gebhart/patrepeval huggingface dataset:
Roles of Specific Amino Acids in the N Terminus of <i>Pseudomonas aeruginosa</i> Flagellin and of Flagellin Glycosylation in the Innate Immune Response (2005)

ABSTRACT The Toll-like receptor 5 (TLR5) binding site has been predicted to be in the N terminus of the flagellin molecule. In order to better define the interaction between the N-terminal amino acids of Pseudomonas aeruginosa flagellin and TLR5, site-specific mutations were generated between residues 88 and 97 of P. aeruginosa PAK flagellin as well as outside of this region. The mutant flagellins were expressed in Escherichia coli BL21(plysS), purified by affinity chromatography, and passed through a polymyxin B column to remove contaminating lipopolysaccharide (LPS). Their ability to stimulate interleukin-8 (IL-8) release from A549 cells was examined. The cloned mutated genes were used to complement a PAK fliC mutant in order to test for effects on motility and on IL-8 release by purified flagellar preparations. All the mutations, single or double, in the predicted TLR5 binding region reduced IL-8 signaling to less than 95% of the wild-type flagellin levels, but the single mutation outside the binding region had no effect. Changes made at two amino acid sites resulted in loss/reduction of motility; however, changes made at single sites, i.e., Q83A, L88A, R90A, M91A, L94A, and Q97A, had no effect on motility. The mutated genes encoding two of the motile but poorly signaling flagellins had no compensatory mutations to allow motility. Thus, while it is speculated that pathogen-associated molecular patterns (PAMPs) have evolved in locations that are essential to maintain function, it appears that there is tolerance for at least single amino acid changes in the PAMP of P. aeruginosa flagellin. The purpose of flagellin glycosylation in P. aeruginosa is unknown. In order to examine its role, if any, in signaling an inflammatory response, we used whole flagella from the motile chromosomal mutant strains PAK rfbC and PAO1 rfbC , which are defective in flagellin glycosylation. IL-8 release from A549 cells stimulated with nonglycosylated flagellar preparations (having less then 1 picogram of LPS/μg) was significantly reduced compared to their respective wild-type flagellar preparations, indicating a role of flagellar glycosylation in the proinflammatory action of Pseudomonas flagellin. The basis of the latter activity is unknown, since the glycosylation sites are found in the D3 domain of flagellins and the TLR5 binding site is located in the D1 domain. Thus, P. aeruginosa flagellin has evolved additional flagellar signaling mechanisms over that described for Salmonella flagellin.
twitter sharing button linkedin sharing button facebook sharing button whatsapp sharing button email sharing button print sharing button Infection following orthopaedic implants and bone surgery (2001)

Forty-seven patients were investigated for early or late postoperative infections of orthopaedic implants and/or bone. A total of 88 isolates were recovered (64 aerobes and 24 anaerobes). Pseudomonas aeruginosa and Staphylococcus epidermidis were the most common causative agents. Anaerobic bacteria were isolated from 16 (34%) patients; 50% of patients with late-onset infection and 10.5% with early-onset infection. In 6 (12.8%) patients, infection was with anaerobic organisms alone. All these patients had retained an extramedullary internal fixation device. Anaerobic microorganisms appear to play a significant role in the pathogenesis of late-onset postoperative infection, especially where there is an extramedullary internal fixation device.
An in situ, energy-dispersive x-ray diffraction study of natural gas conversion by carbon dioxide reforming (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn in situ, energy-dispersive x-ray diffraction study of natural gas conversion by carbon dioxide reformingA. T. Ashcroft, A. K. Cheetham, R. H. Jones, S. Natarajan, J. M. Thomas, D. Waller, and S. M. ClarkCite this: J. Phys. Chem. 1993, 97, 13, 3355–3358Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/j100115a044https://doi.org/10.1021/j100115a044research-articleACS PublicationsRequest reuse permissionsArticle Views214Altmetric-Citations27LEARN 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 options Get e-Alerts
A new archetype for competitive intelligence (1997)

From the Publisher:
McGonagle and Vella maintain that competitive intelligence as we know it is just the first step toward the creation of true corporate intelligence. Their book explores ways in which new channels of communication and new uses of information and intelligence will change corporations, and how these changes can be anticipated in an organization's strategic planning, crisis management, benchmarking, reverse engineering, and defensive intelligence activities. In doing so, they introduce readers to new techniques, such as shadow benchmarking and factual management analysis. Readable, with useful checklists, forms, reminders, and drawings from real world cases, this book will be essential reading for executives in the public and private sectors, and their colleagues in the academic business community.
IPv6 Host-to-Router Load Sharing (2005)

The original IPv6 conceptual sending algorithm does not do load sharing among equivalent IPv6 routers, and suggests schemes that can be problematic in practice.This document updates the conceptual sending algorithm in RFC 2461 so that traffic to different destinations can be distributed among routers in an efficient fashion.
Regulation of CD95 (APO-1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells (1998)

The effect of lipopolysaccharide (LPS) on the expression of CD95 (APO-1/Fas) receptor and ligand (CD95L) was studied in primary cultures of rat liver Kupffer cells (KCs), sinusoidal endothelial cells (SECs), and parenchymal cells (PCs) at the messenger RNA (mRNA) level and by means of immunocytochemistry. LPS treatment of KCs and SECs led to a three- to five-fold increase in CD95L mRNA levels within 6 hours, which declined thereafter. Within 24 hours, the number of KCs and SECs staining positive for CD95L strongly increased. After a lag phase of 12 hours after LPS addition, in both cell types the mRNA levels for the soluble CD95 isoform increased approximately 10-fold; however, the number of KCs and SECs staining positive for transmembrane CD95 remained low and did not significantly increase. Compared with nonparenchymal cells, CD95L mRNA levels in primary hepatocyte cultures were low in the absence and presence of LPS. On the other hand, functionally active CD95 expression markedly increased in response to LPS in these cells. Dexamethasone diminished the LPS-induced stimulation of CD95L expression in nonparenchymal cells but markedly stimulated CD95L expression in PCs. Apoptosis of PCs and thymic lymphocytes was stimulated by the addition of supernatants derived from LPS-treated KC or SEC cultures and was apparently mediated by CD95L as assessed by its sensitivity to inhibitors of the CD95-dependent apoptotic pathway in PCs. The data suggest a complex and timely coordinated interplay between the various liver cell populations with respect to LPS-induced activation of the apoptotic machinery with potential relevance for immunoregulation.
Proteome analysis of antibody‐producing CHO cell lines with different metabolic profiles (2007)

Two-dimensional gel electrophoresis and tandem mass spectrometry were used to identify proteins associated with a metabolic shift during fed-batch cultures of two recombinant antibody-producing CHO cell lines. The first cell line underwent a marked change in lactate metabolism during culture, initially producing lactate and then consuming it, while the second cell line produced lactate for a similar duration but did not later consume it. The first cell line displayed a declining specific antibody productivity during culture, correlating to the 2-D gel results and the intracellular antibody concentration determined by HPLC. Several statistical analysis methods were compared during this work, including a fixed fold-change criterion and t-tests using standard deviations determined in several ways from the raw data and mathematically transformed data. Application of a variance-stabilizing transformation enabled the use of a global empirical standard deviation in the t-tests. Most of the protein spots changing in each cell line did not change significantly in the other cell line. A substantial fraction of the changing proteins were glycolytic enzymes; others included proteins related to antibody production, protein processing, and cell structure. Enolase, pyruvate kinase, BiP/GRP78, and protein disulfide isomerase were found in spots that changed over time in both cell lines, and some protein changes differed from previous reports. These data provide a foundation for future investigation of metabolism in industrially relevant mammalian cell culture processes, and suggest that along with differences between cell types, the proteins expressed in cultures with low lactate concentrations may depend on how those conditions were generated.
Decreased expressions of c-<i>myc</i> and H-<i>ras</i> oncogenes in vitamin E succinate induced morphologically differentiated murine B-16 melanoma cells in culture (1990)

Treatment of B-16 melanoma cells in culture with d-alpha-tocopheryl succinate (vitamin E succinate) at concentrations of 11.3 and 15.1 microM inhibited growth and induced cell differentiation in culture. Vitamin E succinate treatment decreased the levels of c-myc and H-ras specific mRNAs in melanoma cells. Similar results were obtained by the vitamin retinoic acid and the nonvitamin agents R020-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), an inhibitor of cyclic nucleotide phosphodiesterase (0.72 mM), and sodium butyrate (1 mM), which induced differentiation and (or) inhibited growth of melanoma cells in culture. The extent of inhibition of c-myc mRNA was greater than that of H-ras mRNA. These results indicate that vitamin E succinate induced reduction of the levels of c-myc and H-ras mRNAs is related to growth inhibition of melanoma cells in culture.
B‐cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory” (2000)

The rate of elimination of a pathogenic agent is of critical importance for the host and determines the extent and consequences of the infection. Antibody production, along with the activity of other cells of the immune system, plays an important role early and late in the response and contributes to all containment and elimination of the organism. B-cell clones reaching the mature long-lived pool are heterogeneous: some belong to the B1 B-cell subset, some are enriched in the CD21high compartment (mostly marginal zone (MZ)), whereas others recirculate primarily among the B-cell follicles (FO). This segregation is a T-independent, CD40L-independent but BCR/CD19-dependent process. Antigen encounter will recruit antigen-specific cells from the pool of mature B-lymphocytes and activate them to perform effector functions. CD21highCD23low B cells enriched in the MZ of the spleen initiate the early plasmablast wave during the first 3 days of an antibody response against particulate T-independent bacterial antigens. These findings indicate a functional heterogeneity within the mature B-lymphocyte population. MZ B cells and B1 B, in contrast to FO B cells, have the unique capacity to generate effector cells in early stages of the immune response against (particulate) antigens that are scavenged efficiently in these specialized anatomical sites.
Evidence for Elevated Levels of Histamine, Prostaglandin D <sub>2</sub> , and Other Bronchoconstricting Prostaglandins in the Airways of Subjects with Mild Asthma (1990)

Histamine and certain cyclooxygenase products of arachidonic acid have been implicated as mediators of inflammation and are potent constrictors of human airways. Because asthma may represent manifestations of chronic inflammation of the airways, the levels of histamine and six prostanoid mediators were measured in airway fluids obtained by bronchoalveolar lavage (BAL) of 12 normal, 11 allergic rhinitic, and 15 asymptomatic, allergic asthmatic subjects. Simultaneous profiling of prostanoid mediators in individual samples was performed using gas chromatography-mass spectrometry. Levels of PGD2, 9 alpha,11 beta-PGF2 and PGF2 alpha were 12 to 22 times higher in asthmatic than in normal subjects (p less than 0.01), with concentrations in airway fluids of asthmatic subjects after correction for dilution of 3.8, 0.5, and 1.4 nanomolar, respectively. Levels of PGD2 and 9 alpha,11 beta-PGF2 were increased nearly tenfold in asthmatic subjects compared with those in rhinitic subjects (p less than 0.01), distinguishing the subjects with lower airway disease from those with another atopic condition. Histamine levels were increased fourfold in asthmatic subjects compared with those in normal subjects (p less than 0.001); however, similar increases were found in rhinitic subjects. We conclude that elevated levels of multiple mediators with potent bronchoconstricting activity are present in the airways of subjects with mild asthma, indicating that even mild disease is associated with evidence of airway inflammation. The interactions of bronchoconstricting mediators and airway inflammation may play important roles in the pathogenesis of asthma.
<i>In vivo</i> simultaneous comparison of pressor and uterine responses to a single agonist (oxypressin) in estrous rats (1987)

To try to compare receptor compartment kinetics, receptor binding, and binding-response coupling for two smooth muscle types in vivo, pressor and uterine responses to oxypressin, an equipotent analog of oxytocin and vasopressin, were studied simultaneously in urethane-anesthetized, pentolinium-indomethacin treated rats. Access of peptide to the pressor and uterine receptor compartments and peptide-receptor dissociation rate had a negligible effect on the two responses. During both injections and infusions, the blood pressure response seemed to be determined largely by plasma levels of oxypressin. The uterine response to oxypressin, however, was paradoxical. The heights of individual uterine contractions seemed to be determined throughout by plasma oxypressin concentrations. The interval between contractions also seemed to be determined by plasma peptide concentrations during injections. However, as plasma peptide increased and reached steady state during infusion, contraction interval behaved as if plasma peptide concentrations were decreasing. This effect was more marked at the beginning of infusion. The implication of these results is that binding determines the pressor response to oxypressin and binding-response coupling does not change. In contrast, although binding determines the uterine response to oxypressin during injection and binding-response coupling appears constant, some factor in addition to binding affects the contraction interval portion of the uterine response and modifies the apparent binding-response coupling of this parameter during infusion.
The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today (1981)

Evidence that the various common types of cancer are largely avoidable diseases is reviewed. Life-style and other environmental factors are divided into a dozen categories, and for each category the evidence relating those particular factors to cancer onset rates is summarized. Where possible, an estimate is made of the percentage of current U.S. cancer mortality that might have been caused or avoided by that category of factors. These estimates are based chiefly on evidence from epidemiology, as the available evidence from animal and other laboratory studies cannot provide reliable human risk assessments. By far the largest reliably known percentage is the 30% of current U.S. cancer deaths that are due to tobacco, although it is possible that some nutritional factor(s) may eventually be found to be of comparable importance. The percentage of U.S. cancer deaths that are due to tobacco is still increasing, and must be expected to continue to increase for some years yet due to the delayed effects of the adoption of cigarettes in earlier decades. Trends in mortality and in onset rates for many separate types of cancer are studied in detail in appendixes to this paper. Biases in the available data on registration of new cases produce apparent trends in cancer incidence which are spurious. Biases also produce spurious trends in cancer death certification rates, especially among old people. In (and before) middle age, where the biases are smaller, there appear to be a few real increases and a few real decreases in mortality from some particular types of cancer, but there is no evidence of any generalized increase other than that due to tobacco. Moderate increases or decreases due to some new agent(s) or habit(s) might of course be overlooked in such large-scale analyses. But, such analyses do suggest that, apart from cancer of the respiratory tract, the types of cancer that are currently common are not peculiarly modern diseases and are likely to depend chiefly on some longestablished factor(s). (A prospective study utilizing both questionnaires and stored blood and other biological materials might help elucidate these factors.) The proportion of current U.S. cancer deaths attributed to occupational factors is provisionally estimated as 4% (lung cancer being the major contributor to this). This is far smaller than has recently been suggested by various U.S. Government agencies. The matter could be resolved directly by a “case-control” study of lung cancer two or three times larger than the recently completed U.S. National Bladder Cancer Study but similar to it in methodology and unit costs; there are also other reasons for such a study. A fuller summary of conclusions and recommendations comprises the final section of this report.
Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells (2016)

Inner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs. We find that organoid hair cells acquire mechanosensitivity equivalent to functionally mature hair cells in postnatal mice. The organoid hair cells also progress through a similar dynamic developmental pattern of ion channel expression, reminiscent of two subtypes of native vestibular hair cells. We conclude that our 3D culture system can generate large numbers of fully functional sensory cells which could be used to investigate mechanisms of inner ear development and disease as well as regenerative mechanisms for inner ear repair.
Multilayer Piezoelectric Motor Using the First Longitudinal and the Second Bending Vibrations (1995)

A piezoelectric linear motor using a double-mode vibrator was constructed with one of the vibration modes being the first longitudinal and the other, the second bending. In order to reduce driving voltage, a multilayer piezoelectric ceramics vibrator prepared by a cofiring method was used. Moreover, we proposed a new type of supportive mount for the vibrator to facilitate the construction of the motor. In the new method the vibrator is bonded to an attachment plate by an elastic layer. In this paper, characteristics of the motor are described.
The Vascular Ectonucleotidase ENTPD1 Is a Novel Renoprotective Factor in Diabetic Nephropathy (2007)

Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) (also known as CD39) is the dominant vascular ectonucleotidase. By hydrolyzing ATP and ADP to AMP, ENTPD1 regulates ligand availability to a large family of P2 (purinergic) receptors. Modulation of extracellular nucleotide metabolism is an important factor in several acute and subacute models of vascular injury. We hypothesized that aberrant nucleotide signaling would promote chronic glomerular injury in diabetic nephropathy. Inducing diabetes in ENTPD1-null mice with streptozotocin resulted in increased proteinuria and more severe glomerular sclerosis compared with matched diabetic wild-type mice. Diabetic ENTPD1-null mice also had more glomerular fibrin deposition and glomerular plasminogen activator inhibitor-1 (PAI-1) staining than wild-type controls. In addition, ENTPD1-null mice showed increased glomerular inflammation, in association with higher levels of monocyte chemoattractant protein-1 (MCP-1) expression. Mesangial cell PAI-1 and MCP-1 mRNA expression were upregulated by ATP and UTP but not ADP or adenosine in vitro. The stable nucleotide analog ATPgammaS stimulated sustained expression of PAI-1 and MCP-1 in vitro, whereas the stable adenosine analog NECA [5'-(N-ethylcarboxamido)adenosine] downregulated expression of both genes. Extracellular nucleotide-stimulated upregulation of MCP-1 is, at least in part, protein kinase C dependent. We conclude that ENTPD1 is a vascular protective factor in diabetic nephropathy that modulates glomerular inflammation and thromboregulation.
Infrared laser desorption mass spectrometry of oligosaccharides: fragmentation mechanisms and isomer analysis (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfrared laser desorption mass spectrometry of oligosaccharides: fragmentation mechanisms and isomer analysisBernhard. Spengler, Joseph W. Dolce, and Robert J. CotterCite this: Anal. Chem. 1990, 62, 17, 1731–1737Publication Date (Print):September 1, 1990Publication History Published online1 May 2002Published inissue 1 September 1990https://pubs.acs.org/doi/10.1021/ac00216a004https://doi.org/10.1021/ac00216a004research-articleACS PublicationsRequest reuse permissionsArticle Views736Altmetric-Citations110LEARN 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