Back to the drawing board : architecture, sculpture, and the digital image

Wissenschaftliches Kolloquium vom 19. bis 22. April 2007 in Weimar an der Bauhaus-Universität zum Thema: ‚Die Realität des Imaginären. Architektur und das digitale Bild

Are inhaled mRNA vaccines safe and effective? A review of preclinical studies

Introduction: Injected mRNA vaccines have been proven effective and safe in the SARS-CoV-2 pandemic. Using the machinery of the cell, mRNA vaccines translate into an antigen, which triggers an adaptive immune response. The effectiveness of intramuscular administered mRNA vaccines wanes in the months post-vaccination, which makes frequent booster administrations necessary. To make booster administration easier and increase efficacy, pulmonary administration could be investigated. The aim of this literature study was therefore to review the published preclinical (animal) studies on the safety and efficacy of pulmonary administered mRNA vaccines. Areas covered: We first provide background information on mRNA vaccines and immunological mechanisms of vaccination. Thereafter, we provide an evaluation of published animal studies, in which mRNA vaccines (or mRNA containing nanoparticles) were delivered into the lungs. We covered the following areas: biodistribution, cellular uptake, immune response, protection, and safety. All relevant papers were found using PubMed/MEDLINE database. Expert opinion: In our opinion, head-to-head comparison studies examining the safety and efficacy of intramuscular injected and pulmonary administered liquid mRNA vaccines should be performed first. When pulmonary delivered mRNA vaccines are shown to be effective and safe, inhalable dry powder formulations should be engineered. Finally, the tolerability of patients with respiratory diseases should be considered

Carotid Baroreflex Control of Heart Rate is Enhanced during Whole-body Heat Stress

Whole-body heat stress (WBH) reduces orthostatic tolerance. While impaired carotid baroreflex (CBR) function during WBH has been reported, study design considerations may limit interpretation of previous findings. We sought to test the hypothesis that CBR function is unaltered during WBH. CBR function was assessed in ten subjects using 5-sec trials of neck pressure (45, 30 and 15 Torr) and neck suction (-20, -40, -60 and - 80 Torr) during normothermia (NT) and passive WBH (Δ core temp ~1 °C). Analysis of stimulus response curves (4-parameter logistic model) for CBR control of heart rate (CBR-HR) and mean arterial pressure (CBR-MAP), as well as separate 2-way ANOVA of the hypo- and hypertensive stimuli (factor 1: thermal condition, factor 2: chamber pressure) were performed. For CBR-HR, maximal gain was increased during WBH (-0.73±0.37) compared to NT (-0.39±0.11, p=0.03). In addition, the CBR-HR responding range was increased during WBH (32±15) compared to NT (18±8 bpm, p=0.03). Separate analysis of hypertensive stimulation revealed enhanced HR responses during WBH at -40, -60 and -80 Torr (condition*chamber pressure interaction, p=0.049) compared to NT. For CBR-MAP, both logistic analysis and separate 2-way ANOVA revealed no differences during WBH. Therefore, despite marked orthostatic intolerance observed during WBH, CBR control of heart rate (enhanced) and arterial pressure (no change) is well-preserved

Influence of solute doping on the high-temperature deformation behavior of GaAs

The role of isovalent dopants in the high‐temperature deformation of GaAs has been studied in the temperature range 500–1150 °C. Additions of In, Sb, and B increase the critical resolved shear stress for deformation at a given strain rate and result in lowering the dislocation density of as‐grown liquid‐encapsulated Czochralski GaAs crystals. Phosphorus, because of its minor influence on the lattice strain, shows little enhancement of the yield stress. These results are consistent with a solute hardening model, in which the solute atom surrounded tetrahedrally by four Ga or As atoms comprise the hardening cluster. Codoping with In and Si hardens GaAs, but codoping with Si is less effective than the isovalent solutes In, Sb, and B, and produces softening at high temperatures. The effect of solutes on both dislocation nucleation and multiplication are reviewed here

A model for the induction of chromosome aberrations through direct and bystander mechanisms

A state vector model (SVM) for chromosome aberrations and neoplastic transformation has been adapted to describe detrimental bystander effects. The model describes initiation (formation of translocations) and promotion (clonal expansion and loss of contact inhibition of initiated cells). Additional terms either in the initiation model or in the rate of clonal expansion of initiated cells, describe detrimental bystander effects for chromosome aberrations as reported in the scientific literature. In the present study, the SVM with bystander effects is tested on a suitable dataset. In addition to the simulation of non-linear effects, a classical dataset for neoplastic transformation in C3H 10T1/2 cells after alpha particle irradiation is used to show that the model without bystander features can also describe LNT-like dose responses. A published model for bystander induced neoplastic transformation was adapted for chromosome aberration induction and used to compare the results obtained with the different models

Silencing Heat Shock Protein 47 (HSP47) in Fibrogenic Precision-Cut Lung Slices:A Surprising Lack of Effects on Fibrogenesis?

Idiopathic pulmonary fibrosis (IPF) is a chronic disease that is characterized by the excessive deposition of scar tissue in the lungs. As currently available treatments are unable to restore lung function in patients, there is an urgent medical need for more effective drugs. Developing such drugs, however, is challenging because IPF has a complex pathogenesis. Emerging evidence indicates that heat shock protein 47 (HSP47), which is encoded by the gene Serpinh1, may be a suitable therapeutic target as it is required for collagen synthesis. Pharmacological inhibition or knockdown of HSP47 could therefore be a promising approach to treat fibrosis. The objective of this study was to assess the therapeutic potential of Serpinh1-targeting small interfering RNA (siRNA) in fibrogenic precision-cut lung slices prepared from murine tissue. To enhance fibrogenesis, slices were cultured for up to 144 h with transforming growth factor β1. Self-deliverable siRNA was used to knockdown mRNA and protein expression, without affecting the viability and morphology of slices. After silencing HSP47, only the secretion of fibronectin was reduced while other aspects of fibrogenesis remained unaffected (e.g., myofibroblast differentiation as well as collagen secretion and deposition). These observations are surprising as others have shown that Serpinh1-targeting siRNA suppressed collagen deposition in animals. Further studies are therefore warranted to elucidate downstream effects on fibrosis upon silencing HSP47