216 research outputs found
Interdisciplinary curricula in secondary education. How do teachers assess the recently combined subjects?
Im fächerübergreifenden Unterricht sollen Schüler bedeutungsvolles und anwendungsfähiges Wissen erwerben. Die bildungspolitischen Vorgaben in diesem Bereich unterscheiden sich erheblich von Bundesland zu Bundesland. In einer empirischen Studie wird erkundet, wie Lehrkräfte in Baden-Württemberg die dort entwickelten Fächerverbünde einschätzen. (DIPF/Orig.)Interdisciplinary teaching in secondary education aims to provide more meaningful learning environments for all students. Educational policy in this field differs from state to state. This empirical study examines how teachers in Baden-Württemberg view the recently combined subjects in secondary schools. (DIPF/Orig.
Optimal Network Design for Microseismic Monitoring in Urban Areas - A Case Study in Munich, Germany
Well-designed monitoring networks are crucial for obtaining precise locations, magnitudes and source parameters, both for natural and induced microearthqakes. The performance of a seismic network depends on many factors, including network geometry, signal-to-noise ratio (SNR) at the seismic station, instrumentation and sampling rate. Therefore, designing a high-quality monitoring network in an urban environment is challenging due to the high level of anthropogenic noise and dense building infrastructure, which can impose geometrical limitations and elevated construction costs for sensor siting. To address these challenges, we apply a numerical optimization approach to design a microseismic surveillance network for induced earthquakes in the metropolitan area of Munich (Germany), where several geothermal plants exploit a deep hydrothermal reservoir. First of all, we develop a detailed noise model for the city of Munich, to capture the heterogeneous noise conditions. Then, we calculate the expected location precision for a randomly chosen network geometry from the body-wave amplitudes and travel times of a synthetic earthquake catalog considering the modeled local noise level at each network station. In the next step, to find the optimum network configuration, we use a simulated annealing approach in order to minimize the error ellipsoid volume of the linearized earthquake location problem. The results indicate that a surface station network cannot reach the required location precision (0.5 km in epicentre and 2 km in source depth) and detection capability (magnitude of completeness Mc = 1.0) due to the city´s high seismic noise level. In order to reach this goal, borehole stations need to be added to increase the SNR of the microearthquake recordings, the accuracy of their body-wave arrival times and source parameters. The findings help to better quantify the seismic monitoring requirements for a save operation of deep geothermal projects in urban areas
The Signal Sequence Receptor Has a Second Subunit and IsPart of a Translocation Complex in the Endoplasmic Reticulum as Probed by Bifunctional Reagents
Bifunctional cross-linking reagents were used to probe the protein environment in the ER membrane of the signal sequence receptor (SSR), a 34-kD integral membrane glycoprotein (Wiedmann, M., T. V. Kurzchalia, E. Hartmarm, and T. A. Rapoport. 1987. Nature [Lond.]. 328:830-833). The proximity of several polypeptides was demonstrated. A 22-kD glycoprotein was identified tightly bound to the 34-kD SSR even after membrane solubilization. The 34-kD polypeptide, now termed otSSR, and the 22-kD polypeptide, the #SSR, represent a heterodimer. We report on the sequence of the/3SSR, its membrane topology, and on the mechanism of its integration into the membrane. Cross-linking also produced dimers of the a-subunit of the SSR indicating that oligomers of the SSR exist in the ER membrane. Various bifunctional cross-linking reagents were used to study the relation to ER membrane proteins of nascent chains of preprolactin and/3-1actamase at different stages of their translocation through the membrane. The predominant cross-linked products obtained in high yields contained the aSSR, indicating in conjunction with previous results that it is a major membrane protein in the neighborhood of translocating nascent chains of secretory proteins. The results support the existence of a translocon, a translocation complex involving the SSR, which constitutes the specific site of protein translocation across the ER membrane
Living Long and Well: Prospects for a Personalized Approach to the Medicine of Ageing.
Research into ageing and its underlying molecular basis enables us to develop and implement targeted interventions to ameliorate or cure its consequences. However, the efficacy of interventions often differs widely between individuals, suggesting that populations should be stratified or even individualized. Large-scale cohort studies in humans, similar systematic 56 studies in model organisms, and detailed investigations into the biology of ageing can provide individual validated biomarkers and mechanisms, leading to recommendations for targeted interventions. Human cohort studies are already ongoing, and can be supplemented by in silico simulations. Systematic studies in animal models are made possible by the use of inbred strains, or genetic reference populations of mice. Combining both, the comprehensive picture of the various determinants of ageing and healthspan can be studied in detail, and an appreciation of the relevance of results from model organisms to humans emerges. The interactions between genotype and environment, particularly the psychosocial environment, are poorly studied in both humans and model organisms, presenting serious challenges to any approach to a personalized medicine of ageing. To increase success of preventive interventions, we argue that there is a pressing need for an individualized evaluation of interventions such as physical exercise, nutrition, nutraceuticals and calorie restriction mimetics as well as psychosocial and environmental factors, separately and in combination. The expected extension of healthspan enables us to refocus healthcare spending on individual prevention starting in late adulthood, and on the brief period of morbidity at very old age
Quantum transport through STM-lifted single PTCDA molecules
Using a scanning tunneling microscope we have measured the quantum
conductance through a PTCDA molecule for different configurations of the
tip-molecule-surface junction. A peculiar conductance resonance arises at the
Fermi level for certain tip to surface distances. We have relaxed the molecular
junction coordinates and calculated transport by means of the Landauer/Keldysh
approach. The zero bias transmission calculated for fixed tip positions in
lateral dimensions but different tip substrate distances show a clear shift and
sharpening of the molecular chemisorption level on increasing the STM-surface
distance, in agreement with experiment.Comment: accepted for publication in Applied Physics
In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials
Background aims Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell–based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5+ MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice–conforming, MSC-based advanced-therapy medicinal product. Methods To support the development of ABCB5+ MSCs for potential therapeutic topical, intramuscular and intravenous administration, we have tested our product in a series of Good Laboratory Practice–compliant nonclinical in-vivo studies addressing all relevant aspects of biosafety, including potential long-term persistence and proliferation, distribution to nontarget tissues, differentiation into undesired cell types, ectopic tissue formation, tumor formation and local tissue reaction. Results (i) Subcutaneous application of 1 × 107 ABCB5+ MSCs/animal and intravenous application of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice did not result in safety-relevant biodistribution, persistence or proliferation of the cells; (ii) three monthly subcutaneous injections of ABCB5+ MSCs at doses ranging from 1 × 105 to 1 × 107 cells/animal and three biweekly intravenous injections of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice were nontoxic and revealed no tumorigenic potential; and (iii) intramuscular injection of 5 × 106 ABCB5+ MSCs/animal to immunocompromised mice was locally well tolerated. Discussion The present preclinical in vivo data demonstrate the local and systemic safety and tolerability of a novel advanced-therapy medicinal product based on human skin-derived ABCB5+ MSCs
Elaia, Pergamon's maritime satellite:The rise and fall of an ancient harbour city shaped by shoreline migration
Throughout human history, communication and trade have been key to society. Because maritime trade facilitated the rapid transportation of passengers and freight at relatively low cost, harbours became hubs for traffic, trade and exchange. This general statement holds true for the Pergamenian kingdom, which ruled wide parts of today's western Turkey during Hellenistic times. Its harbour, located at the city of Elaia on the eastern Aegean shore, was used extensively for commercial and military purposes. This study reconstructs the coastal evolution in and around the ancient harbour of Elaia and compares the observed environmental modifications with archaeological and historical findings. We use micropalaeontological, sedimentological and geochemical proxies to reconstruct the palaeoenvironmental dynamics and evolution of the ancient harbour. The geoarchaeological results confirm the archaeological and historical evidence for Elaia's primacy during Hellenistic and early Roman times, and the city's gradual decline during the late Roman period. Furthermore, our study demonstrates that Elaia holds a unique position as a harbour city during ancient times in the eastern Aegean region, because it was not greatly influenced by the high sediment supply associated with river deltas. Consequently, no dredging of the harbour basins is documented, creating exceptional geo-bioarchives for palaeoenvironmental reconstructions
Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer:Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses
Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.</p
Gingival crevicular fluid MMP-8-concentrations in patients after acute myocardial infarction
<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the presence of matrix metalloproteinase-8 in the gingival crevicular fluid (GCF) of patients after acute myocardial infarction (AMI).</p> <p>Methods</p> <p>A total of 48 GCF samples from 20 AMI patients, hospitalized at the Department of Cardiology and Angiology of the Johannes Gutenberg University Mainz, were investigated. Besides the myocardial infarction all patients suffered from chronic periodontal disease. Fifty-one GCF samples from 20 healthy age matched individuals with similar periodontal conditions served as controls. The dental examination included the assessment of oral hygiene, gingival inflammation, probing pocket depth, clinical attachment level and X-ray examination. The study was only carried out after the positive consent of the regional ethic commission. A quantitative assessment of aMMP-8 levels in the gingival crevicular fluid was performed with the help of the DentoAnalyzer (Dentognostics GmbH, Jena, Germany), utilising an immunological procedure.</p> <p>Results</p> <p>The aMMP-8 concentrations found in the gingival crevicular fluid of the AMI patients significantly differed (p = 0.001; mean value 30.33 ± 41.99 ng/ml aMMP-8) from the control group (mean value 10.0 ± 10.7 ng/ml aMMP-8). These findings suggest that periodontal inflammation in AMI patients might be associated with higher MMP-8-values compared to the healthy controls.</p> <p>Conclusions</p> <p>The acute myocardial infarction seems to influence the degree of periodontal inflammation, thus the measurement of the gingival crevicular fluid MMP8 levels seems to be a helpful biochemical test to obtain information about the severity of the periodontal disease.</p
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