Cell Host-Microbe Interactions: Turning Pathogen Mechanisms Into Cell's Advantages

Host-Pathogen Interaction is a very vast field of biological sciences, indeed every year many un- known pathogens are uncovered leading to an exponential growth of this field. The present work lyes between its boundaries, touching different aspects of host-pathogen interaction: We have evaluate the permissiveness of Mesenchimal Stem cell (FM-MSC from now on) to all known human affecting herpesvirus. Our study demonstrate that FM-MSC are full permissive to HSV1, HSV2, HCMV and VZV. On the other hand HHV6, HHV7, EBV and HHV8 are susceptible, but failed to activate a lytic infection program. FM-MSC are pluripotent stem cell and have been studied intensely in last decade. FM-MSC are employed in some clinical applications. For this reason it is important to known the degree of susceptibility to transmittable pathogens. Our atten- tion has then moved to bacterial pathogens: we have performed a proteome-wide in silico analy- sis of Chlamydiaceae family, searching for putative Nuclear localization Signal (NLS). Chlamy- diaceae are a family of obligate intracellular parasites. It’s reasonably to think that its members could delivered to nucleus effector proteins via NLS sequences: if that were the case the identifi- cation of NLS carrying proteins could open the way to therapeutic approaches. Our results strengthen this hypothesis: we have identified 72 protein bearing NLS, and verified their func- tionality with in vivo assays. Finally we have conceived a molecular scissor, creating a fusion protein between HIV-1 IN protein and FokI catalytic domain (a deoxyexonuclease domain). Our aim is to obtain chimeric enzyme (trojIN) which selectively identify IN naturally occurring target (HIV LTR sites) and cleaves subsequently LTR carrying DNA (for example integrated HIV1 DNA). Our preliminary results are promising since we have identified trojIN mutated version capable to selectively recognize LTR carrying DNA in an in vitro experiments.

Leonardo Ricci in the United States (1952-1972). A twenty-year American transfer as a turning experience in teaching and design.

The research solved the historiographic lacuna about Leonardo Ricci’s work in the United States focusing on the span 1952-1972 as a fundamental period for the architect's research, which moved from the project for the community space to macrostructures. The considered period is comprised between Ricci’s first travel to the United States and the date of his resignation from the University of Florida, one year before his resignation from the deanship of the faculty of architecture of Florence (1973). The research retraced philologically the stages of Ricci’s activity in the U.S.A. unveiling the premises and results of his American transfer, and to what extent it marked a turning period for his work as educator and designer and for the wider historiographic contest of the Sixties. The American transfer helped him grounding his belief in avoiding a priori morphological results in favor of what he called the “form-act” design method. Ricci’s research in the U.S.A. is described in his books Anonymous (XX century) and City of the Earth (unpublished). In them and in Ricci’s projects one common thread is traceable: the application of the “form-act” as the best tool to conceive urban design, a discipline established in the United States during Ricci’s first stay at M.I.T., in which he encountered the balance point between architecture and urban planning, between the architect’s sign and his being anonymous, between the collective and the individual dimension. With the notions of “anonymous architecture” and “form-act”, Urban Design and “open work” are the key words to understand Ricci’s work in the United States and in Italy. Urban design’s main goal to design the city as a collective work of art was the solution of that dychothomous research that enlivened Ricci’s work and one possible answer to that tension useful for him to seek the truth of architecture.

High-strength steels manufactured via Laser Powder Bed Fusion: effect of post-process heat treatments and surface finishing on microstructure and mechanical properties

Laser Powder Bed Fusion (LPBF) permits the manufacturing of parts with optimized geometry, enabling lightweight design of mechanical components in aerospace and automotive and the production of tools with conformal cooling channels. In order to produce parts with high strength-to-weight ratio, high-strength steels are required. To date, the most diffused high-strength steels for LPBF are hot-work tool steels, maraging and precipitation-hardening stainless steels, featuring different composition, feasibility and properties. Moreover, LPBF parts usually require a proper heat treatment and surface finishing, to develop the desired properties and reduce the high roughness resulting from LPBF. The present PhD thesis investigates the effect of different heat treatments and surface finishing on the microstructure and mechanical properties of a hot-work tool steel and a precipitation-hardening stainless steel manufactured via LPBF. The bibliographic section focuses on the main aspects of LPBF, hot-work tool steels and precipitation-hardening stainless steels. The experimental section is divided in two parts. Part A addresses the effect of different heat treatments and surface finishing on the microstructure, hardness, tensile and fatigue behaviour of a LPBF manufactured hot-work tool steel, to evaluate its feasibility for automotive and racing components. Results indicated the possibility to achieve high hardness and strength, comparable to the conventionally produced steel, but a great sensitivity of fatigue strength on defects and surface roughness resulting from LPBF. Part B investigates the effect of different heat treatments on the microstructure, hardness, tensile and notch-impact behaviour of a LPBF produced precipitation-hardening stainless steel, to assess its feasibility for tooling applications. Results indicated the possibility to achieve high hardness and strength also through a simple Direct Aging, enabling heat treatment simplification by exploiting the microstructural features resulting from LPBF.