Exploring and Enforcing Application Security Guarantees via Program Dependence Graphs

We present Pidgin, a program analysis and understanding tool that allows developers to explore the information flows that exist in programs and specify and enforce security policies that restrict these information flows. Pidgin uses program-dependence graphs (PDGs) to precisely capture the information flows within a program. PDGs can be queried using a custom query language to explore and describe information flows in programs. A developer can specify strong information security policies by asserting that specific queries return no results (i.e., asserting the absence of certain information flows in the program). To check whether a program satisfies a security policy, a developer can simply evaluate the query against a program’s dependence graph. The query language is expressive, supporting a large class of precise, application-specific security guarantees. Pidgin can be used to explore information security guarantees in legacy programs, or to support the specification, enforcement, and modification of information security requirements during program development. We describe the design and implementation of Pidgin and report on using Pidgin both to explore security guarantees in existing open-source applications, and to specify and enforce security guarantees during application development.Engineering and Applied Science

Detecting colorectal cancer using electrical impedance spectroscopy: an ex vivo feasibility study

Objective: Colorectal cancer is the fourth most common cancer worldwide, with a lifetime risk of around 20%. Current solutions do not allow clinicians to objectively assess tissue abnormality during endoscopy and perioperatively. A solution capable of objectively assessing samples in real time could greatly improve the treatment process. A solution that can be integrated in minimally invasive diagnostics and management strategies to provide real-time point-of-care information would be greatly transformative. Electrical impedance spectroscopy (EIS) may provide such a solution. In this paper, we present a feasibility study on using EIS in assessing colorectal tissue. Approach: We performed tetrapolar EIS using ZedScan on excised human colorectal tumour tissue and the matched normal colonic mucosa in 22 freshly resected specimens following elective surgery for colorectal cancer. Histopathological examination was used to confirm the final diagnosis. Statistical significance was assessed with Wilcoxon signed rank test. Main results: Tetrapolar EIS could discriminate cancer with statistically significant results when applying frequencies between 305 Hz – 625 kHz (p < 0.05). 300 Ω was set as the transfer impedance threshold to detect cancer. Thus, the area under the corresponding receiver operating characteristic curve for this threshold was 0.7105. Significance: This feasibility study demonstrates that impedance spectra changes in colorectal cancer tissue are detectable and may be statistically significant, suggesting that EIS has the potential to be the core technology in a novel non-invasive point of care test for detecting colorectal cancer. These results warrant further development and increasing the size of the study with a device specificity designed for colorectal cancer

Neuroendocrine Disruption: More than Hormones are Upset

Only a small proportion of the published research on endocrine-disrupting chemicals (EDC) directly examined effects on neuroendocrine processes. There is an expanding body of evidence that anthropogenic chemicals exert effects on neuroendocrine systems and that these changes might impact peripheral organ systems and physiological processes. Neuroendocrine disruption extends the concept of endocrine disruption to include the full breadth of integrative physiology (i.e., more than hormones are upset). Pollutants may also disrupt numerous other neurochemical pathways to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. Several examples are presented in this review, from both vertebrates and invertebrates, illustrating that diverse environmental pollutants including pharmaceuticals, organochlorine pesticides, and industrial contaminants have the potential to disrupt neuroendocrine control mechanisms. While most investigations on EDC are carried out with vertebrate models, an attempt is also made to highlight the importance of research on invertebrate neuroendocrine disruption. The neurophysiology of many invertebrates is well described and many of their neurotransmitters are similar or identical to those in vertebrates; therefore, lessons learned from one group of organisms may help us understand potential adverse effects in others. This review argues for the adoption of systems biology and integrative physiology to address the effects of EDC. Effects of pulp and paper mill effluents on fish reproduction are a good example of where relatively narrow hypothesis testing strategies (e.g., whether or not pollutants are sex steroid mimics) have only partially solved a major problem in environmental biology. It is clear that a global, integrative physiological approach, including improved understanding of neuroendocrine control mechanisms, is warranted to fully understand the impacts of pulp and paper mill effluents. Neuroendocrine disruptors are defined as pollutants in the environment that are capable of acting as agonists/antagonists or modulators of the synthesis and/or metabolism of neuropeptides, neurotransmitters, or neurohormones, which subsequently alter diverse physiological, behavioral, or hormonal processes to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. By adopting a definition of neuroendocrine disruption that encompasses both direct physiological targets and their indirect downstream effects, from the level of the individual to the ecosystem, a more comprehensive picture of the consequences of environmentally relevant EDC exposure may emerge

Rapid detection of pathological mutations and deletions of the haemoglobin beta gene (HBB) by High Resolution Melting (HRM) analysis and Gene Ratio Analysis Copy Enumeration PCR (GRACE-PCR)

© 2016 The Author(s). Objectives: Inherited disorders of haemoglobin are the world's most common genetic diseases, resulting in significant morbidity and mortality. The large number of mutations associated with the haemoglobin beta gene (HBB) makes gene scanning by High Resolution Melting (HRM) PCR an attractive diagnostic approach. However, existing HRM-PCR assays are not able to detect all common point mutations and have only a very limited ability to detect larger gene rearrangements. The aim of the current study was to develop a HBB assay, which can be used as a screening test in highly heterogeneous populations, for detection of both point mutations and larger gene rearrangements. Methods: The assay is based on a combination of conventional HRM-PCR and a novel Gene Ratio Analysis Copy Enumeration (GRACE) PCR method. HRM-PCR was extensively optimised, which included the use of an unlabelled probe and incorporation of universal bases into primers to prevent interference from common non-pathological polymorphisms. GRACE-PCR was employed to determine HBB gene copy numbers relative to a reference gene using melt curve analysis to detect rearrangements in the HBB gene. The performance of the assay was evaluated by analysing 410 samples. Results: A total of 44 distinct pathological genotypes were detected. In comparison with reference methods, the assay has a sensitivity of 100 % and a specificity of 98 %. Conclusion: We have developed an assay that detects both point mutations and larger rearrangements of the HBB gene. This assay is quick, sensitive, specific and cost effective making it suitable as an initial screening test that can be used for highly heterogeneous cohorts

An Investigation of Pulp Mill Effluents and Their Wood Feedstocks as Potential Neuroendocrine Disruptors of the Fish Reproductive Axis

Common observations of reduced gonad size and spawning inhibition in wild and laboratory raised fish exposed to pulp mill effluents indicate that reproductive neuroendocrine signalling pathways may be upset. This thesis supported the neuroendocrine disruption of reproduction hypothesis by identifying potential disruptors and targets where these impacts may occur. A mechanistic study of the in vivo fathead minnow (FHM) spawning assay used by industry to assess effluent quality showed that ovulation, but not milt production, was impaired. This finding supported the hypothesis that the neuroendocrine cascade that triggers ovulation may be disrupted. I hypothesized that neuroactive constituents previously described in effluents were originating in wood feedstocks and neuroactive extracts of hardwood and conifer feedstocks were identified. Phytochemicals associated with effluents were neuroactive. Structurally similar phenolic phytochemicals showed monoamine oxidase (MAO) inhibition, and resin acid diterpenes displayed glutamic acid decarboxylase (GAD) inhibition. Inhibitors of these enzymes may have impacts on the control of reproduction since MAO metabolizes dopamine, an inhibitor of the neuroendocrine reproductive axis, while GAD synthesizes -aminobutyric acid (GABA), a stimulator of this axis. Bioassay-guided fractionations of effluents and wood feedstocks identified that medium polar extracts of primary- and secondary-treated effluents and balsam fir feedstock contained high GAD inhibitory activity. This activity was associated with chemically complex fractions rather than single active principles. Advanced metabolomic comparison of medium polar extracts of feedstock and treated effluent identified 15 common plant metabolites, demonstrating that phytochemicals entering the mill in wood are surviving pulp production and effluent treatment processes and may be responsible for observed GAD inhibition. Discriminant metabolomics analysis identified 4-acetylpyridine, a novel compound to be described in effluents, as well as two other tentatively identified compounds, as chemical markers of GAD inhibitory effluent fractions. Five tentatively identified chemical markers and (+)-lariciresinol were found in inhibitory balsam fir feedstock fractions. Neuroendocrine pathways that control reproduction in fish, such as dopamine and GABA pathways, are also important drug targets for the treatment of neurological disorders in mammals; therefore these results also have implications for the development of natural health products from phytochemicals and tree extracts common to Canadian forests. By using an interdisciplinary approach (phytochemistry, neuroendocrinology, ecotoxicology), I was able to explore the various implications of my research on the fields of natural health products chemistry and aquatic toxicology

Open Access

Ovulation but not milt production is inhibited in fathead minnows (Pimephales promelas) exposed to a reproductively inhibitory pulp mill effluen

Exploring and Enforcing Application Security Guarantees vis Program Dependence

We present Pidgin, a program analysis and understanding tool that allows developers to explore the information flows that exist in programs and specify and enforce security policies that restrict these information flows. Pidgin uses program-dependence graphs (PDGs) to precisely capture the information flows within a program. PDGs can be queried using a custom query language to explore and describe information flows in programs. A developer can specify strong information security policies by asserting that specific queries return no results (i.e., asserting the absence of certain information flows in the program). To check whether a program satisfies a security policy, a developer can simply evaluate the query against a program’s dependence graph. The query language is expressive, supporting a large class of precise, application-specific security guarantees. Pidgin can be used to explore information security guarantees in legacy programs, or to support the specification, enforcement, and modification of information security requirements during program development. We describe the design and implementation of Pidgin and report on using Pidgin both to explore security guarantees in existing open-source applications, and to specify and enforce security guarantees during application development.Engineering and Applied Science