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Objective
Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels.
Methods
152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions.
Results
In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained.
Conclusion
This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.
Algorithmic design and resilience assessment of energy efficient high-rise water supply systems
(2018)
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.
On obligations in the development process of resilient systems with algorithmic design methods
(2018)
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.
Cheap does not imply cost-effective -- this is rule number one of zeitgeisty system design. The initial investment accounts only for a small portion of the lifecycle costs of a technical system. In fluid systems, about ninety percent of the total costs are caused by other factors like power consumption and maintenance. With modern optimization methods, it is already possible to plan an optimal technical system considering multiple objectives. In this paper, we focus on an often neglected contribution to the lifecycle costs: downtime costs due to spontaneous failures. Consequently, availability becomes an issue.
Planning the layout and operation of a technical system is a common task
for an engineer. Typically, the workflow is divided into consecutive stages: First,
the engineer designs the layout of the system, with the help of his experience or of
heuristic methods. Secondly, he finds a control strategy which is often optimized
by simulation. This usually results in a good operating of an unquestioned sys-
tem topology. In contrast, we apply Operations Research (OR) methods to find a
cost-optimal solution for both stages simultaneously via mixed integer program-
ming (MILP). Technical Operations Research (TOR) allows one to find a provable
global optimal solution within the model formulation. However, the modeling error
due to the abstraction of physical reality remains unknown. We address this ubiq-
uitous problem of OR methods by comparing our computational results with mea-
surements in a test rig. For a practical test case we compute a topology and control
strategy via MILP and verify that the objectives are met up to a deviation of 8.7%.
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.
Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
Detecting synchronization clusters in multivariate time series via coarse-graining of Markov chains
(2007)
In this work, we present a compact, bifunctional chip-based sensor setup that measures the temperature and electrical conductivity of water samples, including specimens from rivers and channels, aquaculture, and the Atlantic Ocean. For conductivity measurements, we utilize the impedance amplitude recorded via interdigitated electrode structures at a single triggering frequency. The results are well in line with data obtained using a calibrated reference instrument. The new setup holds for conductivity values spanning almost two orders of magnitude (river versus ocean water) without the need for equivalent circuit modelling. Temperature measurements were performed in four-point geometry with an on-chip platinum RTD (resistance temperature detector) in the temperature range between 2 °C and 40 °C, showing no hysteresis effects between warming and cooling cycles. Although the meander was not shielded against the liquid, the temperature calibration provided equivalent results to low conductive Milli-Q and highly conductive ocean water. The sensor is therefore suitable for inline and online monitoring purposes in recirculating aquaculture systems.