Bayesian Learning for a Class of Priors with Prescribed Marginals

We present Bayesian updating of an imprecise probability measure, represented by a class of precise multidimensional probability measures. Choice and analysis of our class are motivated by expert interviews that we conducted with modelers in the context of climatic change. From the interviews we deduce that generically, experts hold a much more informed opinion on the marginals of uncertain parameters rather than on their correlations. Accordingly, we specify the class by prescribing precise measures for the marginals while letting the correlation structure subject to complete ignorance. For sake of transparency, our discussion focuses on the tutorial example of a linear two-dimensional Gaussian model. We operationalize Bayesian learning for that class by various updating rules, starting with (a modified version of) the generalized Bayes' rule and the maximum likelihood update rule (after Gilboa and Schmeidler). Over a large range of potential observations, the generalized Bayes' rule would provide non-informative results. We restrict this counter-intuitive and unnecessary growth of uncertainty by two means, the discussion of which refers to any kind of imprecise model, not only to our class. First, we find our class of priors too inclusive and, hence, require certain additional properties of prior measures in terms of smoothness of probability density functions. Second, we argue that both updating rules are dissatisfying, the generalized Bayes' rule being too conservative, i.e., too inclusive, the maximum likelihood rule being too exclusive. Instead, we introduce two new ways of Bayesian updating of imprecise probabilities: a ``weighted maximum likelihood method'' and a ``semi-classical method.'' The former bases Bayesian updating on the whole set of priors, however, with weighted influence of its members. By referring to the whole set, the weighted maximum likelihood method allows for more robust inferences than the standard maximum likelihood method and, hence, is better to justify than the latter.Furthermore, the semi-classical method is more objective than the weighted maximum likelihood method as it does not require the subjective definition of a weighting function. Both new methods reveal much more informative results than the generalized Bayes' rule, what we demonstrate for the example of a stylized insurance model

CCS-Bonds as a superior instrument to incentivize secure carbon sequestration

Geological sequestration of CO2 on a massive scale implies that large area fractions of the underground could become flooded by CO2, imposing a unprecedented regulatory challenge to environmental authorities. Therefore we propose carbon sequestration bonds as complementary, market-based instruments that should further help to manage the risk of decadal-scale CO2 leakage. Such bond schemes address market failures that could occur if the investment behavior of operators under uncertainty differed from society’s preference. For a stylized setup we demonstrate that our bond system has the potential to simultaneously address regulatory challenges stemming from information asymmetries and diverging orders of preference

Airborne observations of newly formed boundary layer aerosol particles under cloudy conditions

This study describes the appearance of ultrafine boundary layer aerosol particles under classical "non-favourable" conditions at the research site of TROPOS (Leibniz Institute for Tropospheric Research). Airborne measurements of meteorological and aerosol properties of the atmospheric boundary layer (ABL) were repeatedly performed with the unmanned aerial system ALADINA (Application of Light-weight Aircraft for Detecting IN-situ Aerosol) during three seasons between October 2013 and July 2015. More than 100 measurement flights were conducted on 23 different days with a total flight duration of 53h. In 26% of the cases, maxima of ultrafine particles were observed close to the inversion layer at altitudes between 400 and 600m and the particles were rapidly mixed vertically and mainly transported downwards during short time intervals of cloud gaps. This study focuses on two measurement days affected by low-level stratocumulus clouds, but different wind directions (NE, SW) and minimal concentrations (<4.6µgm−3) of SO2, as a common indicator for precursor gases at ground. Taken from vertical profiles, the onset of clouds led to a non-linearity of humidity that resulted in an increased turbulence at the local-scale and caused fast nucleation e.g., but in relation to rapid dilution of surrounding air, seen in sporadic clusters of ground data, so that ultrafine particles disappeared in the verticality. The typical "banana shape" of new particle formation (NPF) and growth was not seen at ground and thus these days might not have been classified as NPF event days by pure surface studies

Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3'-Deoxy-3'-[18^{18}F]Fluorothymidine in Preclinical Models of Lung Cancer

3'-Deoxy-3'-[$^{18}$F]fluorothymidine positron emission tomography ([$^{18}$F]FLT-PET) and diffusion-weighted MRI (DW-MRI) are promising approaches to monitor tumor therapy response. Here, we employed these two imaging modalities to evaluate the response of lung carcinoma xenografts in mice after gemcitabine therapy. Caliper measurements revealed that H1975 xenografts responded to gemcitabine treatment, whereas A549 growth was not affected. In both tumor models, uptake of [$^{18}$F]FLT was significantly reduced 6 hours after drug administration. On the basis of the gemcitabine concentration and [$^{18}$F]FLT excretion measured, this was presumably related to a direct competition of gemcitabine with the radiotracer for cellular uptake. On day 1 after therapy, [$^{18}$F]FLT uptake was increased in both models, which was correlated with thymidine kinase 1 (TK1) expression. Two and 3 days after drug administration, [$^{18}$F]FLT uptake as well as TK1 and Ki67 expression were unchanged. A reduction in [$^{18}$F]FLT in the responsive H1975 xenografts could only be noted on day 5 of therapy. Changes in ADC$_{mean}$ in A549 xenografts 1 or 2 days after gemcitabine did not seem to be of therapy-related biological relevance as they were not related to cell death (assessed by caspase-3 IHC and cellular density) or tumor therapy response. Taken together, in these models, early changes of [$^{18}$F]FLT uptake in tumors reflected mechanisms, such as competing gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected growth-inhibitory effects at a later time point. Hence, the time point for [$^{18}$F]FLT-PET imaging of tumor response to gemcitabine is of crucial importance.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under grant agreement number 115151, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. This work was also supported by the Deutsche Forschungsgemeinschaft (DFG), Cells-in-Motion Cluster of Excellence (EXC1003 – CiM), University of Munster (Münster, Germany)

Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3'-Deoxy-3'-[18^{18}F]Fluorothymidine in Preclinical Models of Lung Cancer

3'-Deoxy-3'-[$^{18}$F]fluorothymidine positron emission tomography ([$^{18}$F]FLT-PET) and diffusion-weighted MRI (DW-MRI) are promising approaches to monitor tumor therapy response. Here, we employed these two imaging modalities to evaluate the response of lung carcinoma xenografts in mice after gemcitabine therapy. Caliper measurements revealed that H1975 xenografts responded to gemcitabine treatment, whereas A549 growth was not affected. In both tumor models, uptake of [$^{18}$F]FLT was significantly reduced 6 hours after drug administration. On the basis of the gemcitabine concentration and [$^{18}$F]FLT excretion measured, this was presumably related to a direct competition of gemcitabine with the radiotracer for cellular uptake. On day 1 after therapy, [$^{18}$F]FLT uptake was increased in both models, which was correlated with thymidine kinase 1 (TK1) expression. Two and 3 days after drug administration, [$^{18}$F]FLT uptake as well as TK1 and Ki67 expression were unchanged. A reduction in [$^{18}$F]FLT in the responsive H1975 xenografts could only be noted on day 5 of therapy. Changes in ADC$_{mean}$ in A549 xenografts 1 or 2 days after gemcitabine did not seem to be of therapy-related biological relevance as they were not related to cell death (assessed by caspase-3 IHC and cellular density) or tumor therapy response. Taken together, in these models, early changes of [$^{18}$F]FLT uptake in tumors reflected mechanisms, such as competing gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected growth-inhibitory effects at a later time point. Hence, the time point for [$^{18}$F]FLT-PET imaging of tumor response to gemcitabine is of crucial importance.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under grant agreement number 115151, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. This work was also supported by the Deutsche Forschungsgemeinschaft (DFG), Cells-in-Motion Cluster of Excellence (EXC1003 – CiM), University of Munster (Münster, Germany)

Дизайн-проект ортопедического стула-опоры для детей с ограниченными возможностями

Разработка дизайна ортопедического стула-опоры для реабилитации и обучению правильному сидению детей с нарушением функции мышц шеи, спины, нижних конечностей. Объектом исследования является ортопедический стул-опора. Целью работы является дизайн-проектирование ортопедического стула-опоры для детей с ограниченными возможностями. В результате исследования был разработан дизайн ортопедического стула-опоры. Созданы 3D модель и макет объекта.Development of the design of an orthopedic chair-support for rehabilitation and training in proper seating of children with impaired function of the muscles of the neck, back, lower limbs. The object of the study is an orthopedic chair-support. The aim of the work is to design an orthopedic chair-support for children with disabilities. As a result of the study, the design of an orthopedic chair-support was developed. 3D model and the layout of the object were created

COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus - and R. arrhizus -induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients

Projections of global warming-induced impacts on winter storm losses in the German private household sector

We present projections of winter storm-induced insured losses in the German residential building sector for the 21st century. With this aim, two structurally most independent downscaling methods and one hybrid downscaling method are applied to a 3-member ensemble of ECHAM5/MPI-OM1 A1B scenario simulations. One method uses dynamical downscaling of intense winter storm events in the global model, and a transfer function to relate regional wind speeds to losses. The second method is based on a reshuffling of present day weather situations and sequences taking into account the change of their frequencies according to the linear temperature trends of the global runs. The third method uses statistical-dynamical downscaling, considering frequency changes of the occurrence of storm-prone weather patterns, and translation into loss by using empirical statistical distributions. The A1B scenario ensemble was downscaled by all three methods until 2070, and by the (statistical-) dynamical methods until 2100. Furthermore, all methods assume a constant statistical relationship between meteorology and insured losses and no developments other than climate change, such as in constructions or claims management. The study utilizes data provided by the German Insurance Association encompassing 24 years and with district-scale resolution. Compared to 1971–2000, the downscaling methods indicate an increase of 10-year return values (i.e. loss ratios per return period) of 6–35 % for 2011–2040, of 20–30 % for 2041–2070, and of 40–55 % for 2071–2100, respectively. Convolving various sources of uncertainty in one confidence statement (data-, loss model-, storm realization-, and Pareto fit-uncertainty), the return-level confidence interval for a return period of 15 years expands by more than a factor of two. Finally, we suggest how practitioners can deal with alternative scenarios or possible natural excursions of observed losses