gebhart/patrepeval huggingface dataset:
Evidence for an extended structure of the T-cell co-receptor CD8 alpha as deduced from the hydrodynamic properties of soluble forms of the extracellular region. (1993)

We expressed soluble forms of the human T-cell coreceptor CD8 alpha extracellular region, CD8 alpha 161, and the amino-terminal immunoglobulin-like domain, CD8 alpha 114, in Chinese hamster ovary cells and Escherichia coli, respectively. Both molecules were readily purified to homogeneity in milligram amounts and were recognized by a large panel of monoclonal antibodies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that approximately 70% of CD8 alpha 161 was secreted as a disulfide-linked dimer, but CD8 alpha 114 was not disulfide-linked. To investigate the structural features of CD8 alpha 161 and CD8 alpha 114 under native conditions, we performed gel filtration and sucrose gradient sedimentation analysis. In spite of being partially or totally noncovalently bound, both recombinant molecules were stably associated homodimers, as no monomers could be detected at a fairly low protein concentration (approximately 1 microM). This suggests that the CD8 alpha amino-terminal domain alone strongly contributes to chain association. Determination of the Stokes radius (Rs) and sedimentation coefficient (s20,w) gave results consistent with CD8 alpha 114 having a globular shape and CD8 alpha 161 being an asymmetric molecule. Taking into account the contribution of hydration to the frictional coefficient, we obtained for CD8 alpha 161 an axial ratio of approximately 5, when modeled as a prolate ellipsoid. These results indicate that the elongated structure of CD8 alpha 161 is essentially contributed by the hinge region and help to explain how the CD8 alpha is able to bridge the distance between the T-cell surface and its binding site in the alpha 3 domain of major histocompatibility complex class I molecules on the target cell.
First total synthesis of taxol. 1. Functionalization of the B ring (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFirst total synthesis of taxol. 1. Functionalization of the B ringRobert A. Holton, Carmen Somoza, Hyeong Baik Kim, Feng Liang, Ronald J. Biediger, P. Douglas Boatman, Mitsuru Shindo, Chase C. Smith, Soekchan Kim, and Cite this: J. Am. Chem. Soc. 1994, 116, 4, 1597–1598Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/ja00083a066https://doi.org/10.1021/ja00083a066research-articleACS PublicationsRequest reuse permissionsArticle Views10899Altmetric-Citations542LEARN 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
Super‐framing: a powerful physical layer frame structure for next generation satellite broadband systems (2015)

Summary Following the definition of commercial requirements in different satellite communication market segments, the satellite communications technical module of the Digital Video Broadcasting Project (DVB) took the mandate to develop the extension of the second generation DVB System for satellite broadcasting and unicasting (DVB‐S2) standard in order to achieve higher efficiencies without introducing fundamental changes to the complexity and structure of DVB‐S2. In this paper, we focus on a new powerful physical layer frame structure, known as Super‐Frame (SF), which has been adopted as optional waveform container in Annex E of the recently approved DVB‐S2 eXtension standard specifications. The main contribution of this paper is to provide the rationale, design choices, potential applications and performance gains of the SF structure with particular emphasis on the context of satellite broadband systems. In order to demonstrate the satisfaction of the stated requirements to the SF approach, analytical results of the SF performance are complemented by the performance results obtained from an end‐to‐end testbed and prototype design of modulator and demodulator featuring the SF generation and detection capability. The prototype devices are able to operate at a wide range of signal‐to‐noise ratios and at high symbol rates. Copyright © 2015 John Wiley &amp; Sons, Ltd.
Global Positioning Systems, Inertial Navigation, and Integration (2006)

An updated guide to GNSS and INS, and solutions to real-world GPS/INS problems with Kalman filtering. Written by recognized authorities in the field, this second edition of a landmark work provides engineers, computer scientists, and others with a working familiarity with the theory and contemporary applications of Global Navigation Satellite Systems (GNSS), Inertial Navigational Systems (INS), and Kalman filters
Azobenzene photoswitches for biomolecules (2011)

The photoisomerization of azobenzene has been known for almost 75 years but only recently has this process been widely applied to biological systems. The central challenge of how to productively couple the isomerization process to a large functional change in a biomolecule has been met in a number of instances and it appears that effective photocontrol of a large variety of biomolecules may be possible. This critical review summarizes key properties of azobenzene that enable its use as a photoswitch in biological systems and describes strategies for using azobenzene photoswitches to drive functional changes in peptides, proteins, nucleic acids, lipids, and carbohydrates (192 references).
Inhibition of Myosin Light Chain Kinase by p21-Activated Kinase (1999)

p21-activated kinases (PAKs) are implicated in the cytoskeletal changes induced by the Rho family of guanosine triphosphatases. Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are regulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin light chain (MLC). p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity. MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1. These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation.
Heritable Multiplex Genetic Engineering in Rats Using CRISPR/Cas9 (2014)

The CRISPR/Cas9 system has been proven to be an efficient gene-editing tool for genome modification of cells and organisms. Multiplex genetic engineering in rat holds a bright future for the study of complex disease. Here, we show that this system enables the simultaneous disruption of four genes (ApoE, B2m, Prf1, and Prkdc) in rats in one-step, by co-injection of Cas9 mRNA and sgRNAs into fertilized eggs. We further observed the gene modifications are germline transmittable, and confirmed the off-target mutagenesis and mosaicism are rarely detected by comprehensive analysis. Thus, the CRISPR/Cas9 system makes it possible to efficiently and reliably generate gene knock-out rats.
Identification of a conserved linear epitope at the N terminus of the rabies virus glycoprotein (2004)

A novel, linear B-cell epitope has been identified at the N terminus of the rabies virus (RABV) glycoprotein. Screening of a phage-display library demonstrated that two glycoprotein-specific mAbs recognized a conserved sequence, WxxxDI, which aligned between aa 14 and 19 of the mature glycoprotein. Screening of truncated glycoprotein fragments with both mAbs confirmed the location of the epitope in the N-terminal region. Alignment of amino acid sequences from a range of RABV isolates indicated that the site was conserved in most viruses. Alignment with representatives of other lyssaviruses suggested that it is conserved within phylogroup I, which includes the European bat lyssaviruses, but not phylogroup II. A 12 aa synthetic peptide of this epitope was recognized by both mAbs and sera from a subset of rabies-vaccinated dogs. In a multimeric form, the peptide could induce an epitope-specific response following immunization in rabbits and mice.
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions. (1992)

Mutations caused by oxidative DNA damage may contribute to human disease. A major product of that damage is 8-hydroxyguanine (oh8Gua). Because of differences in experimental design, the base pairing specificity of oh8G in vivo is not completely resolved. Here, oh8dGTP and DNA polymerase were used in two complementary bacteriophage plaque color assays to examine the mutagenic specificity of oh8Gua in vivo. The first is a reversion assay that detects all three single-base substitutions caused by misreading of guanine analogues inserted at a specific site. oh8Gua at that site gave a mutation frequency of 0.7%. Twenty-two of the 23 mutations were G----T substitutions. The second assay, a forward mutation assay, tests the mispairing potential of any altered nucleotide 1) during incorporation as substrate nucleotide, and 2) after multiple incorporations into a single-stranded DNA gap region of M13mp2. Substituting oh8dGTP for dGTP during polymerization produced 16% mutants; two classes of mutations were observed, both caused by pairing of oh8Gua with A. Seventy-six of 78 mutations were A----C substitutions, and two were G----T substitutions. These assays thus illustrate mutagenic replication of oh8Gua as template causing G----T substitutions and misincorporation of oh8Gua as substrate causing A----C substitutions, both caused by oh8Gua.A mispairs.
Role of Natural Killer Cell Alloreactivity in HLA-Mismatched Hematopoietic Stem Cell Transplantation (1999)

Because of the expression of inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I allotypes, a person's natural killer (NK) cells will not recognize and will, therefore, kill cells from individuals lacking his/her KIR epitopes. This study investigated the role of NK cell alloreactivity in human HLA haplotype-mismatched hematopoietic stem cell transplantation and, specifically, the role of the three major NK specificities, ie, those for HLA-C group 1, HLA-C group 2, and HLA-Bw4 alleles. In 20 of 60 donor-recipient pairs, KIR epitope incompatibility and functional analyses of donor NK cell clones predicted donor NK cells could cause graft-versus-host (GVH)/graft-versus-leukemia (GVL) reactions. NK cell clones of donor origin were obtained from transplanted recipients and tested for lysis of recipient's cryopreserved pretransplant lymphocytes. Despite the absence of GVH disease, we detected high frequencies of NK clones which killed recipient's target cells. Lysis followed the rules of NK cell alloreactivity, being blocked only by the MHC class I KIR epitope which was missing in the recipient. The alloreactive NK clones also killed the allogeneic leukemia. Transplants from these KIR epitope incompatible donors had higher engraftment rates. Therefore, a GVL effector and engraftment facilitating mechanism, which is independent of T-cell-mediated GVH reactions, may be operational in HLA mismatched hematopoietic cell transplants.
Nanomedicine Strategies for Drug Delivery to The Ear (2013)

The highly compartmentalized anatomy of the ear aggravates drug delivery, which is used to combat hearing-related diseases. Novel nanosized drug vehicles are thought to overcome the limitations of classic approaches. In this article, we summarize the nanotechnology-based efforts involving nano-objects, such as liposomes, polymersomes, lipidic nanocapsules and poly(lactic-co-glycolic acid) nanoparticles, as well as nanocoatings of implants to provide an efficient means for drug transfer in the ear. Modern strategies do not only enhance drug delivery efficiency, in the inner ear these vector systems also aim for specific uptake into hair cells and spiral ganglion neurons. These novel peptide-mediated strategies for specific delivery are reviewed in this article. Finally, the biosafety of these vector systems is still an outstanding issue, since long-term application to the ear has not yet been assessed.
Exo‐mode of action of cellobiohydrolase Cel48C from Paenibacillus sp. BP‐23 (2003)

Sequence analysis of a Paenibacillus sp. BP-23 recombinant clone coding for a previously described endoglucanase revealed the presence of an additional truncated ORF with homology to family 48 glycosyl hydrolases. The corresponding 3509-bp DNA fragment was isolated after gene walking and cloned in Escherichia coli Xl1-Blue for expression and purification. The encoded enzyme, a cellulase of 1091 amino acids with a deduced molecular mass of 118 kDa and a pI of 4.85, displayed a multidomain organization bearing a canonical family 48 catalytic domain, a bacterial type 3a cellulose-binding module, and a putative fibronectin-III domain. The cloned cellulase, unique among Bacillales and designated Cel48C, was purified through affinity chromatography using its ability to bind Avicel. Maximum activity was achieved at 45 degrees C and pH 6.0 on acid-swollen cellulose, bacterial microcrystalline cellulose, Avicel and cellodextrins, whereas no activity was found on carboxy methyl cellulose, cellobiose, cellotriose, pNP-glycosides or 4-methylumbeliferyl alpha-d-glucoside. Cellobiose was the major product of cellulose hydrolysis, identifying Cel48C as a processive cellobiohydrolase. Although no chromogenic activity was detected from pNP-glycosides, TLC analysis revealed the release of p-nitrophenyl-glycosides and cellodextrins from these substrates, suggesting that Cel48C acts from the reducing ends of the sugar chain. Presence of such a cellobiohydrolase in Paenibacillus sp. BP-23 would contribute to widen up its range of action on natural cellulosic substrates.
生产力与交往——答 H.-P.克鲁格 (1992)

H.-P.克鲁格您是西欧和北美众所周知的少数几位仍然在哲学社会理论领域中对基本的理论综合作大胆尝试的伟人之一。您的哲学展示一种跨学科的定向框架,也许可以把您的理论称之为“交往理性”。您的哲学是对受到批判的社会批判[理论]的启蒙传统所作的带有自我批判性质的新解释。您能同意我的这一简单表述吗? 哈贝马斯亲爱的克鲁格先生,您知道,德国官吏滥用“伟人”和“深切的敬意”这些词的事够多的了。因此,除了谀辞之外,我同意您的表述,甚至可以不加假如或但是。启蒙运动既非始于狄德罗和爱尔维修,又非终
Antibiotic Treatment Alters the Colonic Mucus Layer and Predisposes the Host to Exacerbated Citrobacter rodentium -Induced Colitis (2011)

Antibiotics are often used in the clinic to treat bacterial infections, but the effects of these drugs on microbiota composition and on intestinal immunity are poorly understood. Citrobacter rodentium was used as a model enteric pathogen to investigate the effect of microbial perturbation on intestinal barriers and susceptibility to colitis. Streptomycin and metronidazole were used to induce alterations in the composition of the microbiota prior to infection with C. rodentium. Metronidazole pretreatment increased susceptibility to C. rodentium-induced colitis over that of untreated and streptomycin-pretreated mice, 6 days postinfection. Both antibiotic treatments altered microbial composition, without affecting total numbers, but metronidazole treatment resulted in a more dramatic change, including a reduced population of Porphyromonadaceae and increased numbers of lactobacilli. Disruption of the microbiota with metronidazole, but not streptomycin treatment, resulted in an increased inflammatory tone of the intestine characterized by increased bacterial stimulation of the epithelium, altered goblet cell function, and thinning of the inner mucus layer, suggesting a weakened mucosal barrier. This reduction in mucus thickness correlates with increased attachment of C. rodentium to the intestinal epithelium, contributing to the exacerbated severity of C. rodentium-induced colitis in metronidazole-pretreated mice. These results suggest that antibiotic perturbation of the microbiota can disrupt intestinal homeostasis and the integrity of intestinal defenses, which protect against invading pathogens and intestinal inflammation.
Tagging Morphogenetic Genes by Insertional Mutagenesis in the Yeast Yarrowia lipolytica (2001)

ABSTRACT The yeast Yarrowia lipolytica is distantly related to Saccharomyces cerevisiae , can be genetically modified, and can grow in both haploid and diploid states in either yeast, pseudomycelial, or mycelial forms, depending on environmental conditions. Previous results have indicated that the STE and RIM pathways, which mediate cellular switching in other dimorphic yeasts, are not required for Y. lipolytica morphogenesis. To identify the pathways involved in morphogenesis, we mutagenized a wild-type strain of Y. lipolytica with a Tn 3 derivative. We isolated eight tagged mutants, entirely defective in hyphal formation, from a total of 40,000 mutants and identified seven genes homologous to S. cerevisiae CDC25, RAS2, BUD6, KEX2, GPI7, SNF5 , and PPH21 . We analyzed their abilities to invade agar and to form pseudomycelium or hyphae under inducing conditions and their sensitivity to temperature and to Calcofluor white. Chitin staining was used to detect defects in their cell walls. Our results indicate that a functional Ras-cyclic AMP pathway is required for the formation of hyphae in Y. lipolytica and that perturbations in the processing of extracellular, possibly parietal, proteins result in morphogenetic defects.
Bovine Immunoglobulins: A Review (1969)

Abstract Three classes of immunoglobulins have been identified in the cow: IgG, IgA, and IgM. The IgG immunoglobulins can be divided into two subclasses, IgG1 and IgG2. IgG1 is selectively transported by the udder from the circulation to the lacteal secretions by a mechanism yet to be elucidated. Hence, IgG1 is the principal immunoglobulin for passive immunization of the calf. IgG1 also fixes complement and sensitizes bovine skin. IgG2 appears more homogeneous than IgG1 and occurs in high concentrations in bovine serum. Bovine IgM occurs in serum, colostrum, and milk. IgM is important in the primary immune response, complement fixation, and as an agglutinating antibody of the serum. IgM seems to be especially associated with parasitic infections of Anaplasma . Bovine occurs as IgA in milk and colostrum. Whether secretory IgA, or any other immunoglobulin, is synthesized locally is unknown. Also unknown is the precise role that each immunoglobulin plays in bovine pathology. Transfer of immunity to the offspring is by way of the milk and colostrum, and there is sufficient evidence that colostrum is necessary for immunity to disease. Although IgG1 is selectively concentrated by the bovine mammary tissue, no selectivity has been demonstrated for the highly permeable calf's gut. The reason for the failure of some calves to absorb colostral immunoglobulins is unknown. Additional research endeavors into the distribution, genetics, function, and synthesis of the bovine immunoglobulins are most needed.
Metabolism of hydroxyethylrutosides (HR): metabolism of [14C]-HR in man. (1976)

1. following oral administration of a [14C]-hydroxyethylrutoside (Paroven, Venoruton) preparation (HR) to three subjects, 3.05--5.97% of the administered [14C] was excreted in urine. Unchanged urinary [14C]-hydroxyethylrutosides represented 1.57--1.96% of the total dose. 2. Significant levels of [14C] were detected in plasma within 1 h of oral administration of HR. Peak levels were observed from 2--9 h. 3. The presence in urine of [14C]-3',4',5,7-tetra-O-(beta-hydroxyethyl)rutoside, [14C]-3',4',7-tri-O-(beta-hydroxyethyl)rutoside and [14C]-4',7-di-O-(beta-hydroxyethyl)rutoside was shown by radioscanning and/or spectal methods. 4. Administration of a second oral dose of [14C]-HR to each of the three subjects following extended dosage of nonlabelled HR did not result in any increase in urinary [14C] excretion over that observed after administration of a single oral dose. 5. Observations on urinary excretion in man are compatible with the finding in experimental animals that the major route of hydroxyethylrutoside excretion is via the biliary-enteric route.
Palmitoylation of G protein-coupled receptor kinase, GRK6. Lipid modification diversity in the GRK family. (1994)

GRK6, a 66-kDa serine/threonine protein kinase, is a recently identified member of the G protein-coupled receptor kinase (GRK) family. GRKs are involved in the phosphorylation of seven-transmembrane receptors, a process mediating desensitization of signal transduction. An important feature of these enzymes is their membrane-associated nature, which for some members is stimulus-dependent. The structural basis for this membrane association previously has been shown in different members of the GRK family to include isoprenylation, G protein beta gamma-binding domains, and basic regions to provide electrostatic interactions with phospholipids. We provide evidence that another mechanism includes fatty acid acylation. GRK6, but not other GRKs tested, incorporated tritium after incubation with [3H]palmitate in Sf9 and in COS-7 cells overexpressing the kinase. The incorporated radioactivity was released from the protein by neutral hydroxylamine, indicating the presence of a thioester bond, and was confirmed as palmitic acid by high performance liquid chromatography analysis. Site-directed mutagenesis defined the region of palmitate attachment as a cluster of 3 cysteines (Cys561, Cys562, and Cys565) in the carboxyl-terminal domain of the kinase, consistent with the location of the membrane targeting domains of GRKs 1, 2, 3, and 5. Palmitoylation of GRK6 appears essential for membrane association, since palmitoylated kinase was found only in the membrane fraction. This lipid modification provides a structural basis for potential regulation of the subcellular distribution of GRK6 through acylation/deacylation cycles.
Synthesis of substituted pyridinones from the combination of Fe2(.mu.-CH2)(CO)8 with phosphinimines and alkynes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of substituted pyridinones from the combination of Fe2(.mu.-CH2)(CO)8 with phosphinimines and alkynesChad A. Mirkin, Kuang Lieh Lu, Thomas E. Snead, Gregory L. Geoffroy, and Arnold L. RheingoldCite this: J. Am. Chem. Soc. 1990, 112, 7, 2809–2810Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/ja00163a058https://doi.org/10.1021/ja00163a058research-articleACS PublicationsRequest reuse permissionsArticle Views302Altmetric-Citations16LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts