TY - JOUR A1 - Aboulnaga, E. A. A1 - Zou, H. A1 - Selmer, Thorsten A1 - Xian, M. T1 - Development of a plasmid-based, tunable, tolC-derived expression system for application in Cupriavidus necator H16 JF - Journal of Biotechnology N2 - Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism. As applications of the expression system in C. necator H16, the growth ability on glycerol was enhanced by constitutively expressing the E. coli glpk gene-encoding for glycerol kinase. Likewise, we used the system to overcome the expression toxicity of mevalonate pathway in C. necator H16. With this system, the mevalonate-genes were successfully introduced in the host and the recombinant strains could produce about 200 mg/l mevalonate. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.jbiotec.2018.03.007 SN - 0168-1656 VL - 274 SP - 15 EP - 27 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Albanna, Walid A1 - Kotliar, Konstantin A1 - Lüke, Jan Niklas A1 - Alpdogan, Serdar A1 - Conzen, Catharina A1 - Lindauer, Ute A1 - Clusmann, Hans A1 - Hescheler, Jürgen A1 - Vilser, Walthard A1 - Schneider, Toni A1 - Schubert, Gerrit Alexander T1 - Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis JF - Plos one N2 - Background Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC. Methods A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed. Results A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001). Conclusions To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals. Y1 - 2018 U6 - http://dx.doi.org/10.1371/journal.pone.0204689 VL - 13 IS - 10 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Altherr, Lena A1 - Brötz, Nicolas A1 - Dietrich, Ingo A1 - Gally, Tristan A1 - Geßner, Felix A1 - Kloberdanz, Hermann A1 - Leise, Philipp A1 - Pelz, Peter Franz A1 - Schlemmer, Pia A1 - Schmitt, Andreas T1 - Resilience in mechanical engineering - a concept for controlling uncertainty during design, production and usage phase of load-carrying structures JF - Applied Mechanics and Materials N2 - Resilience as a concept has found its way into different disciplines to describe the ability of an individual or system to withstand and adapt to changes in its environment. In this paper, we provide an overview of the concept in different communities and extend it to the area of mechanical engineering. Furthermore, we present metrics to measure resilience in technical systems and illustrate them by applying them to load-carrying structures. By giving application examples from the Collaborative Research Centre (CRC) 805, we show how the concept of resilience can be used to control uncertainty during different stages of product life. Y1 - 2018 SN - 1662-7482 U6 - http://dx.doi.org/10.4028/www.scientific.net/AMM.885.187 VL - 885 SP - 187 EP - 198 PB - Trans Tech Publications CY - Bäch ER - TY - JOUR A1 - Altherr, Lena A1 - Joggerst, Laura A1 - Leise, Philipp A1 - Pfetsch, Marc E. A1 - Schmitt, Andreas A1 - Wendt, Janine T1 - On obligations in the development process of resilient systems with algorithmic design methods JF - Applied Mechanics and Materials N2 - Advanced computational methods are needed both for the design of large systems and to compute high accuracy solutions. Such methods are efficient in computation, but the validation of results is very complex, and highly skilled auditors are needed to verify them. We investigate legal questions concerning obligations in the development phase, especially for technical systems developed using advanced methods. In particular, we consider methods of resilient and robust optimization. With these techniques, high performance solutions can be found, despite a high variety of input parameters. However, given the novelty of these methods, it is uncertain whether legal obligations are being met. The aim of this paper is to discuss if and how the choice of a specific computational method affects the developer’s product liability. The review of legal obligations in this paper is based on German law and focuses on the requirements that must be met during the design and development process. KW - legal obligations KW - product liability KW - design of technical systems KW - optimization KW - resilience Y1 - 2018 SN - 1662-7482 U6 - http://dx.doi.org/10.4028/www.scientific.net/AMM.885.240 VL - 885 IS - 885 SP - 240 EP - 252 PB - Trans Tech Publications CY - Bäch ER - TY - JOUR A1 - Altherr, Lena A1 - Leise, Philipp A1 - Pfetsch, Marc E. A1 - Schmitt, Andreas T1 - Algorithmic design and resilience assessment of energy efficient high-rise water supply systems JF - Applied Mechanics and Materials N2 - High-rise water supply systems provide water flow and suitable pressure in all levels of tall buildings. To design such state-of-the-art systems, the consideration of energy efficiency and the anticipation of component failures are mandatory. In this paper, we use Mixed-Integer Nonlinear Programming to compute an optimal placement of pipes and pumps, as well as an optimal control strategy.Moreover, we consider the resilience of the system to pump failures. A resilient system is able to fulfill a predefined minimum functionality even though components fail or are restricted in their normal usage. We present models to measure and optimize the resilience. To demonstrate our approach, we design and analyze an optimal resilient decentralized water supply system inspired by a real-life hotel building. KW - MINLP KW - Buffering Capacity KW - Uncertainty KW - Water Supply Networks KW - Booster Stations Y1 - 2018 U6 - http://dx.doi.org/10.4028/www.scientific.net/AMM.885.211 SN - 1662-7482 VL - 885 SP - 211 EP - 223 PB - Trans Tech Publications CY - Bäch ER - TY - JOUR A1 - Balakirski, Galina A1 - Kotliar, Konstantin A1 - Pauly, Karolin J. A1 - Krings, Laura K. A1 - Rübben, Albert A1 - Baron, Jens M. A1 - Schmitt, Laurenz T1 - Surgical Site Infections After Dermatologic Surgery in Immunocompromised Patients: A Single-Center Experience JF - Dermatologic Surgery N2 - BACKGROUND Immunosuppression is often considered as an indication for antibiotic prophylaxis to prevent surgical site infections (SSI) while performing skin surgery. However, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited. PATIENTS AND METHODS All patients of the Department of Dermatology and Allergology at the University Hospital of RWTH Aachen in Aachen, Germany, who underwent hospitalization for a dermatologic surgery between June 2016 and January 2017 (6 months), were followed up after surgery until completion of the wound healing process. The follow-up addressed the occurrence of SSI and the need for systemic antibiotics after the operative procedure. Immunocompromised patients were compared with immunocompetent patients. The investigation was conducted as a retrospective analysis of patient records. RESULTS The authors performed 284 dermatologic surgeries in 177 patients. Nineteen percent (54/284) of the skin surgery was performed on immunocompromised patients. The most common indications for surgical treatment were nonmelanoma skin cancer and malignant melanomas. Surgical site infections occurred in 6.7% (19/284) of the cases. In 95% (18/19), systemic antibiotic treatment was needed. Twenty-one percent of all SSI (4/19) were seen in immunosuppressed patients. CONCLUSION According to the authors' data, immunosuppression does not represent a significant risk factor for SSI after dermatologic surgery. However, larger prospective studies are needed to make specific recommendations on the use of antibiotic prophylaxis while performing skin surgery in these patients. The available data on complications after dermatologic surgery have improved over the past years. Particularly, additional risk factors have been identified for surgical site infections (SSI). Purulent surgical sites, older age, involvement of head, neck, and acral regions, and also the involvement of less experienced surgeons have been reported to increase the risk of the SSI after dermatologic surgeries.1 In general, the incidence of SSI after skin surgery is considered to be low.1,2 However, antibiotics in dermatologic surgeries, especially in the perioperative setting, seem to be overused,3,4 particularly regarding developing antibiotic resistances and side effects. Immunosuppression has been recommended to be taken into consideration as an additional indication for antibiotic prophylaxis to prevent SSI after skin surgery in special cases.5,6 However, these recommendations do not specify the exact dermatologic surgeries, and were not specifically developed for dermatologic surgery patients and treatments, but adopted from other surgical fields.6 According to the survey conducted on American College of Mohs Surgery members in 2012, 13% to 29% of the surgeons administered antibiotic prophylaxis to immunocompromised patients to prevent SSI while performing dermatologic surgery on noninfected skin,3 although this was not recommended by Journal of the American Academy of Dermatology Advisory Statement. Indeed, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited. However, it is possible that due to the insufficient evidence on the risk of SSI occurrence in this patient group, dermatologic surgeons tend to overuse perioperative antibiotic prophylaxis. To make specific recommendations on the use of antibiotic prophylaxis in immunosuppressed patients in the field of skin surgery, more information about the incidence of SSI after dermatologic surgery in these patients is needed. The aim of this study was to fill this data gap by investigating whether there is an increased risk of SSI after skin surgery in immunocompromised patients compared with immunocompetent patients. Y1 - 2018 U6 - http://dx.doi.org/10.1097/DSS.0000000000001615 IS - 44 (12) SP - 1525 EP - 1536 PB - Wolters Kluwer ER - TY - JOUR A1 - Baringhaus, Ludwig A1 - Gaigall, Daniel A1 - Thiele, Jan Philipp T1 - Statistical inference for L²-distances to uniformity JF - Computational Statistics N2 - The paper deals with the asymptotic behaviour of estimators, statistical tests and confidence intervals for L²-distances to uniformity based on the empirical distribution function, the integrated empirical distribution function and the integrated empirical survival function. Approximations of power functions, confidence intervals for the L²-distances and statistical neighbourhood-of-uniformity validation tests are obtained as main applications. The finite sample behaviour of the procedures is illustrated by a simulation study. KW - Integrated empirical distribution (survival) function KW - Goodness-of-fit tests for uniformity KW - Numerical inversion of Laplace transforms KW - Coverage probability KW - Equivalence test Y1 - 2018 U6 - http://dx.doi.org/10.1007/s00180-018-0820-0 SN - 1613-9658 VL - 2018 IS - 33 SP - 1863 EP - 1896 PB - Springer CY - Berlin ER - TY - JOUR A1 - Bernecker, Andreas A1 - Klier, Julia A1 - Stern, Sebastian A1 - Thiel, Lea T1 - Sustaining high performance beyond public-sector pilot projects. Y1 - 2018 IS - September 2018 ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Jabbari, Medisa A1 - Anding, Ralf A1 - Staat, Manfred T1 - Surgical treatment of vaginal vault prolapse using different prosthetic mesh implants: a finite element analysis JF - tm - Technisches Messen N2 - Particularly multiparous elderly women may suffer from vaginal vault prolapse after hysterectomy due to weak support from lax apical ligaments. A decreased amount of estrogen and progesterone in older age is assumed to remodel the collagen thereby reducing tissue stiffness. Sacrocolpopexy is either performed as open or laparoscopic surgery using prosthetic mesh implants to substitute lax ligaments. Y-shaped mesh models (DynaMesh, Gynemesh, and Ultrapro) are implanted in a 3D female pelvic floor finite element model in the extraperitoneal space from the vaginal cuff to the first sacral (S1) bone below promontory. Numerical simulations are conducted during Valsalva maneuver with weakened tissues modeled by reduced tissue stiffness. Tissues are modeled as incompressible, isotropic hyperelastic materials whereas the meshes are modeled either as orthotropic linear elastic or as isotropic hyperlastic materials. The positions of the vaginal cuff and the bladder base are calculated from the pubococcygeal line for female pelvic floor at rest, for prolapse and after repair using the three meshes. Due to mesh mechanics and mesh pore deformation along the loaded direction, the DynaMesh with regular rectangular mesh pores is found to provide better mechanical support to the organs than the Gynemesh and the Ultrapro with irregular hexagonal mesh pores. Insbesondere ältere, mehrgebährende Frauen leiden häufiger an einem Scheidenvorfall nach einer Hysterektomie aufgrund der schwachen Unterstützung durch laxe apikale Bänder. Es wird angenommen, dass eine verringerte Menge an Östrogen und Progesteron im höheren Alter das Kollagen umformt, wodurch die Gewebesteifigkeit reduziert wird. Die Sakrokolpopexie ist eine offene oder laparoskopische Operation, die mit prothetischen Netzimplantaten durchgeführt wird, um laxe Bänder zu ersetzen. Y-förmige Netzmodelle (DynaMesh, Gynemesh und Ultrapro) werden in einem 3D-Modell des weiblichen Beckenbodens im extraperitonealen Raum vom Vaginalstumpf bis zum Promontorium implantiert. Numerische Simulationen werden während des Valsalva-Manövers mit geschwächtem Gewebe durchgeführt, das durch eine reduzierte Gewebesteifigkeit modelliert wird. Die Gewebe werden als inkompressible, isotrop hyperelastische Materialien modelliert, während die Netze entweder als orthotrope linear elastische oder als isotrope hyperlastische Materialien modelliert werden. Die Positionen des Vaginalstumpfs, der Blase und der Harnröhrenachse werden anhand der Pubococcygeallinie aus der Ruhelage, für den Prolaps und nach der Reparatur unter Verwendung der drei Netze berechnet. Aufgrund der Netzmechanik und der Netzporenverformung bietet das DynaMesh mit regelmäßigen rechteckigen Netzporen eine bessere mechanische Unterstützung und eine Neupositionierung des Scheidengewölbes, der Blase und der Urethraachse als Gynemesh und Ultrapro mit unregelmäßigen hexagonalen Netzporen. Y1 - 2018 U6 - http://dx.doi.org/10.1515/teme-2017-0115 SN - 2196-7113 VL - 85 IS - 5 SP - 331 EP - 342 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Staat, Manfred T1 - Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions JF - Computational and Mathematical Methods in Medicine N2 - After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females. Y1 - 2018 U6 - http://dx.doi.org/10.1155/2018/9518076 SN - 1748-6718 VL - 2018 IS - Article ID 9518076 SP - 1 EP - 16 PB - Hindawi CY - New York, NY ER -