Maturation signatures of conventional dendritic cell subtypes in COVID‐19 suggest direct viral sensing

Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, which negatively affects T-cell activation. The presence of effector T cells in patients with mild disease and dysfunctional T cells in severely ill patients suggests that adequate T-cell responses limit disease severity. Understanding how cDCs cope with SARS-CoV-2 can help elucidate how protective immune responses are generated. Here, we report that cDC2 subtypes exhibit similar infection-induced gene signatures, with the upregulation of interferon-stimulated genes and interleukin (IL)-6 signaling pathways. Furthermore, comparison of cDCs between patients with severe and mild disease showed severely ill patients to exhibit profound downregulation of genes encoding molecules involved in antigen presentation, such as MHCII, TAP, and costimulatory proteins, whereas we observed the opposite for proinflammatory molecules, such as complement and coagulation factors. Thus, as disease severity increases, cDC2s exhibit enhanced inflammatory properties and lose antigen presentation capacity. Moreover, DC3s showed upregulation of anti-apoptotic genes and accumulated during infection. Direct exposure of cDC2s to the virus in vitro recapitulated the activation profile observed in vivo. Our findings suggest that SARS-CoV-2 interacts directly with cDC2s and implements an efficient immune escape mechanism that correlates with disease severity by downregulating crucial molecules required for T-cell activation

Explorative data analysis from multiparametric monitoring at the Acuto Field Laboratory (Central Italy) for detecting preparatory conditions to rock block instabilities

This study summarises the research activity carried out in the Acuto Field Laboratory (FR, Italy), where experiments testing the stability of a subvertical rock wall in limestone are ongoing within an abandoned quarry, now devoted to studies focused on the mitigation of geological risks. The research focuses on the natural factors that can prepare a subvertical rock mass to evolve through subsequent rock fall if predisposing conditions are verified. A network of multiparameter monitoring sensors is installed on three different sectors of the rock wall to record both the natural and anthropogenic stressors and the effects of deformation induced by them. In terms of stressors, the multiparametric monitoring system is able to detect the environmental parameters, such as temperature, rainfall, wind, strain, and vibrations. In terms of induced effects on the rock mass, the multiparametric monitoring system is suitable to detect deformation, displacement, and microseismicity. In this paper, the different monitored parameters are presented along with detailed analyses to highlight cause to effect relationships, such as freezing and thawing, to retrieve correlations among different factors. The obtained results represent the first analysis of the data recorded in the three instrumented sectors of the field laboratory and allowed evaluating the role of preparatory factors in inducing rock falls, opening further perspective on numerical modelling or machine learning applications based on monitoring dat

Pediatric T-cell acute lymphoblastic leukemia

The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T-cell ALL (T-ALL) comprises 10–15% of cases. T-ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes, such as differentiation, self-renewal capacity, proliferation, and apoptosis, are targeted and deranged by several types of neoplasia-associated genetic alteration, for example, translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription. Epigenetically, T-ALL is characterized by gene expression changes caused by hypermethylation of tumor suppressor genes, histone modifications, and miRNA and lncRNA abnormalities. Although some genetic and gene expression patterns have been associated with certain clinical features, such as immunophenotypic subtype and outcome, none has of yet generally been implemented in clinical routine for treatment decisions. The recent advent of massive parallel sequencing technologies has dramatically increased our knowledge of the genetic blueprint of T-ALL, revealing numerous fusion genes as well as novel gene mutations. The challenges now are to integrate all genetic and epigenetic data into a coherent understanding of the pathogenesis of T-ALL and to translate the wealth of information gained in the last few years into clinical use in the form of improved risk stratification and targeted therapies. Here, we provide an overview of pediatric T-ALL with an emphasis on the acquired genetic alterations that result in this disease

Three random variable transformations giving Heisenberg-type uncertainty relations

Though intrinsically probabilistic, the 1927 quantum mechanics Heisenberg uncertainty relation is still non-existent as a native Kolmogorov probability construct. This paper fills the gap via three random variable transformations that generate Heisenberg-type uncertainty relations on Kolmogorov probability space without resorting to any quantum mechanics notion or formalism. A sufficient condition is given under which a class of Heisenberg uncertainty relations on is a bounded distributive lattice. Some applications in progress of the above results are anticipated

Three random variable transformations giving Heisenberg-type uncertainty relations

Though intrinsically probabilistic, the 1927 quantum mechanics Heisenberg uncertainty relation is still non-existent as a native Kolmogorov probability construct. This paper fills the gap via three random variable transformations that generate Heisenberg-type uncertainty relations on Kolmogorov probability space ([Omega],[Sigma],[mu]) without resorting to any quantum mechanics notion or formalism. A sufficient condition is given under which a class of Heisenberg uncertainty relations on ([Omega],[Sigma],[mu]) is a bounded distributive lattice. Some applications in progress of the above results are anticipated.Heisenberg uncertainty relation Kolmogorov probability Distributive lattice Boolean algebra Cramer-Rao inequality