Simulation of Bitcoin Transactions to Identify Money Laundering Activities

I termini “blockchain” e “criptovalute”, con quanto ruota loro attorno, sono entrati prepotentemente a far parte del gergo comune. Lo scopo del lavoro di tesi è quello di verificare se, all’interno di una rete blockchain (nello specifico: Bitcoin), sia possibile individuare traffici di denaro che qualcuno tenta di “ripulire”. La tesi non ha alcuna pretesa di esaustività circa le specificità assai tecniche di Bitcoin; la stessa intende lavorare a più alto livello e generare un grafo rappresentativo della nostra rete sociale. Questa, in particolare, è caratterizzata da nodi che individuano gli utenti ed archi orientati che muovono dal mittente al destinatario della transazione. Il peso della transazione, invece, è offerto dall’importo speso in bitcoin. L'utilizzo di tecniche per l'analisi di reti sociali è la chiave per l'interpretazione della relazione fra dati. Gli indici relativi al grado e alla sua distribuzione, come quelli di centralità, possono rivelarsi cruciali. Tuttavia occorre tener presente che, parallelamente alla tecnologia, si evolve la criminalità. La tesi affronta le problematiche dei mixer centralizzati, delle operazioni coinjoin e della necessità di clusterizzare indirizzi Bitcoin appartenenti alla stessa persona fisica. In merito all'ultimo punto, è presente una sezione che estende il tool DiLeNa proprio con l'implementazione di due euristiche fin ora riconosciute dalla letteratura scientifica come quelle maggiormente efficaci. Viene illustrato, inoltre, lo sviluppo di un simulatore volto ad effettuare delle simulazioni che sulla rete Bitcoin reali richiederebbero una mole di tempo elevata. Tale simulatore rispecchia tutte le metriche presenti nello Stato dell'Arte ed implementa anche un algoritmo deterministico per rilevare le transazioni volte al lavaggio del denaro. Infine vengono esposti i risultati e vengono presentati alcuni sviluppi futuri, tra cui: nuove euristiche, de-mixing, training di una rete neurale ed estensione ad altre blockchain

Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain

Background: L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results: A seven-day treatment with L-acetylcarnitine ( 100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain. L-Acetylcarnitine-induced analgesia persisted for at least 14 days after drug withdrawal. In contrast, the analgesic effect of pregabalin, amitryptiline, ceftriaxone, and N-acetylcysteine disappeared seven days after drug withdrawal. L-acetylcarnitine treatment enhanced mGlu2/3 receptor protein levels in the dorsal region of the spinal cord. This effect also persisted for two weeks after drug withdrawal and was associated with increased levels of acetylated histone H3 bound to the Grm2 gene promoter in the dorsal root ganglia. A long-lasting analgesic effect of L-acetylcarnitine was also observed in mice subjected to chronic constriction injury of the sciatic nerve. In these animals, a 14-day treatment with pregabalin, amitryptiline, tramadol, or L-acetylcarnitine produced a significant antiallodynic effect, with pregabalin displaying the greatest efficacy. In mice treated with pregabalin, tramadol or L-acetylcarnitine the analgesic effect was still visible 15 days after the end of drug treatment. However, only in mice treated with L-acetylcarnitine analgesia persisted 37 days after drug withdrawal. This effect was associated with an increase in mGlu2/3 receptor protein levels in the dorsal horns of the spinal cord. Conclusions: Our findings suggest that L-acetylcarnitine has the unique property to cause a long-lasting analgesic effect that might reduce relapses in patients suffering from chronic pain

Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration

Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3g/kg), which caused the death of >70% of Brn-3a+ RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration

Nucleosynthesis And The Inhomogeneous Chemical Evolution Of The Carina Dwarf Galaxy

The detailed abundances of 23 chemical elements in nine bright red giant branch stars in the Carina dwarf spheroidal galaxy are presented based on high-resolution spectra gathered at the Very Large Telescope (VLT) and Magellan telescopes. A spherical model atmospheres analysis is applied using standard methods (local thermodynamic equilibrium and plane-parallel radiative transfer) to spectra ranging from 380 to 680 nm. Stellar parameters are found to be consistent between photometric and spectroscopic analyses, both at moderate and high resolution. The stars in this analysis range in metallicity from -2.9 < [Fe/H] < -1.3, and adopting the ages determined by Lemasle et al., we are able to examine the chemical evolution of Carina's old and intermediate-aged populations. One of the main results from this work is the evidence for inhomogeneous mixing in Carina and therefore for a poor statistical sampling of the supernova contributions when forming stars; a large dispersion in [Mg/Fe] indicates poor mixing in the old population, an offset in the [alpha/Fe] ratios between the old and intermediate-aged populations (when examined with previously published results) suggests that the second star formation event occurred in alpha-enriched gas, and one star, Car-612, seems to have formed in a pocket enhanced in SN Ia/II products. This latter star provides the first direct link between the formation of stars with enhanced SN Ia/II ratios in dwarf galaxies to those found in the outer Galactic halo (Ivans et al.). Another important result is the potential evidence for SNII driven winds. We show that the very metal-poor stars in Carina have not been enhanced in asymptotic giant branch or SN Ia products, and therefore their very low ratios of [Sr/Ba] suggests the loss of contributions from the early SNe II. Low ratios of [Na/Fe], [Mn/Fe], and [Cr/Fe] in two of these stars support this scenario, with additional evidence from the low [Zn/Fe] upper limit for one star. It is interesting that the chemistry of the metal-poor stars in Carina is not similar to those in the Galaxy, most of the other dwarf spheroidal galaxies, or the ultra faint dwarfs, and suggests that Carina may be at the critical mass where some chemical enrichments are lost through SN II driven winds.NSERCNSF AST 99-84073McDonald Observator

mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors

In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable. The developmental decline of mGlu5 receptors coincided with the appearance of mGlu1α receptors in PCs, and both processes were associated with specular changes in CpG methylation in the corresponding gene promoters. It was the mGlu1 receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data obtained with conditional mGlu1α receptor knockout mice and with targeted pharmacological treatments during critical developmental time windows. The suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in mature PCs, suggesting that expression of mGlu1α and mGlu5 receptors is mutually exclusive in PCs. These findings add complexity to the the finely tuned mechanisms that regulate PC biology during development and in the adult life and lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors in PC maturation

Persistent systemic microbial translocation, inflammation, and intestinal damage during Clostridioides difficile infection

Background. Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods. Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results. Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P &lt; .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions. CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated

Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation

BACKGROUND: Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105(+) CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105(-) TCs) and their EVs. METHODS: Maturation of monocyte-derived DCs was studied in presence of CD105(+) CSCs and CD105(-) TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors. RESULTS: The results obtained demonstrate that both CD105(+) CSCs and CD105(-) TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105(+) CSCs was significantly greater than that of CD105(-) TCs. EVs derived from CD105(+) CSCs and in less extent, those derived from CD105(-) TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation. CONCLUSIONS: In conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-2025-z) contains supplementary material, which is available to authorized users

Maternal depression symptoms and internalising problems in the offspring : the role of maternal and family factors

Maternal depression symptoms (MDS) are a robust risk factor for internalising problems (IP) in the offspring. However, the relative importance of MDS and other factors associated with it (i.e. other types of maternal psychopathology, maternal parenting practices, family characteristics) is not well understood. To (a) identify a group of children with high levels of IP between 6 and 12 years using combined maternal and teacher assessments and (b) to quantify the associations between trajectories of MDS during early childhood and children’s IP trajectories before and after controlling for family factors associated with MDS. MDS and family factors were assessed in a population-based sample in Canada (n = 1537) between 5 months and 5 years. The outcome variable was membership in trajectories of teacher- and mother-rated IP between ages 6 and 12 years. Family factors were included as covariates in a multinomial logistic regression model. There was a strong association between MDS and children’s atypically high levels of IP in unadjusted analyses [OR 4.14 (95% CI 2.60; 6.61)]. The association was reduced, but remained strong [2.60 (1.55; 4.36)] when maternal psychopathology, maternal parenting, and family socioeconomic status were entered in the model. MDS, maternal anxiety, and low parental self-efficacy were associated with offspring’s high IP trajectories. MDS is associated with high levels of children’s IP independently of other maternal and family characteristics. Intervention targeting maternal psychopathology and parenting self-efficacy and testing the impact on children’s IP would provide information on the putative causal pathways between maternal and offspring’s symptomatology

Postural Hand Synergies during Environmental Constraint Exploitation

Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms of a synergistic behavior in the generation of hand postures, i.e., using a reduced set of commonly used kinematic patterns. This is in analogy with previous studies showing the presence of such behavior in different tasks, such as grasping. We investigated this hypothesis in experiments performed by six subjects, who were asked to grasp objects from a flat surface. We quantitatively characterized hand posture behavior from a kinematic perspective, i.e., the hand joint angles, in both pre-shaping and during the interaction with the environment. To determine the role of tactile feedback, we repeated the same experiments but with subjects wearing a rigid shell on the fingertips to reduce cutaneous afferent inputs. Results show the persistence of at least two postural synergies in all the considered experimental conditions and phases. Tactile impairment does not alter significantly the first two synergies, and contact with the environment generates a change only for higher order Principal Components. A good match also arises between the first synergy found in our analysis and the first synergy of grasping as quantified by previous work. The present study is motivated by the interest of learning from the human example, extracting lessons that can be applied in robot design and control. Thus, we conclude with a discussion on implications for robotics of our findings