Holomorphic functional calculus in non-Archimedean geometry

The purpose of this thesis is to provide a complete proof of the holomorphic functional calculus theorem for unital commutative Banach algebras over a non-Archimedean field $K$, as introduced by V. G. Berkovich in the book "Spectral Theory and Analytic Geometry over Non-Archimedean Fields". Omitting some further properties that are proven, it says that there is a way to extend any bounded homomorphism $\phi\colon A\to D$ from a $K$-affinoid algebra $A$ to a unital commutative Banach $K$-algebra $D$ to a homomorphism \theta_\phi\colon \Gamma(\Sigma_\phi,O_{M(A)})\to \D, where $\Gamma(\Sigma_\phi,O_{M(A)})$ is the $K$-algebra of $K$-affinoid functions on the spectrum of $\phi$.

Preclinical Models to study the Biology and Therapy of Ovarian Cancer

Ovarian cancer (OC) is one of the most common gynaecological malignancies and a cause of mortality among western women. Standard-of-care treatment consists of platinum/taxane-based chemotherapy, but 5-years survival rate remains low. Germline and somatic mutations in BRCA are present in half of the high grade serous (HGS) ovarian cancer. Olaparib, a PARP inhibitor affecting DNA damage repair pathway, has been approved in the treatment of germline-BRCA-mutated patients. The combination with cediranib, an angiogenesis inhibitor, has shown promising results, increasing progression-free survival in women with recurrent HGS ovarian cancer. In this thesis, patient-derived ovarian cancer xenografts (OC-PDX) were used to study olaparib therapy and mechanisms underlying the observed benefit of the combination. Next Generation Sequencing and gene expression analysis were performed on OC-PDX to identify mutations/aberrations in BRCA1/2 and other genes connected to the DNA repair pathway. A cohort (n=13) of OC-PDX was selected and classified as BRCAness and Not BRCAness, accordingly to their proficiency or deficiency in DNA damage repair. Olaparib and cediranib were administered in short-term (4 weeks) or maintenance (until progression) regimens. Olaparib showed activity in BRCAness OC-PDX; the effect was improved by cediranib, inducing durable responses even after treatment suspension. Of note, the combination was also beneficial in Not BRCAness OC-PDX, promoting stable disease and regression. The effect of the combination on changes in tumor-associated vasculature and hypoxia (likely due to cediranib) and DNA damage repair (due to olaparib), together with preliminary data on gene expression and mutational status, suggested a potential “cumulative” effect of the combination after 4 weeks of treatment. Studies are ongoing, to understand the molecular determinants that accompany the response of OC-PDX to the combination. The results obtained compel us to believe that the combination of olaparib with cediranib is advantageous both in DNA repair proficient and, most importantly, in deficient patients, and has to be administered until tumor progression

One who shares, wins

There has recently been an increase in the number of open access journals showcasing the results of research, free of charge, in an affordable and easy to access online publication. In fact, it's a paradigm shift in publishing, and it has gained so much momentum and has become so favored institutionally that perhaps we can say that the one who shares, wins. We do wish to acknowledge the good that open access has achieved through journal readership, but we also want to mention here some of the problems and challenges brought about by these changes. These are issues we think authors should be aware of before submitting to open access journals

New Perspectives in Liver Transplantation: From Regeneration to Bioengineering

Advanced liver diseases have very high morbidity and mortality due to associated complications, and liver transplantation represents the only current therapeutic option. However, due to worldwide donor shortages, new alternative approaches are mandatory for such patients. Regenerative medicine could be the more appropriate answer to this need. Advances in knowledge of physiology of liver regeneration, stem cells, and 3D scaffolds for tissue engineering have accelerated the race towards efficient therapies for liver failure. In this review, we propose an update on liver regeneration, cell-based regenerative medicine and bioengineering alternatives to liver transplantation

Effects of business recovery strategies on seismic risk and cost-effectiveness of structural retrofitting for business enterprises

Recent earthquakes in Italy have significantly affected productive activities, particularly in business interruption (BI) and, consequently, heavy losses for companies, highlighting the need for appropriate seismic risk assessment and management. To estimate seismic risk accurately, both direct (repair/ replacement) and indirect (BI) losses must be quantified. Companies\u2019 balance sheets can be used to estimate BI losses, which, however, are very sensitive to business recovery strategies (BRSs) devised by corporate managers after the seismic event. The aim of this study is to evaluate the effects of BRSs on seismic risk estimates and consequently on structural retrofitting cost-effectiveness. A loss model (including direct and indirect costs and BRS effects) was defined, based on a real-life case study (a biomedical packaging company that was damaged by the 2012 Italian earthquake but recovered soon after) and was used in parametric risk analyses assessing several types of company vulnerabilities and seismic hazards. In areas with low-to-moderate seismicity, seismic retrofitting of existing reinforced concrete factories may be justified or otherwise, depending on whether BRSs are considered or not

Cytogenetic analysis of the holocentric chromosomes of the aphid Schizaphis graminum

Chromatin organization in the holocentric chromosomes of the aphid Schizaphis graminum has been investigated at a cytological level after C-banding, NOR, Giemsa, DAPI and CMA(3) staining. C-banding technique showed the presence of numerous C bands on the two X chromosomes both in telomeric and intercalary regions, whereas autosomes show a small number of heterochromatic bands. Contrary to the results with other aphid species, in S. graminum the C-banding pattern is peculiar to each chromosome pair, thus allowing the identification of homologues and the reliable reconstruction of a karyotype. These cytogenetic data could be useful for the identification of chromosomal rearrangement eventually occurred between different S. graminum biotypes. Moreover, silver staining and fluorescent in situ hybridization (FISH) with a 28S rDNA probe localized rDNA genes on one telomere of each X chromosome; these are the only brightly fluorescent C-positive regions revealed after CMA(3) staining, whereas all other heterochromatic bands are DAPI positive