Generazione energetica da fonte fotovoltaica - Progetto di impianto

In questa tesi si affronta la questione delle fonti energetiche e si descrive il progetto di un impianto di generazione fotovoltaica di tipo parzialmente integrato su un tetto piano

HIV-1 Tat protein modulates the generation of cytotoxic T cell epitopes by modifying proteasome composition and enzymatic activity

Tat, the trans activation protein of HIV, is produced early upon infection to promote and expand HIV replication and transmission. However, Tat appears to also have effects on target cells, which may affect Ag recognition both during infection and after vaccination. In particular, Tat targets dendritic cells and induces their maturation and Ag-presenting functions, increasing Th1 T cell responses. We show in this work that Tat modifies the catalytic subunit composition of immunoproteasomes in B and T cells either expressing Tat or treated with exogenous biological active Tat protein. In particular, Tat up-regulates latent membrane protein 7 and multicatalytic endopeptidase complex like-1 subunits and down-modulates the latent membrane protein 2 subunit. These changes correlate with the increase of all three major proteolytic activities of the proteasome and result in a more efficient generation and presentation of subdominant MHC-I-binding CTL epitopes of heterologous Ags. Thus, Tat modifies the Ag processing and modulates the generation of CTL epitopes. This may have an impact on both the control of virally infected cells during HIV-1 infection and the use of Tat for vaccination strategies

mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity.

Postmortem studies have revealed increased density of excitatory synapses in the brains of individuals with autism spectrum disorder (ASD), with a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured with resting-state fMRI (rsfMRI). These observations raise the question of whether excess of synapses causes aberrant functional connectivity in ASD. Using rsfMRI, electrophysiology and in silico modelling in Tsc2 haploinsufficient mice, we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity. These deficits are completely rescued by pharmacological inhibition of mTOR. Notably, we further demonstrate that children with idiopathic ASD exhibit analogous cortical-striatal hyperconnectivity, and document that this connectivity fingerprint is enriched for ASD-dysregulated genes interacting with mTOR or Tsc2. Finally, we show that the identified transcriptomic signature is predominantly expressed in a subset of children with autism, thereby defining a segregable autism subtype. Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

The pan-HDAC inhibitor AR42 downregulates CD44 expression, a new circulating prognostic factor for multiple myeloma

Il Mieloma Multiplo (MM) e’ un tumore ematologico che colpisce le plasma cellule (PCs) nel midollo osseo. Lo scambio di informazioni tra le MM-PCs e il microambiente nel midollo osseo, tra le quali quelle dovute alle interazioni cellula-cellula, il rilascio di fattori pro-sopravvivenza e vescicole extracellulari (EV), promuove la sopravvivenza tumorale e la resistenza ai farmaci. All’inizio la mia ricerca si e’ focalizzata sulla caratterizzazione del contenuto proteico delle EVs rilasciate dalle cellule di MM. Tra tutte le protein identificate, la glicoproteina CD44 e’ una delle piu’ abbondanti ed e’ stata gia’ associata, sia in vitro che in vivo, con la resistenza del mieloma multiplo al dexamethasone e alla lenalidomide. L’analisi di 200 campioni di siero estratti da pazienti affetti da mieloma multiplo mostra che il CD44 circolante e trasportato dalle MM-EVs correla con ISS stage e i livelli di β2microglobulina e costituisce un potenziale fattore prognostico, fornendo in questo modo il razionale per successive investigazioni di nuovi biomarker associati con lo stato della malattia. Nonostante le molte opzioni terapeutiche possibili, il MM e’ inevitabilmente associato con la resistenza e la scarsa efficacia farmacologica. Gli inibitori delle istoni-deacetilasi (HDACi) costituiscono una nuova classe di chemioterapici in valutazione in trials clinici per il trattamento di pazienti affetti da mieloma multiplo. Anche se gli studi preclinici sugli HDACi hanno dimostrato la loro attivita’ anti-mieloma, nella clinica i trattamenti con gli HDACi sono purtroppo limitati a causa della loro bassa tollerabilita’. Noi crediamo che gli HDACi possano costituire un valido supporto se impiegati in combinazione con lo standard terapeutico per il mieloma multiplo. In questa tesi mostro che un nuovo panHDACi, l’AR42, abbassa l’espressione del CD44. Questa down-regolazione e’ in parte mediata dal miR-9-5p, il quale sopprime l’espressione dell’insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), uno stabizzatore dell’ RNA messaggero del CD44. Abbiamo dimostrato che l’AR42 aumenta l’attivita’ della lenalidomide sia in cellule primarie di MM isolate da pazienti refrattari al trattamento con la lenalidomide sia in modello murino di mieloma multiplo. In conclusione, i nostri dati suggeriscono una nuova potenziale combinazione terapeutica che modula l’espressione del CD44 e che potrebbe aiutare ad attenuare la resistenza alla lenalidomide nei pazienti affetti da mieloma.Multiple myeloma (MM) is a hematological malignancy of plasma cells (PCs) in the bone marrow. The interplay between MM-PCs and bone marrow microenvironment, including cell-cell contacts and release of pro-survival factors and extracellular vescicles (EV), promotes cancer cell survival and drug resistance. At first my research was focused on the characterization of the proteomic content of EVs secreted by MM cell lines. Among them, the glycoprotein CD44 is one of the most abundant proteins and has been already associated, both in vivo and in vitro, with lenalidomide and dexamethasone resistance in multiple myeloma. The analysis of serum samples from a cohort of 200 MM patients shows that circulating CD44 carried by MM-EVs correlates with ISS stage and β2microglobulin and constitutes a potential prognostic factor, thus providing the rationale to further explore novel molecular players associated with MM disease. Despite multiple treatment options, MM is inevitably associated with drug resistance and poor outcomes. Histone deacetylase inhibitors (HDACi’s) are promising novel chemotherapeutics under evaluation in clinical trials for the treatment of MM patients. Although in preclinical studies HDACi’s have proven anti-myeloma activity, in the clinics single-agent HDACi treatments have been limited due to low tolerability. We believe that HDACi could constitute a valid support if used in combination with the MM state of care. In this thesis I show that a novel pan-HDACi AR42 downregulates CD44. Moreover, the CD44 downregulation is in part mediated by miR-9-5p, targeting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which directly binds to CD44 mRNA and increases its stability. Importantly, we demonstrate that AR42 enhances anti-myeloma activity of lenalidomide in primary MM cells isolated from lenalidomide resistant patients and in MM mouse model. In conclusion, our observations suggest a potential novel combinatorial therapeutic approach modulating CD44 expression, which may help overcome lenalidomide resistance in myeloma patients

Geografie del mondo altro. Prospettive comparative sugli spazi sacri e l’aldilà

Si tratta della curatela di un numero monografico della rivista SMSR su "Geografie del mondo altro Prospettive comparative sugli spazi sacri e l’aldilà"This is the curatorship of the SMSR Theme Section "Otherworld Geographies. Comparative Perspectives on Sacred Spaces and the Afterlife

FPGA-Based Parallel Comparison of Run-Length-Encoded Strings

The length of the longest common subsequence (LCS) between two strings of M and N characters can be computed by O(M×N) dynamic programming algorithms that can execute in O(M + N) on a linear systolic array. If the strings are run-length encoded, LCS can be computed by an O(mN +Mn−mn) algorithm, called RLE-LCS, where m and n are the numbers of runs of the two strings. In this paper we propose a modified RLE-LCS algorithm mappable on a linear systolic array