993 resultados para $PSalomo$lIsrael, König
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Large concrete structures need to be inspected in order to assess their current physical and functional state, to predict future conditions, to support investment planning and decision making, and to allocate limited maintenance and rehabilitation resources. Current procedures in condition and safety assessment of large concrete structures are performed manually leading to subjective and unreliable results, costly and time-consuming data collection, and safety issues. To address these limitations, automated machine vision-based inspection procedures have increasingly been proposed by the research community. This paper presents current achievements and open challenges in vision-based inspection of large concrete structures. First, the general concept of Building Information Modeling is introduced. Then, vision-based 3D reconstruction and as-built spatial modeling of concrete civil infrastructure are presented. Following that, the focus is set on structural member recognition as well as on concrete damage detection and assessment exemplified for concrete columns. Although some challenges are still under investigation, it can be concluded that vision-based inspection methods have significantly improved over the last 10 years, and now, as-built spatial modeling as well as damage detection and assessment of large concrete structures have the potential to be fully automated.
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Recent results in spinal research are challenging the historical view that the spinal reflexes are mostly hardwired and fixed behaviours. In previous work we have shown that three of the simplest spinal reflexes could be self-organised in an agonist-antagonist pair of muscles. The simplicity of these reflexes is given from the fact that they entail at most one interneuron mediating the connectivity between afferent inputs and efferent outputs. These reflexes are: the Myotatic, the Reciprocal Inibition and the Reverse Myotatic reflexes. In this paper we apply our framework to a simulated 2D leg model actuated by six muscles (mono- and bi-articular). Our results show that the framework is successful in learning most of the spinal reflex circuitry as well as the corresponding behaviour in the more complicated muscle arrangement. © 2012 Springer-Verlag.
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The skin secretions of frogs and toads (Anura) have long been a known source of a vast abundance of bioactive substances. In the past decade, transcriptome data of the granular glands of anuran skin has given new impetus to investigations of the putative constituent peptides. Alytes obstetricans was recently investigated and novel peptides with antimicrobial activity were isolated and functionally characterised. However, genetic data for the evolutionarily ancient lineage to which Alytes belongs (midwife toads; Alytidae) remains unavailable.
Here we present the first such genetic data for Alytidae, derived via the granular gland transcriptome of a closely-related species of midwife toad, Alytes maurus. First, we present nucleotide sequences of the entire peptide precursors for four novel antimicrobial peptides (AMPs). The two precursors resemble those from Bombinatoridae in both their structural architecture and amino acid sequence. Each precursor comprises two AMPs as tandem repeats, with a member of the alyteserin-1 family (alyteserin-1Ma: GFKEVLKADLGSLVKGIAAHVAN-NH2 or alyteserin-1Mb: GFKEVLKAGLGSLVKGIPAHVAN-NH2) followed by its corresponding member from the alyteserin-2 family (alyteserin-2Ma: FIGKLISAASGLLSHL-NH2 or alyteserin-2Mb: ILGAIIPLVSGLLSHL-NH2). Synthetic replicates of the four AMPs possessed minimal inhibitory concentrations (MICs) ranging from 9.5 to 300 µM, with the most potent being alyteserin-2Ma. Second, we also cloned the cDNA encoding an alytesin precursor, with the active alytesin exhibiting high sequence identity to bombesin-related peptides from other frogs. All putative mature peptide sequences were confirmed to be present in the skin secretion via LC/MS.
The close structural resemblance of the alyteserin genes that we isolated for A. maurus with those of Bombina provide independent molecular evidence for a close evolutionary relationship between these genera as well as more support for the convergent evolution of the AMP system within anurans. In contrast to the more evolutionarily conserved nature of neuropeptides (including alytesin, which we also isolated), the more variable nature of the AMP system together with the sporadic distribution of AMPs among anuran amphibians fuels in part our hypothesis that the latter system was co-opted secondarily to fulfil a function in the innate immune system, having originally evolved for defence against potential macropredators.
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Background: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian random isation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
Methods: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
Findings: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher p=8×10-13) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with noncarriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13 95% CI 1·69-2·69, p=2×10 -10).
Interpretation: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
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In this study, we investigate the skin secretion of the Madagascan Tomato Frog, Dyscophus guineti, which is characterized by its peculiarly adhesive and viscous nature, with a view toward the function of the member of the Kunitz/bovine pancreatic trypsin inhibitor family (BPTI) it is known to contain. Using “shotgun” cloning of a skin secretion-derived cDNA library, we obtained the full-length sequence of the respective precursor that encodes this trypsin inhibitor. Furthermore, we demonstrated that this enzyme has inhibitory activity against trypsin, but not against thrombin, and also has no antimicrobial activity. Moreover, we confirm that it appears to be the only bioactive peptide in the skin secretion of this species. Using these observations, we attempt to posit a role for this inhibitor. In particular, we hypothesize that the trypsin inhibitor in D. guineti (and possibly other microhylid frogs) maintains the soluble state of the skin secretion during storage in the glands. Upon discharge of the secretion, the trypsin inhibitor, which occurs in low concentrations, can no longer prevent the polymerisation process of other yet unidentified skin proteins, thereby resulting in the conversion of the secretion to its final glue-like state. Thus, the major defensive value of the skin secretion appears to be mechanical, impeding ingestion through a combination of adhesion and the body inflation typical for some microhylid frogs rather than chemical through antimicrobial activity or toxicity.
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Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)
Resumo:
Background: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear.
Methods: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes.
Results: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis.
Conclusions: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)
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Der vorliegende Artikel bezieht sich auf die unterschiedlichen Begrifflichkeiten, die im Umfeld der Wettbewerberforschung in der Literatur Verwendung finden. Neben den Begriffen des angloamerikanischen Sprachraums (Competitive Intelligence, Competitor Intelligence und Competitor Analyse) existieren für den deutschsprachigen Raum (Wettbewerber-, Konkurrenten-, Wettbewerbs- und Konkurrenzanalyse) ebenfalls verschiedenartige Begriffe, denen in der Literatur eine häufig unterschiedliche Verwendung zu Teil wird. Dieser Artikel baut einen Ordnungsansatz auf, der die angesprochenen Begrifflichkeiten in eine Struktur bringt, um somit eine klare inhaltliche Trennung der einzelnen Begriffe sowie eine in Relation bringende Darstellung aufbauen zu können. Dies ermöglicht eine ambiguitätsfreie Verwendung innerhalb der wissenschaftlichen Arbeit durch definitorisch fixierte Begriffsinhalte.
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Der folgende Beitrag fasst die jüngsten Ergebnisse einer Studierendenbefragung zusammen, die im Rahmen des BMBF-geförderten Forschungsprojekts „ZEITLast: Lehrzeit und Lernzeit: Studierbarkeit der BA-/BSc- und MA-/MSc- Studiengänge als Adaption von Lehrorganisation und Zeitmanagement unter Berücksichtigung von Fächerkultur und Neuen Technologien“ im Wintersemester 2010/2011 in den beiden Studiengängen „Informationsmanagement und Informationstechnologie“ und „Polyvalenter 2-Fächer-Bachelor-Studiengang mit Lehramtsoption“ an der Stiftung Universität Hildesheim durchgeführt wurde. Dieser Befragung ging in beiden Studiengängen eine Zeitbudgeterhebung voraus. Zentrale Ergebnisse werden im Folgenden vorgestellt und im Weiteren exemplarisch in den wissenschaftlichen Diskurs eingebunden. Deutlich wird, dass das Gefühl von Belastung nicht auf die reine Zeitinvestition in das Studium zurückzuführen ist, sondern auch in engem Zusammenhang mit der vorherrschenden Lehrorganisation an der Hochschule und den eigenen studentischen Kompetenzen zu sehen ist.
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Der Arbeitsalltag von Wissenschaftlerinnen und Wissenschaftlern hat sich in den letzten Jahren dramatisch verändert. Forschen, Schreiben und Publizieren sind mittlerweile stark durch netzbasierte Anwendungen geprägt. Das digitale Zeitalter aber hat nicht nur neue technische Werkzeuge hervorgebracht, sondern auch neue Wege eröffnet, um Wissen zu generieren und zu verbreiten. Dies gilt sowohl innerhalb der akademischen Welt als auch über diese hinaus. Das Arbeiten mit dem Netz stellt unsere bisherigen etablierten wissenschaftlichen Praktiken in Frage. Forschung wird zunehmend vernetzt, kollaborativ, multimedial, trans- bzw. interdisziplinär durchgeführt. Das vorliegende Handbuch beschreibt diese sich herausbildenden wissenschaftlichen Praktiken. Ziel der Autoren war es dabei, ein praxisnahes und leicht verständliches Handbuch zu schreiben.
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Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.