CONTROLLO DI UN RGV OPERANTE IN UN MAGAZZINO AUTOMATICO

Lo scopo del lavoro di tesi è il progetto e l’implementazione di un controllore logico per il sistema costituito da un Rail Guided Vehicle (RGV) operante in un magazzino automatico che permetta di combinare i vantaggi delle tecniche classiche di sviluppo di codice per i controllori a logica programmabile e l’eliminazione degli svantaggi, quali la mancanza per essi della verifica e della validazione formale. L'implementazione viene effettuata con l’ausilio di una particolare tipologia di reti di Petri, le reti di Petri Signal Interpreted, proposte come vero e proprio linguaggio di programmazione grafico. Successivamente la rete è tradotta automaticamente in codice Intruction List direttamente eseguibile sul PLC di controllo del veicolo

Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma

The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC). It accounts for 70-80% of all renal malignancies representing the third most common urological cancer after prostate and bladder cancer. The identification of non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC may represent a relevant step-forward in ccRCC management. The aim of this study is to evaluate whether specific miRNAs deregulated in ccRCC tissues present altered levels also in urine specimens. To this end we first assessed that miR-21-5p, miR-210-3p and miR-221-3p resulted upregulated in ccRCC fresh frozen tissues compared to matched normal counterparts. Next, we evidenced that miR-210-3p resulted significantly upregulated in 38 urine specimens collected from two independent cohorts of ccRCC patients at the time of surgery compared to healthy donors samples. Of note, miR- 210-3p levels resulted significantly reduced in follow-up samples. These results point to miR-210-3p as a potential non-invasive biomarker useful not only for diagnosis but also for the assessment of complete resection or response to treatment in ccRCC management

Characterizing the tumor microenvironment in rare renal cancer histological types

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies

Performance of the First ANTARES Detector Line

In this paper we report on the data recorded with the first Antares detector line. The line was deployed on the 14th of February 2006 and was connected to the readout two weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first six months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived.Comment: 14 pages, 9 figure

Harnessing the reverse cholesterol transport pathway to favor differentiation of monocyte-derived APCs and antitumor responses

Lipid and cholesterol metabolism play a crucial role in tumor cell behavior and in shaping the tumor microenvironment. In particular, enzymatic and non-enzymatic cholesterol metabolism, and derived metabolites control dendritic cell (DC) functions, ultimately impacting tumor antigen presentation within and outside the tumor mass, dampening tumor immunity and immunotherapeutic attempts. The mechanisms accounting for such events remain largely to be defined. Here we perturbed (oxy)sterol metabolism genetically and pharmacologically and analyzed the tumor lipidome landscape in relation to the tumor-infiltrating immune cells. We report that perturbing the lipidome of tumor microenvironment by the expression of sulfotransferase 2B1b crucial in cholesterol and oxysterol sulfate synthesis, favored intratumoral representation of monocyte-derived antigen-presenting cells, including monocyte-DCs. We also found that treating mice with a newly developed antagonist of the oxysterol receptors Liver X Receptors (LXRs), promoted intratumoral monocyte-DC differentiation, delayed tumor growth and synergized with anti-PD-1 immunotherapy and adoptive T cell therapy. Of note, looking at LXR/cholesterol gene signature in melanoma patients treated with anti-PD-1-based immunotherapy predicted diverse clinical outcomes. Indeed, patients whose tumors were poorly infiltrated by monocytes/macrophages expressing LXR target genes showed improved survival over the course of therapy. Thus, our data support a role for (oxy)sterol metabolism in shaping monocyte-to-DC differentiation, and in tumor antigen presentation critical for responsiveness to immunotherapy. The identification of a new LXR antagonist opens new treatment avenues for cancer patients

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome

IMPORTANCE: Patients with atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson’s disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes, but have not been prospectively studied. OBJECTIVE: To define the distinguishing features of PSP and CBS, and to assess their usefulness in facilitating early diagnosis and separation from PD. DESIGN, SETTING, PARTICIPANTS: Cohort study which recruited APS and PD patients from movement disorder clinics across the UK from September 2015 to December 2018, and will follow up patients over 5 years. APS patients were stratified into PSP-Richardson syndrome, PSP-subcortical (including PSP-parkinsonism and PSP-progressive gait freezing cases), PSP-cortical (including PSP-frontal and PSP/CBS overlap cases), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer’s and CBS-non-Alzheimer’s groups. MAIN OUTCOME MEASURES: Baseline group comparisons were conducted using: 1) Clinical trajectory; 2) Cognitive screening scales; 3) Serum neurofilament light chain (NF-L); 4) TRIM11, ApoE and MAPT genotypes; 5) Volumetric MRI. RESULTS: 222 APS cases (101 PSP, 55 MSA, 40 CBS and 26 indeterminate) were recruited (58% male; mean age at recruitment, 68.3 years). Age-matched controls (n=76) and PD cases (n=1967) were also included. Concordance between the ante-mortem clinical diagnosis and pathological diagnosis was achieved in 12/13 (92%) of PSP and CBS cases coming to post-mortem. Applying the MDS PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP. 49/101 (49%) of reclassified PSP patients did not have classical PSP-Richardson syndrome. PSP-subcortical patients had a longer diagnostic latency and a more benign clinical trajectory than PSP-Richardson syndrome and PSP-cortical (p<0.05). PSP-subcortical was distinguished from PSP-cortical and PSP-Richardson syndrome by cortical volumetric MRI measures (AUC 0.84-0.89), cognitive profile (AUC 0.80-0.83), serum NF-L (AUC 0.75-0.83) and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP subtypes. 8/17 (47%) of CBS patients with CSF analysis were identified as having CBS-Alzheimer’s. CBS-Alzheimer’s patients had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment and higher APOE-ε4 allele frequency than CBS-non-Alzheimer’s (p<0.05, AUC 0.80-0.87). Serum NF-L levels distinguished PD from PSP and CBS (p<0.05, AUC 0.80). CONCLUSIONS AND RELEVANCE: Clinical, therapeutic and epidemiological studies focusing on PSP-Richardson syndrome are likely to miss a large number of patients with underlying PSP-tau pathology. CSF analysis defines a distinct CBS-Alzheimer’s subgroup. PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis

Antioxidant Defenses Predict Long-Term Survival in a Passerine Bird

Normal and pathological processes entail the production of oxidative substances that can damage biological molecules and harm physiological functions. Organisms have evolved complex mechanisms of antioxidant defense, and any imbalance between oxidative challenge and antioxidant protection can depress fitness components and accelerate senescence. While the role of oxidative stress in pathogenesis and aging has been studied intensively in humans and model animal species under laboratory conditions, there is a dearth of knowledge on its role in shaping life-histories of animals under natural selection regimes. Yet, given the pervasive nature and likely fitness consequences of oxidative damage, it can be expected that the need to secure efficient antioxidant protection is powerful in molding the evolutionary ecology of animals. Here, we test whether overall antioxidant defense varies with age and predicts long-term survival, using a wild population of a migratory passerine bird, the barn swallow (Hirundo rustica), as a model.Plasma antioxidant capacity (AOC) of breeding individuals was measured using standard protocols and annual survival was monitored over five years (2006-2010) on a large sample of selection episodes. AOC did not covary with age in longitudinal analyses after discounting the effect of selection. AOC positively predicted annual survival independently of sex. Individuals were highly consistent in their relative levels of AOC, implying the existence of additive genetic variance and/or environmental (including early maternal) components consistently acting through their lives.Using longitudinal data we showed that high levels of antioxidant protection positively predict long-term survival in a wild animal population. Present results are therefore novel in disclosing a role for antioxidant protection in determining survival under natural conditions, strongly demanding for more longitudinal eco-physiological studies of life-histories in relation to oxidative stress in wild populations

The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

From Springer Nature via Jisc Publications RouterHistory: received 2019-09-11, accepted 2020-05-10, registration 2020-05-12, pub-electronic 2020-06-18, online 2020-06-18, collection 2020-12Publication status: PublishedFunder: This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHSAbstract: Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance

Time calibration of the ANTARES neutrino telescope

The ANTARES deep-sea neutrino telescope comprises a three-dimensional array of photomultipliers to detect the Cherenkov light induced by upgoing relativistic charged particles originating from neutrino interactions in the vicinity of the detector. The large scattering length of light in the deep sea facilitates an angular resolution of a few tenths of a degree for neutrino energies exceeding 10 TeV. In order to achieve this optimal performance, the time calibration procedures should ensure a relative time calibration between the photomultipliers at the level of similar to 1 ns. The methods developed to attain this level of precision are described