gebhart/patrepeval huggingface dataset:
Etanercept. Immunex. (2001)

Immunex has developed and launched etanercept, a soluble TNF receptor (TNFR) fusion protein, for the treatment of rheumatoid arthritis (RA). It has also been developed for various TNF-mediated conditions such as congestive heart failure, endometriosis and multiple sclerosis. Etanercept has been launched as a second-line agent in the US for the treatment of moderate-to-severe RA and can be used in conjunction with methotrexate in patients unresponsive to methotrexate alone. It is also available in the EU. In 2000, it was in phase III trials for psoriatic arthritis and an NDA filing for this indication was expected for the first half of 2001. In July 2001, the sBLA was filed, and in September 2001, the FDA granted the sBLA Priority Review status. As of January 2001, etanercept was in phase III trials for congestive heart failure, with sNDA filing expected in 2002; however, by March 2001, these had been halted, as it did not appear that statistical significance would be reached for the efficacy endpoints. Further data analysis was being undertaken at this time, before a final decision was taken. In April 2001, Merrill Lynch reported that development for this indication was to be halted. Sales for the drugs first full quarter on the market in 1999 were US $59.7 million. By November 1999 the drug had made sales of US $500 million; Immunex expected the drug to generate over US $2 billion in annual sales by 2004. In September 2000, Merrill Lynch reported that if sales of the drug continued at the present rate then it is likely that demand would temporarily outstrip supply in 2001. Resolution of the supply issue was expected by 2002. Also in September 2000, Merrill Lynch lowered their estimate of sales in 2001 from US $1 billion to $927 million. In the long-term, Merrill Lynch believed that the drug has the potential to exceed US $5 billion in sales in the US. In April 2001, Merrill Lynch predicted that etanercept prescribed for RA would generate sales of US $71 in 2002 rising to US $600 million in 2005. In October 2001, Morgani Stanley reported that Enbrel continues to be the primary source of revenue of Immunex (US $198.1 million). It was also reported that if launched for CHF, an estimated peak year revenue was likely to be US $500 million. The company maintains a website containing additional information about etanercept at http://www.enbrelinfo.com.
Noise performance and temperature coefficients studies for the back-illuminated, thin silicon pin photodiode arrays (2006)

Noise characteristics of the backlit, pin photodiode arrays having different vertical structures were studied. We showed that in many cases, the non-optical crosstalk between adjacent elements determines the noise performance and detectivity of the array pixels. For the arrays with the structure described in our recent works, the crosstalk always remained well below 0.01%, which allowed reaching the minimum noise level of ~ 10<sup>-15</sup> A/&sqrt;Hz determined by the thermal noise. In contrast, for the arrays built applying conventional structures the crosstalk was two orders of magnitude higher, which noticeably decreased the sensitivity of the pixels increasing their noise and switching their operation towards background-limited performance. The background signal originated from the non-optical crosstalk and produced a noise level significantly higher that the thermal noise. We also compared the temperature coefficients for different arrays. For the structures with improved electrical crosstalk, the measured value of the shunt resistance temperature coefficient was typically below 8 %/C and the responsivity temperature coefficient value did not exceed +0.02 %/C within the spectral range from 450 through 800 nm. The advantages and drawbacks of application of the reported in this work photodiode arrays in high quality imaging systems are discussed.
Anatomy and Biomechanics of the First Ray (1999)

he medial longitudinal arch serves as the chief load-bearing structure in the foot The first ray is a single foot segment consisting of the first metatarsal and first cuneiform bones. 5 Pronation of the subtalar joint lowers the first ray to the ground in early stance 5 and dissipates the shock of heel impact. As body weight moves forward, the mechanics of supination stabilize the medial arch, preparing the foot for the propulsive phase of gait. The dichotomous actions of weight acceptance and weight-bearing stability required of the first ray underscore the importance for clinicians who treat the foot to understand the biomechanics of the first ray.
Leakage-Resistant Blood Vessels in Mice Transgenically Overexpressing Angiopoietin-1 (1999)

Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors. Direct comparison of transgenic mice overexpressing these factors in the skin revealed that the VEGF-induced blood vessels were leaky, whereas those induced by Ang1 were nonleaky. Moreover, vessels in Ang1-overexpressing mice were resistant to leaks caused by inflammatory agents. Coexpression of Ang1 and VEGF had an additive effect on angiogenesis but resulted in leakage-resistant vessels typical of Ang1. Ang1 therefore may be useful for reducing microvascular leakage in diseases in which the leakage results from chronic inflammation or elevated VEGF and, in combination with VEGF, for promoting growth of nonleaky vessels.
A cAMP-Regulated Chloride Channel in Lymphocytes That Is Affected in Cystic Fibrosis (1989)

A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. It is shown here that a chloride channel with kinetic and regulatory properties similar to those described for secretory epithelial cells is present in both T and B lymphocyte cell lines. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in transformed B cells from CF patients is defective. Thus, lymphocytes may be an accessible source of CF tissue for study of this defect, for cloning of the chloride channel complex, and for diagnosis of the disease.
A phase Ib/II open-label study to evaluate the safety and efficacy of TRU-016 in combination with bendamustine versus bendamustine alone in patients with relapsed chronic lymphocytic leukemia. (2011)

e13053 Background: CD37 is a member of the tetraspanin superfamily of molecules, which are implicated in diverse processes including cellular activation and proliferation, cell motility, and cell‐cell adhesion. CD37 is expressed constitutively at high levels on normal and transformed B-cells across a wide range of maturational stages. TRU-016 is a novel humanized anti-CD37 SMIP protein, which is a single chain Fv-Fc fusion protein. Pre-clinical studies have demonstrated that anti-CD37 SMIP protein mediates significantly greater direct and Fc mediated cellular killing of CLL cells than alemtuzumab or rituximab. A dose escalating phase I study in 57 patients with TRU-016 was recently completed. The highest dose tested was 20 mg/kg and a MTD was not reached. Methods: This international, multi-center, Phase Ib/II study is designed to determine a safe and tolerable dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. In the initial dose-escalation phase Ib part of the study, 2 different doses of TRU-016 (15 mg/kg and 20 mg/kg) in combination with bendamustine will be studied in two cohorts of 6 patients each. The dosing of TRU-016 will be weekly for the first two 28-day cycles and then every 14 days for the next four 28-day cycles. Bendamustine (70 mg/m2) is administered after TRU-016 on days 1 and 2 of each 28-day cycle for 6-cycles. The MTD will be defined as the highest dose level of TRU-016 at which ≤1 of 6 patients in a cohort experience a DLT during Cycle 1 of treatment. This dose will subsequently be utilized in the phase II component of the study in which 100 patients will be randomized in a 1:1 ratio to one of two arms: TRU-016 plus bendamustine or bendamustine alone. Clinical activity endpoints will include tumor response, duration of response, time to tumor progression, and progression-free survival. OS and QOL data will also be collected. Results: The phase Ib trial is currently open to accrual and enrollment is estimated to require 6-9 months. Phase 2 enrollment is estimated to require 12–15 months. Conclusions: This trial is registered at www.ClinicalTrials.gov as NCT01188681.
Physicochemical properties of small metal particles in solution: "microelectrode" reactions, chemisorption, composite metal particles, and the atom-to-metal transition (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhysicochemical properties of small metal particles in solution: "microelectrode" reactions, chemisorption, composite metal particles, and the atom-to-metal transitionArnim HengleinCite this: J. Phys. Chem. 1993, 97, 21, 5457–5471Publication Date (Print):May 1, 1993Publication History Published online1 May 2002Published inissue 1 May 1993https://pubs.acs.org/doi/10.1021/j100123a004https://doi.org/10.1021/j100123a004research-articleACS PublicationsRequest reuse permissionsArticle Views6099Altmetric-Citations1486LEARN 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 Get e-Alerts
EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCγ signaling pathway (1998)

A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachments along with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruption of focal adhesions in fibroblasts. We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces the fraction of cells presenting focal adhesions from approximately 60% to approximately 30% within 10 minutes. The dose dependency of focal adhesion disassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in the presence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathways to determine whether these contribute to EGF-induced effects. We have previously demonstrated that phospholipase C(gamma) (PLCgamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find here that short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLCgamma or mobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLCgamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059 that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLCgamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.
Multiple Streptococcus mutans Genes Are Involved in Biofilm Formation (2002)

Streptococcus mutans has been strongly implicated as the principal etiological agent in dental caries. One of the important virulence properties of these organisms is their ability to form biofilms known as dental plaque on tooth surfaces. Since the roles of sucrose and glucosyltransferases in S. mutans biofilm formation have been well documented, we focused our attention on sucrose-independent factors. We have initially identified several mutants that appear to be defective in biofilm formation on abiotic surfaces by an insertional inactivation mutagenesis strategy applied to S. mutans. A total of 27 biofilm-defective mutants were isolated and analyzed in this study. From these mutants, three genes were identified. One of the mutants was defective in the Bacillus subtilis lytR homologue. Another of the biofilm-defective mutants isolated was a yulF homologue, which encodes a hypothetical protein of B. subtilis whose function in biofilm formation is unknown. The vast majority of the mutants were defective in the comB gene required for competence. We therefore have constructed and examined comACDE null mutants. These mutants were also found to be attenuated in biofilm formation. Biofilm formation by several other regulatory gene mutants were also characterized using an in vitro biofilm-forming assay. These results suggest that competence genes as well as the sgp and dgk genes may play important roles in S. mutans biofilm formation.
Physiological tremor amplitude during retinal microsurgery (2002)

Using an instrumented surgical tool, high-precision recordings of hand tremor were taken during vitreoretinal microsurgery. The data obtained using a compact, custom six-degree-of-freedom inertial sensing module were filtered and analyzed to characterize the physiological hand tremor of the surgeon. Tremor during the most delicate part of the procedure was measured at a vector magnitude of 38 /spl mu/m rms. Nontremulous, lower-frequency components of instrument movement were also characterized. The data collected provide an important baseline for design specification and performance evaluation of engineered microsurgical devices.
Mechanistic Insights into Glaucoma Provided by Experimental Genetics The Cogan Lecture (2005)

The objective of this lecture-based review is to summarize some of the mechanistic insights into glaucoma that have been derived from research in mice in my laboratory over the past 10 years. The mouse system provides powerful genetic tools for studying complex, asynchronous diseases such as glaucoma (see Refs. 1, 2). Because of the high degree of conservation of physiological and homeostatic mechanisms between mammals, mice often have the same diseases as do humans, and these diseases develop in a relatively short span of time. Mouse and human diseases often are caused by the same mutant gene or pathway. Although mouse and human diseases are not always identical, mouse studies are providing an important complement to those in humans and other species. This article illustrates several ways in which we have used mice to study different aspects of glaucoma, but it does not attempt to provide a comprehensive literature review. I first focus the discussion on our studies of risk factors for high intraocular pressure (IOP) and then turn to mechanisms that kill retinal ganglion cells (RGCs).
Active mail---a framework for implementing groupware (1992)

Article Active mail—a framework for implementing groupware Share on Authors: Yaron Goldberg View Profile , Marilyn Safran View Profile , Ehud Shapiro View Profile Authors Info & Claims CSCW '92: Proceedings of the 1992 ACM conference on Computer-supported cooperative workDecember 1992 Pages 75–83https://doi.org/10.1145/143457.143464Online:01 December 1992Publication History 35citation652DownloadsMetricsTotal Citations35Total Downloads652Last 12 Months5Last 6 weeks0 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
Synthesis of pyrido[2,3-d]pyrimidine-2,4-diones (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of pyrido[2,3-d]pyrimidine-2,4-dionesStanley WawzonekCite this: J. Org. Chem. 1976, 41, 19, 3149–3151Publication Date (Print):September 1, 1976Publication History Published online1 May 2002Published inissue 1 September 1976https://pubs.acs.org/doi/10.1021/jo00881a017https://doi.org/10.1021/jo00881a017research-articleACS PublicationsRequest reuse permissionsArticle Views300Altmetric-Citations39LEARN 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
INTERACTIONS BETWEEN SATELLITE BACTERIOPHAGE P4 AND ITS HELPERS (1990)

The helper dependence of satellite phage P4 superimposes an additional set of regulatory interactions on those required for the independent maintenance of P4 or its helpers. These interactions allow P4 to exploit a helper phage under a variety of circumstances and can affect expression of the immunity functions and late genes of both phages. The phage P2 lysis/lysogeny decision involves two competing repressors regulating mutually exclusive promoters in the early control region. In the absence of a helper phage, the P4 immunity function plays a role in the choice between lysogeny or the multicopy plasmid state. No evidence exists for a P4-encoded immunity repressor; in P4-lysogenic cells, expression of the P4 DNA replication gene alpha appears to be prevented by premature termination of transcription. Immunity-independent expression of alpha in the multicopy plasmid state involves initiation of transcription at an alternative upstream promoter that is positively regulated by P4 delta protein; the same promoter is activated by P2 Cox protein during derepression of P4 by P2. The mechanism of derepression of P2 by P4 remains to be determined, and the relationship between the P4 immunity and derepression functions and the mutations that allow P4 to grow with a P3 prophage helper is an intriguing area for further exploration. Expression of P2 and P4 late genes is regulated by phage-encoded, zinc-binding transcriptional activators that appear to interact directly with the alpha subunit of RNA polymerase of E. coli. Stimulation of P2 late transcription by P2 Ogr protein depends upon phage DNA replication, whereas activation of transcription from the same promoters by the related P4 delta gene product is replication-independent. Elucidation of the mechanisms underlying these interactions promises to provide new insights into strategies for control of gene expression.
Local Control of Microdomain Orientation in Diblock Copolymer Thin Films with Electric Fields (1996)

Local control of the domain orientation in diblock copolymer thin films can be obtained by the application of electric fields on micrometer-length scales. Thin films of an asymmetric polystyrene-polymethylmethacrylate diblock copolymer, with cylindrical polymethylmethacrylate microdomains, were spin-coated onto substrates previously patterned with planar electrodes. The substrates, 100-nanometer-thick silicon nitride membranes, allow direct observation of the electrodes and the copolymer domain structure by transmission electron microscopy. The cylinders aligned parallel to the electric field lines for fields exceeding 30 kilovolts per centimeter, after annealing at 250&deg;C in an inert atmosphere for 24 hours. This technique could find application in nanostructure fabrication.
SufA – a novel subtilisin-like serine proteinase of Finegoldia magna (2007)

Finegoldia magna is an anaerobic Gram-positive bacterium and commensal, which is also associated with clinically important conditions such as skin and soft tissue infections. This study describes a novel subtilisin-like extracellular serine proteinase of F. magna, denoted SufA (subtilase of Finegoldia magna), which is believed to be the first subtilase described among Gram-positive anaerobic cocci. SufA is associated with the bacterial cell surface, but is also released in substantial amounts during bacterial growth. Papain was used to release SufA from the surface of F. magna and the enzyme was purified by ion-exchange chromatography and gel filtration. A protein band on SDS-PAGE corresponding to the dominating proteolytic activity on gelatin zymography was analysed by MS/MS. Based on the peptide sequences obtained, the sufA gene was sequenced. The gene comprises 3466 bp corresponding to a preprotein of 127 kDa. Like other members of the subtilase family, SufA contains the catalytic triad of aspartic acid, histidine and serine with surrounding conserved residues. A SufA homologue was identified in 33 of 34 investigated isolates of F. magna, as revealed by PCR and immunoprinting. The enzyme forms dimers, which are more proteolytically active than the monomeric protein. SufA was found to efficiently cleave and inactivate the antibacterial peptide LL-37 and the CXC chemokine MIG/CXCL9, indicating that the enzyme promotes F. magna survival and colonization.