gebhart/patrepeval huggingface dataset:
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas (2015)

The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).
Update on Usher syndrome (2009)

Understanding clinical disease progression and molecular pathways is important in the progress towards developing gene therapy to prevent blindness due to Usher syndrome as well as delivering prognostic information to affected individuals.
Isolation, characterization, and chondrogenic potential of human bone marrow-derived multipotential stromal cells (2000)

Multipotential bone marrow stromal cells have the ability to differentiate along multiple connective tissue lineages including cartilage. In this study, we developed an efficient and reproducible procedure for the isolation of stromal cells from bone marrow aspirates of normal human donors based on the expression of endoglin, a type III receptor of the transforming growth factor-beta (TGF-beta) receptor family. We demonstrate that these cells have the ability of multiple lineage differentiation. Stromal cells represented 2-3% of the total mononuclear cells of the marrow. The cells displayed a fibroblastic colony formation in monolayer culture and maintained similar morphology with passage. Expression of cell surface molecules by flow cytometry displayed a stable phenotype with culture expansion. When cocultured with hematopoietic CD34(+) progenitor cells, stromal cells were able to maintain their ability to support hematopoiesis in vitro. Culture expanded stromal cells were placed in a 3-dimensional matrix of alginate beads and cultured in serum-free media in the presence of TGFbeta-3 for chondrogenic lineage progression. Increased expression of type II collagen messenger RNA was observed in the TGFbeta3 treated cultures. Immunohistochemistry performed on sections of alginate beads detected the presence of type II collagen protein. This isolation procedure for stromal cells and the establishment of the alginate culture system for chondrogenic progression will contribute to the understanding of chondrogenesis and cartilage repair.
Nucleotide Sequence and Transcriptional Regulation of the Yeast Recombinational Repair Gene RAD51 (1992)

The RAD51 gene of Saccharomyces cerevisiae is required both for recombination and for the repair of DNA damage caused by X rays. Here we report the sequence and transcriptional regulation of this gene. The RAD51 protein shares significant homology (approximately 50%) over a 70-amino-acid with the RAD57 protein (J.A. Kans and R.K. Mortimer, Gene 105:139-140, 1991), the product of another yeast recombinational repair gene, and also moderate (approximately 27%), but potentially significant, homology with the bacterial RecA protein. The homologies cover a region that encodes a putative nucleotide binding site of the RAD51 protein. Sequences upstream of the coding region for RAD51 protein share homology with the damage response sequence element of RAD54, an upstream activating sequence required for damage regulation of the RAD54 transcript, and also contain two sites for restriction enzyme MluI; the presence of MluI restriction sites has been associated with cell cycle regulation. A 1.6-kb transcript corresponding to RAD51 was observed, and levels of this transcript increased rapidly after exposure to relatively low doses of X-rays. Additionally, RAD51 transcript levels were found to that of a group of genes involved primarily in DNA synthesis and replication which are thought to be coordinately cell cycle regulated. Cells arrested in early G1 were still capable of increasing levels of RAD51 transcript after irradiation, indicating that increased RAD51 transcript levels after X-ray exposure are not solely due to an X-ray-induced cessation of the cell cycle at a period when the level of RAD51 expression is normally high.
Modulation of gamma globin genes expression by histone deacetylase inhibitors: an in vitro study (2014)

Induction of fetal haemoglobin (HbF) is a promising therapeutic approach for the treatment of β-thalassaemia and sickle cell disease (SCD). Several pharmacological agents, such as hydroxycarbamide (HC) and butyrates, have been shown to induce the γ-globin genes (HBG1, HBG2). However, their therapeutic use is limited due to weak efficacy and an inhibitory effect on erythroid differentiation. Thus, more effective agents are needed. The histone deacetylase (HDAC) inhibitors are potential therapeutic haemoglobin (Hb) inducers able to modulate gene expression through pleiotropic mechanisms. We investigated the effects of a HDAC inhibitor, Givinostat (GVS), on erythropoiesis and haemoglobin synthesis and compared it with sodium butyrate and HC. We used an in vitro erythropoiesis model derived from peripheral CD34⁺ cells of healthy volunteers and SCD donors. GVS effects on erythroid proliferation and differentiation and on Hb synthesis were investigated. We found that GVS at high concentrations delayed erythroid differentiation with no specific effect on HBG1/2 transcription. At a low concentration (1 nmol/l), GVS induced Hb production with no effects on cells proliferation and differentiation. The efficacy of GVS 1 mol/l in Hb induction in vitro was comparable to that of HC and butyrate. Our results support the evaluation of GVS as a new candidate molecule for the treatment of the haemoglobinophathies due to its positive effects on haemoglobin production at low and non-toxic concentrations.
A comparison of immunomagnetic separation and direct culture for the isolation of verocytotoxin-producing Escherichia coli 0157 from bovine faeces (1994)

Enrichment culture (EC) in modified buffered peptone water followed by immunomagnetic separation (IMS) with magnetic beads coated with an antibody against Escherichia coli O157 (Dynabeads anti-E. coli O157; Dynal, Oslo) was compared with direct culture on cefixime rhamnose sorbitol MacConkey agar (CR-SMAC) and cefixime tellurite sorbitol MacConkey agar (CT-SMAC) for the isolation of E. coli O157 from bovine faeces. When used to examine bovine faecal suspensions inoculated with 12 different strains of E. coli O157, EC-IMS was c. 100-fold more sensitive for detection of the organism than direct culture on either medium. During monitoring of a dairy herd, E. coli O157 was isolated from 84 (8.2%) of 1024 rectal swabs taken from cattle over a 4-month period; 23 (27.4% of the 84 strains were isolated by both direct culture and IMS (15 of the 23 were isolated on both media, five on CT-SMAC only and three on CR-SMAC only), whereas 61 (72.6%) strains were isolated by IMS only. IMS is a sensitive and simple technique for the isolation of E. coli O157 from bovine faecal samples and should prove useful in elucidating further the epidemiology of this organism.
Identification of a NifL-like protein in a diazotroph of the β-subgroup of the Proteobacteria, Azoarcus sp. strain BH72 c cThe GenBank accession number for the sequence determined in this work is AF518560. (2002)

NifA, the transcriptional activator of nitrogenase (nif) genes, has up to now been described to be regulated in its activity via the sensor NifL only for members of the gamma-subgroup of the PROTEOBACTERIA: This paper reports a functionally similar NifL-like protein outside this group in Azoarcus sp. strain BH72, a diazotrophic grass endophyte belonging to the beta-subgroup of the PROTEOBACTERIA: Its structural genes for nitrogenase (nifHDK) are regulated in response to combined nitrogen and O(2) and expressed endophytically inside rice roots. In order to characterize nitrogen-regulatory genes, an Azoarcus sp. BH72 genomic library was used to select cosmids that complemented a nifA mutation in Azotobacter vinelandii. Sequence analysis of the 3.4 kb genomic region complementing nifA showed two ORFs with sequence identities of 44% to NifL and 61% to NifA of Azotobacter vinelandii. According to Northern blot and reverse transcriptase PCR analysis, the nifLA transcript was more abundant at low combined nitrogen and O(2) levels, results which were corroborated by GUS (beta-glucuronidase) assays using a transcriptional nifL::gusA fusion. N(2) fixation was abolished in a NifLA(-) and a NifA(-) mutant, wild-type fixation being restored by nifLA in trans. The NifLA(-) mutant also failed to activate nifH::gus expression, indicating that NifA is the obligate transcriptional activator for nifHDK. A nifL mutant was diazotrophic and did not show repression of nifH::gusA by ammonium or O(2), suggesting that NifL of Azoarcus sp. strain BH72 has a similar role in inactivating NifA in response to O(2) and combined nitrogen as NifL in bacteria of the gamma-PROTEOBACTERIA:
Factor graphs and the sum-product algorithm (2001)

Algorithms that must deal with complicated global functions of many variables often exploit the manner in which the given functions factor as a product of "local" functions, each of which depends on a subset of the variables. Such a factorization can be visualized with a bipartite graph that we call a factor graph, In this tutorial paper, we present a generic message-passing algorithm, the sum-product algorithm, that operates in a factor graph. Following a single, simple computational rule, the sum-product algorithm computes-either exactly or approximately-various marginal functions derived from the global function. A wide variety of algorithms developed in artificial intelligence, signal processing, and digital communications can be derived as specific instances of the sum-product algorithm, including the forward/backward algorithm, the Viterbi algorithm, the iterative "turbo" decoding algorithm, Pearl's (1988) belief propagation algorithm for Bayesian networks, the Kalman filter, and certain fast Fourier transform (FFT) algorithms.
A Family of Putative Tumor Suppressors Is Structurally and Functionally Conserved in Humans and Yeast (1997)

In Saccharomyces cerevisiae the CDC14 gene is essential for cell cycle progression. Strains carrying the cdc14-1(ts) allele enter the cell cycle and arrest at restrictive temperatures. We have identified two human cDNAs encoding proteins which share sequence identity to the yeast CDC14p. The cell cycle arrest in cdc14-1(ts) can be specifically complemented by the human cDNAs suggesting that they are functionally equivalent to the yeast CDC14 gene. Another clone identified in the search for human CDC14-like proteins corresponded to the putative tumor suppressor gene PTEN/MMAC1 (phosphatase and tensin homologue deleted on chromosome 10 or mutated in multiple advanced cancers 1). Analysis of the PTEN/MMAC1 showed that it did not complement the cdc14-1(ts) allele and that it is more closely related to the yeast open reading frame YNL128W. Human CDC14p and PTEN/MMAC1 were expressed as recombinant proteins, and both were shown to have kinetic properties characteristic of dual specific phosphatases. The human CDC14p was localized in the nucleus while PTEN/MMAC1 has been reported to be localized in the cytoplasm. Our results suggest that CDC14 and YNL128W/PTEN/MMAC1 represent two related, but distinct, families of human and yeast phosphatases.
A language of health in action: Read Codes, classifications and groupings. (1996)

A cornerstone of the Information Management and Technology Strategy of the National Health Service's (NHS) Executive is fully operational, person-based clinical information systems, from which flow all of the data needed for direct and indirect care of patients by healthcare providers, and local and national management of the NHS. The currency of these data flows are firstly Read-coded clinical terms, secondly the classifications, the International, Classification of Disease and Health Related Problems, 10th Revision (ICD-10) and The Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, 4th Revision (OPCS-4), and thirdly Healthcare Resource Groups and Health Benefit Groups, all of which together are called the "language of health", an essential element of the electronic clinical record. This paper briefly describes the three main constituents of the language, and how, together with person-based, fully operational clinical information systems, it enables more effective and efficient healthcare delivery. It also describes how the remaining projects of the IM&T Strategy complete the key components necessary to provide the systems that will enable the flow of person-based data, collected once at the point of care and shared amongst all legitimate users via the electronic patient record.
Mapping the Genetic Architecture of Gene Expression in Human Liver (2008)

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process.
Prevention and Management of Stroke in Sickle Cell Anemia (2006)

As the overall health of patients with sickle cell anemia (SS) improves and diagnostic techniques become more sensitive, physicians are seeing patients with an increasingly wide range of subtle and not-so-subtle brain injury. The major breakthrough in the field of sickle-related brain injury has been the unprecedented success of transcranial Doppler ultrasonography (TCD) to identify asymptomatic patients at high risk of stroke, coupled with chronic transfusion therapy to prevent it. The evidence for TCD screening and preventive treatment is strong and compelling, but there are still important unanswered questions regarding the implications of "silent infarcts" found in the magnetic resonance images (MRIs) of asymptomatic individuals, and the growing awareness of the burden of neuropsychiatric dysfunction in otherwise apparently healthy individuals.
Pressure Pulsing Waterflooding in Dual Porosity Naturally Fractured Reservoirs (1988)

ABSTRACT Conventional waterflooding in naturally fractured reservoirs can be uneconomic due to poor oil recovery performance. A technique to improve the oil recovery performance is pressure pulsing water-flooding. The technique is cyclic and consists of alternately pressuring and depressuring the reservoir. During the pressuring phase, water is injected and forced under high pressure to flow from the fractures into the matrix. Fluids are produced from the reservoir during the depressuring phase. The reservoir pressure is allowed to drop until either the oil production rate becomes too low or the producing gas-oil ratio becomes excessive. Cycles are repeated as long as the process is economic. This paper presents results of a simulation study to determine the important parameters which affect the success of pressure pulsing waterflooding. A dual porosity generalized compositional model was used for the simulations. The results show the success of pressure pulsing waterflooding is dependent on the interconnected fracture network, relative permeabilities and oil fluid properties. The fracture network allows injected water to move rapidly away from the wellbore throughout the reservoir system. Matrix relative permeabilities affect the amount of oil and water retained in the matrix rock during the depressuring phase. Gas collapse during the pressuring phase allows water to enter the matrix rock, and gas evolution in the depressuring phase drives oil from the matrix rock into the surrounding fractures. It is illustrated that the effectiveness of pressure pulsing waterflooding can be improved by conservation of gas in the reservoir and/or by supplemental gas injection in the pulsing cycles before water injection.
[Injectable collagen: an evaluation after 10 years' use as a complement of plastic surgery]. (1994)

This study is designed to review 10 years' experience with the use of american injectable collagens (Zyderm I, Zyderm II, Zyplast) in the field of plastic surgery. After reviewing the characteristics of the product and its immunological aspects, the general principles of use are recalled: preliminary advice, contraindications and precautions, injection technique, timing and calendar of treatment, indications according to various anatomical sites. The dual complementarity between medical treatment of facial ageing by means of this product and the possibilities of plastic surgery according to the stages of ageing are studied in particular detail: technical and strategic complementarity.
Patient Preferences for Different Severities of and Treatments for Overactive Bladder (2011)

: Symptoms of overactive bladder (OAB) can have profound effects on women's quality of life. However, quantitative data on how women value these symptoms and their treatments are limited. We sought to assess women's preferences, which are referred to as utilities, for different severities of and treatment options for OAB.: Eighty women-40 with OAB symptoms and 40 without OAB-were recruited from urogynecology and urology practices at an academic institution from April to November 2009. A single, trained interviewer administered a computerized preference elicitation tool to measure preferences for 4 OAB severity levels (urgency/frequency and mild, moderate, and severe urge incontinence), as well as 3 OAB treatments with and without adverse effects or complications, which included (1) anticholinergic medications, (2) botulinum toxin injection, and (3) sacral neuromodulation. Preferences were assessed using the time trade-off (TTO) method.: Median TTO scores for OAB decreased as severity increased (urgency/frequency, 0.88; mild, 0.92; moderate, 0.85; severe, 0.73). Median TTO scores assigned to anticholinergic medications were higher (0.93) than those for botulinum (0.88) and sacral neuromodulation (0.85), and adverse effects or complications lowered the utilities for each treatment (anticholinergics, 0.88; botulinum, 0.75; and sacral neuromodulation, 0.78).: Women view symptoms of OAB, particularly moderate or severe symptoms, as being quite burdensome. The degree of invasiveness and the number of adverse effect/complications are important contributors to the utilities that women assign to the various treatment options.
An Antibody CDR3-Erythropoietin Fusion Protein (2013)

X-ray crystallographic analysis of a bovine antibody (BLV1H12) revealed a unique scaffold in its ultralong heavy chain complementarity determining region 3 (CDR3H) that folds into a solvent exposed, antiparallel β-stranded "stalk" fused with a disulfide cross-linked "knob" domain. This unusual variable region motif provides a novel approach for generating chimeric antibodies with novel activities. Toward this end, human erythropoietin (hEPO) was substituted for the "knob" domain in this antibody to afford an antibody-hEPO (Ab-hEPO) fusion protein that efficiently expresses in mammalian cells. Ab-hEPO proliferated TF-1 cells with a potency comparable to that of hEPO (EC50 ∼ 0.03 nM) and exhibits a significantly extended plasma half-life (>6 days) in mice relative to hEPO (∼4 h). Mice treated with the Ab-hEPO fusion protein show sustained elevated hematocrit for more than two weeks. This work demonstrates the utility of BLV1H12 CDR3 fusions as a novel approach for generating potent polypeptides with enhanced pharmacological properties.
A new approach to chip size package using meniscus soldering and FPC-bonding (1998)

A chip size package was developed using a tape carrier for interconnection and redistribution of the pads of high pincount integrated circuits (ICs). The complete package is 650 /spl mu/m thick including a 550 /spl mu/m thick chip and a 100 /spl mu/m thick flexible carrier. A three layer tape with gold or gold/nickel surface finish on the copper layer was used as flexible interposer. The production line which was established includes a low cost bumping on wafer level. The chips were provided with electroless Ni bumps on which a layer of eutectic Au-Sn solder was deposited by meniscus soldering. The bonding of these bumps to the flexible substrate was performed by fiber push connection (FPC) technology, a laser bonding method. Mechanical stability between the tape and the chip was achieved by application of a low stress adhesive prior to bonding. In a last step solder balls were placed on the tape and reflowed using a novel solder ball placement machine with an incorporated laser reflow unit. The package obtained is fully surface mount compatible, allowing easy processability.
Peroxynitrite Mediates Neurotoxicity of Amyloid β-Peptide1–42- and Lipopolysaccharide-Activated Microglia (2002)

The amyloid β-peptide (Aβ) activates microglia and promotes the generation of cytokines and oxygen species, including nitric oxide (NO) and tumor necrosis factor α (TNF-α), which can be either neurotoxic or neuroprotective. We show that neuron death in cocultures of rat cortical microglia and neurons activated by lipopolysaccharide (LPS) or Aβ<sub>1–42</sub> plus interferon γ (IFNγ) is caused by short-lived diffusible molecules and follows the generation of superoxide and/or peroxynitrite as determined by electron paramagnetic spectroscopy. Neurotoxicity induced by LPS or Aβ<sub>1–42</sub> plus IFNγ is blocked by inhibitors of NO synthesis and by the peroxynitrite (ONOO<sup>−</sup>) decomposition catalysts FeTMPyP [5,10,15,20-tetrakis(n-methyl-4′-pyridyl)porphinato iron (III) chloride] and FeTPPS [5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride] but not by the TNF-α inhibitor pentoxifylline. The specificity of FeTMPyP for ONOO<sup>−</sup> was confirmed by its ability to block the toxicity of a peroxynitrite donor but not of NO donors or of high levels of superoxide in a yeast mutant lacking superoxide dismutase 1. These results implicate peroxynitrite as a mediator of the toxicity of activated microglia, which may play a major role in Aβ<sub>1–42</sub> neurotoxicity and Alzheimer9s disease.