323 research outputs found

    A Semantic Framework for the Security Analysis of Ethereum smart contracts

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    Smart contracts are programs running on cryptocurrency (e.g., Ethereum) blockchains, whose popularity stem from the possibility to perform financial transactions, such as payments and auctions, in a distributed environment without need for any trusted third party. Given their financial nature, bugs or vulnerabilities in these programs may lead to catastrophic consequences, as witnessed by recent attacks. Unfortunately, programming smart contracts is a delicate task that requires strong expertise: Ethereum smart contracts are written in Solidity, a dedicated language resembling JavaScript, and shipped over the blockchain in the EVM bytecode format. In order to rigorously verify the security of smart contracts, it is of paramount importance to formalize their semantics as well as the security properties of interest, in particular at the level of the bytecode being executed. In this paper, we present the first complete small-step semantics of EVM bytecode, which we formalize in the F* proof assistant, obtaining executable code that we successfully validate against the official Ethereum test suite. Furthermore, we formally define for the first time a number of central security properties for smart contracts, such as call integrity, atomicity, and independence from miner controlled parameters. This formalization relies on a combination of hyper- and safety properties. Along this work, we identified various mistakes and imprecisions in existing semantics and verification tools for Ethereum smart contracts, thereby demonstrating once more the importance of rigorous semantic foundations for the design of security verification techniques.Comment: The EAPLS Best Paper Award at ETAP

    Keras/TensorFlow in Drug Design for Immunity Disorders

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    Homeostasis of the host immune system is regulated by white blood cells with a variety of cell surface receptors for cytokines. Chemotactic cytokines (chemokines) activate their receptors to evoke the chemotaxis of immune cells in homeostatic migrations or inflammatory conditions towards inflamed tissue or pathogens. Dysregulation of the immune system leading to disorders such as allergies, autoimmune diseases, or cancer requires efficient, fast-acting drugs to minimize the long-term effects of chronic inflammation. Here, we performed structure-based virtual screening (SBVS) assisted by the Keras/TensorFlow neural network (NN) to find novel compound scaffolds acting on three chemokine receptors: CCR2, CCR3, and one CXC receptor, CXCR3. Keras/TensorFlow NN was used here not as a typically used binary classifier but as an efficient multi-class classifier that can discard not only inactive compounds but also low- or medium-activity compounds. Several compounds proposed by SBVS and NN were tested in 100 ns all-atom molecular dynamics simulations to confirm their binding affinity. To improve the basic binding affinity of the compounds, new chemical modifications were proposed. The modified compounds were compared with known antagonists of these three chemokine receptors. Known CXCR3 compounds were among the top predicted compounds; thus, the benefits of using Keras/TensorFlow in drug discovery have been shown in addition to structure-based approaches. Furthermore, we showed that Keras/TensorFlow NN can accurately predict the receptor subtype selectivity of compounds, for which SBVS often fails. We cross-tested chemokine receptor datasets retrieved from ChEMBL and curated datasets for cannabinoid receptors. The NN model trained on the cannabinoid receptor datasets retrieved from ChEMBL was the most accurate in the receptor subtype selectivity prediction. Among NN models trained on the chemokine receptor datasets, the CXCR3 model showed the highest accuracy in differentiating the receptor subtype for a given compound dataset

    Designing Secure Ethereum Smart Contracts: A Finite State Machine Based Approach

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    The adoption of blockchain-based distributed computation platforms is growing fast. Some of these platforms, such as Ethereum, provide support for implementing smart contracts, which are envisioned to have novel applications in a broad range of areas, including finance and Internet-of-Things. However, a significant number of smart contracts deployed in practice suffer from security vulnerabilities, which enable malicious users to steal assets from a contract or to cause damage. Vulnerabilities present a serious issue since contracts may handle financial assets of considerable value, and contract bugs are non-fixable by design. To help developers create more secure smart contracts, we introduce FSolidM, a framework rooted in rigorous semantics for designing con- tracts as Finite State Machines (FSM). We present a tool for creating FSM on an easy-to-use graphical interface and for automatically generating Ethereum contracts. Further, we introduce a set of design patterns, which we implement as plugins that developers can easily add to their contracts to enhance security and functionality

    Perinatal nutrient restriction reduces nephron endowment increasing renal morbidity in adulthood: A review

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    Perinatal malnutrition has been included among the causes of renal disease in adulthood. Here, we consider the relationships between early supply of specific nutrients (such as protein, fat, vitamins and electrolytes) and renal endowment. Prenatal and postnatal nutrition mismatch is also discussed. In addition, this article presents the role of nutrition of both mothers and pre-term infants on nephron endowment, with final practical considerations. (C) 2010 Elsevier Ireland Ltd. All rights reserved

    The role of organic compounds in artificial saliva for corrosion studies: evidence from XPS analyses

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    Several formulations of artificial saliva have been used for corrosion studies. The present work focuses on the effect of different saliva formulations on the composition of the surface film formed on CuZn37 brass alloy by X-ray photoelectron spectroscopy (XPS), in order to clarify the corrosion mechanism of historical brass wind instruments when used. Three different saliva solutions, Darvell (D), Carter-Brugirard (C-B) and SALMO, were selected. They differ for the content of the organic compounds. The XPS results show the presence of a film made of CuSCN and zinc-phosphate on the brass exposed to C-B and SALMO. In the case of samples exposed to D formulation, phosphorus is not revealed, a decrease in the zinc content in the film is detected and the S 2p shows the presence of a second component together with the one ascribed to CuSCN. A comparison with the results obtained on the pure metals in the presence of the organic compounds suggests that the formation of zinc and copper complexes may lead to thin and less protective surface film and thus to the observed high corrosion rates

    Heavy metal and metalloid accumulation in wild brown trout (Salmo trutta L., 1758 complex, Osteichthyes: Salmonidae) from a mountain stream in Sardinia by ICP-OES

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    This paper reports heavy metal and metalloid accumulation in wild brown trout (Salmo trutta L., 1758 complex) raised in freshwater and uncontaminated Sardinia system (Italy). Metals are widespread pollutants of aquatic systems, and their contamination can originate from anthropogenic activities such as industrial waste, agricultural and domestic environments, and geochemical release. Fish has a relevant position within the human diet; moreover, fishes can accumulate metals, making them a valuable tool as biomarkers for risk assessment studies. The concentration of 22 metals and metalloids after chemical digestion was assessed by inductively coupled plasma-optic emission spectroscopy (ICP-OES) in both the guts and the edible part (EP, muscle + skin) of brown trout. The results, expressed as μg g−1, showed different levels of accumulation in the EP and guts, following the series Cu > Zn > Ba > Al > Sr > Fe > Pb and Fe > Al > Hg > As > Mn > Cu > Ba > B > Zn > Pb, respectively. PCA analysis showed a fairly good correlation between the total lipid and SAFA content and Cd, Hg, and Pb accumulation in the gut. Non-carcinogenic risk assessment, expressed as THQ (target hazard quotient), showed values far below 1 for all metals in muscles, while high As and Hg contamination of the gut draws attention to possible health risks which should be discarded from the fish before consumption. TR (target cancer risk) values showed alarmingly high values for As and Cd when the fish were consumed entirely (gut + EP), while Pb levels were far below the safety levels

    Determination of Pesticide Residues in IV Range Artichoke (Cynara cardunculus L.) and Its Industrial Wastes

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    Fourth-range products are those types of fresh fruit and vegetables that are ready for raw consumption or after cooking, and belong to organic or integrated cultivations. These products are subject to mild post-harvesting processing procedures (selection, sorting, husking, cutting, and washing), and are afterwards packaged in packets or closed food plates, with an average shelf life of 5–10 days. Artichokes are stripped of the leaves, stems and outer bracts, and the remaining heads are washed with acidifying solutions. The A LC-MS/MS analytical method was developed and validated following SANTE guidelines for the detection of 220 pesticides. This work evaluated the distribution of pesticide residues among the fraction of artichokes obtained during the industrial processing, and the residues of their wastes left on the field were also investigated. The results showed quantifiable residues of one herbicide (pendimethalin) and four fungicides (azoxystrobin, propyzamide, tebuconazole, and pyraclostrobin). Pendimethalin was found in all samples, with the higher values in leaves 0.046 ± 8.2 mg/kg and in field waste 0.30 ± 6.7 mg/kg. Azoxystrobin was the most concentrated in the outer bracts (0.18 ± 2.9 mg/kg). The outer bracts showed the highest number of residues. The industrial waste showed a significant decrease in the number of residues and their concentration

    Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10

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    TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4 ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase 2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38 MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen

    Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10

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    TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR adaptor-induced activation of NF-kB and the IFN regulatory factors have been intensively studied, there is a dearth of information on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4 ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase 2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFRassociated factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38 MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory gen

    Influence of the technological process on the biochemical composition of fresh roe and bottarga from liza ramada and mugil cephalus

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    Bottarga is a high-priced delicacy with high nutritional value, and, in Italy, bottarga from mullets has been recognized to be a traditional food product. The flathead grey mullet Mugil cephalus and the thinlip grey mullet Liza ramada are the main cultured grey mullets in the Mediterranean Sea. In this study, fresh roe and bottarga from these two species were investigated to evaluate the influence of the technological process and the species on their biochemical composition and health advantages. The 1 h/200 g salting-out step did not increase the levels of NaCl in the bottarga, although it highly decreased the levels of some heavy metals like Cu and Al. Processing of fresh roe in bottarga led to an essential modification of the lipid fraction, following a general series of monousatturated fatty acid (MUFA)> poliunsutturated fatti acid (PUFA) > saturated fatty acid (SAFA) and an increase in both !3 and !6 in Liza ramada. Moreover, bottarga showed higher levels of squalene and cholesterol and an increased Essential Amino Acid/Total Amino Acid ratio (EAA/TAA) in both species. In addition to the nutritional benefits for the consumer, the process proposed in this study may represent a reliable tool for local producers to obtain a final bottarga with both a reproducible biochemical composition and organoleptic characteristics
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