end of the dry season to 30.5-34.0% at the end of rainy season. In order to determine the malaria attributable fraction (MAF) of fever, 1021 children from a nearby hospital acted as fever cases and from this separate case-control study the crude MAF was 36%, showing a marked age dependency. Plasmodium falciparum is the most common malaria species in Manhiça. This malaria-mesoendemic area has year-round transmission. The importance of other non-malarial fever-causing conditions among infants was highlighted. Malaria appeared to be a major contributory factor to anaemia in the area.
Neuroprotection against nitric oxide injury with inhibitors of ADP-ribosylation. (1993)

We investigated the effect of nitric oxide (NO) upon CA1 neurons of the hippocampal slice. NO was given via perfusate without oxygen and with glucose concentration increased to 10 mM to prevent hypoxic injury. Exposure to NO for 10 min produced severe neuronal injury, with CA1 orthodromic and antidromic population spike regaining only 3 +/- 3% and 9 +/- 3% of initial amplitude after 1 h recovery. Hypoxic controls in contrast, showed orthodromic and antidromic recovery of 98 +/- 5% and 93 +/- 7%. Good protection from NO-induced injury was seen with 10 mM nicotinamide, an inhibitor of poly-ADP-ribosylation, with CA1 PS recovering to 116 +/- 10% orthodromically, and 96 +/- 4% antidromically. Protection was also seen with 3'-aminobenzamide, another poly-ADP-ribosylation inhibitor, suggesting that poly-ADP-ribosylation may play an important role in NO-mediated neuronal injury.
Targeting pericytes with a PDGF-B aptamer in human ovarian carcinoma models (2010)

Dual targeting of endothelial cells and pericytes holds potential as an anti-vascular therapeutic approach in ovarian carcinoma.