Agent-based simulations for protecting nursing homes with prevention and vaccination strategies

Due to its high lethality amongst the elderly, the safety of nursing homes has been of central importance during the COVID-19 pandemic. With test procedures becoming available at scale, such as antigen or RT-LAMP tests, and increasing availability of vaccinations, nursing homes might be able to safely relax prohibitory measures while controlling the spread of infections (meaning an average of one or less secondary infections per index case). Here, we develop a detailed agent-based epidemiological model for the spread of SARS-CoV-2 in nursing homes to identify optimal prevention strategies. The model is microscopically calibrated to high-resolution data from nursing homes in Austria, including detailed social contact networks and information on past outbreaks. We find that the effectiveness of mitigation testing depends critically on the timespan between test and test result, the detection threshold of the viral load for the test to give a positive result, and the screening frequencies of residents and employees. Under realistic conditions and in absence of an effective vaccine, we find that preventive screening of employees only might be sufficient to control outbreaks in nursing homes, provided that turnover times and detection thresholds of the tests are low enough. If vaccines that are moderately effective against infection and transmission are available, control is achieved if 80% or more of the inhabitants are vaccinated, even if no preventive testing is in place and residents are allowed to have visitors. Since these results strongly depend on vaccine efficacy against infection, retention of testing infrastructures, regular voluntary screening and sequencing of virus genomes is advised to enable early identification of new variants of concern.Comment: Supplementary material is included in the manuscript PD

Rare variants in LRRK1 and Parkinson's disease

Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow- up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance

Non-invasive imaging of ferucarbotran labeled INS-1E cells and rodent islets in vitro and in transplanted diabetic rats

Transplantation of pancreatic islets is a promising strategy for restoring insulin secretion in diabetes mellitus. To monitor transplanted islets, a method to evaluate the distribution in a non-invasive manner in vivo is needed. INS-1E, a stable differentiated insulin secreting cell line, and rodent islets were used to monitor cell transplantation by MRI. For labeling INS-1E cells in vitro, increasing concentrations of Resovist in culture medium were tested. For MR imaging in a clinical 3T scanner, we placed a layer of labeled INS-1E cells between two layers of 4% gelatin. Viability assay was performed. Cell function was evaluated by static incubation assay to assess insulin secretion. For in vivo imaging, iron labeled rodent islets were transplanted into the liver of streptozotocin induced diabetic rats and visualized by MRI. Blood sugar values were controlled and liver tissue was removed for histological analysis. SPIO labeled INS-1E cells did not show altered viability or reduced glucose stimulated insulin secretion in vitro. Double staining of labeled and unlabeled INS-1E cells showed no difference in the staining pattern. Labeling of rodent islets with SPIOs does not reduce their secretory activity or alter their viability. We visualized SPIO-labeled INS-1E cells and rat islets in vitro using a clinical 3T scanner. Diabetic rats transplanted with SPIO-labeled islets became normoglycemic. MR imaging successfully verified the distribution of labeled transplanted cells in vivo. Labeling INS-1E cells and rat islets with SPIOs does not alter their viability, while enabling MR imaging of labeled cells in vitro and within the living organism

The thermoelectric properties of Ge/SiGe based superlattices: from materials to energy harvesting modules

We report recent progresses in the characterization of the vertical electrical and thermal properties of multilayered silicon germanium (SiGe) materials for thermoelectric coolers and generators. Superlattice structures p- and n-type doped with different barriers and quantum well thicknesses were grown by Low Energy Plasma Enhanced Chemical Vapor Deposition. The electrical and thermal characterizations were performed using fully integrated metrology structures, microfabricated on the surface of the sample. Heaters, thermometers and electrical contacts were integrated onto the device to allow a simultaneous measurement of the electrical, thermal and Seebeck coefficient for the extraction of the figure of merit ZT. Enhancements in the Seebeck coefficient up to 450 µV/K and the reduction of the thermal conductivity down to 2.2 W/mK are mainly attributed to the low dimensionality of the system. Preliminary tests on microfabricated modules are performed on a non-optimized material and device dimensions as proof of concept for next generation devices

Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors

Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-beta-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug