A coherent approach to Spacetime Foam

A coherent superposition of N Schwarzschild wormholes is proposed as a model for spacetime foam. Following the subtraction procedure for manifolds with boundaries, we calculate by variational methods the Casimir energy. A proposal for an alternative foamy model formed by N Schwarzschild-Anti-de Sitter wormholes is here considered. Finally, a conjecture about the foam evolution is proposed.Comment: 3 pages. To be submitted to the proceedings of the 3rd Workshop of `Mysteries, Puzzles And Paradoxes In Quantum Mechanics' Gargnano (Italy), 17-23 September 200

Detection of genetic prognostic markers in uveal melanoma biopsies using fluorescence in situ hybridization

PURPOSE: In uveal melanoma, specific chromosomal abnormalities are known to correlate with the risk of metastases; changes in chromosomes 3 and 8q correlate strongly with a decreased survival of the patient, whereas chromosome 6 abnormalities are associated with a better prognosis. Usual

High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages

Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fc gamma receptor (Fc gamma R) Ila and FeyRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.Proteomic

Enhanced induction of SV40 replication from transformed mammalian cells by fusion with UV-irradiated untransformed cells

DNA-damaging agents such as ultraviolet (UV) light are known to cause stimulation of virus replication in SV40-transformed hamster and human cells. The dose-response curves of UV-induced SV40 replication in transformed hamster cells resemble that obtained for UV-enhanced reactivation (ER) and UV-enhanced mutagenesis (EM) of SV40 or herpes viruses in mammalian cells. We have investigated whether UV-enhanced production of SV40 from transformed hamster (THK) and human (NB-E) cells belongs to the same category of conditional responses as ER and EM. To answer this question we have made use of the phenomenon that fusion of the SV40-transformed cells with monkey cells that are permissive to SV40 results in a considerable increase in the production of SV40 virus. When THK or NB-E cells were fused with UV-irradiated CV-1 cells at various times after irradiation, induction of SV40 was further increased with UV-irradiated CV-1 cells at various times after irradiation, induction of SV40 was further increased and reached a maximum value of 2-3 fold when fusion was delayed for 24-48 h after irradiation. The kinetics of enhanced SV40 induction resembled that of ER and EM, suggesting that teh UV-stimulated part of the induction represents one of the pleiotropic responses that are transiently induced in mammalian cells by DNA-damaging agents. Evidence is presented, showing that this transient effect can be induced only in cells that are permissive to SV40 replication. This suggests that the enhanced induction observed after fusion with irradiated monkey cells may be attributed to a transient increase in the activity of 'permissiveness' factors. No enhanced induction was found when the THK or NB-E cells were fused with irradiated rodent cells, that are not or only slightly permissive to SV40 replication. © 1985.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Primary nasal epithelium exposed to house dust mite extract shows activated expression in allergic individuals

Nasal epithelial cells form the outermost protective layer against environmental factors. However, this defense is not just physical; it has been shown that epithelial cells respond by the production of inflammatory mediators that may affect local immune responses. In this research we set out to characterize potential differences between the responses of nasal epithelium from healthy and allergic individuals to house dust mite (HDM) allergen. These differences will help us to define local mechanisms that could contribute to allergic disease expression. Epithelial cells were cultured from nasal biopsies taken from five healthy and five allergic individuals. These cultures were exposed for 24 hours to culture medium containing HDM allergen, or to culture medium alone. Isolated RNA was used for microarray analysis. Gene-ontology of the response in healthy epithelium revealed mainly up-regulation of chemokines, growth factors, and structural proteins. Moreover, we saw increased expression of two transcription factors (NF-{kappa}B and AP-1) and their regulatory members. The expression pattern of epithelium from allergic individuals in the absence of the HDM stimulus suggests that it is already in an activated state. Most striking is that, while the already activated NF-{kappa}B regulatory pathway remained unchanged in allergic epithelium, the AP-1 pathway is down-regulated upon exposure to HDM allergen; this is contrary to what we see in healthy epithelium. Clear differences in the expression pattern exist between epithelial cells isolated from healthy and allergic individuals at baseline and between their responses to allergen exposure; these differences may contribute to the inflammatory response