Upregulation of Anti-Oxidative Stress Response Improves Metabolic Changes in L-Selectin-Deficient Mice but Does Not Prevent NAFLD Progression or Fecal Microbiota Shifts

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem. NAFLD progression involves a complex interplay of imbalanced inflammatory cell populations and inflammatory signals such as reactive oxygen species and cytokines. These signals can derive from the liver itself but also from adipose tissue or be mediated via changes in the gut microbiome. We analyzed the effects of a simultaneous migration blockade caused by L-selectin-deficiency and an enhancement of the anti-oxidative stress response triggered by hepatocytic Kelch-like ECH-associated protein 1 (Keap1) deletion on NAFLD progression. (2) Methods: L-selectin-deficient mice (Lsel^−/−Keap1^flx/flx) and littermates with selective hepatic Keap1 deletion (Lsel^−/−Keap1^Δhepa) were compared in a 24-week Western-style diet (WD) model. (3) Results: Lsel^−/−Keap1^Δhepa mice exhibited increased expression of erythroid 2-related factor 2 (Nrf2) target genes in the liver, decreased body weight, reduced epidydimal white adipose tissue with decreased immune cell frequencies, and improved glucose response when compared to their Lsel^−/−Keap1^flx/flx littermates. Although WD feeding caused drastic changes in fecal microbiota profiles with decreased microbial diversity, no genotype-dependent shifts were observed. (4) Conclusions: Upregulation of the anti-oxidative stress response improves metabolic changes in L-selectin-deficient mice but does not prevent NAFLD progression and shifts in the gut microbiota.     

Experimentelle und analytische Untersuchung des out‐of‐plane‐Verhaltens von unbewehrten Mauerwerkswänden unter Erdbebenbelastung

Experimental and analytical investigation of the seismic out‐of‐plane behavior of unreinforced masonry walls In addition to the vertical and horizontal load‐bearing in‐plane, masonry must also withstand out‐of‐plane loads that occur in earthquake scenarios. The out‐of‐plane behavior of unreinforced masonry walls depends on a variety of parameters and is very complex due to the strong non‐linearity. Current design methods in German codes and various international codes have not been explicitly developed for out‐of‐plane behavior and contain considerable conservatism. In the present work, shaking‐table experiments with heat‐insulating masonry walls have been conducted to investigate the out‐of‐plane behavior of vertical spanning unreinforced masonry walls. As shown in previous numerical investigations, important parameters are neglected in existing design and analysis models and the out‐of‐plane capacity is underestimated significantly. In the conducted experiments the results of these numerical investigations are verified. Furthermore, the development of an analytical design model to determine the force‐displacement relationship and the out‐of‐plane load‐bearing capacity considering all significant parameters is presented.     

Evaluation of the pore morphology formation of the Freeze Foaming process by in situ computed tomography

The so-called Freeze Foaming method aims at manufacturing ceramic cellular scaffolds for diverse applications. One application is dedicated to potential bone replacement material featuring open, micro and interconnected porosity. However, the main challenges of this foaming method is to achieve a homogeneous pore morphology. In a current project, the authors throw light on the bubble/pore and strut formation of this process by in situ computed tomography. This allows for evaluating varying process parameter’s effects on the growth of the ceramic foam during the foaming process. As first result and basis for CT analysis, a stable and reproducible model suspension was developed which resulted in reproducible foam structures. In dependence of selected process parameters like pressure reduction rate or air content in the ceramic suspension resulting Freeze Foams became adjustable with regard to their pore morphology. Pore size and distribution data as well as the porosity were characterized and evaluated accordingly.     

Fatigue strength of fillet‐welded joints at subzero temperatures

Ships and offshore structures may be operated in areas with seasonal freezing temperatures and extreme environmental conditions. While current standards state that attention should be given to the validity of fatigue design curves at subzero temperatures, studies on fatigue strength of structural steel at subzero temperatures are scarce. This study addresses the issue by analysing the fatigue strength of welded steel joints under subzero temperatures. Although critical weld details in large welded structures are mostly fillet‐welded joints, most published data are based on fatigue crack growth rate specimens cut out of butt‐welded joints. This study analyses fillet‐welded specimens at ?20°C and ?50°C against controls at room temperature. Significantly higher fatigue strength was measured in comparison to estimates based on international standards and data from design codes even at temperatures far below the allowed service temperature based on fracture toughness results.     

A model-based approach to associate complexity and robustness in engineering systems

Ever increasing functionality and complexity of products and systems challenge development companies in achieving high and consistent quality. A model-based approach is used to investigate the relationship between system complexity and system robustness. The measure for complexity is based on the degree of functional coupling and the level of contradiction in the couplings. Whilst Suh’s independence axiom states that functional independence (uncoupled designs) produces more robust designs, this study proves this not to be the case for max-/min-is-best requirements, and only to be true in the general sense for nominal-is-best requirements. In specific cases, the independence axiom has exceptions as illustrated with a machining example, showing how a coupled solution is more robust than its uncoupled counterpart. This study also shows with statistical significance, that for max- and min-is-best requirements, the robustness is most affected by the level of contradiction between coupled functional requirements (p = 1.4e?36). In practice, the results imply that if the main influencing factors for each function in a system are known in the concept phase, an evaluation of the contradiction level can be used to evaluate concept robustness.     

Fast 3D imaging of giant unilamellar vesicles using reflected light-sheet microscopy with single molecule sensitivity

Observation of highly dynamic processes inside living cells at the single molecule level is key for a better understanding of biological systems. However, imaging of single molecules in living cells is usually limited by the spatial and temporal resolution, photobleaching and the signal-to-background ratio. To overcome these limitations, light-sheet microscopes with thin selective plane illumination, for example, in a reflected geometry with a high numerical aperture imaging objective, have been developed. Here, we developed a reflected light-sheet microscope with active optics for fast, high contrast, two-colour acquisition of -stacks. We demonstrate fast volume scanning by imaging a two-colour giant unilamellar vesicle (GUV) hemisphere. In addition, the high contrast enabled the imaging and tracking of single lipids in the GUV cap. The enhanced reflected scanning light-sheet microscope enables fast 3D scanning of artificial membrane systems and potentially live cells with single-molecule sensitivity and thereby could provide quantitative and molecular insight into the operation of cells.     

Improving the clinical potential of ultra-high field fMRI using a model-free analysis method based on response consistency

Objective

To develop an analysis method that is sensitive to non-model-conform responses often encountered in ultra-high field presurgical planning fMRI. Using the consistency of time courses over a number of experiment repetitions, it should exclude low quality runs and generate activation maps that reflect the reliability of responses.

Materials and methods

7 T fMRI data were acquired from six healthy volunteers: three performing purely motor tasks and three a visuomotor task. These were analysed with the proposed approach (UNBIASED) and the GLM.

Results

UNBIASED results were generally less affected by false positive results than the GLM. Runs that were identified as being of low quality were confirmed to contain little or no activation. In two cases, regions were identified as activated in UNBIASED but not GLM results. Signal changes in these areas were time-locked to the task, but were delayed or transient.

Conclusion

UNBIASED is shown to be a reliable means of identifying consistent task-related signal changes regardless of response timing. In presurgical planning, UNBIASED could be used to rapidly generate reliable maps of the consistency with which eloquent brain regions are activated without recourse to task timing and despite modified hemodynamics.

     

The traveling heads: multicenter brain imaging at 7 Tesla

Objective

This study evaluates the inter-site and intra-site reproducibility of 7 Tesla brain imaging and compares it to literature values for other field strengths.

Materials and methods

The same two subjects were imaged at eight different 7 T sites. MP2RAGE, TSE, TOF, SWI, EPI as well as B1 and B0 field maps were analyzed quantitatively to assess inter-site reproducibility. Intra-site reproducibility was measured with rescans at three sites.

Results

Quantitative measures of MP2RAGE scans showed high agreement. Inter-site and intra-site reproducibility errors were comparable to 1.5 and 3 T. Other sequences also showed high reproducibility between the sites, but differences were also revealed. The different RF coils used were the main source for systematic differences between the sites.

Conclusion

Our results show for the first time that multi-center brain imaging studies of the supratentorial brain can be performed at 7 T with high reproducibility and similar reliability as at 3T. This study develops the basis for future large-scale 7 T multi-site studies.