A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement

BOVINE STAPHYLOCOCCUS AUREUS MASTITIS: FROM THE MAMMARY IMMUNE RESPONSE TO THE BACTERIA VIRULENCE GENES

Staphylococcus aureus (S. aureus) is one of the most important bacteria in veterinary medicine. In dairy herds, it is a contagious bacterium responsible mainly for subclinical mastitis in cattle, which frequently gives rise to persistent and chronic infection. Mastitis cause considerable economic losses due to i) decreased milk production, (ii) reduced milk quality, and (iii) treatment costs. Mastitis is also a public health problem. Indeed, the strains isolated from infected glands could produce enterotoxins. Three factors interact in mastitis: the host, the pathogen and the environment. This thesis focuses on two main aspects: the host immune response and the virulence factor of S. aureus. The first chapter of the thesis focused on the development of a new mammary gland model to study the innate immune response bacterial infection. The mammary gland is a complex organ, and the immune response is a consequence of the different cell population interactions. Continuous or primary epithelial cell lines have been extensively used to study the mammary gland immune response, but they are composed of a single cell population. Previous studies explored the tissues of lactating cows, unconsidering the possibility of an already triggered immune response. To investigate the innate immune response of the bovine mammary gland, we used an explant of healthy heifer gland. This model allowed us to: i) exclude previous exposure of the udder to microorganisms, which might have damaged the cells and/or triggered an immune response, and ii) consider the interaction of the challenging microorganism with the tissue cell populations. Our aim was to test whether this innovative model might be a valid model to investigate the innate immune response to infection. The study was carried out on 2 mm3-sections of heifer udders, in 2 consecutive trials, using LPS or LTA in the first trial and two different concentrations of S. aureus in the second. Treated and untreated sections were collected after 1h, 3h and 6h incubation; in the first trial, a final time-point at 18h was considered. The mRNA expression of TNF\u3b1, IL-1\u3b2, IL-6, IL-8 and LAP was analyzed by quantitative real-time PCR. Histological examination showed well-preserved morphology of the tissue, and apoptosis only showed a slight, not significant increase throughout the experiment. IL-1\u3b2 and IL-6 were significantly up-regulated, in response to LPS or S. aureus, while TNF-\u3b1 and IL-8 significantly increased only under LPS treatment. LAP expression showed a significant late increase when stimulated by LPS. The immunochemical staining of the sections demonstrated a higher number of T lymphocytes within the alveolar epithelium, in comparison with interstitial localization. Since the explants belonged to pubertal non-pregnant heifers, T cells may be regarded as resident cells, suggesting their participation in the regulation of mammary homeostasis. Therefore, applying our model would give new insights in the investigation of udder pathophysiology. The second chapter of the thesis focused on S. aureus in bovine intrammary infections. Previous literature on the S. aureus-intrammamary suggested that infection might be related to a combination of S. aureus virulence factors beyond host factors. The present study considered 169 isolates from different Italian dairy herds that were classified into four groups based on the prevalence of S. aureus infection at the first testing: low prevalence ( 40 %; HP). We aimed to correlate the presence of virulence genes with the herd prevalence of intramammary infections in order to develop new strategies for the control of S. aureus mastitis. Microarray data were statistically evaluated using binary logistic regression and correspondence analysis to screen the risk factors and the relationship between prevalence group and gene. The analysis showed: (1) 24 genes at significant risk of being detected in all the herds with infection prevalence >5%, including genes belonging to microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), immune evasion and serine proteases; and (2) a significant correlation coefficient between the genes interacting with the host immune response and HP isolates against LP ones. These results support the hypothesis that virulence factors, in addition to cow management, could be related to strain contagiousness, offering new insights into vaccine development

Practical Approach to the Diagnosis of the Vulvo-Vaginal Stromal Tumors: An Overview

Background: The category of the "stromal tumors of the lower female genital tract" encompasses a wide spectrum of lesions with variable heterogeneity, which can be nosologically classified on the basis of their morphologic and immunohistochemical profiles as deep (aggressive) angiomyxoma (DAM), cellular angiofibroma (CAF), angiomyofibroblastoma (AMFB) or myofibroblastoma (MFB). Despite the differential diagnosis between these entities being usually straightforward, their increasingly recognized unusual morphological variants, along with the overlapping morphological and immunohistochemical features among these tumours, may raise serious differential diagnostic problems. Methods and Results: The data presented in the present paper have been retrieved from the entire published literature on the PubMed website about DAM, CAF, AFMB and MFB from 1984 to 2021. The selected articles are mainly represented by small-series, and, more rarely, single-case reports with unusual clinicopathologic features. The present review focuses on the diagnostic clues of the stromal tumours of the lower female genital tract to achieve a correct classification. The main clinicopathologic features of each single entity, emphasizing their differential diagnostic clues, are discussed and summarized in tables. Representative illustrations, including the unusual morphological variants, of each single tumour are also provided. Conclusion: Awareness by pathologists of the wide morphological and immunohistochemical spectrum exhibited by these tumours is crucial to achieve correct diagnoses and to avoid confusion with reactive conditions or other benign or malignant entities

Free and Dissolved Gases in Castrocaro Spa Waters (Italy)

Free and dissolved gases in cold water samples from the Castrocaro spa, Northern Italy, were analyzed for their chemical composition. These gases were interpreted as the result of the binary mixing between a N2- and a CH4-rich component. CO2 is generally a minor constituent. N2/Ar ratios below the air typical value suggest that air saturated water (ASW) is the most likely source of atmospheric-derived components. This atmospheric end-member is predominant in low-salinity waters. Conversely, CH4-enriched gases are mainly associated with brackish to saline waters. The occurrence of minor amounts of light hydrocarbons (C2-C3) indicates a predominant biogenic origin of CH4. The He isotopic composition of the CH4-richest sample (3He/4He = 0.22 Ra) is in the range of values measured for cold seeps and mud volcanoes along the Northern Apennines foothills, and indicates a predominant crustal origin of this gas

Low Energy Effective Action in N=2 Yang-Mills as an Integrated Anomaly

Based on chiral ring relations and anomalies, as described by Cachazo, Douglas, Seiberg and Witten, we argue that the holomorphic effective action in N=2 Yang-Mills theory can be understood as an integrated U(1) anomaly from a purely field theory point of view. In particular, we show that the periods of the Riemann surface arising from the generalized Konishi anomaly can be given a physical interpretation without referring to special geometry. We also discuss consequences for the multi-instanton calculus in N=2 Yang-Mills theory.Comment: 25 pages, 2 figures ; v2: reference adde