Exploratory analysis of the role of circulating microRNA in metastatic melanoma patients

MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles and microRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage and evolution. However, the clinical potential of circulating miRNAs in metastatic melanoma remains largely undefined. From May 2020 to September 2022, we conducted a spontaneous, monocentric, exploratory study on human tissues in vitro, which aimed to evaluate the prognostic and predictive role of circulating miRNAs in metastatic melanoma patients. At the Medical Oncology Unit of Policlinico Sant’Orsola-Malpighi of Bologna, peripheral venous blood samples from patients with metastatic melanoma treated with checkpoint inhibitors (CPI) were collected before the start of CPI (baseline, T0) and longitudinally, approximately every 3 months (T1, T2, etc). Circulating miRNA quantification was performed by droplet digital PCR (Biorad) using an EvaGreen and LNA primer-based assays. QuantaSoft Program (Biorad) calculated the absolute quantifications of each miRNA, indicated as copies/µL. After analysis of the literature, we chose to analyze miR-155-5p, miR-320a and miR-424-5p level. All miRNAs except miR-424-5p show a significantly higher level in plasma of patients who are alive after 1 year of follow-up. High/low levels of baseline miR-155-5p, miR-320a and miR-424-5p are significantly associated with overall survival and progression-free survival. Furthermore, a preliminary analysis on the group of patients who received first-line with anti-PD-1 (N=7), baseline miR-155-5p shows higher levels in responder vs. non responder patients (p 0.06). These data, though promising, are preliminary and need to be further investigated in a larger cohort of patients.

Management Perspectives on Industrial Heritage: an Exploratory Research

The current research project focuses on the analysis of the critical issues of industrial heritage management in Italy and the preservation of organizational history within the reuse projects of former industrial sites. The organizational and managerial perspective is crucial on two levels. Firstly, it is important in the analysis of the original significance of the site, and in particular its organizational history, and its conservation within the new regeneration strategy. Secondly, it is crucial at the phase of management of reuse projects and its feasibility and sustainability analysis. Based on the analysis of the literature, a unique classification of the reuse strategies that can be implemented in order to regenerate former industrial sites has been formulated. The exploratory research thus adapts a multiple case study design. Eight Italian case studies have been chosen, one for each type of regeneration strategy. Each case study is explored as a stand-alone entity through the analysis of the local differences and idiosyncrasies of the specific context, the factors that stood behind the choice of the reuse strategy and the way the reuse project evolved through the years. Then, the current management of each reuse project is analysed. The narration and musealization of the organizational history is investigated through the spatial dimension, the level of content and the level of expression. Secondly, the case studies are compared through a cross-case analysis from three different perspectives: issues on the phase of preparation and implementation of the reuse projects, critical issues behind the current management of new projects and issues on the ways of preservation and narration of organizational history within the new project. The research shows that all regeneration strategies are affected by the conflict between preservation and change, by the issue of materiality and selectivity.

Stability issues in racing motorcycles: an in-depth analysis of the chatter vibration

Racing motorcycles are prone to an unstable oscillatory motion of the swingarm and rear wheel, commonly known as ‘chatter’. This vibration mode typically has a frequency of 17 Hz to 22 Hz and typically occurs during heavy braking manoeuvres. The appearance of chatter can cause reduced rider confidence, and therefore lead to longer lap times during races and the increased risk of crashing. This thesis looks to further the understanding of this mode. It includes the development of a simplified model to explore the effects roll angle and lateral dynamics have on the chatter mode using linear analysis. The mechanisms of instability and parameter sensitivities are also examined. The effects of the nonlinearities present in the minimal model equations of motion are examined, including the identification of limit cycles and their stability, inspecting individual nonlinear terms and their effects, and introducing tyre relaxation and determining the effect it has on the dynamics. Finally, an exploratory study of the mid-corner region of a typical racing manoeuvre is performed in hopes to better understand if any high frequency tyre induced instabilities like chatter can occur.