gebhart/patrepeval huggingface dataset:
Residual risk for cytogenetic abnormalities after prenatal diagnosis by interphase fluorescence in situ hybridization (FISH) (2003)

Results from conventional cytogenetic studies on 21 609 amniotic fluid specimens were analyzed retrospectively to determine the residual risk for a cytogenetic abnormality if interphase FISH, capable of only detecting aneuploidy for chromosomes 13, 18, 21, X and Y, was performed and did not reveal an abnormality. Detection rates (the probability of detecting a cytogenetic abnormality when an abnormality is present) and residual risks (the likelihood of a cytogenetic abnormality, in view of normal interphase FISH results) were calculated for the four major clinical indications for prenatal diagnosis (advanced maternal age, abnormal maternal serum screen indicating increased risk for trisomy 18 or trisomy 21, abnormal maternal serum screen indicating increased risk for neural tube defects and ultrasound abnormality). Differences in detection rates were observed to depend on clinical indication and presence or absence of ultrasound abnormalities. The detection rate ranged from 18.2 to 82.6% depending on the clinical indication. The detection rates of abnormalities significant to the pregnancy being evaluated (i.e. abnormalities excluding familial balanced rearrangements and familial markers) were between 28.6 and 86.4%. The presence of ultrasound abnormalities increased the detection rate from 72.2 to 92.5% for advanced maternal age and from 78.6 to 91.3% for abnormal maternal serum screen, indicating increased risk for trisomy 18 or trisomy 21. With regard to residual risk, the risk for a clinically significant abnormality decreased from 0.9-10.1%, prior to the interphase FISH assay, to a residual risk of 0.6-1.5% following a normal interphase FISH result in the 4 groups studied. Providing patients with detection rates and residual risks, most relevant to their situation (clinical indication and presence or absence of ultrasound abnormality) during counseling, could help them better understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation.
Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice (2013)

β-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption. As a consequence, patients affected by these disorders exhibit iron overload, which is the main cause of morbidity and mortality. HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression. We identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis (Hfe(-/-)) significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by β-thalassemia (HBB(th3/+) mice, referred to hereafter as th3/+ mice) decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis (IE) and splenomegaly, and an increase in total hemoglobin levels. These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, β-thalassemia, and related disorders.
Joint physiology and synovial cell proliferation (1998)

the possibility that the anti-PRL autoantibody could be the cause of HPRL in SLE patients. Moreover, the SWe read with interest the article by Mok et al. interpretation is different from the finding by Hattori [1]. In this paper, as well as in the previous report, the et al. (PRL) and lupus activity in systemic lupus eryth-Hattori et al. found that the autoantibodies to PRL ematosus (SLE ) patients, in spite of the fact that interfere with the real values of serum PRL using the experimental studies using animal models have shown radioimmunoassay (RIA) technique, showing that the sufficient evidence that PRL plays a role in automeasured levels of this hormone are lower than immune rheumatic disease [2]. In contrast, the clinical the real values, i.e. false low levels. In contrast, the trials carried out in humans, including the article by immunoradiometric assay (IRMA) technique Mok et al., have shown contradictory data concerning expressed more confident results. the participation of PRL in SLE and its relationship We are running a transverse design study with a with disease activity. The debate has not yet yielded a large number of SLE patients. At this time, we have satisfactory conclusion. Recently, we carried out an studied 260 SLE patients; of those, 42 have shown analysis using the results from the English language HPRL (16.2%, 95% CI = 11.7-20.7%
Isolating and Estimating Undifferenced GPS Integer Ambiguities (2008)

The limiting factor in ambiguity resolution using undifferenced GPS observables is not the presence of unknown fractional cycle biases in the phase observations, but the presence of code biases in the estimates of the ambiguities. As parameterised in the ‘standard model’ of undifferenced ionosphere-free pseudoranges and carrier phases, the datum for the station and satellite clock parameters is provided by the pseudoranges. The consequence of this is that the estimated ambiguities contain the time-constant portions of both code and phase biases. To overcome this limitation, a new GPS observation model is presented called the ‘decoupled clock model’. This model rigorously accommodates any synchronisation biases (constant or time-varying) that may occur between common-frequency observables and facilitates the estimation of integer ambiguities without explicit differencing. Application of the decoupled clock model to both the standard model of ionosphere-free code and phase observables and the well known widelanephase/ narrowlane-code combination leads to an extended model, whereby simultaneous resolution of 86cm and 11cm ambiguities is possible in principle. It is stressed that the decoupled clock model is significantly more general than the standard model, requiring no assumption about the stability of code or phase biases. The decoupled model can be applied to both network and single-user processing, where the only limitation in single-user processing is that a separate satellite clock parameter must be provided for each observable used (3 in the case of the extended model presented here). General application of the decoupled clock model may explain some of the remaining issues with GPS processing such as the dayboundary clock jumps identified by the IGS time scale, and, with further development, reduce the convergence time of Precise Point Positioning.
Multiwall carbon nanotube elastomeric composites: A review (2007)

Nanostructured materials gained great importance in the past decade on account of their wide range of potential applications in many areas. A large interest is devoted to carbon nanotubes that exhibit exceptional electrical and mechanical properties and can therefore be used for the development of a new generation of composite materials. Nevertheless, poor dispersion and poor interfacial bonding limit the full utilization of carbon nanotubes for reinforcing polymeric media. In this paper, recent advances on carbon nanotubes and their composites will be presented through results of the author's research, essentially based on filled elastomeric networks. The intrinsic potential of carbon nanotubes as reinforcing filler in elastomeric materials will be demonstrated. It will be shown that, despite a poor dispersion, small filler loadings improve substantially the mechanical and electrical behaviors of the soft matrix. With the addition of 1 phr of multiwall carbon nanotubes in a styrene–butadiene copolymer, a 45% increase in modulus and a 70% increase in the tensile length are achieved. Straining effects investigated by atomic force microscopy and infrared and Raman spectroscopies, provide interesting results for the understanding of the mechanical behavior of these nanotube-based composites. All the experimental data lead to the belief that the orientation of the nanotubes plays a major role in the mechanical reinforcement. The strong restriction in equilibrium swelling in toluene with the MWNT content is not ascribed to filler–matrix interfacial interactions but to the occlusion of rubber into the aggregates. On the other hand, carbon nanotubes impart conductivity to the insulator matrix. Between 2 and 4 phr, the conductivity increases by five orders of magnitude reflecting the formation of a percolating network. Changes in resistivity under uniaxial extension completed by AFM observations of stretched composites bring new insights into the properties of these composites by highlighting the contribution of orientational effects.
ChemInform Abstract: PHOSPHORYLATION OF SOME ORGANIC LUMINOPHORS (1984)

Abstract Zur Verbesserung der Löslichkeit sowie zur Erhöhung der Wärme‐ und Photostabilität der Luminophore (I) und (VII) setzt man diese mit Phosphiten, z.B. (II) oder(VIII), und Aldehyden wie (III) bzw. (V) um.
A light stabilizer (Tinuvin 770) that elutes from polypropylene plastic tubes is a potent L-type Ca(2+)-channel blocker. (1993)

A pharmacologically active agent was easily extracted by aqueous or organic solvents from laboratory plastic tubes (Falcon Blue Max) and has been chemically identified as bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate. This compound (approximately 12 micrograms per tube approximately 25 nmol) blocked 1,4-dihydropyridine-sensitive 45Ca2+ uptake into GH3 cells with an IC50 value of 3.6 microM, inhibited Sr2+ currents through L-type Ca2+ channels in A7r5 smooth-muscle cells in whole-cell patch-clamp experiments after extracellular application, and affected the high-affinity binding of Ca2+ entry-blocker ligands to a variety of preparations. Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is a highly potent (IC50 values < 10 nM) inhibitor at the phenylalkylamine- and benzothiazepine-selective drug-binding domains of the alpha 1 subunit of L-type Ca2+ channels. This compound behaves as a heterotropic allosteric regulator for the 1,4-dihydropyridine-selective domain in purified Ca(2+)-channel preparations from rabbit skeletal muscle. (+)-Tetrandrine stimulation of 1,4-dihydropyridine binding to the membrane-bound L-type Ca2+ channel is inhibited by the compound in a competitive manner (Ki value = 6.8 nM). Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is therefore classified as the prototype of another class of L-type Ca(2+)-channel blockers that binds to the alpha 1 subunit at the drug-binding domains selective for (+)-tetrandrine or (+)-cis-diltiazem. This compound is identical to Tinuvin 770, which is used worldwide as a light stabilizer for polyolefins.
Tetramer-based quantification of cytomegalovirus (CMV)–specific CD8+ T lymphocytes in T-cell–depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection (2001)

Recovery of cytomegalovirus (CMV)-specific T-cell-mediated immunity after allogeneic hematopoietic stem cell transplantation (SCT) is critical for protection against CMV disease. The study used fluorochrome-conjugated tetrameric complexes of HLA-A2 molecules loaded with the immunodominant NLVPMVATV (NLV) peptide derived from the CMV protein pp65 to quantify A2-NLV-specific CD8+ T cells in partially T-cell-depleted grafts administered to 27 HLA-A*0201+ patients and to monitor recovery of these T cells during the first 12 months after SCT. None of the 9 CMV-seronegative patients became infected with CMV, whereas 14 of 18 CMV-seropositive patients developed CMV antigenemia after SCT. CMV-seropositive recipients of grafts from CMV-seronegative donors required more preemptive treatment with ganciclovir (GCV) than those of grafts from CMV-seropositive donors (3 [1-6] versus 1 [0-3] courses, respectively; P =.009). The number of A2-NLV-specific CD8+ T cells in the grafts correlated inversely with the number of preemptive GCV courses administered (r = -0.61; P =.01). None of the 9 CMV-seronegative patients mounted a CMV-specific immune response as measured by monitoring A2-NLV-specific CD8+ T cells after SCT. Thirteen of 14 CMV-seropositive patients without CMV disease recovered these T cells. In spite of preemptive GCV treatment, CMV disease developed in 4 patients, who all failed to recover A2-NLV-specific CD8+ T cells after SCT (P =.002). Thus, enumeration of HLA-restricted, CMV-specific CD8+ T cells in the grafts and monitoring of these T cells after SCT may constitute a rapid and sensitive tool to identify SCT recipients at risk for developing CMV disease.
Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma (2014)

ITGB6-targeted immunoliposomes provide a highly efficient approach for targeted drug delivery in colon cancer and thus offer the potential of a novel and promising anticancer strategy for clinical therapy.
Taking steps (1995)

This article presents an interactive technique for moving through an immersive virtual environment (or “virtual reality”). The technique is suitable for applications where locomotion is restricted to ground level. The technique is derived from the idea that presence in virtual environments may be enhanced the stronger the match between proprioceptive information from human body movements and sensory feedback from the computer-generated displays. The technique is an attempt to simulate body movements associated with walking. The participant “walks in place” to move through the virtual environment across distances greater than the physical limitations imposed by the electromagnetic tracking devices. A neural network is used to analyze the stream of coordinates from the head-mounted display, to determine whether or not the participant is walking on the spot. Whenever it determines the walking behavior, the participant is moved through virtual space in the direction of his or her gaze. We discuss two experimental studies to assess the impact on presence of this method in comparison to the usual hand-pointing method of navigation in virtual reality. The studies suggest that subjective rating of presence is enhanced by the walking method provided that participants associate subjectively with the virtual body provided in the environment. An application of the technique to climbing steps and ladders is also presented.
The argon-hydrogen expanding plasma: model and experiments (1995)

An argon expanding cascaded arc plasma, with small amounts (0-10 vol.%) of hydrogen added to the flow, is investigated by means of Thomson-Rayleigh scattering and optical emission spectroscopy. The results, especially the electron density behaviour as a function of the distance from the onset of the expansion, are interpreted by comparison with results of a quasi one-dimensional model. The associative charge exchange reaction between Ar+ ions and H2 molecules plays a dominant role in the model. Assuming that H2 molecules from the wall enter the plasma in the shock region, the large ionization loss can be explained. Good agreement between model and experiment is found for the electron and neutral density and the electron temperature behaviour. This makes plausible the existence of a recirculation flow inside the vacuum vessel, which transports wall-associated hydrogen molecules towards the plasma.
CRISPR-cas gene-editing as plausible treatment of neuromuscular and nucleotide-repeat-expansion diseases: A systematic review (2019)

Here we give a systematic summary on the preclinical development of CRISPR-cas for therapeutic purposes in NMGDs. Furthermore, we address the clinical interpretability of the findings, giving a comprehensive overview of the current state of the art. Duchenne's muscular dystrophy (DMD) paves the way forward, with 26 out of 42 studies reporting different strategies on DMD gene editing in different models of the disease. Most of the strategies aimed for permanent exon skipping by deletion with CRISPR-cas. Successful silencing of the mHTT gene with CRISPR-cas led to successful reversal of the neurotoxic effects in the striatum of mouse models of Huntington's disease. Many other strategies have been explored, including epigenetic regulation of gene expression, in cellular and animal models of: myotonic dystrophy, Fraxile X syndrome, ataxias, and other less frequent dystrophies. Still, before even considering the clinical application of CRISPR-cas, three major bottlenecks need to be addressed: efficacy, safety, and delivery of the systems. This requires a collaborative approach in the research community, while having ethical considerations in mind.
Immunotoxicity and Environment: Immunodysregulation and Systemic Inflammation in Children (2009)

Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.
Effects of acutely raising intracranial pressure on cardiac sympathetic efferent neuron function. (1995)

Cardiac sympathetic efferent neuronal function is obtained by acutely raising intracranial pressure.
Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma (2015)

Lenvatinib (12 mg once daily) demonstrated preliminary efficacy with manageable toxicity and is the recommended dose for phase II studies in patients with HCC and CP-A.
Quantum Molecular Modeling of the Elastinic Tetrapeptide Val-Pro-Gly-Gly (1998)

The free Val-Pro-Gly-Gly tetrapeptide belonging to the Proline-rich sequences of elastin has been studied both theoretically and experimentally. The molecular modelisation was carried out using AM1 and ab initio quantum computations while the conformation in solution was ascertained by circular dichroism spectroscopy performed on the synthesized tetrapeptide. Experimental and theoretical investigations lead to the conclusion that the most probable structure is constituted by a type II beta-turn.
Effect of low-NaCl medium on the envelope glycoproteins of Sindbis virus (1978)

Lowering the NaCl concentration of the medium inhibits the release of Sindbis virus from infected chicks cells at a stage after the nucleocapsids have bound to the membranes of the infected cells. The failure of trypsin treatment to release the inhibited virus and the ratio of the proteins in the inhibited cells make it seem likely that the inhibited virus is all intracellular. Experiments using antisera specific for E1 and E2, the envelope glycoproteins of Sindbis, suggest that the inhibitory effect of low-salt medium is mediated through an effect on E2. Lactoperoxidase radioiodination experiments indicate that, even when cleaved from PE2, E2 is not exposed on the surface of low-NaCl-treated chick cells.
Interleukin‐8 and melanoma growth‐stimulating activity (GRO) are induced by ultraviolet B radiation in human keratinocyte cell lines (1995)

Abstract Ultraviolet radiation can induce the transcription and release of cytokines From keratinocytes (KC's). These cytokines have the potential to modulate local and systemic immunologic responses. In this paper we report that northern blotting showed that human KC and KC lines expressed a 1.2‐1.4 kb transcript for the chemokine and melanoma growth‐stimulatory protein, GRO‐α and that ultraviolet B radiation (UVB) could upregulate the expression of GRO‐α mRNA and protein in the KC line A431. The GRO‐α gene response to UVB was maximal at 48h post‐irradiation with 70 J/m 2 . Reverse transcription‐polymerase chain reaction (RT‐PCR) revealed a 4.5‐fold increase in GRO‐α mRNA over basal levels (p&lt;0.001). GRO‐α protein was measured in the culture media by enzyme‐linked immunosorbent assay (ELISA). Media from unirradiated cultures contained 1166±83 pg/ml GRO‐α protein. After UVB, a time‐dependent increase in GRO‐α protein was seen in the culture media from 6‐48h. At 48h post‐irradiation the GRO‐α protein content was 27583±678 pg/ml, or 23 times the basal level. This protein release could be inhibited by 70% when the cells were pre‐incubated with 10 μg/ml interleukin‐1 receptor antagonist (IL‐1RA). We also show that another potent leukocyte chemoattractant, Interleukin‐8 (IL‐8), was induced in A431 cells by UVB. The induction of IL‐8 mRNA began as early as 3h post‐irradiation, when it reached twice basal levels (p&lt;0.05) and reached 4.5‐fold basal levels at 48h post‐irradiation (p&lt;0.005). Analysis of the conditioned media from the irradiated cells by ELISA revealed that IL‐8 protein accumulation was increased from 162± 16 pg/ml (unirradiated cultures) to 993± 120 pg/ml 24h post‐irradiation. The accumulation increased to 1383± 178 pg/ml, or 9‐fold the basal level by 48h post‐irradiation. Thus keratinocytes are capable of generating chemoattractant factors which enhance melanoma growth after UVB irradiation, which may contribute to the inflammatory infiltrate found in the dermis of sunburned skin.
Incorporation of polymer microspheres within fibrin scaffolds for the controlled delivery of FGF-1 (2004)

The purpose of this work was to examine the feasibility of a hybrid scaffold in which fibroblast growth factor-1 (FGF-1)-encapsulated microspheres are embedded within a fibrin gel. Such a tissue-engineered scaffold could be incorporated into surgical procedures to promote healing while simultaneously delivering therapeutic agents that promote angiogenesis. Fibrin has been extensively studied as an adhesive in plastic and reconstructive surgery and the enhancement of wound healing with embedded growth factors is desirable. We report the release of a fluorescently-labeled model protein, bovine serum albumin (BSA-FITC), from poly(D,L-lactic-co-glycolic acid) microspheres embedded in the fibrin scaffold. The protein release was found to be significantly delayed as compared to microspheres alone during the initial 24 h of release. Additionally, FGF-1 was examined for efficient incorporation into these scaffolds as a potential mitogen for fibroblasts. The optimal concentration of FGF-1 in the media that enhanced NIH-3T3 fibroblast proliferation over 48 h was determined to be 0.1 microg/ml. The release of FGF-1 from microspheres embedded in fibrin gels was compared to FGF-1-encapsulated microspheres alone. The release of FGF-1 from the microsphere/scaffolds was delayed as compared to the release of FGF-1 from microspheres alone. This novel hybrid fibrin/microsphere scaffold is a feasible delivery system for growth factors.