Il processo di ICT Risk Management: Gestione del Programma Strutturato di Sicurezza in Telecom Italia Information Technology

Questo lavoro di tesi è il risultato di uno stage della durata di otto mesi, che si è svolto presso Telecom Italia Information Technology, sede di Roma, nel ruolo di “Junior Analyst” per conto di ELIS Consulting Academy. L’obiettivo della tesi è seguire la realizzazione di un progetto di sicurezza informatica, chiamato “Programma Strutturato di Sicurezza” (PSS), che coinvolge l’intera divisione dell’Information Technology del Gruppo Telecom Italia e, in particolare, la funzione Technical Security (IT.TS). Il PSS è nato all’inizio del 2013 in seguito a controlli effettuati all’interno dell’azienda che hanno rilevato la necessità di dedicare una maggior attenzione alla sicurezza informatica: sono state, infatti, riscontrate vulnerabilità ricorrenti nei sistemi IT tali da generare un elevato rischio potenziale, che potrebbe compromettere la sicurezza delle informazioni e dei servizi erogati da Telecom. L’obiettivo del PSS è rendere il ciclo produttivo di TI.IT pienamente conforme al processo di ICT Risk Management, implementando una serie di attività che rendano trascurabile il rischio residuo dei sistemi IT (ovvero il rischio che permane in seguito all’adozione delle misure di sicurezza). In questo ambito, le principali attività svolte sono state: -Individuazione del perimetro teorico, cioè dell’insieme di sistemi sui quali intervenire per sanare le vulnerabilità (fase di concezione); -Definizione delle attività, mediante le quali sono stati realizzati gli interventi da porre in essere (fase di definizione); -Analisi degli scostamenti, per l’individuazione delle criticità, la proposta di soluzioni a tali criticità e l’analisi degli scostamenti (fase di analisi)

The Impact of Globalisation and Increased Trade Liberalisation on European Regions: Carpi and Prato case studies

The following two studies are included in the studies commissioned by the European Commission – DG REGIO as part of the preparatory work for the “Fifth report on economic and social cohesion”. The full report on “EU regions vulnerable to globalisation and increased trade: "The impact of globalisation and increased trade liberalisation on European regions" coordinated by IGEAT – ULB, Politecnico di Milano and UMS Riate in 2008 can be found in the following web page: http://ec.europa.eu/regional_policy/information/studies/index_en.cfm#

Genes and Aggressive Behavior: Epigenetic Mechanisms Underlying Individual Susceptibility to Aversive Environments

Over the last two decades, the study of the relationship between nature and nurture in shaping human behavior has encountered a renewed interest. Behavioral genetics showed that distinct polymorphisms of genes that code for proteins that control neurotransmitter metabolic and synaptic function are associated with individual vulnerability to aversive experiences, such as stressful and traumatic life events, and may result in an increased risk of developing psychopathologies associated with violence. On the other hand, recent studies indicate that experiencing aversive events modulates gene expression by introducing stable changes to DNA without modifying its sequence, a mechanism known as “epigenetics”. For example, experiencing adversities during periods of maximal sensitivity to the environment, such as prenatal life, infancy and early adolescence, may introduce lasting epigenetic marks in genes that affect maturational processes in brain, thus favoring the emergence of dysfunctional behaviors, including exaggerate aggression in adulthood. The present review discusses data from recent research, both in humans and animals, concerning the epigenetic regulation of four genes belonging to the neuroendocrine, serotonergic and oxytocinergic pathways—Nuclear receptor subfamily 3-group C-member 1 (NR3C1), oxytocin receptor (OXTR), solute carrier-family 6 member 4 (SLC6A4) and monoamine oxidase A (MAOA)—and their role in modulating vulnerability to proactive and reactive aggressive behavior. Behavioral genetics and epigenetics are shedding a new light on the fine interaction between genes and environment, by providing a novel tool to understand the molecular events that underlie aggression. Overall, the findings from these studies carry important implications not only for neuroscience, but also for social sciences, including ethics, philosophy and law

Single-cell-led drug repurposing for Alzheimer's disease

: Alzheimer's disease is the most common form of dementia. Notwithstanding the huge investments in drug development, only one disease-modifying treatment has been recently approved. Here we present a single-cell-led systems biology pipeline for the identification of drug repurposing candidates. Using single-cell RNA sequencing data of brain tissues from patients with Alzheimer's disease, genome-wide association study results, and multiple gene annotation resources, we built a multi-cellular Alzheimer's disease molecular network that we leveraged for gaining cell-specific insights into Alzheimer's disease pathophysiology and for the identification of drug repurposing candidates. Our computational approach pointed out 54 candidate drugs, mainly targeting MAPK and IGF1R signaling pathways, which could be further evaluated for their potential as Alzheimer's disease therapy

Cadmium uptake and translocation in durum wheat varieties differing in grain-Cd accumulation

Wheat grain products are the primary source of dietary Cd-intake for humans. Since varieties differ markedly in grain-Cd accumulation, efforts are needed to find traits associated with low, or high, accumulation. Two durum wheat varieties, selected in a field screening as low (Creso) and high (Svevo) grain-Cd accumulating, were grown on soil spiked with 1.5, 3 and 4.5 mg Cd/kg. Growth patterns, Cd uptake and translocation were investigated at heading and maturity. Cadmium did not affect plant growth and grain yield, but grain-Cd concentration always exceeded the permissible limit of 0.2 mg Cd/kg, and was approximately double in Svevo than in Creso. At maturity, total Cd-uptake increased linearly with supply in Creso, from 13 to 23 μg/plant, and was approximately 18 μg/plant, irrespective of Cd level, in Svevo. Partitioning to shoot was higher in Svevo than in Creso, both at heading and maturity. We suggest that reduced plant height, high root to shoot biomass ratio during vegetative growth and elevated post-heading dry matter accumulation promoted Cd accumulation into grain. Since these traits are common to modern wheat varieties, risks of grain Cd-contamination can increase in the future

Effect of preceding crop on the agronomic and economic performance of durum wheat in the transition from conventional to reduced tillage

Preceding crop greatly affects the agronomic and economic performance of durum wheat, but its interaction with tillage intensity was scarcely investigated at the early transition from conventional to reduced tillage. This work was aimed at studying how preceding crop determines the performance of durum wheat during the early transition from conventional to reduced tillage. To this end, the effect of four preceding crops (sunflower, durum wheat, alfalfa and maize) in interaction with two tillage systems without inversion (RT1 – chisel ploughing, disking twice, and harrowing and RT2 – disking twice and harrowing) and a conventional tillage (CT – mouldboard ploughing, disking twice, and harrowing) was studied on durum wheat in two years of cultivation. The effect of preceding crop on grain yield and yield components of durum wheat was different depending on tillage intensity, and this effect varied depending on the year of cultivation. Grain yield increased by 1.1–4.2 t ha−1 with the increase of the intensity of tillage in both years and all preceding crops, with the only exception of wheat crop following sunflower in 2009–2010 and following maize in 2010–2011. RT2 decreased wheat grain yield when compared with RT1 only with alfalfa as preceding crop. Differences in grain yield among tillage systems and crops preceding wheat in both years were mainly due to variations of mean kernel weight and number of spikes per unit area. The profitability of durum wheat varied according to the year of cultivation, the preceding crop and the tillage system. Overall, in both years profitability was lowest and negative following wheat under reduced tillage system, while it was highest and positive following alfalfa under CT. Reduced growth of durum wheat with reduced tillage systems was mainly consequence of weeds and volunteers plants development and nitrogen availability in soil resulting from nutrient immobilization. It can be concluded that potential yield penalties in durum wheat in the transition from conventional to reduced tillage can be alleviated by an appropriate selection of preceding crops

Effects on human transcriptome of mutated BRCA1 BRCT domain: A microarray study

BACKGROUND: BRCA1 (breast cancer 1, early onset) missense mutations have been detected in familial breast and ovarian cancers, but the role of these variants in cancer predisposition is often difficult to ascertain. In this work, the molecular mechanisms affected in human cells by two BRCA1 missense variants, M1775R and A1789T, both located in the second BRCT (BRCA1 C Terminus) domain, have been investigated. Both these variants were isolated from familial breast cancer patients and the study of their effect on yeast cell transcriptome has previously provided interesting clues to their possible role in the pathogenesis of breast cancer. METHODS: We compared by Human Whole Genome Microarrays the expression profiles of HeLa cells transfected with one or the other variant and HeLa cells transfected with BRCA1 wild-type. Microarray data analysis was performed by three comparisons: M1775R versus wild-type (M1775RvsWT-contrast), A1789T versus wild-type (A1789TvsWT-contrast) and the mutated BRCT domain versus wild-type (MutvsWT-contrast), considering the two variants as a single mutation of BRCT domain. RESULTS: 201 differentially expressed genes were found in M1775RvsWT-contrast, 313 in A1789TvsWT-contrast and 173 in MutvsWT-contrast. Most of these genes mapped in pathways deregulated in cancer, such as cell cycle progression and DNA damage response and repair. CONCLUSIONS: Our results represent the first molecular evidence of the pathogenetic role of M1775R, already proposed by functional studies, and give support to a similar role for A1789T that we first hypothesized based on the yeast cell experiments. This is in line with the very recently suggested role of BRCT domain as the main effector of BRCA1 tumor suppressor activity

Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy. Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out. The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P=0.008, P<0.001, P=0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P< 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P<0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P<0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons-Smith classification) in patients on conservative therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P=0.016) and theta band (P= 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D. In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs

Remobilization of Dry Matter, Nitrogen and Phosphorus in Durum Wheat as Affected by Genotype and Environment

Field studies were carried out to determine dry matter (DM), nitrogen (N) and phosphorus (P) assimilation until anthesis and DM, N and P remobilization during grain filling in wheat. Twentyfive durum wheat (Triticum durum L.) varieties were grown in Tuscany at Grosseto and at Arezzo. At Grosseto 76% of DM was assimilated during pre-anthesis while at Arezzo the amount was 81%. At Grosseto 44% and at Arezzo 35% of N was accumulated until anthesis, while 33% of P was stored until anthesis in both localities. Cultivar differences in DM and N remobilization were positively related to pre-anthesis dry matter and N content at anthesis (r > 0.74). Environmental contraints on carbon, N and P availability in the plant are crucial factors in determining grain yield and N and P content in grain, affecting both accumulation and remobilization. In the low rainfall site of Grosseto, most of the grain yield originated from dry matter accumulation, while in the wetter environment of Arezzo remobilization and accumulation contributed equally to grain yield. Conversely, at Grosseto grain N content relied most on remobilization and at Arezzo remobilization and accumulation contributed equally. Finally, at Grosseto and at Arezzo accumulation of P was the main source of grain P content

Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms

<p>Abstract</p> <p>Background</p> <p>Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying the mutant <it>ABCD1 </it>allele, has been proposed as a mechanism influencing X-linked adrenoleukodystrophy (X-ALD) carrier phenotype, but reported data so far are conflicting.</p> <p>Methods</p> <p>To shed light into this topic we assessed the XCI pattern in peripheral blood mononuclear cells (PBMCs) of 30 X-ALD carriers. Since a frequent problem with XCI studies is the underestimation of skewing due to an incomplete sample digestion by restriction enzymes, leading to variable results, we developed a pyrosequencing assay to identify samples completely digested, on which to perform the XCI assay. Pyrosequencing was also used to quantify <it>ABCD1 </it>allele-specific expression. Moreover, very long-chain fatty acid (VLCFA) levels were determined in the same patients.</p> <p>Results</p> <p>We found severely (≥90:10) or moderately (≥75:25) skewed XCI in 23 out of 30 (77%) X-ALD carriers and proved that preferential XCI is mainly associated with the preferential expression of the mutant <it>ABCD1 </it>allele, irrespective of the manifestation of symptoms. The expression of mutant <it>ABCD1 </it>allele also correlates with plasma VLCFA concentrations.</p> <p>Conclusions</p> <p>Our results indicate that preferential XCI leads to the favored expression of the mutant <it>ABCD1 </it>allele. This emerges as a general phenomenon in X-ALD carriers not related to the presence of symptoms. Our data support the postulated growth advantage of cells with the preferential expression of the mutant <it>ABCD1 </it>allele, but argue against the use of XCI pattern, <it>ABCD1 </it>allele-specific expression pattern and VLCFA plasma concentration as biomarkers to predict the development of symptoms in X-ALD carriers.</p