gebhart/patrepeval huggingface dataset:
Intercellular communication in the immune system: differential expression of connexin40 and 43, and perturbation of gap junction channel functions in peripheral blood and tonsil human lymphocyte subpopulations (2000)

The distribution and function of connexins (integral membrane proteins assembled into gap junction intercellular communication channels) were studied in human lymphocyte subpopulations. The expression of mRNA encoding connexins in peripheral blood and tonsil-derived T, B and natural killer (NK) lymphocytes was examined. Connexin43 (Cx43) mRNA was expressed in peripheral blood and tonsil lymphocytes, but Cx40 mRNA expression was confined to tonsil-derived T and B lymphocytes; Cx26, Cx32, Cx37 and Cx45 were not detected by reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis also demonstrated the presence of Cx40 and Cx43 proteins in T and B lymphocytes in a manner coincidental to the mRNA detection. Stimulation in vitro of T and B lymphocytes with phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), respectively, increased Cx40 and Cx43 protein expression. Flow cytometric analysis, using antibodies to extracellular loop amino acid sequences of connexins, confirmed the surface expression of connexins in all lymphocyte subpopulations. Assembly of connexins into gap junctions providing direct intercellular channels linking attached lymphocytes was demonstrated by using a dye transfer technique. The exchange of dye between lymphocytes was inhibited by a connexin extracellular loop mimetic peptide and alpha-glycyrrhetinic acid, two reagents that restrict intercellular communication across gap junctions. Dye coupling occurred between homologous and heterologous co-cultures of T and B lymphocytes, and was not influenced by their stimulation with PHA and LPS. The connexin mimetic peptide caused a significant decrease in the in vitro synthesis of immunoglobulin M (IgM) by T- and B-lymphocyte co-cultured populations in the presence or absence of stimulation by PHA. The results identify connexins as important cell surface components that modulate immune processes.
An Effector-Reduced Anti- -Amyloid (A ) Antibody with Unique A Binding Properties Promotes Neuroprotection and Glial Engulfment of A (2012)

Passive immunization against β-amyloid (Aβ) has become an increasingly desirable strategy as a therapeutic treatment for Alzheimer's disease (AD). However, traditional passive immunization approaches carry the risk of Fcγ receptor-mediated overactivation of microglial cells, which may contribute to an inappropriate proinflammatory response leading to vasogenic edema and cerebral microhemorrhage. Here, we describe the generation of a humanized anti-Aβ monoclonal antibody of an IgG4 isotype, known as MABT5102A (MABT). An IgG4 subclass was selected to reduce the risk of Fcγ receptor-mediated overactivation of microglia. MABT bound with high affinity to multiple forms of Aβ, protected against Aβ1-42 oligomer-induced cytotoxicity, and increased uptake of neurotoxic Aβ oligomers by microglia. Furthermore, MABT-mediated amyloid plaque removal was demonstrated using in vivo live imaging in hAPP((V717I))/PS1 transgenic mice. When compared with a human IgG1 wild-type subclass, containing the same antigen-binding variable domains and with equal binding to Aβ, MABT showed reduced activation of stress-activated p38MAPK (p38 mitogen-activated protein kinase) in microglia and induced less release of the proinflammatory cytokine TNFα. We propose that a humanized IgG4 anti-Aβ antibody that takes advantage of a unique Aβ binding profile, while also possessing reduced effector function, may provide a safer therapeutic alternative for passive immunotherapy for AD. Data from a phase I clinical trial testing MABT is consistent with this hypothesis, showing no signs of vasogenic edema, even in ApoE4 carriers.
A multinational phase II study of PEP02 (liposome irinotecan) for patients with gemcitabine-refractory metastatic pancreatic cancer. (2011)

4069 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved pharmacokinetics and tumor biodistribution of both CPT-11 and its active metabolite-SN38 compared to the free form drug. PEP02 has showed encouraging safety and efficacy in various tumor types, including significant antitumor activity in a human pancreatic cancer L3.6pl orthotopic nude mouse xenograft model. In previous phase I studies, PEP02 either alone or in combination with 5-FU/LV demonstrated prolonged disease control in 5 of 7 (71%) patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). This phase II study aims to evaluate PEP02 monotherapy as second-line treatment in pts with metastatic, GEM-refractory PC. Methods: Pts were eligible if they had metastatic pancreatic adenocarcinoma, KPS ≥ 70, and progressed following one line of GEM-based therapy. Treatment consisted of PEP02 120 mg/m2 administered as a 90-minute infusion every 3 weeks. A Simon’s 2-stage design was used with 16 pts in the first stage and 39 pts in total; primary objective was 3-month survival rate (OS3-month). Results: Between March 2009 and September 2010, 41 pts were enrolled at 3 centers in the U.S. and Taiwan. Characteristics for the 40 ITT pts: 19 M/21 F; age 39-82 yrs; 25 Asian/15 Caucasian, KPS 100/90/80/70: 7/16/7/10. Mean number of treatment cycles is 5.25 (range, 1-26). Objective response rate is 5% and disease control rate (minor response + stable disease > 2 cycles) is 50%. 10 (30.3%) of 33 pts with elevated baseline CA19-9 have had > 50% biomarker decline. The OS3-month is 75%, with median progression free survival (PFS) and OS of 9 and 21.6 weeks, respectively. There was no correlation between duration of prior GEM-based therapy and survival after PEP02 treatment. The most common G3/4 adverse events are: leucopenia/neutropenia, anemia, diarrhea, and fatigue. Conclusions: This study has already met its primary endpoint (predicted OS3-month ≥ 65%). PEP02 appears to have both activity and tolerable side effects for pts with metastatic, GEM-refractory PC, and represents a promising option for this pt population with few options.
Low-power clock distribution in a multilayer core 3d microprocessor (2008)

Clock distribution networks are extremely critical from a performance and power standpoint. They account for about 20-30% of the total power dissipated in current generation microprocessors. Many three-dimensional (3D) schemes propose to reduce interconnect length to improve performance and decrease power consumption. In this paper we propose a clock distribution network for a 3D multilayer core microprocessor. The 3D microprocessor floor plan has a single core folded onto multiple layers. A separate layer for the clock distribution network is proposed in the 3D microprocessor. This arrangement of a 3D chip stack reduces (a) power lost in long interconnects at block level and (b) in the clock distribution. Simulation results indicate a 15-20% power saving for this clock distribution scheme as compared to a 2D structure. A methodology for turning off the global clock grid along with the logic for an entire layer in a 3D stack is also proposed. Simulation results indicate an additional 8-10% savings in power with minimal impact on the critical parameters of the clock grid.
Transport of Gases and Vapors in Glassy and Rubbery Polymers (2006)

This chapter contains sections titled: Background and Phenomenology Effects of Gas and Polymer Properties on Transport Coefficients Effect of Pressure on Transport Parameters Effect of Temperature on Transport Parameters Structure/Property Relations Conclusions References
Neurotrophins Redirect p75NTR from a Clathrin‐Independent to a Clathrin‐Dependent Endocytic Pathway Coupled to Axonal Transport (2007)

The p75 neurotrophin receptor (p75(NTR)) plays multiple roles in neuronal physiology through interactions with many ligands and coreceptors. However, its intracellular neuronal trafficking prior to and after neurotrophin activation is still poorly characterized. We have previously shown that in response to nerve growth factor (NGF), p75(NTR) is retrogradely transported along the axons of motor neurons (MNs) in carriers shared with NGF, brain-derived neurotrophic factor and the tyrosine kinase receptor TrkB. Here, we report that NGF does not enhance the internalization or degradation of p75(NTR), which undergoes a rapid dynamin-dependent and clathrin-independent recycling process in MNs. Instead, incubation of cells with NGF leads to the redirection of a pool of plasma membrane p75(NTR) into clathrin-coated pits. The subsequent internalization of p75(NTR) via clathrin-mediated endocytosis, as well as the activity of Rab5, are essential for the sorting of the p75(NTR)-containing endosomes to the axonal retrograde transport pathway and for the delivery of p75(NTR) to the soma. Our findings suggest that the spatial regulation of p75(NTR) signalling is controlled by these ligand-driven routes of endocytosis.
Regulation of Cl-/HCO3- exchange in the rabbit cortical collecting tubule. (1991)

Cl-/HCO3- exchange is present in all three cell types of the rabbit cortical collecting tubule, yet may mediate a different function in each cell type. The purpose of this study was to characterize further the location, function, and regulation of Cl-/HCO3- exchange in two cell types using measurements of intracellular pH (pHi). In the principal cell there was no evidence for apical Cl-/HCO3- exchange, including no change in pHi with increases in luminal HCO3-. The principal cell possesses a basolateral Cl-/HCO3- exchanger that is inactive normally but stimulated by intracellular alkalosis. Decreased PCO2 results in increased pHi associated with activation of Cl-/HCO3- exchange and partial recovery of pHi. In contrast, the beta-intercalated cell possesses an apical Cl-/HCO3- exchanger and alkalinizes with increases in luminal HCO3-. Also in contrast to the principal cell, the beta-intercalated cell apical Cl-/HCO3- exchanger does not appear to be involved in pHi regulation and may be specifically modified for transcellular HCO3- transport. In conclusion, the separate Cl-/HCO3- exchangers in the principal cell and the beta-intercalated cell not only have opposite polarity but are regulated differently.
4-Quinazolinones. II. Self-condensation of anthranilamide (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT4-Quinazolinones. II. Self-condensation of anthranilamideSatyesh C. PakrashiCite this: J. Org. Chem. 1971, 36, 5, 642–645Publication Date (Print):March 1, 1971Publication History Published online1 May 2002Published inissue 1 March 1971https://pubs.acs.org/doi/10.1021/jo00804a007https://doi.org/10.1021/jo00804a007research-articleACS PublicationsRequest reuse permissionsArticle Views226Altmetric-Citations7LEARN 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
Polyunsaturated monoglycerides and a pregnadiene in defensive glands of the water beetle Agabus affinis (2000)

In addition to the C21 steroid 15alpha-hydroxypregna-4,6-dien-3,20-dione, four 1- or 2-acylated polyunsaturated monoglycerides, 1- or 2-(cis-5,8,11,14-eicosatetraenoyl)-glycerol and 1- or 2-(cis-5,8,11,14,17-eicosapentaenoyl)glycerol were identified as constituents of the prothoracic defensive gland secretion of the dytiscid beetle Agabus affinis by gas chromatography-mass spectrometry of trimethylsilylated gland extracts. In a feeding assay with minnows, synthetic samples of the two 2-acylated monoglycerides showed only a weak activity as a feeding deterrent. For that reason, other possible functions of the monoglycerides are discussed, such as roles as emulsifiers of cannabimimetics.
Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization: implications of the phosphatidylinositol 3-kinase pathway. (2002)

Genomic abnormalities at 348 loci encoding genes that may contribute to lung cancer transformation and progression were assessed using array comparative genomic hybridization in 21 squamous carcinomas (SqCas) and 16 adenocarcinomas (AdCas). Hierarchical clustering showed a clear pattern of gains and losses for the SqCas, whereas the pattern for AdCas was less distinct. Cross-validated classification using a K-nearest-neighbor assigned, on average, 32 of 37 samples to their proper histological subtype. The most noticeable differences between SqCas and AdCas were gain of chromosome 3q22-q26 and loss of chromosome 3p. These occurred almost exclusively in SqCas. The region of recurrent increase is approximately 30 Mb in extent, ranging from EVI1 to TFRC. PIK3CA, the alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is in this region. The PIK3CA copy number increase was validated using fluorescence in situ hybridization to lung cancer tissue microarrays. Activity of the downstream PI3K effector protein kinase B (PKB) was higher in SqCas than in AdCas and was correlated with PIK3CA copy number (r = 0.75), suggesting that these copy number increases contribute to activation of PI3K signaling in SqCas of the lung.
Addition of Fish Oil to Cream Cheese Affects Lipid Oxidation, Sensory Stability and Microstructure (2012)

The objective of this study was to investigate the differences in the oxidative stability during storage of fish oil enriched cream cheeses when fish oil was added either as neat oil or pre-emulsified oil with sodium caseinate, whey protein isolate, or a combination of milk proteins and phospholipids as emulsifier. Results showed that the addition of fish oil decreased the oxidative stability of cream cheeses regardless of the addition method, especially when the cheese was stored longer than five weeks. The oxidative stability of fish oil enriched cream cheeses was highest when fish oil was added as neat oil or in a delivery emulsion prepared with a combination of milk proteins and phospholipids. Adding the fish oil in a delivery emulsion prepared with whey protein or caseinate resulted in a less oxidative stable product. It was furthermore shown that the microstructure of the cream cheeses was affected by fish oil addition, and it was suggested that the change in microstructure was partly responsible for the oxidative stability of the cream cheeses.
High-speed VLSI architecture for parallel Reed-Solomon decoder (2003)

This paper presents high-speed parallel RS(255,239) decoder architecture using a modified Euclidean algorithm for the high-speed fiber optic systems. Pipelining and parallelizing allow inputs to be received at very high fiber optic rates and outputs to be delivered at correspondingly high rates with minimum delay. Parallel processing architecture results in a speed-ups of as much as or more than 10 Gbits/s, since the maximum achievable clock frequency is generally bounded by the critical path of the modified Euclidean algorithm block. The parallel RS decoders have been designed and implemented with the 0.1 3-/spl mu/m CMOS standard cell technology in a supply voltage of 1.1V. It is suggested that a parallel RS decoder, which can keep up with optical transmission rates, i.e., 10 Gbits/s and beyond, could be implemented. The proposed channel=4 parallel RS decoder operates at a clock frequency of 770 MHz and has a throughput of 26.6 Gbits/s.
Towards Protein Surface Mimetics (1998)

Proteins are generally poor drug candidates due to bioavailability problems that stem from conformational instability, susceptibility to proteolytic degradation, poor membrane penetration, and unfavourable pharmacokinetics. Since many proteins exert their biological activity through relatively small regions of their folded surfaces, their actions could in principle be reproduced by much smaller designers molecules that retain these localised bioactive surfaces but have potentially improved pharmacokinetic/dynamic properties. Unlike proteins, smaller peptides generally lack well defined three dimensional structure in aqueous solution and tend to be conformationally mobile. Considerable progress has been made in recent years towards the use of molecular constraints to stabilise bioactive conformations. By affixing or incorporating templates that fix secondary and tertiary structures of small peptides, synthetic molecules (protein surface mimetics) can be devised to mimic the localised elements of protein structure that constitute bioactive surfaces. This is a promising growth area of medicinal chemistry that could impact significantly on biology and medicine. In this perspective review we summarise and prescribe methods for mimicking individual elements of secondary structure (helices, turns, strands, sheets) and for assembling their combinations into tertiary structures (helix bundles, multiple loops, helix-loop-helix motifs). A detailed understanding of the features that stabilise secondary and tertiary structures is the key to developing appropriate templates to support and correctly position residues in smaller folded surfaces. The goal is to direct critical amino acids (or surrogates) into the same conformational space and orientation as in bioactive surfaces of a native protein, yet retain sufficient flexibility to bind cooperatively, and with complementarity, to a given receptor. The requirements of size, shape, and directionality for templates to control peptide assembly and folding are discussed in relation to selected mimetics of secondary and tertiary structures. Particularly striking is the general tendency for protease inhibitors and MHC-binding peptides to adopt strand conformations; agonists and antagonists for G protein-coupled receptors to predominate in turn structures; transcription factors, cytokines and DNA/RNA-binding motifs to be helical; and antigen-recognition segments of antibodies to involve multiple loops.
Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation (1993)

Recombinant Epstein-Barr viruses (EBV) with a translation termination codon mutation inserted into the nuclear protein 3A (EBNA-3A) or 3C (EBNA-3C) open reading frame were generated by second-site homologous recombination. These mutant viruses were used to infect primary B lymphocytes to assess the requirement of EBNA-3A or -3C for growth transformation. The frequency of obtaining transformants infected with a wild-type EBNA-3A recombinant EBV was 10 to 15%. In contrast, the frequency of obtaining transformants infected with a mutant EBNA-3A recombinant EBV was only 1.4% (9 mutants in 627 transformants analyzed). Transformants infected with mutant EBNA-3A recombinant virus could be obtained only by coinfection with another transformation-defective EBV which provided wild-type EBNA-3A in trans. Cells infected with mutant EBNA-3A recombinant virus lost the EBNA-3A mutation with expansion of the culture. The decreased frequency of recovery of the EBNA-3A mutation, the requirement for transformation-defective EBV coinfection, and the inability to maintain the EBNA-3A mutation indicate that EBNA-3A is essential or critical for lymphocyte growth transformation and that the EBNA-3A mutation has a partial dominant negative effect. Five transformants infected with mutant EBNA-3C recombinant virus EBV were also identified and expanded. All five also required wild-type EBNA-3C in trans. Serial passage of the mutant recombinant virus into primary B lymphocytes resulted in transformants only when wild-type EBNA-3C was provided in trans by coinfection with a transformation-defective EBV carrying a wild-type EBNA-3C gene. A secondary recombinant virus in which the mutated EBNA-3C gene was replaced by wild-type EBNA-3C was able to transform B lymphocytes. Thus, EBNA-3C is also essential or critical for primary B-lymphocyte growth transformation.
CITE NLM: natural-language searching in an online catalog (1983)

L'acces public au catalogue online de la National Library of Medicine (NLM) par l'intermediaire du prototype CITE (Computerized information transfer in english) offre des possibilites uniques de recherche telles que: entree des questions en langage naturel, affichage automatique des vedettes matieres medicales, strategie de recherche tres rigoureuse, sortie classee des documents, feedback de pertinence immediat possible de l'utilisateur final permettant un affinement de la recherche. Le systeme permet aussi des options pour la presentation des resultats (titres, abstracts etc...) (INTD)
Centimetre scale assembly of vertically aligned and close packed semiconductor nanorods from solution (2009)

Assembly of CdS nanorods (8 x 100 nm) into vertically aligned arrays over very large areas on a substrate either as a monolayer or several multilayers is shown by electrophoresis.
Object-based queries using color points of interest (2002)

Image retrieval systems based on the query-by-example paradigm usually imply a global description of the image. An approach involving points of interest has been developed and comes to light with object/sub-image retrieval tasks which require more local descriptors. However, this solution is not optimal, since it is limited to gray value images. We propose a local image descriptor based on color points of interest, i.e. points extracted and characterized from a color signal at one go. This local characterization is then involved in an image indexing and retrieval approach which is dedicated to object or sub-image retrieval. The entire approach is evaluated on two image databases with various contents and some particular results of object retrieval show the relevance of our approach.
Regulation of smooth muscle cell growth by endothelium-derived factors. (1994)

The endothelium is a source of molecules that either stimulate or inhibit the proliferation of the underlying smooth muscle cells. In the normal, healthy vessel wall the smooth muscle cells are quiescent, but they proliferate when damage to the endothelium occurs. The implication of such observations is that although the endothelium provides a source of growth factors, their stimulatory activity on smooth muscle cells is countered by endothelium-derived growth inhibitors. The inhibitors appear to comprise at least 3 distinct types of molecules: heparin/heparan sulfate; transforming growth factor beta; and nitric oxide. Each molecule inhibits growth of cultured smooth muscle cells by mechanisms that remain to be elucidated and are discussed in this communication. Heparin/heparan sulfate is the most thoroughly characterized of the 3, and has been used for clinical intervention to prevent restenosis. Transforming growth factor beta exhibits bimodal activity on growth, acting as a stimulant at low levels and as an inhibitor at elevated concentrations. Nitric oxide mediated vasorelaxation is dependent upon activation of soluble guanylate cyclase. Because elevation of cyclic guanosine monophosphate in smooth muscle cells depresses their proliferation, nitric oxide would appear to possess the properties necessary to inhibit vascular smooth muscle cell proliferation.