gebhart/patrepeval huggingface dataset:
Modification of Clearance of Therapeutic and Potentially Therapeutic Proteins (2001)

Advances in biochemistry, protein chemistry and molecular biology over the last twenty-five years have spurred the increased use and development of proteins as injectable therapeutic agents. Introduction of proteins into the circulation exposes them to numerous different cells, enzymes and routes of extravasation that contribute to their clearance and their catabolism. Overly rapid clearance, particularly of small proteins, can limit therapeutic efficacy. Many strategies have been devised to retard the clearance of therapeutic or potentially therapeutic proteins, but relatively few proteins with clearance-retarding modifications are in clinical use. Proteins have been chemically modified towards this end by covalent attachment of polyethylene glycol or dextran chains or by protein-protein cross-linking. Genetic modification has also been employed to fuse proteins of interest to long-lived plasma proteins like albumin or immunoglobulins, or portions of these proteins. While all modifications may reduce the biological activity of the protein of interest or elicit antibody formation in recipient animals or patients, there now exists sufficient experience in this area that an optimal clearance-extending strategy can often be designed and successfully executed. With the explosive growth of genomic and proteomic information, an exponentially increasing number of engineered proteins are likely to be developed, with a probable need for clearance-related modification.
Analysis of gene expression profiles (2002)

We approach the class discovery and leaf ordering problems using spectral graph partitioning methodologies. For class discovery or clustering, we present a min-max cut hierarchical clustering method and show it produces subtypes quite close to human expert labeling on the lymphoma dataset with 6 classes. On optimal leaf ordering for displaying the gene expression data, we present a sequential ordering method that can be computed in O(n2) time which also preserves the cluster structure. We also show that the well known statistic methods such as F-statistic test and the principal component analysis are very useful in gene expression analysis.
Novel and improved methods of writing Bragg gratings with phase masks (1995)

The authors demonstrate the importance of spatial coherence of the writing beam for inscribing Bragg gratings with a phase mask. Bragg gratings were written using a normal excimer laser with the fiber placed at various distances away from the phase mask. This was repeated with an excimer laser that was modified to improve the beam spatial coherence showing dramatic improvement in the ability to inscribe gratings. Tunability of the inscribed Bragg grating wavelength, utilizing a single phase mask in conjunction with the improved spatial coherence of the excitation source, is demonstrated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
NO-donating aspirin inhibits the activation of NF-κB in human cancer cell lines and Min mice (2008)

Nitric oxide-donating aspirin (NO-ASA) is a promising agent for the control of cancer, whose mechanism of action remains unclear. NF-kappaB is an important signaling molecule in the pathogenesis of cancer. We studied in several human colon (HT-29, HCT-15, LoVo, HCT116 and SW-480), pancreatic (BxPC-3, MIA PaCa-2) and breast (MDA-MB-231 and MCF-7) cancer cell lines, the effect of NO-ASA on NF-kappaB activation, determined by electrophoretic mobility shift assays, immunofluorescence and western blot analyses of nuclear proteins. NO-ASA inhibited NF-kappaB activation, as early as 30 min and with IC(50)s ranging between 0.83 and 64 microM. Such inhibition was also observed at NO-ASA concentrations that had an insignificant or marginal effect on cell growth. The effect of NO-ASA on NF-kappaB binding to DNA was significantly correlated with its effect on cell growth (P < 0.05) indicating that the growth inhibitory effect of NO-ASA may be mediated by its effect on NF-kappaB. Compared with control, NO-ASA decreased NF-kappaB activation in intestinal epithelial cells of APC(min+/-) mice by 38.4% (P < 0.01). Western blot and immunofluorescence analyses revealed that the nuclear levels of the p50 and p65 NF-kappaB subunits were virtually unaffected, suggesting an inhibitory mechanism different from suppressed subunit translocation into the nucleus. Inhibition of NF-kappaB activation by NO-ASA may account, at least in part, for its chemopreventive efficacy.
The use of gastrointestinal intubation studies for controlled release development (2009)

The following recommendations are made regarding intubation studies: (i) no intubation study is recommended for compounds with high permeability, since these compounds are likely to be well absorbed from the colon; (ii) compounds with moderate permeability may require an intubation study if the dog colon and in silico models predict a marginally acceptable CR concentration-time profile; (iii) use a dose that approximates 1 h of the intended CR delivery rate; (iv) use the smallest volume possible; (v) define and record tubing placement; (vi) use a thermodynamically stable solution or/and suspension.
Specificity of unsaturated fatty acid-regulated expression of the Saccharomyces cerevisiae OLE1 gene. (1992)

The Saccharomyces cerevisiae OLE1 gene encodes the delta-9 fatty acid desaturase, an enzyme which forms the monounsaturated palmitoleic (16:1) and oleic (18:1) fatty acids from palmitoyl (16:0) or stearoyl (18:0) CoA. Previous studies demonstrated that OLE1 mRNA levels and desaturase enzyme activity are repressed when either 16:1 delta-9 and 18:1 delta-9 are added to the growth medium (1). The polyunsaturate, linoleic acid (18:2, delta-9,12), which is not a product of the enzyme, is also a strong repressor. The specificity of the OLE1 transcriptional regulatory sensor was examined by testing the response of OLE1 promoter-lacZ fusion reporter genes to fatty acids that differ in chain length, degree of unsaturation and double bond positions. Monounsaturated and polyunsaturated fatty acids that contain a delta-9 double bond are strong repressors of reporter gene activity and native OLE1 mRNA levels. Monounsaturated fatty acids containing double bonds in the delta-10, delta-11, or delta-5 positions showed no repression of reporter enzyme levels although they were rapidly incorporated into membrane lipids and some supported growth of an OLE1 gene disrupted strain. Although 17:1 delta-10 does not repress OLE1 transcription, lipid analysis showed that it replaces almost all of the endogenous 16:1 delta-9 and 18:1 delta-9 in cellular lipids and OLE1 mRNA levels are strongly repressed. This suggests that additional systems regulate desaturase activity by post-transcriptional mechanisms that differ from the transcriptional sensor in their responses to specific fatty acids.
A dosage alternative for H2-receptor antagonists--constant infusion. (1986)

Control of gastric acid is accomplished either by buffering it with antacids or by preventing acid secretion with H2-receptor antagonists. Advantages of antacids are their rapid onset of action and the possibility of precisely titrating intragastric pH. In practice, however, they are cumbersome to use because they must be administered frequently (often hourly) and thus require excessive nursing time. In addition, their use often leads to undesirable side effects, such as diarrhea. Cimetidine and ranitidine are H2-receptor antagonists that differ primarily in their potency, ranitidine being four to ten times more potent than cimetidine. With either drug, the patient's intragastric pH falls below 5 by about the fourth hour after the dose. One way to avoid the peaks and valleys of acid secretory control is to use constant infusion. Infusion rates of 50 mg/hr of cimetidine preceded by loading doses of 300 mg of cimetidine often produce a constant intragastric pH above 5. It is essential that intragastric above 5. It is essential that intragastric pH be checked and infusion rates increased or antacids added if pH drops below 5. Bauer used constant infusion of cimetidine in patients with upper gastrointestinal bleeding. He found constant infusion more successful, but his end-point was merely to stabilize the patient before surgery. At UC Davis, we compared constant infusion with intermittent dosing (300 mg of cimetidine every six hours) in patients admitted to the intensive care unit with upper gastrointestinal bleeding.
Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo (2011)

The homeostatic control mechanisms regulating human leukocyte numbers are poorly understood. Here, we assessed the role of phagocytes in this process using human immune system (HIS) BALB/c Rag2(-/-)IL-2Rγc(-/-) mice in which human leukocytes are generated from transplanted hematopoietic progenitor cells. Interactions between signal regulatory protein alpha (SIRPα; expressed on phagocytes) and CD47 (expressed on hematopoietic cells) negatively regulate phagocyte activity of macrophages and other phagocytic cells. We previously showed that B cells develop and survive robustly in HIS mice, whereas T and natural killer (NK) cells survive poorly. Because human CD47 does not interact with BALB/c mouse SIRPα, we introduced functional CD47/SIRPα interactions in HIS mice by transducing mouse CD47 into human progenitor cells. Here, we show that this procedure resulted in a dramatic and selective improvement of progenitor cell engraftment and human T- and NK-cell homeostasis in HIS mouse peripheral lymphoid organs. The amount of engrafted human B cells also increased but much less than that of T and NK cells, and total plasma IgM and IgG concentrations increased 68- and 35-fold, respectively. Whereas T cells exhibit an activated/memory phenotype in the absence of functional CD47/SIRPα interactions, human T cells accumulated as CD4(+) or CD8(+) single-positive, naive, resting T cells in the presence of functional CD47/SIRPα interactions. Thus, in addition to signals mediated by T cell receptor (TCR)/MHC and/or IL/IL receptor interactions, sensing of cell surface CD47 expression by phagocyte SIRPα is a critical determinant of T- and NK-cell homeostasis under steady-state conditions in vivo.
Methotrexate for Rheumatoid Arthritis (1994)

Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information.
Strong suppression of tumor growth by insulin‐like growth factor‐binding protein‐related protein 1/tumor‐derived cell adhesion factor/mac25 (2007)

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has been shown to induce cellular senescence or apoptosis of breast and prostate cancer cell lines in vitro. To examine whether IGFBP-rP1 acts as a tumor-suppressive protein in vivo, we established two model systems. Expression of IGFBP-rP1 in the human bladder carcinoma cell line EJ-1 was blocked by RNA interference. Human colon cancer cell line DLD-1, which did not express endogenous IGFBP-rP1, was transfected with an IGFBP-rP1 expression vector. When injected intraperitoneally or subcutaneously into nude mice, the IGFBP-rP1-expressing EJ-1 and DLD-1 cell lines grew poorly, whereas the IGFBP-rP1 non-producers grew rapidly and produced large tumors. In monolayer culture the IGFBP-rP1 producers and non-producers grew similarly in each model, whereas in soft agar culture the former produced far less colonies than the latter. The IGFBP-rP1 producers had IGFBP-rP1 bound to the cell surface, and adhered more efficiently to fibronectin and laminin-5 than the respective non-producers. Expression of IGFBP-rP1 did not affect the efficiency of insulin signaling. These results demonstrate that IGFBP-rP1 strongly suppresses tumor growth by an insulin-independent or insulin-like growth factor-independent mechanism. Cell surface IGFBP-rP1 may reduce the anchorage-independent growth ability, leading to the marked loss of tumorigenicity.
Mass-sensing, multianalyte microarray immunoassay with imaging detection (1998)

Miniaturization of ligand binding assays may reduce costs by decreasing reagent consumption, but it is less apparent that miniaturized assays can simultaneously exceed the sensitivity of macroscopic techniques by analyte "harvesting" to exploit the total analyte mass available in a sample. Capture reagents (avidin or antibodies) immobilized in 200-microm diameter zones are shown to substantially deplete analyte from a liquid sample during a 1-3-h incubation, and the assays that result sense the total analyte mass in a sample rather than its concentration. Detection of as few as 10(5) molecules of analyte per zone is possible by fluorescence imaging in situ on the solid phase using a near-infrared dye label. Single and multianalyte mass-sensing sandwich array assays of the IgG subclasses show the sensitivity and specificity of ELISA methods but use less than 1/100 the capture antibody required by the 96-well plate format.
SMALL FRENCH FIRM'S BOLD DREAM (2007)

RETURN TO ISSUEPREVNewsNEXTSMALL FRENCH FIRM'S BOLD DREAMMetabolic Explorer hopes to beat chemical industry majors in the fermentation game for BULK CHEMICALSPATRICIA L. SHORTView Author Information C&EN LONDONCite this: Chem. Eng. News 2007, 85, 35, 26–27Publication Date (Print):August 27, 2007Publication History Published online29 October 2010Published inissue 27 August 2007https://pubs.acs.org/doi/10.1021/cen-v085n035.p026https://doi.org/10.1021/cen-v085n035.p026newsACS PublicationsCopyright © 2007 American Chemical SocietyArticle Views15Altmetric-Citations3LEARN 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 options SUBJECTS:Carbohydrates,Fermentation,Manufacturing,Petrochemicals Get e-Alerts
Spray‐dried plasma deficient in high‐molecular‐weight multimers of von Willebrand factor retains hemostatic properties (2018)

Comparable coagulability was observed in FFP and SpDP. The apparent paradox between vWF-ristocetin cofactor assay and vWF-mediated platelet adhesion may be explained by the increase in smaller multimers of vWF in SpDP, producing different outcomes in these assays.
Global Gene Expression Profiling in Escherichia coliK12 (2002)

Leucine-responsive regulatory protein (Lrp) is a global regulatory protein that affects the expression of multiple genes and operons in bacteria. Although the physiological purpose of Lrp-mediated gene regulation remains unclear, it has been suggested that it functions to coordinate cellular metabolism with the nutritional state of the environment. The results of gene expression profiles between otherwise isogenic lrp(+) and lrp(-) strains of Escherichia coli support this suggestion. The newly discovered Lrp-regulated genes reported here are involved either in small molecule or macromolecule synthesis or degradation, or in small molecule transport and environmental stress responses. Although many of these regulatory effects are direct, others are indirect consequences of Lrp-mediated changes in the expression levels of other global regulatory proteins. Because computational methods to analyze and interpret high dimensional DNA microarray data are still an early stage, much of the emphasis of this work is directed toward the development of methods to identify differentially expressed genes with a high level of confidence. In particular, we describe a Bayesian statistical framework for a posterior estimate of the standard deviation of gene measurements based on a limited number of replications. We also describe an algorithm to compute a posterior estimate of differential expression for each gene based on the experiment-wide global false positive and false negative level for a DNA microarray data set. This allows the experimenter to compute posterior probabilities of differential expression for each individual differential gene expression measurement.
Graph-based Semantic Relatedness for Named Entity Disambiguation (2009)

Natural Language is a mean to express and discuss about concepts, objects, events, i.e. it carries semantic contents. The SemanticWeb aims at tightly coupling contents with their precise meanings. One of the ultimate roles of Natural Language Processing techniques is identifying the meaning of the text, providing effective ways to make a proper linkage between textual references and real world objects. This work adresses the problem of giving a sense to proper names in a text, that is automatically associating words representing Named Entities with their identities. The proposed methodology for Named Entity Disambiguation is based on Semantic Relatedness Scores obtained with a graph based model overWikipedia.We show that, without building a Bag of Words representation of text, but only considering named entities within the text, the proposed paradigm achieves results competitive with the state of the art on a news story dataset.
Safety and Immunogenicity of 26-Valent Group A Streptococcus Vaccine in Healthy Adult Volunteers (2005)

On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.
Increasing the Transparency of Research Papers with Explorable Multiverse Analyses (2019)

We present explorable multiverse analysis reports, a new approach to statistical reporting where readers of research papers can explore alternative analysis options by interacting with the paper itself. This approach draws from two recent ideas: i) multiverse analysis, a philosophy of statistical reporting where paper authors report the outcomes of many different statistical analyses in order to show how fragile or robust their findings are; and ii) explorable explanations, narratives that can be read as normal explanations but where the reader can also become active by dynamically changing some elements of the explanation. Based on five examples and a design space analysis, we show how combining those two ideas can complement existing reporting approaches and constitute a step towards more transparent research papers.
Chemistry of the Cure of Poly(p-phenylene sulfide) (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of the Cure of Poly(p-phenylene sulfide)Richard T. HawkinsCite this: Macromolecules 1976, 9, 2, 189–194Publication Date (Print):March 1, 1976Publication History Published online1 May 2002Published inissue 1 March 1976https://pubs.acs.org/doi/10.1021/ma60050a001https://doi.org/10.1021/ma60050a001research-articleACS PublicationsRequest reuse permissionsArticle Views988Altmetric-Citations147LEARN 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-Alertsclose Get e-Alerts
Re-Thinking CNN Frameworks for Time-Sensitive Autonomous-Driving Applications: Addressing an Industrial Challenge (2019)

Vision-based perception systems are crucial for profitable autonomous-driving vehicle products. High accuracy in such perception systems is being enabled by rapidly evolving convolution neural networks (CNNs). To achieve a better understanding of its surrounding environment, a vehicle must be provided with full coverage via multiple cameras. However, when processing multiple video streams, existing CNN frameworks often fail to provide enough inference performance, particularly on embedded hardware constrained by size, weight, and power limits. This paper presents the results of an industrial case study that was conducted to re-think the design of CNN software to better utilize available hardware resources. In this study, techniques such as parallelism, pipelining, and the merging of per-camera images into a single composite image were considered in the context of a Drive PX2 embedded hardware platform. The study identifies a combination of techniques that can be applied to increase throughput (number of simultaneous camera streams) without significantly increasing per-frame latency (camera to CNN output) or reducing per-stream accuracy.