gebhart/patrepeval huggingface dataset:
Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity. (2003)

Rad51 is an essential component of the homologous DNA repair pathway and has been implicated as a determinant of cellular radiosensitivity. Gleevec is a relatively specific inhibitor of c-Abl, a tyrosine kinase that can play a role in the regulation Rad51. The aim of this study was to determine the effects of Gleevec on Rad51 levels and the radiosensitivity of two human glioma cell lines and a nonimmortalized normal human fibroblast cell line. Exposure of both glioma cell lines to radiation resulted in an increase in Rad51 expression; Gleevec treatment alone reduced Rad51 expression. When glioma cells were pretreated with Gleevec, radiation-induced Rad51 expression and nuclear foci formation were reduced. Accordingly, pretreatment of the glioma cells with Gleevec resulted in an enhancement in their radiosensitivity. These data indicate that Gleevec enhances radiation-induced tumor cell killing and suggest that the mechanism involves the reduction in Rad51 levels. In contrast to the glioma cell lines, radiation or Gleevec treatments had no effect on Rad51 expression or foci formation in the normal fibroblast cells. Consistent with these observations, Gleevec did not modify the radiosensitivity of the normal cell line. These results suggest that Rad51 expression is subject to different regulatory processes in the glioma and normal cell lines and further suggest that Rad51 may be an appropriate target for selectively enhancing the radiosensitivity of brain tumor cells.
Amputation for reflex sympathetic dystrophy (1995)

We have reviewed 28 patients with reflex sympathetic dystrophy (RSD) who had 34 amputations in 31 limbs. The amputations had been performed for untenable pain (5), recurrent infection (14) or to improve residual function (15). Only two patients were relieved of pain by amputation, and this could not be predicted. Ten of 14 patients were cured of infection and 9 of 15 patients had improvement of residual function. In 28 of the amputations, RSD recurred in the stump, especially after amputation at a level which was not free from symptoms. Because of recurrence of RSD in the stump or severe hyperpathia only two patients wear a prosthesis. Despite this 24 patients were satisfied with the results.
Construction, expression and characterization of humanized antibodies directed against the human alpha/beta T cell receptor (1991)

Completely humanized antibodies with specificity for the human alpha/beta TCR have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 CD regions and human EU framework regions were synthesized and replaced into previously isolated genomic fragments. These fragments were inserted into mammalian expression vectors containing the human kappa and gamma 1 C region exons. Two variants were constructed each containing selected BMA 031 amino acids within the human frameworks. The humanized genes were transfected into Sp2/0 hybridoma cells by electroporation and transfectomas secreting humanized antibody were isolated. Levels of antibody expression up to 7 pg/cell/24 h were obtained. The humanized antibody, BMA 031-EUCIV2, competed poorly with murine BMA 031 for binding to T cells. BMA 031-EUCIV3, however, bound specifically to T cells and competed effectively with both the murine BMA 031 antibody and a previously constructed chimeric BMA 031 antibody for binding to these cells. The relative affinity of BMA 031-EUCIV3 was about 2.5 times lower than BMA 031. The ability to promote antibody dependent cell-mediated cytolysis was significantly enhanced with the engineered antibodies as compared to murine BMA 031. Humanized BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft vs host disease, and autoimmunity.
Advances in Non-Peptide Glucagon Receptor Antagonists (1999)

This review deals with glucagon receptor antagonism as a possible treatm ent of Type 2 diabetes. The role of glucagon in animal models has been studied by glucagon antibodies as model antagonists. Depending upon the animal model studied, selective glucagon deficiency produced by immunone utralisation suggests that glucagon plays a modest (rats) to substantial (rabbits) role in the maintenance of euglycaemia and is an important dia betogenic factor. These data strongly suggest that glucagon antagonism may be a beneficial and safe therapeutic approach for the treatment of T ype 2 diabetes. Further, the progress on non-peptide glucagon receptor antagonists is reviewed with special focus on the different classes of g lucagon receptor antagonists published, namely quinoxalines /pyrrolo[1,2 -a]quinoxalines, mercaptobenzimidazoles, 2-pyridyl-3,5-diarylpyrroles, q uinoline hydrazones, 4-phenylpyridines, and alkylidene hydrazides.
Plasma microRNA biomarkers for detection of mild cognitive impairment (2012)

Early stages of many neurodegenerative diseases, such as Alzheimer's disease, vascular and frontotemporal dementia, and Parkinson's disease, are frequently associated with Mild Cognitive Impairment (MCI). A minimally invasive screening test for early detection of MCI may be used to select optimal patient groups in clinical trials, to monitor disease progression and response to treatment, and to better plan patient clinical care. Here, we examined the feasibility of using pairs of brain-enriched plasma microRNA (miRNA), at least one of which is enriched in synapses and neurites, as biomarkers that could differentiate patients with MCI from age-matched controls. The identified biomarker pairs fall into two sets: the "miR-132 family" (miR-128/miR-491-5p, miR-132/miR-491-5p and mir-874/miR-491-5p) and the "miR-134 family" (miR-134/miR-370, miR-323-3p/miR-370 and miR-382/miR-370). The area under the Receiver-Operating Characteristic curve for the differentiation of MCI from controls using these biomarker pairs is 0.91-0.95, with sensitivity and specificity at 79%-100% (miR-132 family) and 79%-95% (miR-134 family), and p〈0.001. In a separate longitudinal study, the identified miRNA biomarker pairs successfully detected MCI in majority of patients at asymptomatic stage 1-5 years prior to clinical diagnosis. The reported biomarker pairs also appear useful for detecting age-related brain changes. Further testing in a larger study is necessary for validation of these results.
A Comprehensive Human Linkage Map with Centimorgan Density (1994)

In the last few years there have been rapid advances in developing genetic maps for humans, greatly enhancing our ability to localize and identify genes for inherited disorders. Through the collaborative efforts of three large groups generating microsatellite markers and the efforts of the 110 CEPH collaborators, a comprehensive human linkage map is presented here. It consists of 5840 loci, of which 970 are uniquely ordered, covering 4000 centimorgans on the sex-averaged map. Of these loci, 3617 are polymerase chain reaction-formatted short tandem repeat polymorphisms, and another 427 are genes. The map has markers at an average density of 0.7 centimorgan, providing a resource for ready transference to physical maps and achieving one of the first goals of the Human Genome Project--a comprehensive, high-density genetic map.
Detection of atmospheric pollutants: a correlation technique (1975)

The objective of this effort was to derive suitable correlation functions for monitoring the atmosphere for specified pollutants by remote ir sensing techniques. The correlation function for a particular target pollutant is calculated by the simplex optimization method. This technique constrains the response of the gas detection system to less than some arbitrary constraint limit for background changes while optimizing system response to the target pollutant. The response to a target pollutant was 2 to 3 times greater than any background induced change over a period of 2 weeks. The technique is applicable to a wide range of spectral analytical problems and may apply to process control as well as remote sensing techniques, particularly in pollution monitoring applications.
Mechanical characterization of high‐performance graphene oxide incorporated aligned fibroporous poly(carbonate urethane) membrane for potential biomedical applications (2015)

ABSTRACT In this article, we report the development of graphene oxide (GO) reinforced electrospun poly(carbonate urethane) (PCU) nanocomposite membranes intended for biomedical applications. In this study, we aimed to improve the mechanical properties of PCU fibroporous electrospun membranes through fiber alignment and GO incorporation. Membranes with 1, 1.5, and 3% loadings of GO were evaluated for their morphology, mechanical properties, crystallinity, biocompatibility, and hemocompatibility. The mechanical properties were assessed under both static and dynamic conditions to explore the tensile characteristics and viscoelastic properties. The results show that GO presented a good dispersion and exfoliation in the PCU matrix, contributing to an increase in the mechanical performance. The static mechanical properties indicated a 55% increase in the tensile strength, a 127% increase in toughness for 1.5 wt % GO loading and the achievement of a maximum strength reinforcement efficiency value at the same loading. Crystallinity changes in membranes were examined by X‐ray diffraction analysis. In vitro cytotoxicity tests with L‐929 fibroblast cells and percentage hemolysis tests with fresh venous blood displayed the membranes to be cytocompatible with acceptable levels of hemolytic characteristics. Accordingly, these results highlight the potential of this mechanically improved composite membrane's application in the biomedical field. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 41809.
Human α-synuclein-harboring familial Parkinson's disease-linked Ala-53 → Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice (2002)

Mutations in alpha-synuclein (alpha-Syn) cause Parkinson's disease (PD) in a small number of pedigrees with familial PD. Moreover, alpha-Syn accumulates as a major component of Lewy bodies and Lewy neurites, intraneuronal inclusions that are neuropathological hallmarks of PD. To better understand the pathogenic relationship between alterations in the biology of alpha-Syn and PD-associated neurodegeneration, we generated multiple lines of transgenic mice expressing high levels of either wild-type or familial PD-linked Ala-30 --> Pro (A30P) or Ala-53 --> Thr (A53T) human alpha-Syns. The mice expressing the A53T human alpha-Syn, but not wild-type or the A30P variants, develop adult-onset neurodegenerative disease with a progressive motoric dysfunction leading to death. Pathologically, affected mice exhibit neuronal abnormalities (in perikarya and neurites) including pathological accumulations of alpha-Syn and ubiquitin. Consistent with abnormal neuronal accumulation of alpha-Syn, brain regions with pathology exhibit increases in detergent-insoluble alpha-Syn and alpha-Syn aggregates. Our results demonstrate that the A53T mutant alpha-Syn causes significantly greater in vivo neurotoxicity as compared with other alpha-Syn variants. Further, alpha-Syn-dependent neurodegeneration is associated with abnormal accumulation of detergent-insoluble alpha-Syn.
Cycloid vs. harmonic drives for use in high ratio, single stage robotic transmissions (2012)

Harmonic and cycloid drives are both compact, high ratio transmissions appropriate for use in anthropomorphic robots, although cycloid drives are rarely used in the field. This paper describes the design parameters for cycloid drives and shows the results of six cycloid models designed to match corresponding harmonic drives. Cycloid drive models were compared with manufacturing data from corresponding harmonic drives with respect to maximum gear ratio, transmission thickness, efficiency, backlash/gear ratio ripple, and reflected inertia. Cycloid drive designs were found to be thinner, more efficient, and to have lower reflected inertia than corresponding harmonic drives. However, the cycloid designs had larger gear ratio ripple and substantial backlash, and they could not meet the maximum gear ratio provided by the corresponding harmonic drives in two out of six models for equal applied torques. Two cycloid drives were manufactured to confirm efficiency predictions and demonstrated moderate to high efficiency across a range of output torques. Cycloid drives should be considered for robotic and prosthetic applications where smaller thickness/higher efficiency requirements dominate over low backlash/gear ratio ripple considerations.
Functional verification methodology of Chameleon processor (1996)

Article Functional verification methodology of Chameleon processor Share on Authors: Françoise Casaubieilh Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Anthony McIsaac Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Mike Benjamin Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Mike Bartley Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , François Pogodalla Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Frédéric Rocheteau Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Mohamed Belhadj Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Jeremy Eggleton Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Gérard Mas Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Geoff Barrett Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile , Christian Berthet Chameleon Programme, SGS-THOMSON Microelectronics Chameleon Programme, SGS-THOMSON MicroelectronicsView Profile Authors Info & Claims DAC '96: Proceedings of the 33rd annual Design Automation ConferenceJune 1996 Pages 421–426https://doi.org/10.1145/240518.240599Online:01 June 1996Publication History 23citation408DownloadsMetricsTotal Citations23Total Downloads408Last 12 Months5Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
The human leucocyte antigen (HLA) system. (2002)

KEYWORDS Immunogenetics; HLA; MHC; molecular biology ABSTRACT The discovery of Major Histocompatibility Complex (MHC) and its involvement in graft rejection, immune response and the genetic basis of disease associations lead to the birth of this new field of science called Immunogenetics. This field is important not only in basic biomedical research but also in clinical medicine. The growth of this field was further substantiated by the various International Histocompatibility Workshops. Solutions to idiopathic syndromes and autoimmune diseases come from the field of Immunology, Immunogenetics and Molecular biology. In studying the genetic basis of disease susceptibility in human beings, one has to have a different approach because predictive experimental mating cannot be achieved in humans as in animal models; moreover the generation time is longer. One approach is through a study of randomly selected patients and comparing their results with those of controls and the other is through a study of affected families (nuclear or extended) and looking for the mode of inheritance of the disease with relation to genetic markers. Nonetheless the sampling stratification, sample heterogeneity, disease heterogeneity, and age at onset, epidemiological conditions and other socio-biological factors limit these studies. Essentially attempts are to be made to control these parameters and achieve a meaningful conclusion. The current concepts of antigen presentation to immunocompetent cells indicate that antigen processing takes place in the acid environment of the endosomes of antigen presenting cells. Proteolytic degradation of the antigenic proteins results in peptides of different fragments, which are subsequently presented by MHC molecules after they are bound to peptide binding site of the MHC molecules which can bind a variety of peptides having in common, a peptide backbone. These immunogenic peptides (held snugly in the groove by hydrogen bonds between the MHC protein and the peptide backbone) on antigen presenting cells, with the MHC molecule and T-cell receptor on T-cells form a stable trimolecular complex. Thus MHC molecules and alpha beta T-cell receptors or gamma delta T-cell receptor play a major role in the subsequent immune response. The polymorphism of the MHC molecules and T-cell receptor may play an important role in the antigen recognition process. It is possible that a few of the many alleles of a given HLA locus may provide a more stable trimolecular complex than others, thus resulting in a 'high responder status' of an individual than the rest of the alleles. This field of HLA system has been evolving very fast and therefore an updated HLA system review has been provided.
C23 Interacts with B23, A Putative Nucleolar‐Localization‐Signal‐Binding Protein (1996)

The human protein C23 (nucleolin) is a major nucleolar protein. Its interactions with other proteins were studied with the two-hybrid system which identified nucleolar protein B23 (nucleophosmin) as being associated with C23. Both proteins were co-immunoprecipitated from HeLa cell nuclear extract by either monoclonal anti-C23 or monoclonal anti-B23. Binding studies utilizing deletion mutants indicated that the binding of C23 and B23 involves specific motifs. In addition to an approximately 46-amino-acid-binding domain in B23 (amino acids 194-239), amino acids 540-628 of C23 were required for binding; this region of C23 is required for the nucleolar localization. In addition, nucleolar protein p120 was also found to be co-immunoprecipitated with B23. A fragment of p120 containing a functional nucleolar localization signal bound to the truncated binding domain of B23, as did C23. These results suggest that the interaction of C23 and B23 may represent a nucleolar-targeting mechanism in which B23 acts as a nucleolar-localization signal-binding protein.
Hyperbranched polymers for controlled release of cisplatin (2008)

Hyperbranched polymers based on a polyether and polyester have been modified and used as macromolecular ligands for the anticancer drug cisplatin, giving controlled release of the drug over 7 days.
Structural Basis of Functional Group Activation by Sulfotransferases in Complex Metabolic Pathways (2012)

Sulfated molecules with diverse functions are common in biology, but sulfonation as a method to activate a metabolite for chemical catalysis is rare. Catalytic activity was characterized and crystal structures were determined for two such "activating" sulfotransferases (STs) that sulfonate β-hydroxyacyl thioester substrates. The CurM polyketide synthase (PKS) ST domain from the curacin A biosynthetic pathway of Moorea producens and the olefin synthase (OLS) ST from a hydrocarbon-producing system of Synechococcus PCC 7002 both occur as a unique acyl carrier protein (ACP), ST, and thioesterase (TE) tridomain within a larger polypeptide. During pathway termination, these cyanobacterial systems introduce a terminal double bond into the β-hydroxyacyl-ACP-linked substrate by the combined action of the ST and TE. Under in vitro conditions, CurM PKS ST and OLS ST acted on β-hydroxy fatty acyl-ACP substrates; however, OLS ST was not reactive toward analogues of the natural PKS ST substrate bearing a C5-methoxy substituent. The crystal structures of CurM ST and OLS ST revealed that they are members of a distinct protein family relative to other prokaryotic and eukaryotic sulfotransferases. A common binding site for the sulfonate donor 3'-phosphoadenosine-5'-phosphosulfate was visualized in complexes with the product 3'-phosphoadenosine-5'-phosphate. Critical functions for several conserved amino acids in the active site were confirmed by site-directed mutagenesis, including a proposed glutamate catalytic base. A dynamic active-site flap unique to the "activating" ST family affects substrate selectivity and product formation, based on the activities of chimeras of the PKS and OLS STs with exchanged active-site flaps.
OX40 costimulation turns off Foxp3+ Tregs (2007)

OX40 is a recently identified T-cell costimulatory molecule that belongs to the TNF/TNFR superfamily. OX40 can be expressed by both activated T effector cells and Foxp3(+) Tregs. It is well known that OX40 delivers a potent costimulatory signal to T effector cells, but very little is known about the role of OX40 in regulating the suppressor properties of Foxp3(+) Tregs and the de novo generation of new inducible Foxp3(+) Tregs from T effector cells. In the present study, we found, by using a newly created foxp3gfp knockin model, that OX40 was dispensable for the genesis and suppressor functions of naturally arising CD4(+)Foxp3(+) Tregs, but stimulating OX40 on the Foxp3(+) Tregs abrogated their ability to suppress T effector cell proliferation, IFN-gamma production, and T effector cell-mediated allograft rejection. OX40 costimulation did not significantly affect proliferation and survival of the naturally arising Foxp3(+) Tregs, but profoundly inhibited Foxp3 gene expression. Importantly, OX40 costimulation to T effector cells prevented the induction of new inducible Foxp3(+) Tregs from T effector cells. Our study identified OX40 as a key negative regulator of Foxp3(+) Tregs and may have important clinical implications in models of transplantation and autoimmunity.
Protection of rats from compound 48/80-induced lethality. A simple test for inhibitors of mast cell-mediated shock. (1978)

The dose of 0.5 mg/kg i.v. of compound 48/80 was lethal in 97.2% of the injected rats. Observations before death and at autopsy were in accordance with the basic effect of compound 48/80 in rats i.e. the sustained release of mast cell mediators, whose action on the cardiovascular system leads to circulatory collapse. The administration of drugs with various pharmacological effects before the intravenous challenge with compound 48/80 allowed us to conclude that the following effects are not sufficient to prevent the lethal shock: inhibition of prostaglandin biosynthesis; H2-histamine antagonism; cholinergic, alpha- or beta-adrenergic blockade; beta-adrenergic stimulation; CNS-effects of antidepressants, hypnotics, sedatives, neuroleptics or narcotic analgesics; ganglion blockade; glucocorticoid or cromoglycate-like activity. Dose-dependent protection from the lethal reaction was obtained with compounds known to exert a single or several actions of the following types: oxatomide-like inhibition of mast cell mediator release; h1-histamine antagonism; serotonin antagonism. Quantitatively, however, when measured in in vitro systems these effects are poorly related to the protection from lethal compound 48/80 challenge. The new test offers the advantage of a simple, comprehensive measure of the potency of a compound to prevent mast cell-mediated shock.
Ambient condition-processing strategy for improved air-stability and efficiency in mixed-cation perovskite solar cells (2020)

Fabrication of efficient halide perovskite solar cells under ambient conditions and their stability remain a challenge due to the sensitivity of halide perovskites to moisture, oxygen, light, and temperature.