gebhart/patrepeval huggingface dataset:
Uncharged stereoregular nucleic acid analogs. 1. Synthesis of a cytosine-containing oligomer with carbamate internucleoside linkages (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUncharged stereoregular nucleic acid analogs. 1. Synthesis of a cytosine-containing oligomer with carbamate internucleoside linkagesEugene P. Stirchak, James E. Summerton, and Dwight D. WellerCite this: J. Org. Chem. 1987, 52, 19, 4202–4206Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September 1987https://pubs.acs.org/doi/10.1021/jo00228a010https://doi.org/10.1021/jo00228a010research-articleACS PublicationsRequest reuse permissionsArticle Views367Altmetric-Citations45LEARN 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
Essential stem cell methods (2009)

This is a fast moving field and these detailed methods will help drive advances in stem cell research. The editors have hand-selected step-by-step methods from researchers with extensive reputations and expertise. This volume, as part of the Reliable Lab Solutions series, delivers busy researchers a handy, time-saving source for the best methods and protocols in stem cells. * Provides powerful research opportunities for those interested in purusing work in pluripotent stem cells, disease modelling, and....
Synthesis of Ultrathin Films of Prussian Blue by Successive Ion Adsorption Technique (2002)

Abstract Ultrathin films of Prussian blue (PB) were successfully prepared on substrates by the successive ion adsorption technique that consisted of alternate immersions of a substrate into solutions of Fe2+ and Fe(CN)63-. The PB films showed stable electrochemical redox and electrochromic properties.
Expression of the extraneuronal monoamine transporter in RPE and neural retina (2000)

In situ hybridization analysis showed that OCT3 is expressed in mouse RPE and in several cell types of the neural retina, including photoreceptor, ganglion, amacrine, and horizontal cells. The expression of OCT3 in RPE was confirmed by Northern blot analysis and RT-PCR. The characteristics of MPP( +) uptake in cultured ARPE-19 cells included the stimulation of transport by alkaline pH, high affinity (K(t) = 28 +/- 4 microM), competition with several cationic drugs and monoamine neurotransmitters and sensitivity to steroids. In addition, the uptake of MPP(+) in RPE cells was inhibited by dopamine and histamine with IC(50) values (concentration needed for 50% inhibition) of 637 +/- 84 microM and 150 +/- 20 microM, respectively. CONCLUSIONS. This study provides the first report on the expression and function of an organic cation transporter, OCT3, in the eye and in particular the RPE. The data have physiological and pharmacological relevance as it is likely that OCT3 participates in the clearance of dopamine and histamine from the subretinal space and may also play a key role in the disposition of the retinal neurotoxin MPP(+).
The Clinical Significance of Positive Blood Cultures in the 1990s: A Prospective Comprehensive Evaluation of the Microbiology, Epidemiology, and Outcome of Bacteremia and Fungemia in Adults (1997)

To assess changes since the mid-1970s, we reviewed 843 episodes of positive blood cultures in 707 patients with septicemia. The five most common pathogens were Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci (CNS), Klebsiella pneumoniae, and Enterococcus species. Although CNS were isolated most often, only 12.4% were clinically significant. Half of all episodes were nosocomial, and a quarter had no recognized source. Leading identifiable sources included intravenous catheters, the respiratory and genitourinary tracts, and intraabdominal foci. Septicemia-associated mortality was 17.5%. Patients who received appropriate antimicrobial therapy throughout the course of infection had the lowest mortality (13.3%). Multivariate analysis showed that age (relative risk [RR], 1.80), microorganism (RR, 2.27), source of infection (RR, 2.86), predisposing factors (RR, 1.98), blood pressure (RR, 2.29), body temperature (RR, 2.04), and therapy (RR, 2.72) independently influenced outcome. Bloodstream infections in the 1990s are notable for the increased importance of CNS as both contaminants and pathogens, the proportionate increase in fungi and decrease in anaerobes as pathogens, the emergence of Mycobacterium avium complex as an important cause of bacteremia in patients with advanced human immunodeficiency virus infection, and the reduction in mortality associated with infection.
Structural Basis for a Ca 2+ -Sensing Function of the Metabotropic Glutamate Receptors (1998)

The metabotropic glutamate receptors (mGluRs) are widely distributed in the brain and play important roles in synaptic plasticity. Here it is shown that some types of mGluRs are activated not only by glutamate but also by extracellular Ca2+ (Ca2+o). A single amino acid residue was found to determine the sensitivity of mGluRs to Ca2+o. One of the receptors, mGluR1alpha, but not its point mutant with reduced sensitivity to Ca2+o, caused morphological changes when transfected into mammalian cells. Thus, the sensing of Ca2+o by mGluRs may be important in cells under physiological condition.
Novel device structures by selective epitaxial growth (SEG) (1987)

In the last few years, great interest has been generated in the selective growth of single crystal silicon in seed windows of an SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> mask in order to fabricate novel device structures for VLSI/ULSI device technology. This increased interest in selective epitaxial growth (SEG) and its derivitives, simultaneous single/poly deposition (SSPD) and epitaxial lateral overgrowth (ELO) have led to several key processing breakthroughs that are currently changing the future direction and usage of silicon epitaxy. This paper will describe: 1) the key SEG processing breakthroughs that have occurred over the last 25 years, 2) some of the current limitations still observed with SEG processing and, 3) some of the novel device structures that are possible through the use of SEG techniques.
Adaptive Thresholding for the DigitalDesk (1993)

Introduction to the problem The image produced by a video camera pointing at black printing on a white sheet of paper is not truly black and white. This image is grey-scale (or colour) no matter where the camera is pointed. Unless lighting on the desk is carefully controlled, video images of paper lying on the desk are poor
Identification and removal of immunogenicity in therapeutic proteins. (2007)

The development of anti-therapeutic protein immune responses in patients can be a severe complication of treatment with this class of pharmaceuticals. Antibodies generated against therapeutic proteins limit the clinical efficacy of these agents by neutralizing their biological activity and/or enhancing their clearance. An assessment of the propensity of protein therapeutics to elicit immune responses in patients is likely to become an essential part of their preclinical development. It is clear that CD4+ T-cells are an important factor in the development of long-lived, class-switched, high-affinity antitherapeutic protein antibodies. The increased risk of immunogenicity that is attributed to the presence of T-cell epitopes in therapeutic protein sequences has led to the development of a variety of methods for locating T-cell epitopes and identifying binding peptide amino acids that are important for interacting with either major histocompatibility complex class II molecules or the T-cell receptors. Manipulation of these key residues to disrupt these interactions while maintaining biological activity can result in modified therapeutic proteins with reduced immunogenicity.
Tbx1 is regulated by forkhead proteins in the secondary heart field† (2006)

Transcriptional regulation in a tissue-specific and quantitative manner is essential for developmental events, including those involved in cardiovascular morphogenesis. Tbx1 is a T-box-containing transcription factor that is responsible for many of the defects observed in 22q11 deletion syndrome in humans. Tbx1 is expressed in the secondary heart field (SHF) and is essential for cardiac outflow tract (OFT) development. We previously reported that Tbx1 is regulated by sonic hedgehog by means of forkhead (Fox) transcription factors in the head mesenchyme and pharyngeal endoderm, but how it is regulated in the SHF is unknown. Here, we show that Tbx1 expression in the SHF is regulated by Fox proteins through a combination of two evolutionarily conserved Fox binding sites in a dose-dependent manner. Cell fate analysis using the Tbx1 enhancer suggests that SHF-derived Tbx1-expressing cells contribute extensively to the right ventricular myocardium as well as the OFT during early development and ultimately give rise to the right ventricular infundibulum, pulmonary trunk, and pulmonary valves. These results suggest that Fox proteins are involved in most, if not all, Tbx1 expression domains and that Tbx1 marks a subset of SHF-derived cells, particularly those that uniquely contribute to the right-sided outflow tract and proximal pulmonary artery.
Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells (2008)

Notch signaling is involved in tumorigenesis, but its role in B-chronic lymphocytic leukemia (B-CLL) pathogenesis is not completely defined. This study examined the expression and activation of Notch receptors in B-CLL cells and the role of Notch signaling in sustaining the survival of these cells. Our results show that B-CLL cells but not normal B cells constitutively express Notch1 and Notch2 proteins as well as their ligands Jagged1 and Jagged2. Notch signaling is constitutively activated in B-CLL cells, and its activation is further increased in B-CLL cells, which resist spontaneous apoptosis after 24-hour ex vivo culture. Notch stimulation by a soluble Jagged1 ligand increases B-CLL cell survival and is accompanied by increased nuclear factor-kappa B (NF-kappaB) activity and cellular inhibitor of apoptosis protein 2 (c-IAP2) and X-linked inhibitor of apoptosis protein (XIAP) expression. In contrast, Notch-signaling inhibition by the gamma-secretase inhibitor I (GSI; z-Leu-Leu-Nle-CHO) and the specific Notch2 down-regulation by small-interfering RNA accelerate spontaneous B-CLL cell apoptosis. Apoptotic activity of GSI is accompanied by reduction of NF-kappaB activity and c-IAP2 and XIAP expression. Overall, our findings show that Notch signaling plays a critical role in B-CLL cell survival and apoptosis resistance and suggest that it could be a novel potential therapeutic target.
Humanized Radioiodinated Minibody For Imaging of Prostate Stem Cell Antigen–Expressing Tumors (2008)

Imaging PSCA-positive prostate cancer is feasible using an intermediate size antibody fragment at 21 hours.
Does transcatheter aortic valve implantation mean the end of surgical aortic valve replacement? (2010)

Although the results of the early TAVI experience are promising, longer-term follow-up is necessary before the procedure can be extended to lowerrisk patients. Many issues are not yet resolved, including the long-term effects of paravalvular leaks (which occur in most TAVI patients), the true stroke rate in TAVI patients (which is probably in the range of 5% to 6%), and the need for permanent pacemaker implantation (which ranges from 5% to 40% in TAVI patients, depending upon the device used). As the procedure is extended into the lower-risk population, these issues will assume greater import than they have in the population currently in treatment—very elderly, high-risk patients with limited life expectancy. As in the coronary-revascularization paradigm of percutaneous coronary intervention versus coronary artery bypass grafting, there will be increasing adoption of the transcatheter approach. Just as the rumors of the demise of surgical bypass were premature, conventional AVR will continue to be the predominant technique for the treatment of aortic stenosis during at least the next decade. Although the percentage of patients treated by a transcatheter approach will continue to increase, regulatory and reimbursement factors are likely to be the primary determinants of the rate of adoption.
A cost-effective maximum likelihood receiver for multicarrier systems (2003)

Equalization structures for maximum likelihood (ML) reception of data transmitted over intersymbol interference channels are studied. The equalizer that is best for the ML receiver is derived from a general theory of decision-aided equalization. The resulting optimum equalizers are linear and do not use previous decisions. If the equalizer complexity is permitted to be infinite, then a general optimum class of structures is derived that includes the decision feedback equalizer and the lesser-known autoregressive moving average filters. When a complexity constraint is also imposed on the equalizer, one of the structures in this class will be best for a given ML receiver. The best structure is found by a simple search procedure, which is given. The results indicate that near-optimum performance can be achieved by using this approach at a great computational reduction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Increased sialic acid density in surface glycoprotein of transformed and malignant cells--a general phenomenon? (1973)

Summary Established lines of malignant (MBVIA) and nonmalignant (MBIII) lymphoblasts, baby hamster kidney cells (BHK21/C13), BHK21/C13 cells transformed by polyoma virus, 3T3 mouse fibroblasts, 3T3 cells transformed by SV40 virus, spontaneously transformed 3T3 cells (3T3-f), rat liver cells (RLC), and Novikoff hepatoma N1S1-67 cells were studied in this investigation. Each homologous pair of proliferating cells was differentially labeled with l-fucose-14C and -3H for detection of increased sialic acid density in glycoprotein components of the transformed cell surface. The change was detectable by the faster elution from Sephadex G-50 or Bio-Gel P-10 of the trypsin- and Pronase-digested material of malignant as compared with nonmalignant cells, and the coincidence of elution profiles following neuraminidase treatment. This change was encountered in all cells studied; the greatest change was in 3T3-f cells and the smallest was in SV40-3T3 cells, in which it could be established only by gel filtration over Bio-Gel P-10. Increased sialylation of glycoprotein components has thus been demonstrated for 3 types of cells, namely, lymphoblast, fibroblast, and epithelioid cells cultured in vitro, and for 3 carcinogenic determinants, namely, viral, chemical, and “spontaneous.” We suggest that the transformed cell surface—being unable to modulate its expression as a function of the cell cycle in the manner of normal cells—is blocked in a condition of increased sialyl extension resembling that of the normal mitotic cell surface, and thus counteracts functional contract relations between cells.
The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy (2020)

Inducible T cell costimulator (ICOS, cluster of differentiation (CD278)) is an activating costimulatory immune checkpoint expressed on activated T cells. Its ligand, ICOSL is expressed on antigen-presenting cells and somatic cells, including tumour cells in the tumour microenvironment. ICOS and ICOSL expression is linked to the release of soluble factors (cytokines), induced by activation of the immune response. ICOS and ICOSL binding generates various activities among the diversity of T cell subpopulations, including T cell activation and effector functions and when sustained also suppressive activities mediated by regulatory T cells. This dual role in both antitumour and protumour activities makes targeting the ICOS/ICOSL pathway attractive for enhancement of antitumour immune responses. This review summarises the biological background and rationale for targeting ICOS/ICOSL in cancer together with an overview of the principal ongoing clinical trials that are testing it in combination with anti-cytotoxic T lymphocyte antigen-4 and anti-programmed cell death-1 or anti-programmed cell death ligand-1 based immune checkpoint blockade.
Sustained Release of Cisplatin in Dogs from an Injectable Implant Delivery System (1996)

Cisplatin was incorporated into an in-situ forming biodegradable implant delivery system (ATRIGELO) consisting of a biodegradable polymer dissolved in a pharmaceutically acceptable solvent. The polymer solution with the suspended cisplatin was injected subcutaneously into the flank or shoulder of six healthy beagle dogs where the water-insoluble polymer precipitated upon contact with body fluids and formed a solid implant for the controlled release of the drug. Each dog received four injections, spaced thirty days apart, of a formulation containing either poly(DL-lactide-co-caprolactone) (PLC) or pely(DL-lactide-co-glycolide) (PLGA) dissolved in dimethyl sulfoxide (DM8O) and loaded with 8% by weight cisplatin. Dosage levels of 70, 105, and 157.5 mg/m 2 were used to determine dosage escalation effects. Injections of the same formulations without the drug served as controls. Samples of blood were taken at appropriate times over the four months of treatment and analyzed for platinum concentration by atomic absorption spectroscopy. Local tissue and systemic toxicities were also determined. Both formulations exhibited sustained release of cisplatin with peak serum concentrations of platinum being attained in about two days followed by gradually decreasing platinum levels to day thirty. Consistent drug release profiles were observed for each of the four thirty-day treatment periods. The dosage escalation results exhibited an approximate 50% increase in peak platinum levels and area-under-the-curve (AUC) values for each 50% increase in drug dose. Local tissue toxicity to the cisplatin-containing implants was variable and appeared to be unrelated to dose level or direction number. Tissue reaction to the implants without drug was minimal indicating a role of cisplatin in the tissue reactions. Systemic toxicity, as judged by clinical parameters and clinicopathologic evaluation, was not noted at any dose level or injection time.
Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation (2007)

Multiple signaling pathways, including Wnt signaling, participate in animal development, stem cell biology, and human cancer. Although many components of the Wnt pathway have been identified, unresolved questions remain as to the mechanism by which Wnt binding to its receptors Frizzled and Low-density lipoprotein receptor-related protein 6 (LRP6) triggers downstream signaling events. With live imaging of vertebrate cells, we show that Wnt treatment quickly induces plasma membrane-associated LRP6 aggregates. LRP6 aggregates are phosphorylated and can be detergent-solubilized as ribosome-sized multiprotein complexes. Phospho-LRP6 aggregates contain Wnt-pathway components but no common vesicular traffic markers except caveolin. The scaffold protein Dishevelled (Dvl) is required for LRP6 phosphorylation and aggregation. We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization.
Azathioprine Suppresses Ezrin-Radixin-Moesin-Dependent T Cell-APC Conjugation through Inhibition of Vav Guanosine Exchange Activity on Rac Proteins (2006)

We have shown recently that the azathioprine metabolite 6-Thio-GTP causes immunosuppression by blockade of GTPase activation in T lymphocytes. In the present study, we describe a new molecular mechanism by which 6-Thio-GTP blocks GTPase activation. Although 6-Thio-GTP could bind to various small GTPases, it specifically blocked activation of Rac1 and Rac2 but not of closely related Rho family members such as Cdc42 and RhoA in primary T cells upon stimulation with alphaCD28 or fibronectin. Binding of 6-Thio-GTP to Rac1 did not suppress Rac effector coupling directly but blocked Vav1 exchange activity upon 6-Thio-GTP hydrolysis, suggesting that 6-Thio-GTP loading leads to accumulation of 6-Thio-GDP-loaded, inactive Rac proteins over time by inhibiting Vav activity. In the absence of apoptosis, blockade of Vav-mediated Rac1 activation led to a blockade of ezrin-radixin-moesin dephosphorylation in primary T cells and suppression of T cell-APC conjugation. Azathioprine-generated 6-Thio-GTP thus prevents the development of an effective immune response via blockade of Vav activity on Rac proteins. These findings provide novel insights into the immunosuppressive effects of azathioprine and suggest that antagonists of the Vav-Rac signaling pathway may be useful for suppression of T cell-dependent pathogenic immune responses.
Powerline Communications (2003)

Abstract The usage of electrical power supply networks for voice and data transmission, called Powerline Communications (PLC), allows realization of telecommunication systems without laying new transmission cables and therefore, saving costs and time. The PLC technology becomes nowadays more and more attractive, particularly in so‐called “last mile” networks. The main reasons for that are the deregulation of the telecommunications market and the fact that the access networks are still property of incumbent network providers. However, the powerline grids are not designed for data transmission which causes some specific performance problems in PLC networks; unfavorable noise behavior, powerful attenuation, changing impedance, electro‐magnetic compatibility with wireless services, etc. PLC networks have to operate with a limited signal power, which reduces data rates and network distances, and increases their sensitivity to disturbances. Therefore, efficient modulation and MAC layer as well as capable error handling have to be designed for PLC systems.