gebhart/patrepeval huggingface dataset:
Antibody-directed Fibrinolysis (1989)

An investigation was made to determine whether it is possible to attract tissue plasminogen activator (tPA) to the site of a thrombus by means of an antibody with affinites for both tPA and fibrin. A bispecific antibody conjugate was constructed by cross-linking two monoclonal antibodies: one specific for tPA, the other specific for fibrin. The bispecific antibody enhanced fibrinolysis by capturing tPA at the site of a fibrin deposit. In an in vitro quantitative fibrinolysis assay, the relative fibrinolytic potency of tPA bound to the bispecific antibody was 13 times greater than that of tPA and 200 times greater than that of urokinase. When fibrin was treated with the bispecific antibody before being mixed with tPA, the relative fibrinolytic potency of tPA was enhanced 14-fold. This capture also occurred when the concentration of tPA present in the assay was less than the concentration of tPA present in normal human plasma. In a human plasma clot assay, samples containing both the bispecific antibody and tPA exhibited significantly more lysis than did samples containing tPA alone. In spite of the increased clot lysis effected by the presence of bispecific antibody, there was no significant increase in fibrinogen or alpha 2-antiplasmin degradation at equal tPA concentrations. The ability of the bispecific antibody to concentrate exogenous tPA in vivo was then examined in the rabbit jugular vein model. Systemic infusion of a small amount of tPA (10,000 units) produced no significant increment in thrombolysis over the level of spontaneous lysis (14 +/- 8%). However, the simultaneous infusion of 10,000 units of tPA and 2 mg of bispecific antibody resulted in 42 +/- 14% (p less than 0.01) lysis. These results suggest that a molecule capable of binding both fibrin and tPA with high affinity could enhance thrombolysis in the circulation by capturing endogenous tPA.
Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2 (2006)

Deregulation of the Sonic hedgehog pathway has been implicated in an increasing number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation and differentiation through activation of the transcription factor Gli. The activity of mammalian Smoothened is controlled by three different hedgehog proteins, Indian, Desert, and Sonic hedgehog, through their interaction with the Smoothened inhibitor Patched. However, the mechanisms of signal transduction from Smoothened are poorly understood. We show that a kinase which regulates signaling by many "conventional" 7TM G-protein-coupled receptors, G protein-coupled receptor kinase 2 (GRK2), participates in Smoothened signaling. Expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription. Moreover, knockdown of endogenous GRK2 by short hairpin RNA (shRNA) significantly reduces signaling in response to the Smoothened agonist SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo M2. We find that GRK2 promotes the association between active Smoothened and beta-arrestin 2. Indeed, Gli-dependent signaling, mediated by coexpression of Smoothened and GRK2, is diminished by beta-arrestin 2 knockdown with shRNA. Together, these data suggest that GRK2 plays a positive role in Smoothened signaling, at least in part, through the promotion of an association between beta-arrestin 2 and Smoothened.
Spectral sharing across 2G-3G systems (2004)

3G schemes with large bandwidth occupancy (e.g. UMTS) are gradually being introduced in response to the growing demand for non-voice services. Meanwhile, 2G systems (e.g., GSM, IS-95) still represent the main source for profit of carriers, and continues to exist for years to come. As a result, a coexistence of 2G and 3G systems is emerging that is likely to last for at least a few years. To optimize spectral efficiency, we show how a 2G/3G sharing strategy enables corporations to make optimal use of the 2G/3G spectral bands that they own. Specifically, we propose an efficient 2G/3G spectral sharing satisfying the following criteria: (1) the sharing strategy provides flexible system capacity over noncontiguous bandwidth, (2) it is able to dynamically update quantities of borrowed spectrum and borrowing duration, and (3) it ensures both lender and borrower to optimize their spectral efficiency and revenues. Specifically, assuming that 2G and 3G networks are DS-CDMA based, we propose an efficient technique supporting spectral sharing across networks by: (1) utilizing a new family of orthogonal spreading codes labeled carrier interferometry (CI) codes, capable of serving as a flexible replacement for the usual Hadamard-Walsh (HW) code; and (2) replacing the usual sinc(/spl middot/) and raised cosine chip shape by a multi-carrier chip shape. Simulation results show a significant beneficial effect via the proposed spectral sharing, e.g., increased capacity of 50% and 100% (in terms of numbers of users) with no loss in BER performance.
Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis (2006)

Cell migration on 2D surfaces is governed by a balance between counteracting tractile and adhesion forces. Although biochemical factors such as adhesion receptor and ligand concentration and binding, signaling through cell adhesion complexes, and cytoskeletal structure assembly/disassembly have been studied in detail in a 2D context, the critical biochemical and biophysical parameters that affect cell migration in 3D matrices have not been quantitatively investigated. We demonstrate that, in addition to adhesion and tractile forces, matrix stiffness is a key factor that influences cell movement in 3D. Cell migration assays in which Matrigel density, fibronectin concentration, and beta1 integrin binding are systematically varied show that at a specific Matrigel density the migration speed of DU-145 human prostate carcinoma cells is a balance between tractile and adhesion forces. However, when biochemical parameters such as matrix ligand and cell integrin receptor levels are held constant, maximal cell movement shifts to matrices exhibiting lesser stiffness. This behavior contradicts current 2D models but is predicted by a recent force-based computational model of cell movement in a 3D matrix. As expected, this 3D motility through an extracellular environment of pore size much smaller than cellular dimensions does depend on proteolytic activity as broad-spectrum matrix metalloproteinase (MMP) inhibitors limit the migration of DU-145 cells and also HT-1080 fibrosarcoma cells. Our experimental findings here represent, to our knowledge, discovery of a previously undescribed set of balances of cell and matrix properties that govern the ability of tumor cells to migration in 3D environments.
Contribution of CAF-I to Anaphase-Promoting-Complex-Mediated Mitotic Chromatin Assembly in Saccharomyces cerevisiae (2005)

The anaphase-promoting complex (APC) is required for mitotic progression and genomic stability. Recently, we demonstrated that the APC is also required for mitotic chromatin assembly and longevity. Here, we investigated the role the APC plays in chromatin assembly. We show that apc5(CA) mutations genetically interact with the CAF-I genes as well as ASF1, HIR1, and HIR2. When present in multiple copies, the individual CAF-I genes, CAC1, CAC2, and MSI1, suppress apc5(CA) phenotypes in a CAF-1- and Asf1p-independent manner. CAF-I and the APC functionally overlap, as cac1delta cac2delta msi1delta (caf1delta) cells expressing apc5(CA) exhibit a phenotype more severe than that of apc5(CA) or caf1delta. The Ts- phenotypes observed in apc5(CA) and apc5(CA) caf mutants may be rooted in compromised histone metabolism, as coexpression of histones H3 and H4 suppressed the Ts- defects. Synthetic genetic interactions were also observed in apc5(CA) asf1delta cells. Furthermore, increased expression of genes encoding Asf1p, Hir1p, and Hir2p suppressed the apc5(CA) Ts- defect in a CAF-I-dependent manner. Together, these results suggest the existence of a complex molecular mechanism controlling APC-dependent chromatin assembly. Our data suggest the APC functions with the individual CAF-I subunits, Asf1p, and the Hir1p and Hir2p proteins. However, Asf1p and an intact CAF-I complex are dispensable for CAF-I subunit suppression, whereas CAF-I is necessary for ASF1, HIR1, and HIR2 suppression of apc5(CA) phenotypes. We discuss the implications of our observations.
A new dark quencher for use in genetic analysis (2003)

A novel, long-wavelength, non-fluorescent quencher (LQ), based on 1,4-diaminoanthraquinone, has been incorporated at the 3' and 5'-termini of oligonucleotides. The quencher has been used in Molecular beacons, efficiently quenching the long wavelength fluorophore, Cy5.
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (2018)

Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361 .).
Absolute Configuration of Scyphostatin (2000)

[reaction: see text] The absolute configuration of the side chain of scyphostatin (1) has been established. The chemical degradation of 1 gave 4 and 9, which correspond to the C7'-C12' and C13'-C16' fragments of the natural products, respectively. The spectroscopic data and [alpha]D values of both compounds were compared to those of authentic samples. The results show that the absolute configuration of 1 is 8'R,10'S,14'R.
Demonstration of apoptosis-associated cleavage products of DNA, complement activation products SC5b-9 and C3d/dg, and immune complexes CIC-C3d, CIC-IgA, and CIC-IgG in the urine of patients with membranous glomerulonephritis. (2003)

There is an association of complement activation and apoptosis with membranous glomerulonephritis. Correlation analysis suggests that the excretion of apoptosis-associated 180 bp nucleosomes, SC5b-9, C3d/dg, and immune complexes containing IgA and IgG in the urine of patients with active membranous glomerulonephritis does not depend solely on the passive transport together with other proteins, but is probably an independent active process.
Circadian system of mice integrates brief light stimuli (1998)

Light is the primary sensory stimulus that synchronizes or entrains the internal circadian rhythms of animals to the solar day. In mammals photic entrainment of the circadian pacemaker residing in the suprachiasmatic nuclei is due to the fact that light at certain times of day can phase shift the pacemaker. In this study we show that the circadian system of mice can integrate extremely brief, repeated photic stimuli to produce large phase shifts. A train of 2-ms light pulses delivered as one pulse every 5 or 60 s, with a total light duration of 120 ms, can cause phase shifts of several hours that endure for weeks. Single 2-ms pulses of light were ineffective. Thus these data reveal a property of the mammalian circadian clock: it can integrate and store latent sensory information in such a way that a series of extremely brief photic stimuli, each too small to cause a phase shift individually, together can cause a large and long-lasting change in behavior.
Leveraging change blindness for redirection in virtual environments (2011)

We present change blindness redirection, a novel technique for allowing the user to walk through an immersive virtual environment that is considerably larger than the available physical workspace. In contrast to previous redirection techniques, this approach, based on a dynamic environment model, does not introduce any visual-vestibular conflicts from manipulating the mapping between physical and virtual motions, nor does it require breaking presence to stop and explicitly reorient the user. We conducted two user studies to evaluate the effectiveness of the change blindness illusion when exploring a virtual environment that was an order of magnitude larger than the physical walking space. Despite the dynamically changing environment, participants were able to draw coherent sketch maps of the environment structure, and pointing task results indicated that they were able to maintain their spatial orientation within the virtual world. Only one out of 77 participants across both both studies definitively noticed that a scene change had occurred, suggesting that change blindness redirection provides a remarkably compelling illusion. Secondary findings revealed that a wide field-of-view increases pointing accuracy and that experienced gamers reported greater sense of presence than those with little or no experience with 3D video games.
Age-related Macular Degeneration (2000)

10-20% of individuals over the age of 65 suffer from age-related macular degeneration (AMD), the leading cause of severe visual impairment in humans living in developed countries. The pathogenesis of this complex disease is poorly understood, and no efficient therapy or prevention exists to date. A precondition for AMD appears to be the accumulation of the age pigment lipofuscin in lysosomes of retinal pigment epithelial (RPE) cells. In AMD, these cells seem to die by apoptosis with subsequent death of photoreceptor cells, and light may accelerate the disease process. Intracellular factors leading to cell death are not known. Here we show that the lipophilic cation N-retinyl-N-retinylidene ethanolamine (A2E), a lipofuscin component, induces apoptosis in RPE and other cells at concentrations found in human retina. Apoptosis is accompanied by the appearance of the proapoptotic proteins cytochrome c and apoptosis-inducing factor in the cytoplasm and the nucleus. Biochemical examinations show that A2E specifically targets cytochrome oxidase (COX). With both isolated mitochondria and purified COX, A2E inhibits oxygen consumption synergistically with light. Inhibition is reversed by the addition of cytochrome c or cardiolipin, a negatively charged phospholipid that facilitates the binding of cytochrome c to membranes. Succinate dehydrogenase activity is not altered by A2E. We suggest that A2E can act as a proapoptotic molecule via a mitochondria-related mechanism, possibly through site-specific targeting of this cation to COX. Loss of RPE cell viability through inhibition of mitochondrial function might constitute a pivotal step toward the progressive degeneration of the central retina.
Elevated Expression of ISG15 in Tumor Cells Interferes with the Ubiquitin/26S Proteasome Pathway (2006)

IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation.
Myeloid-associated differentiation antigens on stem cells and their progeny identified by monoclonal antibodies (1983)

Abstract Within the hematopoietic system, monoclonal antibodies reactive with antigenic determinants, expressed in a lineage- and stage-restricted fashion, can be used to map myeloid differentiation. We have generated a series of monoclonal antibodies that reacts with myeloid-associated determinants on committed myeloid stem cells and their progeny. Their reactivity with peripheral blood cells was identified by immunofluorescence assays, with bone marrow cells by fluorescence- activated cell sorting, and with committed hematopoietic progenitor cells by both cytotoxic assays and fluorescence-activated cell sorting. Antibody 1G10, which has previously been reported to react with cells of the granulocytic lineage and with a minor subset of mature monocytes, was shown to react with granulocyte-macrophage colony- forming units (CFU-GM). Three antibodies not previously characterized (T5A7, L4F3, L1B2) were shown to react with both granulocytic and monocytic cells and in fluorescence-activated cell sorting studies to detectably stain granulocytic cells at different stages of maturation. These three antibodies also react with CFU-GM, two (L4F3 and L1B2) reacting with all CFU-GM, while T5A7 reacts with only a portion of the day 7 CFU-GM. Antibody L4F3 also reacts with a portion of erythroid burst-forming units (BFU-E). In contrast, the previously reported antibody 5F1, which reacts with monocytic cells, nucleated erythroid cells, and platelets, was shown to react with erythroid colony-forming units (CFU-E). Potential applications of these antibodies to studies of normal and malignant hematopoiesis are discussed.
Discovery and investigation of lead compounds as binders to the Extra‐Domain B of the angiogenesis marker, fibronectin (2003)

Abstract Angiogenesis, the growth of new blood vessels from preexisting vessels, is a rare event in the adult (except in the case of the female reproductive cycle), but is a characteristic feature of diseases such as cancer, blinding ocular disorders (e.g., retinopathies), and rheumatoid arthritis. The ED‐B domain of fibronectin, a domain of 91 amino acids, inserted by a mechanism of alternative splicing of the primary transcript into the fibronectin molecule, is a high‐quality marker of angiogenesis and a target for molecular intervention, characterized by a high number of acidic residues on its surface, as well as some solvent‐exposed hydrophobic residues. A library of 113 low molecular‐weight organic compounds, containing both an aromatic moiety and at least one positive charge, was screened for binding to the ED‐B domain, using two‐dimensional heteronuclear NMR spectroscopy. One lead compound, 2,2‐diphenylethylamine, was found that binds specifically to the ED‐B domain, albeit with a dissociation constant in the millimolar range. Chemical modification of this scaffold revealed structural determinants required for binding, as well as amino acid residues in the ED‐B domain responsible for the interaction. The results presented represent the basis for the development of high‐affinity, low molecular‐weight binders by using a linked‐fragment approach or elongating the scaffold by means of combinatorial chemistry. Drug Dev. Res. 58:268–282, 2003. © 2003 Wiley‐Liss, Inc.
Citation Indexing-Its Theory and Application in Science, Technology, and Humanities (1980)

Citation indexing-its theory and application in science, technology, and humanities , Citation indexing-its theory and application in science, technology, and humanities , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Design and synthesis of a versatile DNA-cleaving metallopeptide structural domain (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign and synthesis of a versatile DNA-cleaving metallopeptide structural domainDaniel F. Shullenberger, Paula Denney Eason, and Eric C. LongCite this: J. Am. Chem. Soc. 1993, 115, 23, 11038–11039Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/ja00076a091https://doi.org/10.1021/ja00076a091research-articleACS PublicationsRequest reuse permissionsArticle Views184Altmetric-Citations44LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
Induction of bone formation in an adenoid cystic carcinoma of the maxillary sinus by adoptive immunotherapy involving intra-arterial injection of lymphokine-activated killer cells and recombinant interleukin-2 in combination with radiotherapy. (1990)

A patient with an adenoid cystic carcinoma of the maxillary sinus was treated by adoptive immunotherapy involving intra-arterial injection of lymphokine-activated killer cells (a total number of 7 x 10(7) cells) and recombinant interleukin-2 (a total dose of 2.75 x 10(7) units) in combination with radiotherapy (60Co; total irradiation dose of 5,000 rads). Consequently, it was found that bone formation was induced in the treated tumor, which was then replaced completely by lamellar bone tissue with myxomatous stroma. This finding indicates that the tumor cells composing certain adenoid cystic carcinoma can be converted into normal-appearing, bone-forming cells by current therapy and this differentiation phenomenon leads to cure of the tumor.
Fish & chips: single chip silicon mems ctdl salinity, temperature, pressure and light sensor for use in fisheries research (2005)

A single-chip silicon MEMS CTDL multi sensor for use in aqueous environments is presented. The new sensor chip consists of a conductivity sensor based on platinum electrodes (C), an ion-implanted thermistor temperature sensor (T), a piezoresistive pressure sensor (D for depth/pressure) and an ion-implanted p-n junction light sensor (L). The design and fabrication process is described. A temperature sensitivity of 0.8 /spl times/ 10/sup -3/K/sup -1/ has been measured and detailed analysis of conductivity measurement data shows a cell constant of 81 cm/sup -1/.
Color To Colorant Conversions In A Colorimetric Separation System (1990)

Within several years of establishment of the CIE's Standard Observer, Neugebauer based upon it a device-independent interpretation of ink mixture in halftone color reproduction. Despite limitations of the model, his approach is of fundamental importance at a time in which document preparation in distributed computing environments is coming of age. Fruition of this technology demands a device independent or colorimetric method for representing and rendering color. A commercial, digital system for implementing such an approach (Kodak Designmaster® 8000) has been described and will be reviewed here with particular regard to the output of color imagery on four-color printers. Inversion of Neugebauer's model for conversion of color to device specific signals must be constrained by the color gamut of the output medium and the utilization of the black printer (Gray Component Replacement). The interaction of the black printer with the device gamut and its effect on image quality and metamerism will receive detailed consideration. It will be shown that colorimetry is a powerful tool in maintaining accurate color reproduction during substitution of black for chromatic components, but that properties of the colorants must also be considered in order to realize commercially acceptable GCR. Section 7 of the paper is an enumeration of summary conclusions.