Monte Carlo model for ion mobility and diffusion for characteristic electric fields in nanodosimetry

The quantification of the effects of space radiation for manned spaceflight can be approximated by nanodosimetric measurements. For the development of nanodosimetric detectors, a Monte Carlo model for ion mobility and diffusion for characteristic electric fields is presented. This model can be used to describe the interactions of ions in their parent gas based solely on commonly known input parameters, such as the ionization potential, kinetic diameter, molar mass, and polarizability of the gas. A model for approximating the resonant charge exchange cross section has been proposed, requiring only the ionization energy and mass of the parent gas as input parameters. The method proposed in this work was tested against experimental drift velocity data for a wide range of gases (helium, neon, nitrogen, argon, krypton, carbon monoxide, carbon dioxide, oxygen, propane). The transverse diffusion coefficients were compared to experimental values for helium, nitrogen, neon, argon, and propane gas. With the Monte Carlo code and resonant charge exchange cross section approximation model presented in this work, it is now possible to calculate an estimate of the drift velocities, transverse diffusion, and thus the ion mobility of ions in their parent gas. This is essential for further nanodosimetric detector development, as those parameters are often not well known for the gas mixtures used in nanodosimetry

Shopping Cart System: Load Balancing and Fault Tolerance in the OSGi Service Platform

The main purpose of this paper was to find a simple solution for load balancing and fault tolerance in OSGi. The challenge was to implement a highly available web application such as a shopping cart system with load balancing and fault tolerance, without having to change the core of OSGi

Racial-ethnic, gender identity, and sexual orientation disparities in COVID-19-related social and health outcomes: A decomposition analysis

Despite the growing literature on racial-ethnic disparities during the pandemic, less is known about the explanatory mechanisms of these disparities and inequalities across other axes, such as gender and sexual identities. We studied the levels and sources of racial-ethnic, gender identity, and sexual minority disparities in social (i.e., unmet resource needs) and health (i.e., hospitalization) outcomes among individuals diagnosed with COVID-19, hypothesizing differential age structure, underlying health, and work and living arrangements as contributors to inequalities. Using large-scale administrative data from Chicago and adjusting for covariates, we found substantial racial-ethnic and gender identity disparities in both outcomes, and weak evidence of sexual minority disparities in unmet needs. Subsequent decomposition analyses revealed that living in larger households, having a higher share of non-adult cases, and facing higher burdens of chronic illness, obesity, and unemployment each statistically significantly drove racial-ethnic disparities in unmet needs, but these together explained less than 15% of the disparities. Similarly, about 20% of the Black-White gap in hospitalization resulted from disparities in underlying health and unemployment, whereas a higher proportion of non-adult cases or higher unemployment rates respectively proved the only significant pathways to partially explain transgender individuals’ disadvantages in unmet needs (12%) or hospitalization (6%). These findings highlight the importance of considering multiple dimensions of social differences in studying health disparities, the vulnerabilities of transgender and non-adult communities during the pandemic, and the valid yet quite limited roles of previously suggested sociodemographic factors in accounting for COVID-19-related categorical inequalities

Targeting and tracing of specific DNA sequences with dTALEs in living cells

Epigenetic regulation of gene expression involves, besides DNA and histone modifications, the relative positioning of DNA sequences within the nucleus. To trace specific DNA sequences in living cells, we used programmable sequence-specific DNA binding of designer transcription activator-like effectors (dTALEs). We designed a recombinant dTALE (msTALE) with variable repeat domains to specifically bind a 19-bp target sequence of major satellite DNA. The msTALE was fused with green fluorescent protein (GFP) and stably expressed in mouse embryonic stem cells. Hybridization with a major satellite probe (3D-fluorescent in situ hybridization) and co-staining for known cellular structures confirmed in vivo binding of the GFP-msTALE to major satellite DNA present at nuclear chromocenters. Dual tracing of major satellite DNA and the replication machinery throughout S-phase showed co-localization during mid to late S-phase, directly demonstrating the late replication timing of major satellite DNA. Fluorescence bleaching experiments indicated a relatively stable but still dynamic binding, with mean residence times in the range of minutes. Fluorescently labeled dTALEs open new perspectives to target and trace DNA sequences and to monitor dynamic changes in subnuclear positioning as well as interactions with functional nuclear structures during cell cycle progression and cellular differentiation

Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)

Background: Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation. Methods: 7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naive, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS. Results: Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization. Conclusions: Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity

Understanding beliefs related to physical activity in people living with axial Spondyloarthritis : a theory-informed qualitative study

Background: People living with axial Spondyloarthrtis (axSpA) have an increased risk of cardiovascular diseases, which can be reduced by regular physical activity (PA) and its subset of cardiorespiratory training (CRT). To fulfil their crucial role in PA promotion, physiotherapists and other health professionals need to understand the beliefs that people living with axSpA possess concerning general PA and CRT. The aim of this study is to explore these behavioural, normative and control beliefs. Methods: A qualitative descriptive design approach was chosen. Five semi-structured focus group interviews with 24 individuals living with axSpA were performed. Data was analysed using structured thematic qualitative content analysis. Results: People with axSpA possessed multifaceted behavioural, normative and control beliefs concerning general PA and CRT. Behavioural beliefs revealed a positive attitude towards general PA, with participants mentioning numerous physical, psychological, and social benefits and only few risks. However, the conceptual difference between general PA and CRT, and the relevance of CRT, was unclear to some participants. Normative beliefs were expressed as the beliefs of significant others that influenced their motivation to comply with such beliefs, e.g. spouses, other people living with axSpA, rheumatologists. Regarding control beliefs, general PA and CRT were both mentioned as effective self-management strategies to control the disease. From experience, a high level of self-discipline, as well as technology, were shown to be useful. Conclusions: General PA is understood to be an important self-management strategy for people with axSpA and most participants build general PA into their daily routines. They believe that general PA beneficially impacts personal health and wellbeing. However, some participants are unaware of the difference between general PA and CRT and the important impact that this difference could have on their health. The consequences of CRT promotion for people living with axSpA should be the subject of further research