Trust economics feasibility study

We believe that enterprises and other organisations currently lack sophisticated methods and tools to determine if and how IT changes should be introduced in an organisation, such that objective, measurable goals are met. This is especially true when dealing with security-related IT decisions. We report on a feasibility study, Trust Economics, conducted to demonstrate that such methodology can be developed. Assuming a deep understanding of the IT involved, the main components of our trust economics approach are: (i) assess the economic or financial impact of IT security solutions; (ii) determine how humans interact with or respond to IT security solutions; (iii) based on above, use probabilistic and stochastic modelling tools to analyse the consequences of IT security decisions. In the feasibility study we apply the trust economics methodology to address how enterprises should protect themselves against accidental or malicious misuse of USB memory sticks, an acute problem in many industries

The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons.

BACKGROUND: While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve), islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. RESULTS: To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2), is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K+ conductance (IKfast) and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of IKfast to show that increased Eve specifically down regulates the Slowpoke (a BK Ca2+-gated potassium channel), but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRalpha-96Aa (a nicotinic acetylcholine receptor subunit). Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRalpha-96Aa. CONCLUSION: Taken together, our findings demonstrate, for the first time, that Eve is sufficient to regulate both voltage- and ligand-gated currents in motoneurons, extending its known repertoire of action beyond its already characterized role in axon guidance. Our data are also consistent with a common developmental program that utilizes a defined set of transcription factors to determine both morphological and functional neuronal properties

A Focused Sequent Calculus Framework for Proof Search in Pure Type Systems

Basic proof-search tactics in logic and type theory can be seen as the root-first applications of rules in an appropriate sequent calculus, preferably without the redundancies generated by permutation of rules. This paper addresses the issues of defining such sequent calculi for Pure Type Systems (PTS, which were originally presented in natural deduction style) and then organizing their rules for effective proof-search. We introduce the idea of Pure Type Sequent Calculus with meta-variables (PTSCalpha), by enriching the syntax of a permutation-free sequent calculus for propositional logic due to Herbelin, which is strongly related to natural deduction and already well adapted to proof-search. The operational semantics is adapted from Herbelin's and is defined by a system of local rewrite rules as in cut-elimination, using explicit substitutions. We prove confluence for this system. Restricting our attention to PTSC, a type system for the ground terms of this system, we obtain the Subject Reduction property and show that each PTSC is logically equivalent to its corresponding PTS, and the former is strongly normalising iff the latter is. We show how to make the logical rules of PTSC into a syntax-directed system PS for proof-search, by incorporating the conversion rules as in syntax-directed presentations of the PTS rules for type-checking. Finally, we consider how to use the explicitly scoped meta-variables of PTSCalpha to represent partial proof-terms, and use them to analyse interactive proof construction. This sets up a framework PE in which we are able to study proof-search strategies, type inhabitant enumeration and (higher-order) unification

Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis

First published online: September 20, 2013BACKGROUND: Improving our understanding of the relationship between the genotype and the drug resistance phenotype of Mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. Studies that use direct genetic manipulation to identify the mutations that cause M. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutation's contribution to the drug resistance phenotype. METHODS: We systematically reviewed the literature for publications reporting allelic exchange experiments in any of the resistance-associated M. tuberculosis genes. We included studies that introduced single point mutations using specialized linkage transduction or site-directed/in vitro mutagenesis and documented a change in the resistance phenotype. RESULTS: We summarize evidence supporting the causal relationship of 54 different mutations in eight genes (katG, inhA, kasA, embB, embC, rpoB, gyrA and gyrB) and one intergenic region (furA-katG) with resistance to isoniazid, the rifamycins, ethambutol and fluoroquinolones. We observed a significant role for the strain genomic background in modulating the resistance phenotype of 21 of these mutations and found examples of where the same drug resistance mutations caused varying levels of resistance to different members of the same drug class. CONCLUSIONS: This systematic review highlights those mutations that have been shown to causally change phenotypic resistance in M. tuberculosis and brings attention to a notable lack of allelic exchange data for several of the genes known to be associated with drug resistance.This work was supported by the Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to H. N.-G.), the National Institutes of Health/Fogarty International Center (1K01 TW009213 to K.R.J.), departmental funds of the pulmonary division of Massachusetts General Hospital to M. R. F. and the National Institutes of Health/NIAID (U19 A1076217 to M.B.M.)

Towards an embedding of Graph Transformation in Intuitionistic Linear Logic

Linear logics have been shown to be able to embed both rewriting-based approaches and process calculi in a single, declarative framework. In this paper we are exploring the embedding of double-pushout graph transformations into quantified linear logic, leading to a Curry-Howard style isomorphism between graphs and transformations on one hand, formulas and proof terms on the other. With linear implication representing rules and reachability of graphs, and the tensor modelling parallel composition of graphs and transformations, we obtain a language able to encode graph transformation systems and their computations as well as reason about their properties

Resource-Bound Quantification for Graph Transformation

Graph transformation has been used to model concurrent systems in software engineering, as well as in biochemistry and life sciences. The application of a transformation rule can be characterised algebraically as construction of a double-pushout (DPO) diagram in the category of graphs. We show how intuitionistic linear logic can be extended with resource-bound quantification, allowing for an implicit handling of the DPO conditions, and how resource logic can be used to reason about graph transformation systems

Logics for Petri nets with propagating failures

Petri nets play a central role in the formal modelling of a wide range of complex systems and scenarios. Their ability to handle with both concurrency and resource awareness justifies their spread in the current formal development practices. On the logic side, Dynamic Logics are widely accepted as the de facto formalisms to reason about computational systems. However, as usual, the application to new situations raises new challenges and issues. The ubiquity of failures in the execution of current systems, interpreted in these models as triggered events that are not followed by the corresponding transition, entails not only the adjustment of these structures to deal with this reality, but also the introduction of new logics adequate to this emerging phenomenon. This paper contributes to this challenge by exploring a combination of two previous works of the authors, namely the Propositional Dynamic Logic for Petri Nets [1] and a parametric construction of multi-valued dynamic logics presented in [13]. This exercise results in a new family of Dynamic Logics for Petri Nets suitable to deal with firing failures.publishe

Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses