gebhart/patrepeval huggingface dataset:
Strong similarities in antigen fine specificity among DRB1 * 1302 -restricted tetanus toxin tt830-843-specific TCRs in spite of highly heterogeneous CDR3. (1995)

We investigated the Ag fine specificity of four TCRs that shared the same V beta segment but used V alpha s of three different subfamilies and displayed highly heterogeneous alpha and beta CDR3. The TCRs recognized the tetanus toxin tt830-843 (QYIKANSKFIGITE) epitope presented by DRB1*1302. By using a large panel of monosubstituted peptide analogues, we first defined the requirements for tt830-843 binding to DRB1*1302. We found that three residues, I832, N835, and G840, were critical for the interaction with DRB1*1302. Residues potentially contacted by the four TCRs were functionally defined by measuring the IL-2 response to the analogues. Except for the first and the last three residues, as well as I832 and G340, all of the others appeared to provide contacts with the four TCRs, indicating a considerable overlapping in the way these TCRs interact with the peptide. More importantly, and contrary to expectations, the two TCRs expressing the same V alpha/V beta germ-line segments showed a strikingly similar reactivity toward nearly all substitutions; moreover, more pronounced differences were observed when comparing TCRs using different V alpha segments. These results indicate that TCRs with entirely distinct CDR3s in the context of conserved V segments may not differ substantially in the way they recognize the ligand, and may provide new insights into understanding the formation of TCR/peptide/MHC ternary complexes. During these studies, we noticed that analogues with nonconservative substitutions at I832, which bound very unstably to DRB1*1302, could effectively stimulate T cells, suggesting a role of the TCR in contributing toward stabilization of peptide binding.
Fluorometric Determination of DNA in Aquatic Microorganisms by Use of Hoechst 33258 (1982)

A method for the determination of microbial DNA in aquatic environments by the use of Hoechst 33258 has been developed. With unsophisticated instrumentation and simple extraction procedures, it is possible to detect from 0.05 to 10 mug of DNA in bacterial cultures or natural water samples. The method is specific for DNA; DNase I treatment of extracts of natural microbial populations removed 95 to 100% of the observed fluorescence. DNA content ranged from 165 ng ml for relatively eutrophic Potomac River water to 27 ng ml for coastal Atlantic Ocean water and was correlated to an acridine orange direct count (r = 0.90).
General suitability of techniques for in situ detection of apoptosis in small intestinal epithelium (2003)

The present study was designed to evaluate different techniques for the in situ detection of apoptosis in human and rat small intestinal epithelium. The techniques included light microscopy (LM) and transmission electron microscopy (TEM) observation of epoxy resin-embedded tissue, scanning electron microscopy (SEM), TUNEL assay, and antibodies directed against caspase cleavage products of caspase 3, cytokeratin 18 (CK 18), and apoptotic single-strand DNA (ssDNA). All techniques, if the labeling was positive, showed apoptotic cells exclusively at the villus tip. LM and TEM were the most reliable and revealed morphological signs typical of cells that have died via apoptosis. SEM indicated the extension of the process. The antibody recognizing cleaved caspase 3 could be considered an appropriate marker for apoptotic epithelial cells in human and rat small intestine. However, the majority of epithelial cells lining the proximal small intestinal villus contained only low levels of intact CK 18. Therefore, sufficient amounts of cleaved CK 18 for immunohistochemical detection were not generated during apoptosis, rendering the application of the antibody inappropriate. The antibody detecting formamide-denatured ssDNA in apoptotic cells was both suitable and reliable; however, the particular staining procedure used compromised the tissue preservation. In comparison to this, the TUNEL assay was less reliable. Although it was performed with a commercially available ready-to-use kit, its application conditions had to be adjusted for each specimen on the basis of the findings produced by other techniques.
Best Value: How Local Authorities in Northern Ireland are Consulting with Stakeholders (2003)

This paper investigates how local authorities in Northern Ireland have dealt with the consultation
aspect of the Best Value initiative, with specific reference to engagement with stakeholders. Having
briefly looked at the history of, and the rationale behind, Best Value and the requirements it places
on local authorities, some of the disadvantages of the scheme are outlined. The paper then
introduces some of the tenets of stakeholder theory, particularly those of Freeman, and investigates
the wide range of stakeholders that any council will have. The responsibilities of a Northern Ireland
local authority are then compared with those of one in England, and other differences pertaining to
demographics are explored. Then the results of a document content analysis of both Corporate
Plans and Best Value Performance Plans are presented, with each Northern Ireland local authority
being placed in a certain category depending on how they are dealing with the question of
consultation, and interacting with their stakeholders. The paper concludes by surmising that it is a
moot point whether all stakeholders can ever meaningfully play their part in a local authority’s
decision-making process; however, there are encouraging signs that local authorities are making
progress towards engaging with their stakeholders.
InAs/GaAs Quantum-Dot Lasers Monolithically Grown on Si, Ge, and Ge-on-Si Substrates (2013)

The realization of semiconductor lasers on Si substrates will enable the fabrication of complex optoelectronic circuits. This will permit the creation of the long-dreamed chip-to-chip and system-to-system optical interconnects. This paper reports recent developments in our work on InAs/GaAs quantum-dot (QD) lasers monolithically grown on Si, Ge, and Ge-on-Si (Ge/Si) substrates. A thin AlAs nucleation layer (NL) was first investigated for the growth of InAs/GaAs QDs on Si substrates. The AlAs NL enables more defects to be confined in the interface between the GaAs epitaxial layer and Si substrate, and hence leads to higher photoluminescence intensity for InAs/GaAs QDs. Room-temperature lasing at 1.29 μm with a threshold current density of 650 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> was demonstrated with the use of an AlAs NL. The growth of InAs/GaAs QDs on Ge and Ge/Si substrates was further studied. A low threshold current density of ~200 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> for 1-mm long QD lasers has been demonstrated for QD lasers grown on Ge substrates by using Ga prelayer technique. This growth technique has also been explored for Ge/Si substrates. Room-temperature lasing at 1.28 μm with threshold current density of ~164 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and lasing operation up to 84°C has been demonstrated for a 3-mm long device.
The Role of Negative Costimulators During Parasitic Infections (2008)

Activation of T lymphocytes through TCR signalling takes place within the context of numerous other cell surface proteins. To prevent unnecessary activation of T cells the immune system has developed an intricate balance between positive and negative costimulatory signals. Positive costimulatory signals determine whether antigen recognition by T cells leads to full activation or to anergy/death. In contrast, the expression of negative costimulatory molecules by T cells such as cytotoxic T lymphocyte antigen 4 (CTLA-4) mediates the regulation of an immune response and thus plays a pivotal role in the maintenance of peripheral tolerance. The new members of the CD28 family members, programmed death-1 (PD-1) and B and T lymphocyte attenuator (BTLA) are expressed more broadly on various immune cells and are also induced upon inflammation. There is increasing evidence that negative costimulators are critically involved in the regulation of immune responses against parasitic infections. The production of pro-inflammatory cytokines is often required to control parasites but the same cytokines contribute to immunopathology. Recent studies indicate that these negative costimulators are not redundant but fulfil specific functions in different tissues. This might represent a means to provoke a fine-tuning of the immune response and to define tissue specific limits of inflammation that ensure proper physiological function of the respective organ. Thus, negative costimulators represent possible drug targets since their blockade leads to an increased immune response whereas their ligation dampens T cell activation and thereby might prevent immunopathology. This review examines the role of negative costimulators during parasitic infections, and we also discuss their therapeutic potential.
Isolation and expression of murine and rabbit cDNAs encoding an alpha 1,2-mannosidase involved in the processing of asparagine-linked oligosaccharides (1994)

We have isolated a full-length cDNA clone encoding a murine alpha 1,2-mannosidase involved in the processing of mammalian Asn-linked oligosaccharides. Oligonucleotide primers were designed based on peptide sequences derived from the purified rabbit liver enzyme and were used to generate a 1011-base pair probe using the polymerase chain reaction. This probe was used to isolate clones from rabbit and mouse cDNA libraries. The full-length murine cDNA clone encodes a 655-amino acid type II transmembrane protein with a 43-amino acid cytoplasmic tail, a single transmembrane domain, and a large COOH-terminal catalytic domain containing two potential N-glycosylation sites. Stable transfection of the murine alpha 1,2-mannosidase cDNA into mouse L cells resulted in a approximately 22-fold overexpression of alpha 1,2-mannosidase activity. Three transcripts were detected in rabbit tissues, whereas two were found in rat and mouse tissues. The sequences of the rabbit and mouse cDNA clones indicate that the multiple transcripts differ in the length of their 3' sequences as a result of the use of multiple polyadenylation signals. Immunolocalization detected cross-reactive material in a juxtanuclear pattern consistent with the Golgi complex. The catalytic portion of the murine alpha 1,2-mannosidase was found to bear a strong similarity to the processing alpha 1,2-mannosidase from Saccharomyces cerevisiae.
Cell-Directed Assembly of Lipid-Silica Nanostructures Providing Extended Cell Viability (2006)

Amphiphilic phospholipids were used to direct the formation of biocompatible, uniform silica nanostructures in the presence of Saccharomyces cerevisiae and bacterial cell lines. The cell surfaces organize multilayered phospholipid vesicles that interface coherently with the silica host and help relieve drying stresses that develop with conventional templates. These host structures maintain cell accessibility, addressability, and viability in the absence of buffer or an external fluidic architecture. The cell surfaces are accessible and can be used to localize added proteins, plasmids, and nanocrystals. Prolonged cell viability combined with reporter protein expression enabled stand-alone cell-based sensing.
Chemical and immunological characterization of the 21-kDa ADP-ribosylation factor of adenylate cyclase. (1988)

The ADP-ribosylation factor (ARF) is a 21-kDa GTP-binding protein cofactor in the cholera toxin-catalyzed ADP-ribosylation of the stimulatory regulatory subunit of adenylate cyclase. Purified bovine brain ARF was digested with cyanogen bromide, and peptides were purified and sequenced. Approximately 25-30% of the protein was sequenced in this manner. Peptides contained consensus sequences for GTP-binding proteins but were distinct from any of the previously published GTP-binding proteins. Antibodies were raised in rabbits against both protein and synthetic peptide fragments of ARF. Specific ARF immunoreactivity was detected in every eukaryotic tissue or cell examined, including yeast, slime mold, and man. No ARF immunoreactivity was observed when Escherichia coli proteins were tested. Immunoblotting revealed the majority of ARF to be present in the 100,000 x g supernatant. Immunological cross-reactivity with the cytosolic factor indicate that it and ARF are likely to be the same protein. ARF is shown to be myristylated at the amino terminus. The potential role of myristylation in cellular localization is discussed.
Mechanism of Activation and Functional Significance of the Lipolysis-Stimulated Receptor. Evidence for a Role as Chylomicron Remnant Receptor (1995)

In cultured human and rat cells, the lipolysis-stimulated receptor (LSR), when activated by free fatty acids (FFA), mediates the binding of apoprotein B- and apoprotein E-containing lipoproteins and their subsequent internalization and degradation. To better understand the physiological role of LSR, we developed a biochemical assay that optimizes both the activation and binding steps and, thus, allows the estimation of the number of LSR binding sites expressed in the livers of living animals. With this technique, a strong inverse correlation was found in rats between the apparent number of LSR binding sites in liver and the postprandial plasma triglyceride concentration (r = -0.828, p < 0.001, n = 12). No correlation existed between the number of LSR and plasma triglycerides measured in the same animals after 24 h of fasting. The same membrane binding assay was used to elucidate the mechanism by which FFA induce lipoprotein binding to LSR. The LSR activation step was mediated by direct interaction of FFA with LSR candidate proteins of apparent molecular masses of 115 and 90 kDa and occurred independently of the membrane lipid environment. The FFA-induced conformational shift that revealed the lipoprotein binding site remained fully reversible upon removal of the FFA. However, occupancy of the site by the apoprotein ligand stabilized the active form of LSR. Comparison of the effect of different FFA alone or in combination indicated that the same binding site is revealed by different FFA and that the length and saturation of the FFA monomeric carbon chain are critical in determining the potency of the FFA activating effect. We propose that the LSR pathway represents a limiting step for the cellular uptake of intestinally derived triglyceride-rich lipoproteins and speculate that FFA liberated by lipolysis initiate this process by altering the conformation of LSR to reveal the lipoprotein binding site.
Substantial biases in ultra-short read data sets from high-throughput DNA sequencing (2008)

Novel sequencing technologies permit the rapid production of large sequence data sets. These technologies are likely to revolutionize genetics and biomedical research, but a thorough characterization of the ultra-short read output is necessary. We generated and analyzed two Illumina 1G ultra-short read data sets, i.e. 2.8 million 27mer reads from a Beta vulgaris genomic clone and 12.3 million 36mers from the Helicobacter acinonychis genome. We found that error rates range from 0.3% at the beginning of reads to 3.8% at the end of reads. Wrong base calls are frequently preceded by base G. Base substitution error frequencies vary by 10- to 11-fold, with A > C transversion being among the most frequent and C > G transversions among the least frequent substitution errors. Insertions and deletions of single bases occur at very low rates. When simulating re-sequencing we found a 20-fold sequencing coverage to be sufficient to compensate errors by correct reads. The read coverage of the sequenced regions is biased; the highest read density was found in intervals with elevated GC content. High Solexa quality scores are over-optimistic and low scores underestimate the data quality. Our results show different types of biases and ways to detect them. Such biases have implications on the use and interpretation of Solexa data, for de novo sequencing, re-sequencing, the identification of single nucleotide polymorphisms and DNA methylation sites, as well as for transcriptome analysis.
A Double-Blind, Randomized, Placebo-Controlled Study of Pimobendan in Dogs with Dilated Cardiomyopathy (2002)

A double-blind, randomized, placebo-controlled study was conducted to examine the effect on heart failure class and survival of pimobendan, an oral calcium-sensitizing inodilator, in dogs with dilated cardiomyopathy (DCM). Pimobendan (0.3-0.6 mg/kg body weight/d) or placebo was administered to English Cocker Spaniels (CSs; n = 10) and Doberman Pinschers (DPs: n = 10) that had DCM in addition to background therapy of furosemide, enalapril, and digoxin. Addition of pimobendan to standard triple therapy was associated with a significant improvement in heart failure class, regardless of breed (P < .02, Mann-Whitney rank sum test). Overall, 8 of 10 animals in the pimobendan-treated group, and 1 of 10 animals in the placebo group improved their heart failure status by at least I modified New York Heart Association functional class after initial stabilization (P = .005, Fisher's exact test). Pimobendan had no significant effect on survival in the CSs (P = 0.77, log-rank test), but DPs treated with pimobendan had significantly longer survival times compared with placebo (P < .02, log-rank test), with a median survival time of 329 days in the pimobendan group compared with 50 days in the placebo group, and a hazard ratio of 3.4 (95% confidence interval 1.4-39.8). Pimobendan resulted in significant improvement in heart failure class when added to standard therapy in this group of dogs with DCM, and may have contributed to improved survival in DPs.
Calorie Restriction in Nonhuman Primates: Implications for Age-Related Disease Risk (1998)

Calorie restriction (CR)—undernutrition without malnutrition—ranks among the most reproducible and widely used research paradigms in gerontologic research. This intervention is the only manipulation that has been shown consistently to extend the life span, delay onset and slow tumor progression, and retard physiologic aging in many systems. A large body of literature exists documenting these remarkable effects in such diverse short-lived species as rotifers, water fleas, fish, spiders, hamsters, and laboratory mice and rats. However, it is not known if CR has similar effects in longer-lived species more closely related to humans. Two major studies in rhesus monkeys, one at the National Institute on Aging and the other at the University of Wisconsin, were begun several years ago to address this question. Two similar studies focusing mostly on disease end points such as obesity, diabetes, and cardiovascular disease are also underway at the University of Maryland and Bowman-Gray School of Medicine. These studies have clearly shown that most physiologic responses assessed in monkeys on CR parallel the extensive literature on rodents. This article focuses on data related to various risk factors for age-associated diseases, in particular diabetes and cardiovascular disease. Although it will be several more years before definitive results regarding life span are available, emerging data from the monkey studies strongly suggest that CR alters several disease risk factors and may affect postmaturational aging in some systems. Therefore, it is likely that this nutritional intervention will result in at least moderate increases in the primate life span related to amelioration of certain age-related diseases and their complications.
Electronic and steric effects in nucleophilic aromatic substitution. Reaction by phenoxides as nucleophiles in dimethyl sulfoxide (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectronic and steric effects in nucleophilic aromatic substitution. Reaction by phenoxides as nucleophiles in dimethyl sulfoxideG. Bartoli, F. Ciminale, and P. E. TodescoCite this: J. Org. Chem. 1975, 40, 7, 872–874Publication Date (Print):April 1, 1975Publication History Published online1 May 2002Published inissue 1 April 1975https://pubs.acs.org/doi/10.1021/jo00895a012https://doi.org/10.1021/jo00895a012research-articleACS PublicationsRequest reuse permissionsArticle Views258Altmetric-Citations11LEARN 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
Real-Time Simulation of Robot Controlled Belt Grinding Processes of Sculptured Surfaces (2004)

Industrial robots are introduced to belt grinding processes of free-formed surface with elastic wheel nowadays in order to obtain high quality product and high efficiency. However, it is a laborious task to plan grinding paths and write programs for the robot. To release people from it partially, it is necessary to simulate the belt grinding processes which are useful for path generating and dynamic robot control. In this paper, we present a framework of the robot controlled belt grinding simulation system and some key issues in it. We enhance the global removal model to local process model, which can simulate the grinding process more exactly. We also point out the bottleneck of the real-time simulation and put forward a neural network based regression method to meet this difficulty. At the end of the paper, some simple simulation examples are given.
Transcriptionally active nuclei are selective in mature multinucleated osteoclasts (2010)

Multinucleation is indispensable for the bone-resorbing activity of mature osteoclasts. Although multinucleation is evident in mature osteoclasts and certain other cell types, putative regulatory networks among nuclei remain poorly characterized. To address this issue, transcriptional activity of each nucleus in a multinucleated osteoclast was assessed by detecting the distributions of nuclear proteins by immunocytochemistry and primary transcripts by RNA FISH. Patterns of epigenetic histone markers governing transcription as well as localization of tested nuclear receptor proteins appeared indistinguishable among nuclei in differentiated Raw264 cells and mouse mature osteoclasts. However, RNAPII-Ser5P/2P and NFATc1 proteins were selectively distributed in certain nuclei in the same cell. Similarly, the distributions of primary transcripts for osteoclast-specific genes (Nfatc1, Ctsk and Acp5) as well as a housekeeping gene (beta-tubulin) were limited in certain nuclei within individual cells. By fusing two Raw264 cell lines that stably expressed ZsGreen-NLS and DsRed-NLS proteins, transmission of nuclear proteins across all of the nuclei in a cell could be observed, presumably through the shared cytoplasm. Taken together, we conclude that although nuclear proteins are diffusible among nuclei, only certain nuclei within a multinucleated osteoclast are transcriptionally active.