63 research outputs found

    Development and Validation of a Remote-Controlled Test Platform for Bicycle Dynamics

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    Through the electrification of bicycles, the implementation of new active and passive safety systems becomes possible. Examples for such systems are bicycle ABS, TU Delft - Fall Prevention Bicycle, Bosch Help Connect (eCall System for bicycles), airbag helmets and many others. One of the main difficulties in developing and testing such safety systems is, that test riders should not be exposed to high risks when testing early prototypes. Thus, an automated or remote-controlled test platform for the analysis of bicycle dynamics and for testing of newly developed safety systems could boost the development of such systems and make it safer. The main difficulty when developing such a test platform, which has been addressed in this work, is stabilizing it at low speeds (1.5 m/s - 4.5 m/s) and being capable of tracking a desired yaw rate, only using a steer actuator. In the following, the development of such a test platform is described and first experimental results are presented

    A robust algorithm for implicit description of immersed geometries within a background mesh

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    The paper presents a robust algorithm, which allows to implicitly describe and track immersed geometries within a background mesh. The background mesh is assumed to be unstructured and discretized by tetrahedrons. The contained geometry is assumed to be given as triangulated surface. Within the background mesh, the immersed geometry is described implicitly using a discontinuous distance function based on a level-set approach. This distance function allows to consider both, “double-sided” geometries like membrane or shell structures, and “single-sided” objects for which an enclosed volume is univocally defined. For the second case, the discontinuous distance function is complemented by a continuous signed distance function, whereas ray casting is applied to identify the closed volume regions. Furthermore, adaptive mesh refinement is employed to provide the necessary resolution of the background mesh. The proposed algorithm can handle arbitrarily complicated geometries, possibly containing modeling errors (i.e., gaps, overlaps or a non-unique orientation of surface normals). Another important advantage of the algorithm is the embarrassingly parallel nature of its operations. This characteristic allows for a straightforward parallelization using MPI. All developments were implemented within the open source framework “KratosMultiphysics” and are available under the BSD license. The capabilities of the implementation are demonstrated with various application examples involving practice-oriented geometries. The results finally show, that the algorithm is able to describe most complicated geometries within a background mesh, whereas the approximation quality may be directly controlled by mesh refinement

    Manufacturing of W/steel composites using electro-discharge sintering process

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    Tungsten-steel metal matrix composites are consolidated using electro-discharge sintering. At first steel and tungsten powders are sintered separately and then 25 vol% W, 50 vol% W and 75 vol% W mixed powders are sintered. A thorough process parametric study is carried out involving analysis of the influence of particle size distribution, sintering pressure, and discharge energy on the maximum discharge current and obtained residual porosity. Thermal expansion coefficient and the specific heat capacity of the optimized sintered composites are almost same as their theoretical values, however the thermal conductivities and the mechanical properties are lower than the expected values

    Cytogenetic analysis of sympatric Trachelyopterus Valenciennes 1840 (Siluriformes, Auchenipteridae) species reveals highly conserved karyotypes despite the geographic distance

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    Trachelyopterus Valenciennes 1840 species exhibit striking morphological and cytogenetic similarities, leading to persistent taxonomic challenges. This research focuses on Trachelyopterus galeatus Linnaeus 1766 and Trachelyopterus porosus Eigenmann & Eigenmann 1888, both widely distributed throughout South America and often sympatric, facilitating cytogenetic comparisons. These taxonomic entities are noteworthy for their extensive geographical ranges within the genus. We examined two populations of T. galeatus and T. porosus collected from sympatric sites in the Amazon and Pantanal regions. Both species had the same diploid number and simple Ag-NORs. The 18S rDNA sites were found in only one subtelocentric chromosome pair. Meanwhile, the 5S rDNA sites were found on two distinct chromosomal pairs, with differences in the chromosomal morphology and site position among the species, constituting the most efficient chromosomal marker to distinguish them. The 5S rDNA pattern differed between species but remained consistent between populations of the same species. Minor differences were observed between the T. galeatus populations, probably related to chromosomal rearrangements. In contrast, despite the considerable geographical distance, no cytogenetic differences were detected among the T. porosus populations. Overall, the congruence between cytogenetic and morphological characteristics, combined with our findings from sympatric samples and existing data from geographically separated populations of Trachelyopterus, indicates that the cytogenetic is a promising tool for species differentiation and for delving into the cytotaxonomic and evolutionary aspects of Auchenipteridae

    An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation

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    Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day −55 and −27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day −70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research

    Limitations of the MELD score in predicting mortality or need for removal from waiting list in patients awaiting liver transplantation

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    <p>Abstract</p> <p>Background</p> <p>Decompensated cirrhosis is associated with a poor prognosis and liver transplantation provides the only curative treatment option with excellent long-term results. The relative shortage of organ donors renders the allocation algorithms of organs essential. The optimal strategy based on scoring systems and/or waiting time is still under debate.</p> <p>Methods</p> <p>Data sets of 268 consecutive patients listed for single-organ liver transplantation for nonfulminant liver disease between 2003 and 2005 were included into the study. The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores of all patients at the time of listing were used for calculation. The predictive ability not only for mortality on the waiting list but also for the need for withdrawal from the waiting list was calculated for both scores. The Mann-Whitney-U Test was used for the univariate analysis and the AUC-Model for discrimination of the scores.</p> <p>Results</p> <p>In the univariate analysis comparing patients who are still on the waiting list and patients who died or were removed from the waiting list due to poor conditions, the serum albumin, bilirubin INR, and CTP and MELD scores as well as the presence of ascites and encephalopathy were significantly different between the groups (p < 0.05), whereas serum creatinine and urea showed no difference.</p> <p>Comparing the predictive abilities of CTP and MELD scores, the best discrimination between patients still alive on the waiting list and patients who died on or were removed from the waiting list was achieved at a CTP score of ≥9 and a MELD score of ≥14.4. The sensitivity and specificity to identify mortality or severe deterioration for CTP was 69.0% and 70.5%, respectively; for MELD, it was 62.1% and 72.7%, respectively. This result was supported by the AUC analysis showing a strong trend for superiority of CTP over MELD scores (AUROC 0.73 and 0.68, resp.; p = 0.091).</p> <p>Conclusion</p> <p>The long term prediction of mortality or removal from waiting list in patients awaiting liver transplantation might be better assessed by the CTP score than the MELD score. This might have implications for the development of new improved scoring systems.</p

    Does Intraspecific Size Variation in a Predator Affect Its Diet Diversity and Top-Down Control of Prey?

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    It has long been known that intraspecific variation impacts evolutionary processes, but only recently have its potential ecological effects received much attention. Theoretical models predict that genetic or phenotypic variance within species can alter interspecific interactions, and experiments have shown that genotypic diversity in clonal species can impact a wide range of ecological processes. To extend these studies to quantitative trait variation within populations, we experimentally manipulated the variance in body size of threespine stickleback in enclosures in a natural lake environment. We found that body size of stickleback in the lake is correlated with prey size and (to a lesser extent) composition, and that stickleback can exert top-down control on their benthic prey in enclosures. However, a six-fold contrast in body size variance had no effect on the degree of diet variation among individuals, or on the abundance or composition of benthic or pelagic prey. Interestingly, post-hoc analyses revealed suggestive correlations between the degree of diet variation and the strength of top-down control by stickleback. Our negative results indicate that, unless the correlation between morphology and diet is very strong, ecological variation among individuals may be largely decoupled from morphological variance. Consequently we should be cautious in our interpretation both of theoretical models that assume perfect correlations between morphology and diet, and of empirical studies that use morphological variation as a proxy for resource use diversity

    An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation

    Get PDF
    Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day −55 and −27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day −70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research

    An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

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    The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity.The MANCO project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 101003651). This work made use of the Dutch national e infrastructure with the support of the SURF Cooperative using grant no. EINF-2453. This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) - 398066876/GRK 2485/1; BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G, Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20)N

    An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

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    The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other Variants of Concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and/or hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs, and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.The MANCO project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101003651). This work made use of the Dutch national e-infrastructure with the support of the SURF Cooperative using grant no. EINF-2453. This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) -398066876/GRK 2485/1; BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G, Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20)Peer reviewe
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