A new, evidence-based, theory for knowledge reuse in security risk analysis

Security risk analysis (SRA) is a key activity in software engineering but requires heavy manual effort. Community knowledge in the form of security patterns or security catalogs can be used to support the identification of threats and security controls. However, no evidence-based theory exists about the effectiveness of security catalogs when used for security risk analysis. We adopt a grounded theory approach to propose a conceptual, revised and refined theory of SRA knowledge reuse. The theory refinement is backed by evidence gathered from conducting interviews with experts (20) and controlled experiments with both experts (15) and novice analysts (18). We conclude the paper by providing insights into the use of catalogs and managerial implications

Ares I-X Flight Test Philosophy

In response to the Vision for Space Exploration, the National Aeronautics and Space Administration (NASA) has defined a new space exploration architecture to return humans to the Moon and prepare for human exploration of Mars. One of the first new developments will be the Ares I Crew Launch Vehicle (CLV), which will carry the Orion Crew Exploration Vehicle (CEV), into Low Earth Orbit (LEO) to support International Space Station (ISS) missions and, later, support lunar missions. As part of Ares I development, NASA will perform a series of Ares I flight tests. The tests will provide data that will inform the engineering and design process and verify the flight hardware and software. The data gained from the flight tests will be used to certify the new Ares/Orion vehicle for human space flight. The primary objectives of this first flight test (Ares I-X) are the following: Demonstrate control of a dynamically similar integrated Ares CLV/Orion CEV using Ares CLV ascent control algorithms; Perform an in-flight separation/staging event between an Ares I-similar First Stage and a representative Upper Stage; Demonstrate assembly and recovery of a new Ares CLV-like First Stage element at Kennedy Space Center (KSC); Demonstrate First Stage separation sequencing, and quantify First Stage atmospheric entry dynamics and parachute performance; and Characterize the magnitude of the integrated vehicle roll torque throughout the First Stage (powered) flight. This paper will provide an overview of the Ares I-X flight test process and details of the individual flight tests

Precise Analysis of Purpose Limitation in Data Flow Diagrams

Data Flow Diagrams (DFDs) are primarily used for modelling functional properties of a system. In recent work, it was shown that DFDs can be used to also model non-functional properties, such as security and privacy properties, if they are annotated with appropriate security- and privacy-related information. An important privacy principle one may wish to model in this way is purpose limitation. But previous work on privacy-aware DFDs (PA-DFDs) considers purpose limitation only superficially, without explaining how the purpose of DFD activators and flows ought to be specified, checked or inferred. In this paper, we define a rigorous formal framework for (1) annotating DFDs with purpose labels and privacy signatures, (2) checking the consistency of labels and signatures, and (3) inferring labels from signatures. We implement our theoretical framework in a proof-of concept tool consisting of a domain-specific language (DSL) for specifying privacy signatures and algorithms for checking and inferring purpose labels from such signatures. Finally, we evaluate our framework and tool through a case study based on a DFD from the privacy literature

Contextualisation of Data Flow Diagrams for security analysis

Data flow diagrams (DFDs) are popular for sketching systems for subsequent threat modelling. Their limited semantics make reasoning about them difficult, but enriching them endangers their simplicity and subsequent ease of take up. We present an approach for reasoning about tainted data flows in design-level DFDs by putting them in context with other complementary usability and requirements models. We illustrate our approach using a pilot study, where tainted data flows were identified without any augmentations to either the DFD or its complementary models

Vps34p differentially regulates endocytosis from the apical and basolateral domains in polarized hepatic cells

Using a microinjection approach to study apical plasma membrane protein trafficking in hepatic cells, we found that specific inhibition of Vps34p, a class III phosphoinositide 3 (PI-3) kinase, nearly perfectly recapitulated the defects we reported for wortmannin-treated cells (Tuma, P.L., C.M. Finnegan, J.-H Yi, and A.L. Hubbard. 1999. J. Cell Biol. 145:1089–1102). Both wortmannin and injection of inhibitory Vps34p antibodies led to the accumulation of resident apical proteins in enlarged prelysosomes, whereas transcytosing apical proteins and recycling basolateral receptors transiently accumulated in basolateral early endosomes. To understand how the Vps34p catalytic product, PI(3)P, was differentially regulating endocytosis from the two domains, we examined the PI(3)P binding protein early endosomal antigen 1 (EEA1). We determined that EEA1 distributed to two biochemically distinct endosomal populations: basolateral early endosomes and subapical endosomes. Both contained rab5, although the latter also contained late endosomal markers but was distinct from the transcytotic intermediate, the subapical compartment. When PI(3)P was depleted, EEA1 dissociated from basolateral endosomes, whereas it remained on subapical endosomes. From these results, we conclude that PI(3)P, via EEA1, regulates early steps in endocytosis from the basolateral surface in polarized WIF-B cells. However, PI(3)P must use different machinery in its regulation of the apical endocytic pathway, since later steps are affected by Vps34p inhibition

Effect of Malondialdehyde-Acetaldehyde-Protein Adducts on the Protein Kinase C-Dependent Secretion of Urokinase-Type Plasminogen Activator in Hepatic Stellate Cells

Previous studies from our laboratory have shown that malondialdehyde-acetaldehyde-protein adducts (MAA adducts) are formed in hepatocytes of ethanol-fed rats and directly influence the hepatic stellate cells (HSCs) to induce their secretion of chemokines and to up-regulate their expression of adhesion molecules. Since protein kinase C (PKC) is known to play a major role in many diverse intracellular signal transduction processes, we investigated whether MAA adducts influence the function of HSCs via a PKC-dependent pathway. HSCs in culture were exposed to MAA adducts, and PKC activity was determined. We observed a time- and concentration-dependent activation of PKC when cultures were exposed to BSA-MAA as compared with unmodified BSA. Using PKC isoform-specific inhibitors, we also showed that BSA-MAA induces the activation of a specific isoform of PKC, PKC-a, in HSCs. No activation of PKC was observed when HSCs were exposed to other aldehyde adducts such as BSA-acetaldehyde or BSA-malondialdehyde, indicating that the effects of MAA adducts on HSCs were somewhat specific. We further examined whether the observed increase in PKC activation induced by MAA adducts in HSCs, in turn, causes a functional effect. We observed that BSA-MAA induces the increased secretion of urokinase-type plasminogen activator, a key component of the plasmin-generating system, and that PKC activation is necessary for this enhanced urokinase-type plasminogen activator secretion. These results indicate that MAA adducts via a PKC-mediated pathway may regulate plasmin-mediated matrix degradation in the liver, thereby contributing to the progression of hepatic fibrosis

Molecular details of quinolone–DNA interactions: solution structure of an unusually stable DNA duplex with covalently linked nalidixic acid residues and non-covalent complexes derived from it

Quinolones are antibacterial drugs that are thought to bind preferentially to disturbed regions of DNA. They do not fall into the classical categories of intercalators, groove binders or electrostatic binders to the backbone. We solved the 3D structure of the DNA duplex (ACGCGU-NA)(2), where NA denotes a nalidixic acid residue covalently linked to the 2′-position of 2′-amino-2′-deoxyuridine, by NMR and restrained torsion angle molecular dynamics (MD). In the complex, the quinolones stack on G:C base pairs of the core tetramer and disrupt the terminal A:U base pair. The displaced dA residues can stack on the quinolones, while the uracil rings bind in the minor groove. The duplex-bridging interactions of the drugs and the contacts of the displaced nucleotides explain the high UV-melting temperature for d(ACGCGU-NA)(2) of up to 53°C. Further, non-covalently linked complexes between quinolones and DNA of the sequence ACGCGT can be generated via MD using constraints obtained for d(ACGCGU-NA)(2). This is demonstrated for unconjugated nalidixic acid and its 6-fluoro derivative. The well-ordered and tightly packed structures thus obtained are compatible with a published model for the quinolone–DNA complex in the active site of gyrases

Proteomics Reveal a Concerted Upregulation of Methionine Metabolic Pathway Enzymes, and Downregulation of Carbonic Anhydrase-III, in Betaine Supplemented Ethanol-Fed Rats

We employed a proteomic profiling strategy to examine the effects of ethanol and betaine diet supplementation on major liver protein level changes. Male Wistar rats were fed control, ethanol or betaine supplemented diets for 4 weeks. Livers were removed and liver cytosolic proteins resolved by onedimensional and two-dimensional separation techniques. Significant upregulation of betaine homocysteine methyltransferase-1, methionine adenosyl transferase-1, and glycine N-methyltransferase were the most visually prominent protein changes observed in livers of rats fed the betaine supplemented ethanol diet. We hypothesise that this concerted upregulation of these methionine metabolic pathway enzymes is the protective mechanism by which betaine restores a normal metabolic ratio of liver S-adenosylmethionine to S-adenosylhomocysteine. Ethanol also induced significant downregulation of carbonic anhydrase- III protein levels which was not restored by betaine supplementation. Carbonic anhydrase-III can function to resist oxidative stress, and we therefore hypothesise that carbonic anhydrase-III protein levels compromised by ethanol consumption, contribute to ethanol-induced redox stress

Assessment of treatment outcomes of multidrug-resistant tuberculosis patients in D R Congo: A study based on drug regimens used between 2007 to 2017: Évaluation des issues thérapeutiques des patients atteints de la tuberculose à bacilles multi résistants : étude basée sur les régimes de médicaments utilisés en République Démocratique du Congo de 2007 à 2017

Context. Little is known about therapeutic successes in MDR-TB patients under regimens containing second-line molecules. The present study aimed to assess therapeutic outcomes in patients under therapeutic regimens applied in DR Congo. Methods. This historical cohort study has included confirmed MDR-TB patients who received treatment between 2007 and 2017 in 218 TB centers in DR Congo. Treatment outcome and survival at 36 months were analyzed using Zscore and chi square test. Kaplan-Meier method was performed to describe survival and Log Rank test helped in comparing curve based on the therapeutical regimen. Factors associated with therapeutic success and mortality predictors were assessed using multivariate logistic regression and Cox regression analysis, respectively. Results. The therapeutic success in the study group (n=1,724) was 72% (range 68-74%) for all regimen combined. The average death rate was 12.8% although the group of patients receiving Cyclosérine and Ofloxacine was the most affected (16%). The death rate was significantly higher in patients living in urban areas (15.2% versus 14.9%, p = 0.013) and also among MDR-TB/HIV co-infected patients (28.4% vs 15.7%, p<0.001) patients. The median survival of the study group was 722.7 days compared to 601.1 days for MDR-TB/HIV co-infected patients, and 736.7 days for HIV negative patients (p<0.001). Conclusion. Therapeutic successes are significant for the short regimen. However, the death rate remains high when Cycloserine and Ofloxacin are included in the regimen. The predictors of mortality are HIV infection and living in urban areas. Contexte. L’issue thérapeutique de la tuberculose multi résistante (TB-MR) sous les molécules de deuxième intention n’est pas très bien connue. La présente étude a évalué les régimes thérapeutiques appliqués, en termes de succès thérapeutique et de survie. Méthodes. L’étude de cohorte historique a inclu les patients TB-MR confirmés et traités entre 2007 et 2017 dans 218 centres de tuberculose en RD Congo. L’issue thérapeutique et la survie à 36 mois ont été analysées. Le score Z ou le test de chi carré ont comparé des issues. La méthode de Kaplan-Meier a décrit les courbes de survie et le test de Log Rank a comparé la survie en fonction du regime therapeutique. Les facteurs associés au succès thérapeutique et les prédicteurs de mortalité ont été analysés respectivement, par l’analyse multivariée de régression logistique et de Cox. Résultats. Dans le groupe étudié (n=1724), le succès thérapeutique a été de 72% (68-74%) pour l’ensemble des régimes. Le taux était plus élevé pour le régime court (74%) et plus faible pour le régime contenant la Cyclosérine et l’Ofloxacine (68%). La moyenne de décès était de 12,8% ; mais plus élevée dans le groupe sous regime contenant la Cyclosérine et l’Ofloxacine (16%). Le taux de décès était significativement plus élevé en milieu urbain (15,2% versus 14,9 %, p = 0,013) et également chez les sujets co-infectés par la MDR-TB  et le VIH (28.4% vs 15.7%, p <0,001). La survie médiane dans le groupe était de 722,7 jours contre 601,1 jours chez les co-infectés MDR-TB/VIH, et de 736,7 jours) chez les patients VIH négatifs (p<0,001). Conclusion. Les succès thérapeutiques sont acceptables en particulier, pour le régime court ; toutefois, le taux de décès demeure encore très élevé dans le groupe sous Cyclosérine et Ofloxacine. Les prédicteurs de mortalité sont l’infection à VIH et la vie citadine. &nbsp

Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome

Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection