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The manufacturing share of laser powder bed fusion (L-PBF) increases in industrial application, but still many process steps are manually operated. Additionally, it is not possible to achieve tight dimensional tolerances or low surfaces roughness. Hence, a process chain has to be set up to combine additive manufacturing (AM) with further machining technologies. To achieve a continuous workpiece flow as basis for further industrialization of L-PBF, the paper presents a novel substrate system and its application on L-PBF machines and post-processing. The substrate system consists of a zero-point clamping system and a matrix-like interface of contact pins to be substantially connected to the workpiece within the L-PBF process.
"To assess the habitability of the icy environments in the solar system, for example, on Mars, Europa, and Enceladus, the scientific analysis of material embedded in or underneath their ice layers is very important. We consider self-steering robotic ice melting probes to be the best method to cleanly access these environments, that is, in compliance with planetary protection standards. The required technologies are currently developed and tested."
NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.
In this paper we report on CO2 Meter, a do-it-yourself carbon dioxide measuring device for the classroom. Part of the current measures for dealing with the SARS-CoV-2 pandemic is proper ventilation in indoor settings. This is especially important in schools with students coming back to the classroom even with high incidents rates. Static ventilation patterns do not consider the individual situation for a particular class. Influencing factors like the type of activity, the physical structure or the room occupancy are not incorporated. Also, existing devices are rather expensive and often provide only limited information and only locally without any networking. This leaves the potential of analysing the situation across different settings untapped. Carbon dioxide level can be used as an indicator of air quality, in general, and of aerosol load in particular. Since, according to the latest findings, SARS-CoV-2 can be transmitted primarily in the form of aerosols, carbon dioxide may be used as a proxy for the risk of a virus infection. Hence, schools could improve the indoor air quality and potentially reduce the infection risk if they actually had measuring devices available in the classroom. Our device supports schools in ventilation and it allows for collecting data over the Internet to enable a detailed data analysis and model generation. First deployments in schools at different levels were received very positively. A pilot installation with a larger data collection and analysis is underway.
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.