@article{KuchlerGuenthnerRibeiroetal.2023, author = {Kuchler, Timon and G{\"u}nthner, Roman and Ribeiro, Andrea and Hausinger, Renate and Streese, Lukas and W{\"o}hnl, Anna and Kesseler, Veronika and Negele, Johanna and Assali, Tarek and Carbajo-Lozoya, Javier and Lech, Maciej and Adorjan, Kristina and Stubbe, Hans Christian and Hanssen, Henner and Kotliar, Konstantin and Haller, Berhard and Heemann, Uwe and Schmaderer, Christoph}, title = {Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation}, volume = {26}, publisher = {Springer Nature}, address = {Dordrecht}, doi = {10.1007/s10456-023-09885-6}, pages = {547 -- 563}, year = {2023}, abstract = {Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42\% ± 1.77\% vs. 4.64\% ± 2.59\%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5-190.2] vs. 189.1 [179.4-197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8-0.9] vs. 0.88 [0.8-0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = - 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.}, language = {en} } @article{KuertenKotliarFuestetal.2021, author = {Kuerten, David and Kotliar, Konstantin and Fuest, Matthias and Walter, Peter and Hollstein, Muriel and Plange, Niklas}, title = {Does hemispheric vascular regulation differ significantly in glaucoma patients with altitudinal visual field asymmetry? A single-center, prospective study}, series = {International Ophthalmology}, volume = {41}, journal = {International Ophthalmology}, number = {41}, editor = {Neri, Piergiorgio}, publisher = {Springer}, address = {Berlin}, isbn = {1573-2630}, doi = {10.1007/s10792-021-01876-0}, pages = {3109 -- 3119}, year = {2021}, abstract = {Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.}, language = {en} } @article{AlbannaConzenWeissetal.2021, author = {Albanna, Walid and Conzen, Catharina and Weiss, Miriam and Seyfried, Katharina and Kotliar, Konstantin and Schmidt, Tobias Philip and Kuerten, David and Hescheler, J{\"u}rgen and Bruecken, Anne and Schmidt-Trucks{\"a}ss, Arno and Neumaier, Felix and Wiesmann, Martin and Clusmann, Hans and Schubert, Gerrit Alexander}, title = {Non-invasive assessment of neurovascular coupling after aneurysmal subarachnoid hemorrhage: a prospective observational trial using retinal vessel analysis}, series = {Frontiers in Neurology}, volume = {12}, journal = {Frontiers in Neurology}, number = {12}, issn = {1664-2295}, doi = {10.3389/fneur.2021.690183}, pages = {1 -- 15}, year = {2021}, abstract = {Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.}, language = {en} } @article{WerfelGuenthnerHapfelmeieretal.2022, author = {Werfel, Stanislas and G{\"u}nthner, Roman and Hapfelmeier, Alexander and Hanssen, Henner and Kotliar, Konstantin and Heemann, Uwe and Schmaderer, Christoph}, title = {Identification of cardiovascular high-risk groups from dynamic retinal vessel signals using untargeted machine learning}, series = {Cardiovascular Research}, volume = {118}, journal = {Cardiovascular Research}, number = {2}, editor = {Guzik, Tomasz J.}, publisher = {Oxford University Press}, address = {Oxford}, issn = {0008-6363}, doi = {10.1093/cvr/cvab040}, pages = {612 -- 621}, year = {2022}, abstract = {Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.}, language = {en} } @article{MalanHamerKaeneletal.2020, author = {Malan, Leone and Hamer, Mark and K{\"a}nel, Roland von and Kotliar, Konstantin and Wyk, Roelof D. van and Lambert, Gavin W. and Vilser, Walthard and Ziemssen, Tjalf and Schlaich, Markus P. and Smith, Wayne and Magnusson, Martin and Wentzel, Annemarie and Myburgh, Carlien E. and Steyn, Hendrik S. and Malan, Nico T.}, title = {Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study}, series = {Cardiovascular Journal of Africa}, volume = {26}, journal = {Cardiovascular Journal of Africa}, number = {31}, publisher = {Clinics Cardive Publishing}, address = {Durbanville}, issn = {1680-0745}, doi = {10.5830/CVJA-2020-031}, pages = {1 -- 12}, year = {2020}, language = {en} } @article{StreeseKotliarDeiserothetal.2020, author = {Streese, Lukas and Kotliar, Konstantin and Deiseroth, Arne and Infanger, Denis and Gugleta, Konstantin and Schmaderer, Christoph and Hanssen, Henner}, title = {Retinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial}, series = {Scandinavian Journal of Medicine and Science in Sports}, volume = {30}, journal = {Scandinavian Journal of Medicine and Science in Sports}, number = {2}, publisher = {Wiley}, address = {Oxford}, issn = {1600-0838}, doi = {10.1111/sms.13560}, pages = {272 -- 280}, year = {2020}, abstract = {The aim of this study was to investigate, for the first time, the effects of high-intensity interval training (HIIT) on retinal microvascular endothelial function in cardiovascular (CV) risk patients. In the randomized controlled trial, middle-aged and previously sedentary patients with increased CV risk (aged 58 ± 6 years) with ≥ two CV risk factors were randomized into a 12-week HIIT (n = 33) or control group (CG, n = 36) with standard physical activity recommendations. A blinded examiner measured retinal endothelial function by flicker light-induced maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the area under the arteriolar (AFarea) and venular (VFarea) flicker curve using a retinal vessel analyzer. Standardized assessments of CV risk factors, cardiorespiratory fitness, and retinal endothelial function were performed before and after HIIT. HIIT reduced body mass index, fat mass, and low-density lipoprotein and increased muscle mass and peak oxygen uptake (VO2peak). Both ADmax (pre: 2.7 ± 2.1\%, post: 3.0 ± 2.2\%, P = .018) and AFarea (pre: 32.6 ± 28.4\%*s, post: 37.7 ± 30.6\%*s, P = .016) increased after HIIT compared with CG (ADmax, pre: 3.2 ± 1.8\%, post: 2.9 ± 1.8\%, P = .254; AFarea, pre: 41.6 ± 28.5\%*s, post: 37.8 ± 27.0\%*s, P = .186). Venular function remained unchanged after HIIT. There was a significant association between ∆-change VO2peak and ∆-changes ADmax and AFarea (P = .026, R² = 0.073; P = .019, R² = 0.081, respectively). 12-weeks of HIIT improved retinal endothelial function in middle-aged patients with increased CV risk independent of the reduction in classical CV risk factors. Exercise has the potential to reverse or at least postpone progression of small vessel disease in older adults with increased CV risk under standard medication. Dynamic retinal vessel analysis seems to be a sensitive tool to detect treatment effects of exercise interventions on retinal microvascular endothelial function in middle-aged individuals with increased CV risk.}, language = {en} } @article{HamouKotliarTanetal.2020, author = {Hamou, Hussam Aldin and Kotliar, Konstantin and Tan, Sonny Kian and Weiß, Christel and Blume, Christian and Clusmann, Hans and Schubert, Gerrit Alexander and Albanna, Walid}, title = {Surgical nuances and placement of subgaleal drains for supratentorial procedures—a prospective analysis of efficacy and outcome in 150 craniotomies}, series = {Acta Neurochirurgica}, volume = {2020}, journal = {Acta Neurochirurgica}, number = {162}, publisher = {Springer Nature}, address = {Cham}, issn = {0942-0940}, doi = {10.1007/s00701-019-04196-6}, pages = {729 -- 736}, year = {2020}, abstract = {Background For supratentorial craniotomy, surgical access, and closure technique, including placement of subgaleal drains, may vary considerably. The influence of surgical nuances on postoperative complications such as cerebrospinal fluid leakage or impaired wound healing overall remains largely unclear. With this study, we are reporting our experiences and the impact of our clinical routines on outcome in a prospectively collected data set. Method We prospectively observed 150 consecutive patients undergoing supratentorial craniotomy and recorded technical variables (type/length of incision, size of craniotomy, technique of dural and skin closure, type of dressing, and placement of subgaleal drains). Outcome variables (subgaleal hematoma/CSF collection, periorbital edema, impairment of wound healing, infection, and need for operative revision) were recorded at time of discharge and at late follow-up. Results Early subgaleal fluid collection was observed in 36.7\% (2.8\% at the late follow-up), and impaired wound healing was recorded in 3.3\% of all cases, with an overall need for operative revision of 6.7\%. Neither usage of dural sealants, lack of watertight dural closure, and presence of subgaleal drains, nor type of skin closure or dressing influenced outcome. Curved incisions, larger craniotomy, and tumor size, however, were associated with an increase in early CSF or hematoma collection (p < 0.0001, p = 0.001, p < 0.01 resp.), and larger craniotomy size was associated with longer persistence of subgaleal fluid collections (p < 0.05). Conclusions Based on our setting, individual surgical nuances such as the type of dural closure and the use of subgaleal drains resulted in a comparable complication rate and outcome. Subgaleal fluid collections were frequently observed after supratentorial procedures, irrespective of the closing technique employed, and resolve spontaneously in the majority of cases without significant sequelae. Our results are limited due to the observational nature in our single-center study and need to be validated by supportive prospective randomized design.}, language = {en} } @article{RamoshabaHuismanLammertynetal.2020, author = {Ramoshaba, Nthai E. and Huisman, Hugo W. and Lammertyn, Leandi and Kotliar, Konstantin and Schutte, Aletta E. and Smith, Wayne}, title = {Retinal microvasculature and masked hypertension in young adults: the African-PREDICT study}, series = {Hypertension Research}, journal = {Hypertension Research}, number = {43}, publisher = {Springer Nature}, address = {Osaka}, issn = {1348-4214}, doi = {10.1038/s41440-020-0487-0}, pages = {1231 -- 1238}, year = {2020}, abstract = {Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20-30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R² = 0.267, β = -0.097 (95\% CI = -0.165; -0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95\% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life.}, language = {en} } @article{NeumaierKotliarHaerenetal.2021, author = {Neumaier, Felix and Kotliar, Konstantin and Haeren, Roel Hubert Louis and Temel, Yasin and L{\"u}ke, Jan Niklas and Seyam, Osama and Lindauer, Ute and Clusmann, Hans and Hescheler, J{\"u}rgen and Schubert, Gerrit Alexander and Schneider, Toni and Albanna, Walid}, title = {Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca v 2.3-Deficient Mice—An in- vivo Evaluation Using Retinal Vessel Analysis (RVA)}, series = {Frontiers in Neurology}, volume = {12}, journal = {Frontiers in Neurology}, publisher = {Frontiers}, doi = {10.3389/fneur.2021.659890}, pages = {1 -- 11}, year = {2021}, language = {en} } @article{MuschallikMolinnusBongaertsetal.2017, author = {Muschallik, Lukas and Molinnus, Denise and Bongaerts, Johannes and Pohl, Martina and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Siegert, Petra and Selmer, Thorsten}, title = {(R,R)-Butane-2,3-diol Dehydrogenase from Bacillus clausii DSM 8716T: Cloning and Expression of the bdhA-Gene, and Initial Characterization of Enzyme}, series = {Journal of Biotechnology}, volume = {258}, journal = {Journal of Biotechnology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-1656}, doi = {10.1016/j.jbiotec.2017.07.020}, pages = {41 -- 50}, year = {2017}, abstract = {The gene encoding a putative (R,R)-butane-2,3-diol dehydrogenase (bdhA) from Bacillus clausii DSM 8716T was isolated, sequenced and expressed in Escherichia coli. The amino acid sequence of the encoded protein is only distantly related to previously studied enzymes (identity 33-43\%) and exhibited some uncharted peculiarities. An N-terminally StrepII-tagged enzyme variant was purified and initially characterized. The isolated enzyme catalyzed the (R)-specific oxidation of (R,R)- and meso-butane-2,3-diol to (R)- and (S)-acetoin with specific activities of 12 U/mg and 23 U/mg, respectively. Likewise, racemic acetoin was reduced with a specific activity of up to 115 U/mg yielding a mixture of (R,R)- and meso-butane-2,3-diol, while the enzyme reduced butane-2,3-dione (Vmax 74 U/mg) solely to (R,R)-butane-2,3-diol via (R)-acetoin. For these reactions only activity with the co-substrates NADH/NAD+ was observed. The enzyme accepted a selection of vicinal diketones, α-hydroxy ketones and vicinal diols as alternative substrates. Although the physiological function of the enzyme in B. clausii remains elusive, the data presented herein clearly demonstrates that the encoded enzyme is a genuine (R,R)-butane-2,3-diol dehydrogenase with potential for applications in biocatalysis and sensor development.}, language = {en} } @article{GeierLehnertzBialonski2015, author = {Geier, Christian and Lehnertz, Klaus and Bialonski, Stephan}, title = {Time-dependent degree-degree correlations in epileptic brain networks: from assortative to dissortative mixing}, series = {Frontiers in Human Neuroscience}, journal = {Frontiers in Human Neuroscience}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1662-5161}, doi = {10.3389/fnhum.2015.00462}, year = {2015}, language = {en} } @article{UysalCreutzFiratetal.2022, author = {Uysal, Karya and Creutz, Till and Firat, Ipek Seda and Artmann, Gerhard and Teusch, Nicole and Temiz Artmann, Ayseg{\"u}l}, title = {Bio-functionalized ultra-thin, large-area and waterproof silicone membranes for biomechanical cellular loading and compliance experiments}, series = {Polymers}, volume = {14}, journal = {Polymers}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2073-4360}, pages = {2213}, year = {2022}, abstract = {Biocompatibility, flexibility and durability make polydimethylsiloxane (PDMS) membranes top candidates in biomedical applications. CellDrum technology uses large area, <10 µm thin membranes as mechanical stress sensors of thin cell layers. For this to be successful, the properties (thickness, temperature, dust, wrinkles, etc.) must be precisely controlled. The following parameters of membrane fabrication by means of the Floating-on-Water (FoW) method were investigated: (1) PDMS volume, (2) ambient temperature, (3) membrane deflection and (4) membrane mechanical compliance. Significant differences were found between all PDMS volumes and thicknesses tested (p < 0.01). They also differed from the calculated values. At room temperatures between 22 and 26 °C, significant differences in average thickness values were found, as well as a continuous decrease in thicknesses within a 4 °C temperature elevation. No correlation was found between the membrane thickness groups (between 3-4 µm) in terms of deflection and compliance. We successfully present a fabrication method for thin bio-functionalized membranes in conjunction with a four-step quality management system. The results highlight the importance of tight regulation of production parameters through quality control. The use of membranes described here could also become the basis for material testing on thin, viscous layers such as polymers, dyes and adhesives, which goes far beyond biological applications.}, language = {en} } @article{TemizArtmannKurulgandemirciFıratetal.2021, author = {Temiz Artmann, Ayseg{\"u}l and Kurulgan demirci, Eylem and F{\i}rat, Ipek Seda and Oflaz, Hakan and Artmann, Gerhard}, title = {Recombinant activated protein C (rhAPC) affects lipopolysaccharide-induced mechanical compliance changes and beat frequency of mESC-derived cardiomyocyte monolayers}, series = {SHOCK}, journal = {SHOCK}, publisher = {Wolters Kluwer}, address = {K{\"o}ln}, issn = {1540-0514}, doi = {10.1097/SHK.0000000000001845}, year = {2021}, language = {en} } @article{BialonskiCaronSchloenetal.2016, author = {Bialonski, Stephan and Caron, David A. and Schloen, Julia and Feudel, Ulrike and Kantz, Holger and Moorthi, Stefanie D.}, title = {Phytoplankton dynamics in the Southern California Bight indicate a complex mixture of transport and biology}, series = {Journal of Plankton Research}, volume = {38}, journal = {Journal of Plankton Research}, number = {4}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1464-3774}, doi = {10.1093/plankt/fbv122}, pages = {1077 -- 1091}, year = {2016}, abstract = {The stimulation and dominance of potentially harmful phytoplankton taxa at a given locale and time are determined by local environmental conditions as well as by transport to or from neighboring regions. The present study investigated the occurrence of common harmful algal bloom (HAB) taxa within the Southern California Bight, using cross-correlation functions to determine potential dependencies between HAB taxa and environmental factors, and potential links to algal transport via local hydrography and currents. A simulation study, in which Lagrangian particles were released, was used to assess travel times due to advection by prevailing ocean currents in the bight. Our results indicate that transport of some taxa may be an important mechanism for the expansion of their distributions into other regions, which was supported by mean travel times derived from our simulation study and other literature on ocean currents in the Southern California Bight. In other cases, however, phytoplankton dynamics were rather linked to local environmental conditions, including coastal upwelling events. Overall, our study shows that complex current patterns in the Southern California Bight may contribute significantly to the formation and expansion of HABs in addition to local environmental factors determining the spatiotemporal dynamics of phytoplankton blooms.}, language = {en} } @article{Gaigall2023, author = {Gaigall, Daniel}, title = {Allocating and forecasting changes in risk}, series = {Journal of risk}, volume = {25}, journal = {Journal of risk}, number = {3}, editor = {AitSahlia, Farid}, publisher = {Infopro Digital Risk}, address = {London}, issn = {1755-2842}, doi = {10.21314/JOR.2022.048}, pages = {1 -- 24}, year = {2023}, abstract = {We consider time-dependent portfolios and discuss the allocation of changes in the risk of a portfolio to changes in the portfolio's components. For this purpose we adopt established allocation principles. We also use our approach to obtain forecasts for changes in the risk of the portfolio's components. To put the approach into practice we present an implementation based on the output of a simulation. Allocation is illustrated with an example portfolio in the context of Solvency II. The quality of the forecasts is investigated with an empirical study.}, language = {en} } @article{Gaigall2023, author = {Gaigall, Daniel}, title = {On the applicability of several tests to models with not identically distributed random effects}, series = {Statistics : A Journal of Theoretical and Applied Statistics}, volume = {57}, journal = {Statistics : A Journal of Theoretical and Applied Statistics}, publisher = {Taylor \& Francis}, address = {London}, isbn = {0323-3944}, issn = {1029-4910}, doi = {10.1080/02331888.2023.2193748}, pages = {14 Seiten}, year = {2023}, abstract = {We consider Kolmogorov-Smirnov and Cram{\´e}r-von-Mises type tests for testing central symmetry, exchangeability, and independence. In the standard case, the tests are intended for the application to independent and identically distributed data with unknown distribution. The tests are available for multivariate data and bootstrap procedures are suitable to obtain critical values. We discuss the applicability of the tests to random effects models, where the random effects are independent but not necessarily identically distributed and with possibly unknown distributions. Theoretical results show the adequacy of the tests in this situation. The quality of the tests in models with random effects is investigated by simulations. Empirical results obtained confirm the theoretical findings. A real data example illustrates the application.}, language = {en} } @article{GaigallGerstenberg2023, author = {Gaigall, Daniel and Gerstenberg, Julian}, title = {Cram{\´e}r-von-Mises tests for the distribution of the excess over a confidence level}, series = {Journal of Nonparametric Statistics}, journal = {Journal of Nonparametric Statistics}, publisher = {Taylor \& Francis}, issn = {1048-5252 (Print)}, doi = {10.1080/10485252.2023.2173958}, year = {2023}, abstract = {The Cram{\´e}r-von-Mises distance is applied to the distribution of the excess over a confidence level. Asymptotics of related statistics are investigated, and it is seen that the obtained limit distributions differ from the classical ones. For that reason, quantiles of the new limit distributions are given and new bootstrap techniques for approximation purposes are introduced and justified. The results motivate new one-sample goodness-of-fit tests for the distribution of the excess over a confidence level and a new confidence interval for the related fitting error. Simulation studies investigate size and power of the tests as well as coverage probabilities of the confidence interval in the finite sample case. A practice-oriented application of the Cram{\´e}r-von-Mises tests is the determination of an appropriate confidence level for the fitting approach. The adoption of the idea to the well-known problem of threshold detection in the context of peaks over threshold modelling is sketched and illustrated by data examples.}, language = {en} } @article{LiphardtFernandezGonzaloAlbrachtetal.2023, author = {Liphardt, Anna-Maria and Fernandez-Gonzalo, Rodrigo and Albracht, Kirsten and Rittweger, J{\"o}rn and Vico, Laurence}, title = {Musculoskeletal research in human space flight - unmet needs for the success of crewed deep space exploration}, series = {npj Microgravity}, volume = {9}, journal = {npj Microgravity}, number = {Article number: 9}, publisher = {Springer Nature}, issn = {2373-8065}, doi = {10.1038/s41526-023-00258-3}, pages = {1 -- 9}, year = {2023}, abstract = {Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper "Human Physiology - Musculoskeletal system", this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback.}, language = {en} } @article{BayerTemizArtmannDigeletal.2020, author = {Bayer, Robin and Temiz Artmann, Ayseg{\"u}l and Digel, Ilya and Falkenstein, Julia and Artmann, Gerhard and Creutz, Till and Hescheler, J{\"u}rgen}, title = {Mechano-pharmacological testing of L-Type Ca²⁺ channel modulators via human vascular celldrum model}, series = {Cellular Physiology and Biochemistry}, volume = {54}, journal = {Cellular Physiology and Biochemistry}, publisher = {Cell Physiol Biochem Press}, address = {D{\"u}sseldorf}, issn = {1421-9778}, doi = {10.33594/000000225}, pages = {371 -- 383}, year = {2020}, abstract = {Background/Aims: This study aimed to establish a precise and well-defined working model, assessing pharmaceutical effects on vascular smooth muscle cell monolayer in-vitro. It describes various analysis techniques to determine the most suitable to measure the biomechanical impact of vasoactive agents by using CellDrum technology. Methods: The so-called CellDrum technology was applied to analyse the biomechanical properties of confluent human aorta muscle cells (haSMC) in monolayer. The cell generated tensions deviations in the range of a few N/m² are evaluated by the CellDrum technology. This study focuses on the dilative and contractive effects of L-type Ca²⁺ channel agonists and antagonists, respectively. We analyzed the effects of Bay K8644, nifedipine and verapamil. Three different measurement modes were developed and applied to determine the most appropriate analysis technique for the study purpose. These three operation modes are called, particular time mode" (PTM), "long term mode" (LTM) and "real-time mode" (RTM). Results: It was possible to quantify the biomechanical response of haSMCs to the addition of vasoactive agents using CellDrum technology. Due to the supplementation of 100nM Bay K8644, the tension increased approximately 10.6\% from initial tension maximum, whereas, the treatment with nifedipine and verapamil caused a significant decrease in cellular tension: 10nM nifedipine decreased the biomechanical stress around 6,5\% and 50nM verapamil by 2,8\%, compared to the initial tension maximum. Additionally, all tested measurement modes provide similar results while focusing on different analysis parameters. Conclusion: The CellDrum technology allows highly sensitive biomechanical stress measurements of cultured haSMC monolayers. The mechanical stress responses evoked by the application of vasoactive calcium channel modulators were quantified functionally (N/m²). All tested operation modes resulted in equal findings, whereas each mode features operation-related data analysis.}, language = {en} } @article{DigelTemizArtmannNishikawaetal.2004, author = {Digel, Ilya and Temiz Artmann, Ayseg{\"u}l and Nishikawa, K. and Artmann, Gerhard}, title = {Cluster air-ion effects on bacteria and moulds}, series = {Biomedizinische Technik. 49 (2004), H. Erg.-Bd. 2}, journal = {Biomedizinische Technik. 49 (2004), H. Erg.-Bd. 2}, isbn = {0932-4666}, pages = {1040 -- 1041}, year = {2004}, language = {en} }