gebhart/patrepeval huggingface dataset:
Response and progression in recurrent malignant glioma (1999)

In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II chemotherapy trials.We reviewed the records of patients from 8 consecutive phase II trials, including 225 patients with recurrent glioblastoma multiforme and 150 with recurrent anaplastic astrocytoma.Median age was 45 years (range, 15-82) and median Karnofsky performance score was 80 (range, 60-100).Forty-one patients (11%) had more than two prior resections and/or more than two prior chemotherapy regimens.Best response was complete (n = 1) or partial (n = 33) in 34 patients (9%).Median time to response was 14 weeks, and median response duration was 44 weeks.Simon-Makuch estimates for 52-week progression-free survival for patients progression-free at 13 weeks were 48% for response and 28% for nonresponse.When response was treated as a time-dependent covariate in a Cox proportional hazards regression analysis, response was associated with signi cantly lower failure rates (hazard ratio 0.5; 95% con dence interval 0.3-0.8;P = 0.0016).This study showed that response in recurrent glioma is associated with a signi cant reduction in progression rates.
The branchial arches and HGF are growth-promoting and chemoattractant for cranial motor axons (2000)

During development, cranial motor neurons extend their axons along distinct pathways into the periphery. For example, branchiomotor axons extend dorsally to leave the hindbrain via large dorsal exit points. They then grow in association with sensory ganglia, to their targets, the muscles of the branchial arches. We have investigated the possibility that pathway tissues might secrete diffusible chemorepellents or chemoattractants that guide cranial motor axons, using co-cultures in collagen gels. We found that explants of dorsal neural tube or hindbrain roof plate chemorepelled cranial motor axons, while explants of cranial sensory ganglia were weakly chemoattractive. Explants of branchial arch mesenchyme were strongly growth-promoting and chemoattractive for cranial motor axons. Enhanced and oriented axon outgrowth was also elicited by beads loaded with Hepatocyte Growth Factor (HGF); antibodies to this protein largely blocked the outgrowth and orientation effects of the branchial arch on motor axons. HGF was expressed in the branchial arches, whilst Met, which encodes an HGF receptor, was expressed by subpopulations of cranial motor neurons. Mice with targetted disruptions of HGF or Met showed defects in the navigation of hypoglossal motor axons into the branchial region. Branchial arch tissue may thus act as a target-derived factor that guides motor axons during development. This influence is likely to be mediated partly by Hepatocyte Growth Factor, although a component of branchial arch-mediated growth promotion and chemoattraction was not blocked by anti-HGF antibodies.
Evaluation of a multiplex PCR method to detect enteroaggregative Escherichia coli (2006)

Enteroaggregative Escherichia coli (EAEC) has been implicated in sporadic diarrhea in children and adults and has been identified as the cause of several outbreaks worldwide. The HEp-2 test remains the gold standard for identification of this pathotype. A 60-65 MDa plasmid encodes the aggregative adherence fimbriae (AAF/I and AAF/II), a transcriptional activator (aggR gene), the enteroaggregative heat-stable enterotoxin EAST1 (astA gene) and a cytotoxin (Pet). The standard assay for EAEC is performed only in research laboratories, because it is expensive, labor intensive and time-consuming. The Polymerase Chain Reaction (PCR) offers the possibility of rapid diagnosis. In the current study, a multiplex PCR assay which checks aggR and astA genes was designed. Eigthy-eight E. coli strains, isolated from children with acute diarrhea in Mendoza, Argentina, were characterized by the reference method (HEp-2 assay), and by aggR-astA PCR. A strong correlation between the presence of the specific marker aggR and the reference test was found. The astA gene had a similar distribution between aggregative and localized strains, indicating that this gene could not be considered as a marker of EAEC. We conclude that aggR may be used to identify EAEC, using the PCR method as a screening test.
Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma (2010)

Classical Hodgkin lymphoma (cHL) and mediastinal large B-cell lymphoma (MLBCL) are lymphoid malignancies with certain shared clinical, histologic, and molecular features. Primary cHLs and MLBCLs include variable numbers of malignant cells within an inflammatory infiltrate, suggesting that these tumors escape immune surveillance. Herein, we integrate high-resolution copy number data with transcriptional profiles and identify the immunoregulatory genes, PD-L1 and PD-L2, as key targets at the 9p24.1 amplification peak in HL and MLBCL cell lines. We extend these findings to laser-capture microdissected primary Hodgkin Reed-Sternberg cells and primary MLBCLs and find that programmed cell death-1 (PD-1) ligand/9p24.1 amplification is restricted to nodular sclerosing HL, the cHL subtype most closely related to MLBCL. Using quantitative immunohistochemical methods, we document the association between 9p24.1 copy number and PD-1 ligand expression in primary tumors. In cHL and MLBCL, the extended 9p24.1 amplification region also included the Janus kinase 2 (JAK2) locus. Of note, JAK2 amplification increased protein expression and activity, specifically induced PD-1 ligand transcription and enhanced sensitivity to JAK2 inhibition. Therefore, 9p24.1 amplification is a disease-specific structural alteration that increases both the gene dosage of PD-1 ligands and their induction by JAK2, defining the PD-1 pathway and JAK2 as complementary rational therapeutic targets.
New Glycomimetics:  Anomeric Sulfonates, Sulfenamides, and Sulfonamides (2006)

The synthesis of a variety of new 1-thio-D-glucopyranose derivatives oxidized at the sulfur atom is described, including seven 1-C-sulfonic acids, three sulfonate esters, three sulfinate esters, an S,S'-diglycosyl thiolsulfonate and thiolsulfinate, four S-glycosyl sulfenamides, an S-glycosyl sulfinamide, and two S-glycosyl sulfonamides. These compounds possess unusual anomeric functionality that might be resistant or even inhibitory to normal enzymatic carbohydrate processing, and therefore, they may be of future use in studies of enzyme inhibition, structure, mechanism, and function.
The pelvic floor sequelae of childbirth. (1996)

For centuries the structure and function of the pelvic floor and anal sphincter have remained enigmatic. Great strides made in new imaging techniques over the last decade has enabled a better understanding of this complex and dynamic structure. We can now explore pelvic floor dysfunction.
Biomedical applications of MEMS (2002)

Exploiting the materials and processing techniques developed for integrated circuits, silicon micromachining technology has been responsible for fundamental improvements in many, diverse fields of biomedicine. This paper reviews current state-of-the-art biomedical applications of micromachining technology such as pressure sensors and biochemical sensors. In addition, we discuss significant new biomedical innovations on the horizon which make use of micromachining techniques and processes.
Hepatitis C Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3′ Nontranslated Region Are Essential for Virus Replication In Vivo (2000)

Hepatitis C virus (HCV) infection is a widespread major human health concern. Significant obstacles in the study of this virus include the absence of a reliable tissue culture system and a small-animal model. Recently, we constructed full-length HCV cDNA clones and successfully initiated HCV infection in two chimpanzees by intrahepatic injection of in vitro-transcribed RNA (A. A. Kolykhalov et al., Science 277:570-574, 1997). In order to validate potential targets for development of anti-HCV therapeutics, we constructed six mutant derivatives of this prototype infectious clone. Four clones contained point mutations ablating the activity of the NS2-3 protease, the NS3-4A serine protease, the NS3 NTPase/helicase, and the NS5B polymerase. Two additional clones contained deletions encompassing all or part of the highly conserved 98-base sequence at the 3' terminus of the HCV genome RNA. The RNA transcript from each of the six clones was injected intrahepatically into a chimpanzee. No signs of HCV infection were detected in the 8 months following the injection. Inoculation of the same animal with nonmutant RNA transcripts resulted in productive HCV infection, as evidenced by viremia, elevated serum alanine aminotransferase, and HCV-specific seroconversion. These data suggest that these four HCV-encoded enzymatic activities and the conserved 3' terminal RNA element are essential for productive replication in vivo.
MicroRNA Expression Aids the Preoperative Diagnosis of Pancreatic Ductal Adenocarcinoma (2012)

Pancreatic ductal adenocarcinomas show differential expression of miRNAs compared to benign pancreatic lesions. A select panel of miRNAs aids the distinction between pancreatic lesions in cytology specimens.
Novel therapeutic strategies targeting HIV integrase (2012)

Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds.
Disk Failures in the Real World: What Does an MTTF of 1,000,000 Hours Mean to You? (CMU-PDL-06-111) (2018)

Component failure in large-scale IT installations such as cluster supercomputers or internet service providers is becoming an ever larger problem as the number of processors, memory chips and disks in a single cluster approaches a million. In this paper, we present and analyze field-gathered disk replacement data from five systems in production use at three organizations, two supercomputing sites and one internet service provider. About 70,000 disks are covered by this data, some for an entire lifetime of 5 years. All disks were high-performance enterprise disks (SCSI or FC), whose datasheet MTTF of 1,200,000 hours suggest a nominal annual failure rate of at most 0.75%. We find that in the field, annual disk replacement rates exceed 1%, with 2-4% common and up to 12% observed on some systems. This suggests that field replacement is a fairly different process than one might predict based on datasheet MTTF, and that it can be quite variable installation to installation. We also find evidence that failure rate is not constant with age, and that rather than a significant infant mortality effect, we see a significant early onset of wear-out degradation. That is, replacement rates in our data grew constantly with age, an effect often assumed not to set in until after 5 years of use. In our statistical analysis of the data, we find that time between failure is not well modeled by an exponential distribution, since the empirical distribution exhibits higher levels of variability and decreasing hazard rates. We also find significant levels of correlation between failures, including autocorrelation and long-range dependence.
Advances in Fluorescent Tracking of Nucleic Acids in Living Cell (2006)

Nucleic acids are typically detected in morphologically preserved fixed cells and tissues using in situ hybridization techniques. This review discusses a variety of established and more challenging fluorescence-based methods for the detection and tracking of DNA or RNA sequences in living cells. Over the past few years, various fluorescent in vivo labeling methods have been developed, and dedicated microscope and image analysis tools have been designed. These advances in technologies indicate that live-cell imaging of nucleic acids is likely to become a standard research tool for understanding genome organization and gene expression regulation in the near future. Recent live-cell imaging studies have already provided important insights into the dynamic behaviors of chromatin and RNAs in the cell.
Human Parainfluenza Virus Infection of the Airway Epithelium: Viral Hemagglutinin-Neuraminidase Regulates Fusion Protein Activation and Modulates Infectivity (2009)

Three discrete activities of the paramyxovirus hemagglutinin-neuraminidase (HN) protein, receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein, each affect the promotion of viral fusion and entry. For human parainfluenza virus type 3 (HPIV3), the effects of specific mutations that alter these functions of the receptor-binding protein have been well characterized using cultured monolayer cells, which have identified steps that are potentially relevant to pathogenesis. In the present study, proposed mechanisms that are relevant to pathogenesis were tested in natural host cell cultures, a model of the human airway epithelium (HAE) in which primary HAE cells are cultured at an air-liquid interface and retain functional properties. Infection of HAE cells with wild-type HPIV3 and variant viruses closely reflects that seen in an animal model, the cotton rat, suggesting that HAE cells provide an ideal system for assessing the interplay of host cell and viral factors in pathogenesis and for screening for inhibitory molecules that would be effective in vivo. Both HN's receptor avidity and the function and timing of F activation by HN require a critical balance for the establishment of ongoing infection in the HAE, and these HN functions independently modulate the production of active virions. Alterations in HN's F-triggering function lead to the release of noninfectious viral particles and a failure of the virus to spread. The finding that the dysregulation of F triggering prohibits successful infection in HAE cells suggests that antiviral strategies targeted to HN's F-triggering activity may have promise in vivo.
Oligomers on the Brain: the Emerging Role of Soluble Protein Aggregates in Neurodegeneration. (2004)

Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein fibrils characterize many different neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, Huntington's disease, and the transmissible 'prion' dementias. There is strong evidence from genetic, transgenic mouse and biochemical studies to support the idea that the accumulation of protein aggregates in the brain plays a seminal role in the pathogenesis of these diseases. How monomeric proteins ultimately convert to highly polymeric deposits is unknown. However, studies employing, synthetic, cell-derived and purified recombinant proteins suggest that amyloid proteins first come together to form soluble low n-oligomers. Further association of these oligomers results in higher molecular weight assemblies including so-called 'protofibrils' and 'ADDLs' and these eventually exceed solubility limits until, finally, they are deposited as amyloid fibrils. With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction.
Variational inference for Dirichlet process mixtures (2006)

Dirichlet process (DP) mixture models are the cornerstone of nonparametric Bayesian statistics, and the development of Monte-Carlo Markov chain (MCMC) sampling methods for DP mixtures has enabled the application of nonparametric Bayesian methods to a variety of practical data analysis problems. However, MCMC sampling can be prohibitively slow, and it is important to explore alternatives. One class of alternatives is provided by variational methods, a class of deterministic algorithms that convert inference problems into optimization problems (Opper and Saad 2001; Wainwright and Jordan 2003). Thus far, variational methods have mainly been explored in the parametric setting, in particular within the formalism of the exponential family (Attias 2000; Ghahramani and Beal 2001; Blei et al. 2003). In this paper, we present a variational inference algorithm for DP mixtures. We present experiments that compare the algorithm to Gibbs sampling algorithms for DP mixtures of Gaussians and present an application to a large-scale image analysis problem.
Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzymeRalph P. Robinson and Kathleen M. DonahueCite this: J. Org. Chem. 1992, 57, 26, 7309–7314Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December 1992https://pubs.acs.org/doi/10.1021/jo00052a054https://doi.org/10.1021/jo00052a054research-articleACS PublicationsRequest reuse permissionsArticle Views195Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Bioenergetics breakdown in Alzheimer's disease: targets for new therapies. (2011)

Alzheimer's disease is rapidly growing worldwide and yet there is no cure for it. Currently available drugs only provide symptomatic relief and do not intervene in disease process sufficiently enough to prevent or cure it. Characteristic features of this disease are decline in neuronal mass and cognitive functions. The most dominant hypothesis proposed for pathogenesis of this disease is called “amyloid hypothesis". It states that excessive production of amyloid peptides called abeta peptides (Aβ) is the underlying cause of neuronal death and dysfunction. However, recent drugs designed based on amyloid hypothesis have failed in clinical trails, demanding fresh assessment. Early and persistent molecular events in this disease progression are energy deficiency and high oxidative stress in the neurons. Our review will put together a disease model based on known human and animal data with regards to breakdown in neuronal energy generation. The model will integrate energy deficits as the cause of neuronal dysfunction and abeta peptide production culminating in catastrophic loss of cognitive functions. Finally, based on this model, we will also suggest enzyme targets in neuronal bioenergetics pathway for design and development of new disease modifying therapies.
<title>Computer Image Processing And Recognition</title> (1980)

An introduction to the computer image processing and recognition techniques applied for accurately locating an object are presented in this paper. The accurate measurement of three dimensional position requires a camera calibration process as well as the determination of corresponding image points in two images. The accuracy of the three dimensional measurement depends upon the accuracy of the image matching solution. Since there are a variety of image matching techniques, the pattern recognition guidelines are reviewed which indicate that the optimum features are nonlinear, a posteriori probabilities of the measurements. These optimum features also maximize the trace of the between class scattermatrix normalized by the mixture scattermatrix. However, the theoretical guidelines do not indicate simple measurement methods for the optimum features. Therefore, some experimental examples are presented which illustrate some practical solutions to the problem.
Evidence concerning the mechanism of insulin-receptor interaction and the structure of the insulin receptor from biological properties of covalently linked insulin dimers (1983)

Covalently linked insulin dimers have been prepared by cross-linking two insulin monomers with a flexible suberoyl chain at either the B1 phenylalanine or the B29 lysine residue. Binding potencies of dimers determined by inhibition of binding of 125I-insulin to isolated rat liver plasma membranes or adipocytes were 2.5-7-fold greater than their abilities to stimulate lipogenesis in adipocytes. Rates of liver plasma-membrane-associated degradation of labelled insulin and dimers, measured by gel filtration, were similar at 37 degrees C. Binding and lipogenesis potencies of dimers prepared by substitution of each monomeric half of an asymmetrical dimer with desoctapeptide insulin, an almost inactive derivative, implicated the B1-cross-linked monomeric half as predominantly interacting with the insulin receptor. These results suggest that (1) dimers bind univalently to a bivalent insulin-receptor complex, in which the two individual binding subunits are arranged with anti-parallel symmetry and (2) the mechanism by which insulin binds and initiates its biological responses requires a conformational change within the insulin-receptor complex and/or in the insulin molecule for full biological expression.