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Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.
Der Verfasser beschäftigt sich mit der Frage des Glaubensübertritts in einem Asylverfahren. Dabei nimmt er Zeitpunkt, Art und Umstände des Religionswechsels in den Blick. Ferner untersucht er, wie die sogenannte Konversion von den zuständigen Behörden und Gerichten zu behandeln und zu bewerten ist. Einführend gibt er einen Überblick zum völkerrechtlichen Schutz der Religions- und Weltanschauungsfreiheit sowie typischen Gefährdungslagen. Überdies befasst er sich mit den Rechtsgrundlagen des Asyl- und Flüchtlingsschutzrechts und stellt Verbindungen zum Flucht- und Verfolgungsgrund der Religion her.
Schwerpunkt bildet die Untersuchung der Verfahrensstadien, in denen die Konversion relevant wird. Dabei berücksichtigt der Verfasser die nationale und europäische Rechtsprechung. Von besonderer Bedeutung sind die Ausführungen zum Zusammenspiel von staatlichen Ermittlungspflichten und Mitwirkungsgeboten von Asylantragstellenden, wobei den Besonderheiten des grund- und menschenrechtlichen Mehrebenensystems Rechnung getragen wird.
Zentral sind ferner die Ausführungen zum Umgang mit Taufurkunden und sonstigen Bescheinigungen über die religiöse Überzeugung. Besonderes Gewicht liegt auf der verfassungsrechtlichen Stellung der Religionsgemeinschaften und der Frage, ob die Entscheidung einer Religionsgemeinschaft, ein neues Mitglied aufzunehmen, die Behörde im Asylverfahren bindet. Diesem Problem widmet sich der Verfasser unter Heranziehung der relevanten Literaturstimmen und einschlägigen Rechtsprechung.
Der rechtswissenschaftliche Beitrag bietet den beteiligten Akteuren nicht nur eine Einführung in das Themengebiet des Glaubensübertritts im Asylverfahren, sondern gibt den Lesenden auch eine praxistaugliche Handlungsunterstützung rund um die wichtigsten Fragen einer Konversion im Asylverfahren an die Hand. Praktische Bezüge entstehen beispielsweise dadurch, dass wichtige Impulse und Empfehlungen für eine gleichermaßen moderne, rechtsstaatliche und grundrechtsorientierte Verfahrensführung entwickelt werden.
Objective: This study assesses the short-term and intermediate effects of preschool training stimulating phonological awareness and letter-sound correspondence for children at risk of developing dyslexia. Moreover, we examined whether training reduced the frequency of subsequent dyslexic problems. Method: 25 children at risk of developing dyslexia were trained with Horen, Lauschen, Lernen 1 und 2 (Kuspert & Schneider, 2008; Plume & Schneider, 2004) by their kindergarten teachers and were compared with 60 untrained at-risk children. Results:The training revealed a significant short-term effect: The phonological awareness of trained at-risk children increased significantly over that of untrained at-risk children. However, there were no differences in phonological awareness, spelling, and reading ability between the first-graders in the training and control group. Furthermore, reading problems were reduced in the training group. Conclusions: In the future, phonological awareness as well as additional predictors should be included when identifying children vulnerable to developing dyslexia. Moreover, in order to prevent dyslexia, additional prerequisite deficits need to be identified, alleviated, and their effects evaluated.
Uncertainty is an essential part of atmospheric processes and thus inherent to weather forecasts. Nevertheless, weather forecasts and warnings are still predominately issued as deterministic (yes or no) forecasts, although research suggests that providing weather forecast users with additional information about the forecast uncertainty can enhance the preparation of mitigation measures. Communicating forecast uncertainty would allow for a provision of information on possible future events at an earlier time. The desired benefit is to enable the users to start with preparatory protective action at an earlier stage of time based on the their own risk assessment and decision threshold. But not all users have the same threshold for taking action. In the course of the project WEXICOM (‘Wetterwarnungen: Von der Extremereignis-Information zu Kommunikation und Handlung’) funded by the Deutscher Wetterdienst (DWD), three studies were conducted between the years 2012 and 2016 to reveal how weather forecasts and warnings are reflected in weather-related decision-making. The studies asked which factors influence the perception of forecasts and the decision to take protective action and how forecast users make sense of probabilistic information and the additional lead time. In a first exploratory study conducted in 2012, members of emergency services in Germany were asked questions about how weather warnings are communicated to professional endusers in the emergency community and how the warnings are converted into mitigation measures. A large number of open questions were selected to identify new topics of interest. The questions covered topics like users’ confidence in forecasts, their understanding of probabilistic information as well as their lead time and decision thresholds to start with preparatory mitigation measures. Results show that emergency service personnel generally have a good sense of uncertainty inherent in weather forecasts. Although no single probability threshold could be identified for organisations to start with preparatory mitigation measures, it became clear that emergency services tend to avoid forecasts based on low probabilities as a basis for their decisions. Based on this findings, a second study conducted with residents of Berlin in 2014 further investigated the question of decision thresholds. The survey questions related to the topics of the perception of and prior experience with severe weather, trustworthiness of forecasters and confidence in weather forecasts, and socio-demographic and social-economic characteristics. Within the questionnaire a scenario was created to determine individual decision thresholds and see whether subgroups of the sample lead to different thresholds. The results show that people’s willingness to act tends to be higher and decision thresholds tend to be lower if the expected weather event is more severe or the property at risk is of higher value. Several influencing factors of risk perception have significant effects such as education, housing status and ability to act, whereas socio-demographic determinants alone are often not sufficient to fully grasp risk perception and protection behaviour. Parallel to the quantitative studies, an interview study was conducted with 27 members of German civil protection between 2012 and 2016. The results show that the latest developments in (numerical) weather forecasting do not necessarily fit the current practice of German emergency services. These practices are mostly carried out on alarms and ground truth in a reactive manner rather than on anticipation based on prognosis or forecasts. As the potential consequences rather than the event characteristics determine protective action, the findings support the call and need for impact-based warnings. Forecasters will rely on impact data and need to learn the users’ understanding of impact. Therefore, it is recommended to enhance weather communication not only by improving computer models and observation tools, but also by focusing on the aspects of communication and collaboration. Using information about uncertainty demands awareness about and acceptance of the limits of knowledge, hence, the capabilities of the forecaster to anticipate future developments of the atmosphere and the capabilities of the user to make sense of this information.
Flood damage can be mitigated if the parties at risk are reached by flood warnings and if they know how to react appropriately. To gain more knowledge about warning reception and emergency response of private households and companies, surveys were undertaken after the August 2002 and the June 2013 floods in Germany. Despite pronounced regional differences, the results show a clear overall picture: in 2002, early warnings did not work well; e.g. many households (27 %) and companies (45 %) stated that they had not received any flood warnings. Additionally, the preparedness of private households and companies was low in 2002, mainly due to a lack of flood experience. After the 2002 flood, many initiatives were launched and investments undertaken to improve flood risk management, including early warnings and an emergency response in Germany. In 2013, only a small share of the affected households (5 %) and companies (3 %) were not reached by any warnings. Additionally, private households and companies were better prepared. For instance, the share of companies which have an emergency plan in place has increased from 10% in 2002 to 34% in 2013. However, there is still room for improvement, which needs to be triggered mainly by effective risk and emergency communication. The challenge is to continuously maintain and advance an integrated early warning and emergency response system even without the occurrence of extreme floods.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Produktion unter Risiko
(2007)
Mit der hier vorliegenden Arbeit wird ein mikroökonomisches Multiagentenmodell eines Produktionssektors vorgeschlagen. Das Modell folgt einem post-walrasianischem Ungleichgewichtsansatz und beschreibt optimierende Agenten der Produktionsseite. Diese berücksichtigen in probabilistischen Nebenbedingungen Risiken des Cash Flow, die sich aus unsicheren Absatzmengen ergeben. Produzenten stehen in monopolistischer Konkurrenz und lernen durch Beobachten. Wird vorliegendes Modell in ein Totalmodell integriert, so wird es möglich, die sich aus der Klimadebatte ergebenden, notwendigen Veränderungen im Investitions- und Produktionsverhalten zu diskutieren und darzustellen.
Ziel ist die Überprüfung der kurz- und mittelfristigen Wirksamkeit einer vorschulischen Förderung des Mengen- und Zahlenverständnisses bei Kindern mit einem Risiko für die Entwicklung einer Rechenstörung. Es wurden 32 Risikokinder mit einer Kombination aus den Förderprogrammen Mathematik im Vorschulalter und Mengen, zählen, Zahlen im letzten Kindergartenjahr von den Erzieherinnen trainiert und mit 38 untrainierten Risikokindern verglichen. Hinsichtlich der kurzfristigen Wirksamkeit zeigten sich positive Trainingseffekte auf die numerischen Leistungen im letzten Kindergartenjahr. Es ließen sich keine signifikanten mittelfristigen Trainingseffekte auf die Rechenleistungen im zweiten Halbjahr der 1. Klasse finden. Das eingesetzte vorschulische Präventionsprogramm leistete danach einen wichtigen Beitrag zur kurzfristigen Verbesserung der mathematischen Basiskompetenzen.
Ziel ist die Überprüfung der kurz- und mittelfristigen Wirksamkeit einer vorschulischen Förderung des Mengen- und Zahlenverständnisses bei Kindern mit einem Risiko für die Entwicklung einer Rechenstörung. Es wurden 32 Risikokinder mit einer Kombination aus den Förderprogrammen Mathematik im Vorschulalter und Mengen, zählen, Zahlen im letzten Kindergartenjahr von den Erzieherinnen trainiert und mit 38 untrainierten Risikokindern verglichen. Hinsichtlich der kurzfristigen Wirksamkeit zeigten sich positive Trainingseffekte auf die numerischen Leistungen im letzten Kindergartenjahr. Es ließen sich keine signifikanten mittelfristigen Trainingseffekte auf die Rechenleistungen im zweiten Halbjahr der 1. Klasse finden. Das eingesetzte vorschulische Präventionsprogramm leistete danach einen wichtigen Beitrag zur kurzfristigen Verbesserung der mathematischen Basiskompetenzen.