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  1. Article ; Online: Tailoring the V-Model for Optics

    Peer-Phillip Ley / Marvin Knöchelmann / Alexander Wolf / Roland Lachmayer

    Applied Sciences, Vol 12, Iss 7798, p

    A Methodology for Optomechatronic Systems

    2022  Volume 7798

    Abstract: The integration of optical technologies into once purely mechatronic systems enables innovative functions, but simultaneously increases the complexity of previous mechatronic system development. Therefore, a process has been elaborated to develop these ... ...

    Abstract The integration of optical technologies into once purely mechatronic systems enables innovative functions, but simultaneously increases the complexity of previous mechatronic system development. Therefore, a process has been elaborated to develop these so-called optomechatronic systems by Knöchelmann at the Institute of Product Development at Leibniz University Hanover, which is based on the V-Model of VDI 2206 and can be applied to various fields of application. For a target-oriented development in a specific product context and for systems with competing main requirements, detailing and adapting the process is recommended. High-resolution lighting systems are one of them, where requirements for high optical efficiency and image quality lead to a conflict of objectives. Focusing on the optics domain, Ley elaborated methods for the preliminary and detailed design of high-resolution lighting systems to address the aforementioned conflict of objectives. This contribution focuses on the integration of Ley’s design methods into Knöchelmann’s process model within the phases of system design and domain-specific design, allowing us to analyze the impact of the system design on the fulfillment of main requirements to achieve an optimal solution of the conflict of objectives. To illustrate this, the integrated process model is described using an example from automotive lighting technology.
    Keywords optomechatronics ; development methodologies ; V-model ; optics design ; high-resolution lighting systems ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
    Subject code 600
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid

    Qili Wang / Alexander Wolf / Sebahat Ozkan / Ludovic Richert / Yves Mely / Sylvette Chasserot-Golaz / Stéphane Ory / Stéphane Gasman / Nicolas Vitale

    Frontiers in Molecular Biosciences, Vol

    2023  Volume 10

    Abstract: Although there is mounting evidence indicating that lipids serve crucial functions in cells and are implicated in a growing number of human diseases, their precise roles remain largely unknown. This is particularly true in the case of neurosecretion, ... ...

    Abstract Although there is mounting evidence indicating that lipids serve crucial functions in cells and are implicated in a growing number of human diseases, their precise roles remain largely unknown. This is particularly true in the case of neurosecretion, where fusion with the plasma membrane of specific membrane organelles is essential. Yet, little attention has been given to the role of lipids. Recent groundbreaking research has emphasized the critical role of lipid localization at exocytotic sites and validated the essentiality of fusogenic lipids, such as phospholipase D (PLD)-generated phosphatidic acid (PA), during membrane fusion. Nevertheless, the regulatory mechanisms synchronizing the synthesis of these key lipids and neurosecretion remain poorly understood. The vacuolar ATPase (V-ATPase) has been involved both in vesicle neurotransmitter loading and in vesicle fusion. Thus, it represents an ideal candidate to regulate the fusogenic status of secretory vesicles according to their replenishment state. Indeed, the cytosolic V1 and vesicular membrane-associated V0 subdomains of V-ATPase were shown to dissociate during the stimulation of neurosecretory cells. This allows the subunits of the vesicular V0 to interact with different proteins of the secretory machinery. Here, we show that V0a1 interacts with the Arf nucleotide-binding site opener (ARNO) and promotes the activation of the Arf6 GTPase during the exocytosis in neuroendocrine cells. When the interaction between V0a1 and ARNO was disrupted, it resulted in the inhibition of PLD activation, synthesis of phosphatidic acid during exocytosis, and changes in the timing of fusion events. These findings indicate that the separation of V1 from V0 could function as a signal to initiate the ARNO-Arf6-PLD1 pathway and facilitate the production of phosphatidic acid, which is essential for effective exocytosis in neuroendocrine cells.
    Keywords chromaffin cells ; V-ATPase ; phospholipase D ; phospholipids ; neurosecretion ; membrane fusion ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?

    Katharina Rump / Björn Koos / Dominik Ziehe / Patrick Thon / Tim Rahmel / Lars Palmowski / Britta Marko / Alexander Wolf / Andrea Witowski / Zainab Bazzi / Maha Bazzi / Jennifer Orlowski / Michael Adamzik / Lars Bergmann / Matthias Unterberg

    International Journal of Molecular Sciences, Vol 25, Iss 1, p

    2024  Volume 610

    Abstract: Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 ( Aqp5 ) knockdown provided enhanced sepsis survival in a ... ...

    Abstract Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 ( Aqp5 ) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential AQP5 inhibitors provide sulfonamides and their derivatives. In this study, we tested the hypothesis that sulfonamides reduce AQP5 expression in different conditions. The impact of sulfonamides on AQP5 expression and immune cell migration was examined in cell lines REH and RAW 264.7 by qPCR, Western blot and migration assay. Subsequently, whether furosemide and methazolamide are capable of reducing AQP5 expression after LPS incubation was investigated in whole blood samples of healthy volunteers. Incubation with methazolamide (10 −5 M) and furosemide (10 −6 M) reduced AQP5 mRNA and protein expression by about 30% in REH cells. Pre-incubation of the cells with methazolamide reduced cell migration towards SDF1-α compared to non-preincubated cells to control level. Pre-incubation with methazolamide in PBMCs led to a reduction in LPS-induced AQP5 expression compared to control levels, while furosemide failed to reduce it. Methazolamide appears to reduce AQP5 expression and migration of immune cells. However, after LPS administration, the reduction in AQP5 expression by methazolamide is no longer possible. Hence, our study indicates that methazolamide is capable of reducing AQP5 expression and has the potential to be used in sepsis prophylaxis.
    Keywords aquaporins ; AQP5 ; sepsis ; sulfonamides ; methazolamide ; furosemide ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Distraction Potential of Vehicle-Based On-Road Projection

    Tobias Glück / Tobias Biermann / Alexander Wolf / Sören Budig / Arved Ziebehl / Marvin Knöchelmann / Roland Lachmayer

    Applied Sciences, Vol 11, Iss 12030, p

    2021  Volume 12030

    Abstract: With regard to autonomous driving, on-road projections cannot only be used for communication with the driver but also with other road users. Our study aims to investigate the distraction potential for other road users when on-road projections (e.g., for ... ...

    Abstract With regard to autonomous driving, on-road projections cannot only be used for communication with the driver but also with other road users. Our study aims to investigate the distraction potential for other road users when on-road projections (e.g., for driver assistance) are used to communicate with the driver of the projecting vehicle. We perform this investigation in a blind study with 38 test persons who are overtaken six times on a constant motorway section by the projection vehicle. The distraction potential is examined with an eye-tracking system, which detects the direction of the subjects’ gaze. In addition, the subjects’ physiological perception of the headlight projection is recorded with a questionnaire afterward. Several test subjects looked at the projection for less than one second, which is well below the critical threshold for the distraction of 1.6 s. In the interviews, on the other hand, only one of the 38 test persons stated that a projection on the road was recognized. For the examined scenario, it is therefore deduced that on-road projections with the selected symbol shape and brightness do not lead to critical distraction.
    Keywords DMD ; on-road projection ; driver assistance system ; eye-tracking ; autonomous driving ; test person study ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
    Subject code 380
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: SCANPY

    F. Alexander Wolf / Philipp Angerer / Fabian J. Theis

    Genome Biology, Vol 19, Iss 1, Pp 1-

    large-scale single-cell gene expression data analysis

    2018  Volume 5

    Abstract: Abstract Scanpy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene ... ...

    Abstract Abstract Scanpy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene regulatory networks. Its Python-based implementation efficiently deals with data sets of more than one million cells (https://github.com/theislab/Scanpy). Along with Scanpy, we present AnnData, a generic class for handling annotated data matrices (https://github.com/theislab/anndata).
    Keywords Single-cell transcriptomics ; Machine learning ; Scalability ; Graph analysis ; Clustering ; Pseudotemporal ordering ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2018-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Evaluation of Active Shoulder Exoskeleton Support to Deduce Application-Oriented Optimization Potentials for Overhead Work

    Johannes Sänger / Zhejun Yao / Tim Schubert / Alexander Wolf / Carla Molz / Jörg Miehling / Sandro Wartzack / Thomas Gwosch / Sven Matthiesen / Robert Weidner

    Applied Sciences, Vol 12, Iss 10805, p

    2022  Volume 10805

    Abstract: Repetitive overhead work with a heavy load increases the risk for work-related shoulder disorders. Occupational exoskeletons supporting arm elevation are potential solutions to reduce that risk by lowering the physical strains on the shoulder. Many ... ...

    Abstract Repetitive overhead work with a heavy load increases the risk for work-related shoulder disorders. Occupational exoskeletons supporting arm elevation are potential solutions to reduce that risk by lowering the physical strains on the shoulder. Many studies have reported a reduction in shoulder stress in various overhead tasks by using such exoskeletons. However, the support demand can vary in each phase of motion as well as in each individual task. This paper presents a laboratory study with five participants to evaluate the influence of the support level of an active shoulder exoskeleton in different motion phases (e.g., arm lifting, screw-in, and arm lowering of two overhead tasks) to identify the potential optimization of support at each phase. Results show that the support level of the exoskeleton should be adapted to the motion phase of the two chosen tasks. A higher support force is desired for the screw phase compared to the arm lifting and lowering phases, and the support level needs to be reduced immediately for arm lowering after the screw phase. The time for switching the support levels can be recognized by the electric current of the screwdriver.
    Keywords human–machine interaction ; biomechanical analysis ; sEMG ; interaction forces ; user experience ; power tool ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
    Subject code 004
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Mind the Gap—Deciphering GPCR Pharmacology Using 3D Pharmacophores and Artificial Intelligence

    Theresa Noonan / Katrin Denzinger / Valerij Talagayev / Yu Chen / Kristina Puls / Clemens Alexander Wolf / Sijie Liu / Trung Ngoc Nguyen / Gerhard Wolber

    Pharmaceuticals, Vol 15, Iss 1304, p

    2022  Volume 1304

    Abstract: G protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant and well-studied protein targets, yet unanswered questions in the field leave significant gaps in our understanding of their nuanced structure and function. Three- ... ...

    Abstract G protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant and well-studied protein targets, yet unanswered questions in the field leave significant gaps in our understanding of their nuanced structure and function. Three-dimensional pharmacophore models are powerful computational tools in in silico drug discovery, presenting myriad opportunities for the integration of GPCR structural biology and cheminformatics. This review highlights success stories in the application of 3D pharmacophore modeling to de novo drug design, the discovery of biased and allosteric ligands, scaffold hopping, QSAR analysis, hit-to-lead optimization, GPCR de-orphanization, mechanistic understanding of GPCR pharmacology and the elucidation of ligand–receptor interactions. Furthermore, advances in the incorporation of dynamics and machine learning are highlighted. The review will analyze challenges in the field of GPCR drug discovery, detailing how 3D pharmacophore modeling can be used to address them. Finally, we will present opportunities afforded by 3D pharmacophore modeling in the advancement of our understanding and targeting of GPCRs.
    Keywords ligand-based pharmacophores ; structure-based pharmacophores ; virtual screening ; drug design ; machine learning ; molecular dynamics ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 612
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Case Report

    Samuel Nunn / Johannes Kersten / Marijana Tadic / Alexander Wolf / Birgid Gonska / Elina Hüll / Hanna Dietenberger / Wolfgang Rottbauer / Dominik Buckert

    Frontiers in Medicine, Vol

    Myocarditis After COVID-19 Vaccination – Case Series and Literature Review

    2022  Volume 9

    Abstract: BackgroundThe ongoing COVID-19 pandemic demands a series of measures and, above all, the vaccination of a substantial proportion of the population. Acute myocarditis is a rare complication of the widely used mRNA-based vaccines.Case PresentationWe ... ...

    Abstract BackgroundThe ongoing COVID-19 pandemic demands a series of measures and, above all, the vaccination of a substantial proportion of the population. Acute myocarditis is a rare complication of the widely used mRNA-based vaccines.Case PresentationWe present a case series of four patients (three men and one woman, 16 to 47 years old) with acute pericarditis/myocarditis 3 to 17 days after mRNA vaccination. They presented with chest pain, fever, and flu-like symptoms. Diagnosis was made based on the synopsis of clinical presentation, elevated levels of troponin T and NT-proBNP, impaired systolic function on echocardiography, and findings in non-invasive tissue characterization by cardiovascular magnetic resonance imaging. Two patients also underwent endomyocardial biopsies. As none of the patients showed signs of cardiogenic shock, they were discharged from ward care only a few days after their initial presentations.ConclusionsOur data are consistent with other case reports of myocarditis early after mRNA vaccination and demonstrate the need for multimodal diagnostics. In view of its rarity and mild course, the risk–benefit ratio of vaccination remains positive compared to potential SARS-CoV-2 infection.
    Keywords SARS-CoV-2 ; myocarditis ; mRNA vaccines ; echocardiography ; cardiovascular magnetic resonance (CMR) ; endomyocardial biopsy (EMB) ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Modeling metal forming of a magnesium alloy using an adapted material model

    Alexander Wolf / Niklas Küsters / Sven Bräunling / Daniel Weck / Kristina Kittner / Maik Gude / Ulrich Prahl / Alexander Brosius

    Engineering Reports, Vol 4, Iss 7-8, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract Modeling sheet metal forming of materials for lightweight construction requires an understanding of their plastic behavior in different loading directions. The presented work focuses on twin‐roll‐casted magnesium alloy AZ31. It is characterized ... ...

    Abstract Abstract Modeling sheet metal forming of materials for lightweight construction requires an understanding of their plastic behavior in different loading directions. The presented work focuses on twin‐roll‐casted magnesium alloy AZ31. It is characterized by unique mechanical properties compared to other magnesium alloys due to the employed twin‐roll‐casting‐process. In general, magnesium alloys with their hexagonal closed‐packed structure possess a complex forming behavior including a deformation‐induced anisotropy evolution. In the context of a fast design approach, an adaptation of the Yield2000‐2d criteria usually used for body‐centered cubic or face‐centered cubic materials is tested. The goal is a simple, versatile material model which parameters are determined just by tensile tests with moderate testing effort. In the investigated model, the yield locus definition is modified by adding a term for the yield exponent evolution during the forming process. The modeling approach is presented and the necessary tests for material data acquisition and evaluation are described. After experimental identification of the model parameters, the material model is applied in a forming simulation. The investigation provides promising results matching well with experimental data. Thus, the application of this model in a fast design step is feasible, offering valuable data like deformed shape, process‐related material properties and induced stresses for further processing.
    Keywords deep drawing ; lightweight design ; plastic behavior ; yield locus evolution ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Electronic computers. Computer science ; QA75.5-76.95
    Subject code 670
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Symptom burden correlates to impairment of diffusion capacity and exercise intolerance in long COVID patients

    Johannes Kersten / Alexander Wolf / Luis Hoyo / Elina Hüll / Marijana Tadic / Stefanie Andreß / Sascha d’Almeida / Dominik Scharnbeck / Eva Roder / Petra Beschoner / Wolfgang Rottbauer / Dominik Buckert

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Abstract After acute infection with the SARS-CoV-2 virus, a considerable number of patients remains symptomatic with pathological changes in various organ systems. This study aimed to relate the physical and mental burden of symptoms of long COVID ... ...

    Abstract Abstract After acute infection with the SARS-CoV-2 virus, a considerable number of patients remains symptomatic with pathological changes in various organ systems. This study aimed to relate the physical and mental burden of symptoms of long COVID patients to the findings of a somatic evaluation. In patients with persistent long COVID symptoms three months after acute infection we assessed physical and mental health status using the SF-36 questionnaire. The cohort was dichotomised by the results (upper two quartiles vs. lower to quartiles) and compared with regard to transthoracic echocardiography, body plethysmography (including diffusion capacity), capillary blood gas analysis and 6-min walk test (6-MWT). From February 22 to September 13, 2021, 463 patients were prospectively examined, of which 367 completed the SF-36 questionnaire. A positive correlation between initial disease severity (need for hospitalization, intensive care medicine) and resulting symptom burden at follow-up could be demonstrated. Patients with impaired subjective physical and mental status were significantly more likely to be women. There was a significant correlation between symptom severity and reduced exercise tolerance in the 6-MWT (495.6 ± 83.7 m vs 549.7 ± 71.6 m, p < 0.001) and diffusion capacity for carbon monoxide (85.6 ± 14.3% of target vs 94.5 ± 14.4, p < 0.001). In long COVID patients, initial disease severity is correlated with symptom burden after at least 3 months of follow-up. Highly symptomatic long COVID patients show impaired diffusion capacity and 6-MWT despite average or mildly affected mechanical lung parameters. It must be further differentiated whether this corresponds to a transient functional impairment or whether it is a matter of defined organ damage.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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