Hochschulbibliothekszentrum des Landes Nordrhein-Westfalen (hbz)
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Impacts from cascading multi-hazards using hypergraphs: a case study from the 2015 Gorkha earthquake in Nepal
No full text<jats:p>Abstract. This study introduces a new approach to multi-hazard risk assessment, leveraging hypergraph theory to model the interconnected risks posed by cascading natural hazards. Traditional single-hazard risk models fail to account for the complex interrelationships and compounding effects of multiple simultaneous or sequential hazards. By conceptualising risks within a hypergraph framework, our model overcomes these limitations, enabling efficient simulation of multi-hazard interactions and their impacts on infrastructure. We apply this model to the 2015 Mw 7.8 Gorkha earthquake in Nepal as a case study, demonstrating its ability to simulate the primary and secondary effects of the earthquake on buildings and roads across the whole earthquake-affected area. The model predicts the overall pattern of earthquake-induced building damage and landslide impacts, albeit with a tendency towards over-prediction. Our findings underscore the potential of the hypergraph approach for multi-hazard risk assessment, offering advances in rapid computation and scenario exploration for cascading geo-hazards. This approach could provide valuable insights for disaster risk reduction and humanitarian contingency planning, where the anticipation of large-scale trends is often more important than the prediction of detailed impacts.
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Mechanically Interlocked Molecular Rotors on Pb(100)
No full textThe mechanical coupling between molecules represents a promising route for the development of molecular machines. Constructing molecular gears requires easily rotatable and mutually interlocked pinions. Using scanning tunneling microscopy (STM), it is demonstrated that aluminum phthalocyanine (AlPc) molecules on Pb(100) exhibit these properties. Unlike other phthalocyanines on this substrate, isolated AlPc molecules fluctuate between two azimuthal orientations. Density functional theory (DFT) calculations confirm two stable orientations of single molecules and indicate a relatively low rotation barrier. In STM-constructed dimers and trimers, fluctuations diminish, and various molecular orientations are stabilized. Induced collective rotation of all molecules in the trimers is observed, demonstrating their mechanical interlocking. Potential functions describing angle and distance dependencies of intermolecular and molecule-substrate interactions are derived from DFT calculations of dimers; 52 experimentally determined trimer geometries are reproduced using these potentials. This intuitive approach may prove to be useful in modeling larger structures beyond the scope of quantum mechanical descriptions
Differential expression and modulation of EBI2 and 7α,25-OHC synthesizing (CH25H, CYP7B1) and degrading (HSD3B7) enzymes in mouse and human brain vascular cells
No full textThe endogenous ligand for the EBI2 receptor, oxysterol 7α,25OHC, crucial for immune responses, is finely regulated by CH25H, CYP7B1 and HSD3B7 enzymes. Lymphoid stromal cells and follicular dendritic cells within T cell follicles maintain a gradient of 7α,25OHC, with stromal cells increasing and dendritic cells decreasing its concentration. This gradient is pivotal for proper B cell positioning in lymphoid tissue. In the animal model of multiple sclerosis, the experimental autoimmune encephalomyelitis, the levels of 7α,25OHC rapidly increase in the central nervous system driving the migration of EBI2 expressing immune cells through the blood-brain barrier (BBB). To explore if blood vessel cells in the brain express these enzymes, we examined normal mouse brain microvessels and studied changes in their expression during inflammation. Ebi2 was abundantly expressed in endothelial cells, pericytes/smooth muscle cells, and astrocytic endfeet. Ch25h, Cyp7b1, and Hsd3b7 were variably detected in each cell type, suggesting their active involvement in oxysterol 7α,25OHC synthesis and gradient maintenance under normal conditions. Significant species-specific differences emerged in EBI2 and the enzyme levels between mouse and human BBB-forming cells. Under acute inflammatory conditions, Ebi2 and synthesizing enzyme modulation occurred in the brain, with the magnitude and direction of change based on the enzyme. Lastly, in an in vitro astrocyte migration model, CYP7B1 inhibitor clotrimazole, as well as EBI2 antagonist, NIBR189, inhibited lipopolysaccharide-induced cell migration indicating the involvement of EBI2 and its ligand in brain cell migration under inflammatory conditions
Development of a multi-epitope chimeric vaccine in silico against Babesia bovis, Theileria annulata, and Anaplasma marginale using computational biology tools and reverse vaccinology approach
No full textThe three rickettsial parasites- Babesia bovis, Theileria annulata and Anaplasma Marginale are responsible for causing Babesiosis, Theileriosis and Anaplasmosis among cattle. These diseases exist due to spreading of infected ticks. A large number of cattle were found to suffer from mixed infections caused by the three parasites at the same time. Due to these reasons cattle have been devoid of milk production with reduced meat availability. Hence, it is a matter of urgency for the immunity of cattle to exhibit resilience against all three rickettsial parasites. It could be possible if trials are carried out after producing a subunit chimeric vaccine against the rickettsial protozoan parasites and introducing it into the bloodstream of the cattle species. In this paper, we have used the process of reverse vaccinology to conduct a study in which we have developed a multi-epitope subunit chimeric vaccine against three protozoan parasites. We constructed three chimeric vaccine sequences from which only one chimeric vaccine construct was found to be an effective and efficient vaccine which is stable with high solubility and negative allergenicity. Following that, we performed molecular docking of the refined chimeric vaccine construct with Rp-105 and TLR-9. It was observed that the chimeric vaccines interacted with the receptors with high binding energy. Immune simulation was also performed to determine the potentiality of the chimeric vaccine for eliciting an immune response. The best-designed chimeric vaccine construct was then reverse transcribed and adapted for the host E. coli K12 strain which was later inserted into the pET28a (+) vector for the cloning and expression of the vaccine. The study could be a good initiative for the development of an effective chimeric vaccine against bovine parasites
Healthcare resource utilization and costs in immunodeficient patients receiving subcutaneous Ig: Real-world evidence from France
No full textBACKGROUND: Subcutaneous immunoglobulin (SCIg) replacement therapy is indicated for patients with hypogammaglobulinemia caused by primary (PID) and secondary immunodeficiencies (SID). OBJECTIVE: To compare healthcare resource utilization (HCRU) and related direct medical costs of patients in France treated with weekly conventional SCIg (cSCIg) vs monthly hyaluronidase-facilitated SCIg (fSCIg). METHODS: This retrospective study of Ig-naïve patients with PID or SID newly receiving a SCIg between 2016 and 2018, extracted from the French National Healthcare reimbursement database (SNDS), analyzed the SCIg-related HCRU and reimbursed costs generated from in-hospital (hospitalizations and SCIg doses) or at-home (nurse visits [NV] and pump provider visits [PPV], drug doses) SCIg administration. RESULTS: Overall, 2,012 patients (PID:534; SID:1,478) were analyzed. The follow-up duration varied between 7.5 and 8.7 months according to sub-groups. Compared with fSCIg-treated patients, monthly mean rates of NV and PPV were respectively 2.5 and 3.1 times higher in PID, and 1.6 and 3.1 times higher in SID cSCIg-treated patients. Monthly mean rates for SCIg administration-related hospitalizations were lower overall, while their costs were 1.6 and 1.8 times higher for cSCIg than fSCIg subgroups, in PIDs and SIDs respectively; these results are due to more frequent hospitalizations with fSCIg being mainly shorter, without stayover. Total HCRU costs from the French NHI’s perspective were estimated to be lower with fSCIg vs cSCIg, in PIDs and SIDs. CONCLUSION: This study provides real-world evidence of SCIg administration in a large French population. Patients with PID or SID treated with fSCIg had fewer at-home HCRU and lower overall costs for in-hospital or at-home SCIg administration compared with cSCIg-treated patients
Risk Profiles for Chronic Stress in Employees of Nursing Homes and the Role of Physical Activity : A Regression Tree Analysis
No full text<jats:p> Abstract: Background: Employees of nursing homes are facing numerous stressors. As chronic stress and nursing turnover are a major concern in societies dealing with staff shortages and overloaded health care systems, a better understanding of the combined effects of stressors and the identification of risk patterns are crucial as well as the potential of physical activity as a resource or stressor. Aims: To address this issue, this study aims to (1) identify individual stress risk profiles and (2) analyze the effect of physical activity on stress in employees of nursing homes. Method: 275 employees (79.2% female and 70.5% aged older than 35 years) completed a survey. Using a machine learning method, a regression tree analysis was performed. Results: The combination of high work-privacy conflict and high role conflict was identified as a very high-risk profile for chronic stress in elderly care. Within the regression tree, work-privacy conflict was identified as the strongest determinant of individual chronic stress values. Vigorous occupational physical activity was the only relevant physical activity parameter positively correlated with stress values and thus acted as a stressor. Physical activity did not act as a resource. Limitations: The exploratory analyses of this study are limited due to the cross-sectional nature of the data. Conclusion: The study provides valuable insights to healthcare managers and policymakers on ways to reduce stress in employees of nursing homes and underlines the physical activity paradox. </jats:p>
Determination of the Time-frequency Features for Impulse Components in EEG Signals
No full text<jats:title>Abstract</jats:title>
<jats:p>Accurately identifying the timing and frequency characteristics of impulse components in EEG signals is essential but limited by the Heisenberg uncertainty principle. Inspired by the visual system’s ability to identify objects and their locations, we propose a new method that integrates a visual system model with wavelet analysis to calculate both time and frequency features of local impulses in EEG signals. We develop a mathematical model based on invariant pattern recognition by the visual system, combined with wavelet analysis using Krawtchouk functions as the mother wavelet. Our method precisely identifies the localization and frequency characteristics of the impulse components in EEG signals. Tested on task-related EEG data, it accurately detected blink components (0.5 to 1 Hz) and separated muscle artifacts (16 Hz). It also identified muscle response durations (298 ms) within the 1 to 31 Hz range in emotional reaction studies, offering insights into both individual and typical emotional responses. We further illustrated how the new method circumvents the uncertainty principle in low-frequency wavelet analysis. Unlike classical wavelet analysis, our method provides spectral characteristics of EEG impulses invariant to time shifts, improving the identification and classification of EEG components.</jats:p>
Assessing Arterial Patterns in the Motor Cortex With 7 Tesla Magnetic Resonance Imaging and Vessel Distance Mapping
No full textLeveraging high-resolution 7 T magnetic resonance imaging (MRI) and vessel distance mapping (VDM), the arterial supply patterns and dominances of the motor cortex, which could previously only be studied postmortem, were assessed in vivo and fully noninvasively. Beyond vessel patterns and dominances, the potential relation between the vascularization and the motor cortex thickness was studied. Twenty-one healthy participants underwent 7 T MRI scans to map arterial supply and motor cortex at 0.45 mm isotropic resolution. The motor cortex vasculature was segmented manually with vessel-specific labels. VDM was utilized to estimate the vessel-specific supply regions and, subsequently, assess vessel patterns and dominances. Statistical tests were applied to test if the vasculature impacts mean motor cortical thickness estimates. Vessel patterns, that is the presence of supplying vessels, were classified as three-, four-, and five-vessel patterns with a prevalence of 26.3%, 50.0%, and 23.7%, respectively. Vessel dominance, that is the ratio of supply volumes, of the ACA branches showed dominance of the pericallosal artery, callosomarginal artery, and equal contribution, in 34.2%, 34.2%, and 31.6% of the cases, respectively. For the MCA groups, the prevalence of precentral group dominance, central group dominances, and equal contribution was 13.2%, 34.2%, and 52.6%, respectively. Although the central and precentral groups were found in all hemispheres, the postcentral group was found in 28.9% of hemispheres with highly variable supply contribution. Statistical tests returned no significance for the effect of vessel patterns and dominances on the mean motor cortex thickness. With 7 T MRI and VDM, the motor cortex vascularization can be assessed fully noninvasively and longitudinally while providing overall good concordance with previous post mortem studies. Our comprehensive analysis of arterial motor cortex vascularization showed considerable variability between hemispheres, rendering the usage of pattern-specific atlases and analysis more suitable than single normative representations. The successful translation from post mortem to in vivo enables the study of vascular reserve in disorders affecting the motor cortex, such as ALS, and can be translated to other brain regions and neurodegenerative diseases in the future
Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function
No full textAdhesion G protein-coupled receptors (aGPCRs) are expressed in all organs and are involved in various mechanobiological processes. They are heavily alternatively spliced, forecasting an extraordinary molecular structural diversity. Here, we uncovered the existence of unconventional single-transmembrane (1TM)-containing ADGRL/Cirl proteins devoid of the conventional GPCR layout (i.e., the 7TM signaling unit) in Drosophila. These 1TM proteins are made as a result of intron retention and provide an N-terminal fragment that acts as an interactor to allow Gαo-dependent signaling through conventional 7TM-containing Cirl isoforms encoded by the same gene. This molecular mechanism determines sensory precision of neurons in response to mechanical stimulation in vivo. This action mode of aGPCR provides a promising entry point for experimental and therapeutic approaches to intervene in aGPCR signaling and implicates alternative splicing as a physiological strategy to express a given aGPCR together with its molecular interactor
Specific presynaptic functions require distinct Drosophila Cav2 splice isoforms
No full textAt many vertebrate synapses, presynaptic functions are tuned by expression of different Cav2 channels. Most invertebrate genomes contain only one Cav2 gene. The Drosophila Cav2 homolog, cacophony (cac), induces synaptic vesicle release at presynaptic active zones (AZs). We hypothesize that Drosophila cac functional diversity is enhanced by two mutually exclusive exon pairs that are not conserved in vertebrates, one in the voltage sensor and one in the loop binding Caβ and Gβγ subunits. We find that alternative splicing in the voltage sensor affects channel activation voltage. Only the isoform with the higher activation voltage localizes to AZs at the glutamatergic Drosophila larval neuromuscular junction and is imperative for normal synapse function. By contrast, alternative splicing at the other alternative exon pair tunes multiple aspects of presynaptic function. While expression of one exon yields normal transmission, expression of the other reduces channel number in the AZ and thus release probability. This also abolishes presynaptic homeostatic plasticity. Moreover, reduced channel number affects short-term plasticity, which is rescued by increasing the external calcium concentration to match release probability to control. In sum, in Drosophila alternative splicing provides a mechanism to regulate different aspects of presynaptic functions with only one Cav2 gene