Security metrics for object-oriented designs

Several studies have developed metrics for software quality attributes of object-oriented designs such as reusability and functionality. However, metrics which measure the quality attribute of information security have received little attention. Moreover, existing security metrics measure either the system from a high level (i.e. the whole system’s level) or from a low level (i.e. the program code’s level). These approaches make it hard and expensive to discover and fix vulnerabilities caused by software design errors. In this work, we focus on the design of an object-oriented application and define a number of information security metrics derivable from a program’s design artifacts. These metrics allow software designers to discover and fix security vulnerabilities at an early stage, and help compare the potential security of various alternative designs. In particular, we present security metrics based on composition, coupling, extensibility, inheritance, and the design size of a given object-oriented, multi-class program from the point of view of potential information flow.

New insights into Crustal Contributions to Large-volume Rhyolite Generation in the Mid-Tertiary Sierra Madre Occidental Province, Mexico, revealed by U Pb Geochronology

Voluminous (≥3·9 × 105 km3), prolonged (∼18 Myr) explosive silicic volcanism makes the mid-Tertiary Sierra Madre Occidental province of Mexico one of the largest intact silicic volcanic provinces known. Previous models have proposed an assimilation–fractional crystallization origin for the rhyolites involving closed-system fractional crystallization from crustally contaminated andesitic parental magmas, with <20% crustal contributions. The lack of isotopic variation among the lower crustal xenoliths inferred to represent the crustal contaminants and coeval Sierra Madre Occidental rhyolite and basaltic andesite to andesite volcanic rocks has constrained interpretations for larger crustal contributions. Here, we use zircon age populations as probes to assess crustal involvement in Sierra Madre Occidental silicic magmatism. Laser ablation-inductively coupled plasma-mass spectrometry analyses of zircons from rhyolitic ignimbrites from the northeastern and southwestern sectors of the province yield U–Pb ages that show significant age discrepancies of 1–4 Myr compared with previously determined K/Ar and 40Ar/39Ar ages from the same ignimbrites; the age differences are greater than the errors attributable to analytical uncertainty. Zircon xenocrysts with new overgrowths in the Late Eocene to earliest Oligocene rhyolite ignimbrites from the northeastern sector provide direct evidence for some involvement of Proterozoic crustal materials, and, potentially more importantly, the derivation of zircon from Mesozoic and Eocene age, isotopically primitive, subduction-related igneous basement. The youngest rhyolitic ignimbrites from the southwestern sector show even stronger evidence for inheritance in the age spectra, but lack old inherited zircon (i.e. Eocene or older). Instead, these Early Miocene ignimbrites are dominated by antecrystic zircons, representing >33 to ∼100% of the dated population; most antecrysts range in age between ∼20 and 32 Ma. A sub-population of the antecrystic zircons is chemically distinct in terms of their high U (>1000 ppm to 1·3 wt %) and heavy REE contents; these are not present in the Oligocene ignimbrites in the northeastern sector of the Sierra Madre Occidental. The combination of antecryst zircon U–Pb ages and chemistry suggests that much of the zircon in the youngest rhyolites was derived by remelting of partially molten to solidified igneous rocks formed during preceding phases of Sierra Madre Occidental volcanism. Strong Zr undersaturation, and estimations for very rapid dissolution rates of entrained zircons, preclude coeval mafic magmas being parental to the rhyolite magmas by a process of lower crustal assimilation followed by closed-system crystal fractionation as interpreted in previous studies of the Sierra Madre Occidental rhyolites. Mafic magmas were more probably important in providing a long-lived heat and material flux into the crust, resulting in the remelting and recycling of older crust and newly formed igneous materials related to Sierra Madre Occidental magmatism.

Incremental entrepreneurship : best practice professionalization across generations

This chapter will introduce Australia’s Dennis family – a case of ‘incremental entrepreneurship’ in the business transition from the first to the second generation. Following the second generation’s formal involvement and ownership in the business, Dennis Family Corporation (DFC) undertook a major professionalization process to formalize the family business and ensure its continued success. The members of the second generation have successfully sustained the entrepreneurial spirit of their family business (albeit in a different style), adding value to the firm in an ‘incremental’ manner. Throughout the chapter there will be a strong emphasis on the family element of DFC and the roles that each family member has played. Bert Dennis, as the founder and incumbent leader of the firm, has witnessed major changes to the business he built from the ground up. His children, in particular his son Grant Dennis as the primary next generation issue champion, have seen the changes from another perspective – ensuring the business remains within the family into the second generation and beyond. The professionalization process was sparked by a commitment from the second generation to continue to ‘make a real go’ of the family business rather than simply liquidating and distributing the assets. The dedication of all the family members to this objective has ensured the success of this process, and ultimately, the longevity of the firm. Although DFC has become more ‘professional’, it has not lost its entrepreneurial character; rather, it has improved the ways in which entrepreneurialism is fostered and pursued in the company. In essence, this case outlines how the implementation of appropriate governance and management practices has allowed the Dennis family to overcome the challenges and maximize the opportunities associated with owning and operating a multigenerational family fi rm. From a theoretical perspective, this case uses the concepts of entrepreneurial orientation (EO) (Lumpkin and Dess 1996) and the resource- based view (RBV) (Habbershon and Williams 1999; Barney 1991; Wernerfelt 1984) to demonstrate how the fi rm has leveraged its familiness to foster an enduring spirit of entrepreneurship and to maintain a sustained competitive advantage.

Enhancing resilience in indigenous people: The integration of individual, family and community interventions

This paper describes a number of interventions being developed to address the emotional, social and behavioural problems experienced by Aboriginal people in Australia. These are: the We-Al-Li program to help people deal with the impact of transgenerational trauma; and the RAP Indigenous Parenting Program. It is argued that the emotional well being of indigenous people will be enhanced through the integration of interventions targeting the individual, family and community.

Quality metrics for assessing security-critical computer programs

Existing secure software development principles tend to focus on coding vulnerabilities, such as buffer or integer overflows, that apply to individual program statements, or issues associated with the run-time environment, such as component isolation. Here we instead consider software security from the perspective of potential information flow through a program’s object-oriented module structure. In particular, we define a set of quantifiable "security metrics" which allow programmers to quickly and easily assess the overall security of a given source code program or object-oriented design. Although measuring quality attributes of object-oriented programs for properties such as maintainability and performance has been well-covered in the literature, metrics which measure the quality of information security have received little attention. Moreover, existing securityrelevant metrics assess a system either at a very high level, i.e., the whole system, or at a fine level of granularity, i.e., with respect to individual statements. These approaches make it hard and expensive to recognise a secure system from an early stage of development. Instead, our security metrics are based on well-established compositional properties of object-oriented programs (i.e., data encapsulation, cohesion, coupling, composition, extensibility, inheritance and design size), combined with data flow analysis principles that trace potential information flow between high- and low-security system variables. We first define a set of metrics to assess the security quality of a given object-oriented system based on its design artifacts, allowing defects to be detected at an early stage of development. We then extend these metrics to produce a second set applicable to object-oriented program source code. The resulting metrics make it easy to compare the relative security of functionallyequivalent system designs or source code programs so that, for instance, the security of two different revisions of the same system can be compared directly. This capability is further used to study the impact of specific refactoring rules on system security more generally, at both the design and code levels. By measuring the relative security of various programs refactored using different rules, we thus provide guidelines for the safe application of refactoring steps to security-critical programs. Finally, to make it easy and efficient to measure a system design or program’s security, we have also developed a stand-alone software tool which automatically analyses and measures the security of UML designs and Java program code. The tool’s capabilities are demonstrated by applying it to a number of security-critical system designs and Java programs. Notably, the validity of the metrics is demonstrated empirically through measurements that confirm our expectation that program security typically improves as bugs are fixed, but worsens as new functionality is added.

A novel SNP in COMT is associated with alcohol dependence but not opiate or nicotine dependence: a case control study

Background It is well established that COMT is a strong candidate gene for substance use disorder and schizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with schizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680 and rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated. Methods To determine whether COMT is important in substance dependence, rs165774 and rs4680 were genotyped and haplotyped in patients with nicotine, alcohol and opiate dependence. Results The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine or opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG genotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a weak association with alcohol dependence at the allele level that did not reach significance at the genotype level but it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed association with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcohol-dependent cases. Conclusions Our study provides further support for the importance of the COMT in alcohol dependence in addition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common molecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is potentially important for future studies of comorbidity. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Prenatal Vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation

In a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin d deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin d-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin d deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin d status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

25 million years to break a continent : early to middle Miocene rifting and syn-extensional magmatism in the southern Gulf of California

Cenozoic extension in western Mexico has been divided into two episodes separated by the change from convergence to oblique divergence at the plate boundary. The Gulf Extensional Province is thought to have started once subduction ended at ~12.5 Ma whereas early extension is classified as Basin and Range. Mid-Miocene volcanism of the Comondú group has been considered as a subduction-related arc, whereas post ~12.5 Ma volcanism would be extension-related. Our new integration of the continental onshore and offshore geology of the south-east Gulf region, backed by tens of Ar-Ar and U-Pb ages and geochemical studies, document an early-mid Miocene rifting and extension-related bimodal to andesitic magmatism prior to subduction termination. Between ~21 and 11 Ma a system of NNW-SSE high-angle extensional faults rifted the western side of the Sierra Madre Occidental (SMO) ignimbrite plateau. In Nayarit, rhyolitic domes and some basalts were emplaced along this extensional belt at 18-17 Ma. These rocks show strong antecrystic inheritance but an absence of Mesozoic and older xenocrysts, suggesting a genesis in the mid-upper crust triggered by extension-induced basaltic influx. In Sinaloa, large grabens were floored by huge dome complexes at ~21-17 Ma and filled by continental sediments with interlayered basalts dated at 15 Ma. Mid-Miocene volcanism, including the largely volcaniclastic Comondú strata in Baja California, was thus emplaced in rift basins and appears associated to decompression melting rather than subduction. Along the coast, flat-lying basaltic lava flows dated at 11-10 Ma are exposed just above the present sea level. Here crustal thickness is 25-20 Km, almost half that in the core of the SMO, implying significant lithosphere stretching before ~11 Ma. This mafic pulse, with relatively high Ti but still clear Nb-Ta negative spikes, may be related to the detachment of the lower part of the subducted slab, allowing asthenosphere to flow into parts of the mantle previously fluxed by subduction fluids. Very uniform OIB-like lavas appear in late Pliocene and Pleistocene, only 18 m.y. after the onset of rifting and ~9 m.y. after the end of subduction. Our study shows that rifting began much earlier than Late Miocene and progressively overwhelmed subduction in generating magmatism.

Construct Redundancy in Process Modeling Grammars: Improving the Explanatory Power of Ontological Analysis

Conceptual modelling supports developers and users of information systems in areas of documentation, analysis or system redesign. The ongoing interest in the modelling of business processes has led to a variety of different grammars, raising the question of the quality of these grammars for modelling. An established way of evaluating the quality of a modelling grammar is by means of an ontological analysis, which can determine the extent to which grammars contain construct deficit, overload, excess or redundancy. While several studies have shown the relevance of most of these criteria, predictions about construct redundancy have yielded inconsistent results in the past, with some studies suggesting that redundancy may even be beneficial for modelling in practice. In this paper we seek to contribute to clarifying the concept of construct redundancy by introducing a revision to the ontological analysis method. Based on the concept of inheritance we propose an approach that distinguishes between specialized and distinct construct redundancy. We demonstrate the potential explanatory power of the revised method by reviewing and clarifying previous results found in the literature.

Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene

Focal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13, which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.

Late Oligocene to Middle Miocene rifting and synextensional magmatism in the southwestern Sierra Madre Occidental, Mexico : the beginning of the Gulf of California rift

Although Basin and Range–style extension affected large areas of western Mexico after the Late Eocene, most consider that extension in the Gulf of California region began as subduction waned and ended ca. 14–12.5 Ma. A general consensus also exists in considering Early and Middle Miocene volcanism of the Sierra Madre Occidental and Comondú Group as subduction related, whereas volcanism after ca. 12.5 Ma is extension related. Here we present a new regional geologic study of the eastern Gulf of California margin in the states of Nayarit and Sinaloa, Mexico, backed by 43 new Ar-Ar and U-Pb mineral ages, and geochemical data that document an earlier widespread phase of extension. This extension across the southern and central Gulf Extensional Province began between Late Oligocene and Early Miocene time, but was focused in the region of the future Gulf of California in the Middle Miocene. Late Oligocene to Early Miocene rocks across northern Nayarit and southern Sinaloa were affected by major approximately north-south– to north-northwest– striking normal faults prior to ca. 21 Ma. Between ca. 21 and 11 Ma, a system of north-northwest–south-southeast high angle extensional faults continued extending the southwestern side of the Sierra Madre Occidental. Rhyolitic domes, shallow intrusive bodies, and lesser basalts were emplaced along this extensional belt at 20–17 Ma. Rhyolitic rocks, in particular the domes and lavas, often show strong antecrystic inheritance but only a few Mesozoic or older xenocrysts, suggesting silicic magma generation in the mid-upper crust triggered by an extension induced basaltic infl ux. In northern Sinaloa, large grabens were occupied by huge volcanic dome complexes ca. 21–17 Ma and filled by continental sediments with interlayered basalts dated as 15–14 Ma, a stratigraphy and timing very similar to those found in central Sonora (northeastern Gulf of California margin). Early to Middle Miocene volcanism occurred thus in rift basins, and was likely associated with decompression melting of upper mantle (inducing crustal partial melting) rather than with fluxing by fluids from the young and slow subducting microplates. Along the eastern side of the Gulf of California coast, from Farallón de San Ignacio island offshore Los Mochis, Sinaloa, to San Blas, Nayarit, a strike distance of >700 km, flat lying basaltic lavas dated as ca. 11.5–10 Ma are exposed just above the present sea level. Here crustal thickness is almost half that in the unextended core of the adjacent Sierra Madre Occidental, implying signifi cant lithosphere stretching before ca. 11 Ma. This mafic pulse, with subdued Nb-Ta negative spikes, may be related to the detachment of the lower part of the subducted slab, allowing an upward asthenospheric flow into an upper mantle previously modified by fluid fluxes related to past subduction. Widespread eruption of very uniform oceanic island basalt–like lavas occurred by the late Pliocene and Pleistocene, only 20 m.y. after the onset of rifting and ~9 m.y. after the end of subduction, implying that preexisting subduction-modified mantle had now become isolated from melt source regions. Our study shows that rifting across the southern-central Gulf Extensional Province began much earlier than the Late Miocene and provided a fundamental control on the style and composition of volcanism from at least 30 Ma. We envision a sustained period of lithospheric stretching and magmatism during which the pace and breadth of extension changed ca. 20–18 Ma to be narrower, and again after ca. 12.5 Ma, when the kinematics of rifting became more oblique.

A possible role for mitochondrial dysfunction in migraine

Migraine is a common neurological disorder characterised by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia and occasionally visual sensory disturbances. Migraine is a complex disease caused by an interplay between predisposing genetic variants and environmental factors. It affects approximately 12 % of studied Caucasian populations with affected individuals being predominantly female. Genes involved in neurological, vascular or hormonal pathways have all been implicated in predisposition towards developing migraine. All of these are nuclear encoded genes, but given the role of mitochondria in a number of neurological disorders and in energy production it is possible that mitochondrial variants may play a role in the pathogenesis of this disease. Mitochondrial DNA has been a useful tool for studying population genetics and human genetic diseases due to the clear inheritance shown through successive generations. Given the clear gender bias found in migraine patients it may be important to investigate X-linked inheritance and mitochondrial-related variants in this disorder. This paper explores the possibility that mitochondrial DNA changes may play a role in migraine. Few variants in the mitochondrial genome have so far been investigated in migraine and new studies should be aimed towards investigating the role of mitochondrial DNA in this common disorder.

Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.

Investigation of hormone receptor genes in migraine

Migraine is a common neurological condition with a complex mode of inheritance. Steroid hormones have long been implicated in migraine, although their role remains unclear. Our investigation considered that genes involved in hormonal pathways may play a role in migraine susceptibility. We therefore investigated the androgen receptor (AR) CAG repeat, and the progesterone receptor (PR) PROGINS insert by cross-sectional association analysis. The results showed no association with the AR CAG repeat in our study group of 275 migraineurs and 275 unrelated controls. Results of the PR PROGINS analysis showed a significant difference in the same cohort, and in an independent follow-up study population of 300 migraineurs and 300 unrelated controls. Analysis of the genotypic risk groups of both populations together indicated that individuals who carried the PROGINS insert were 1.8 times more likely to suffer migraine. Interaction analysis of the PROGINS variant with our previously reported associated ESR1 594A variant showed that individuals who possessed at least one copy of both risk alleles were 3.2 times more likely to suffer migraine. Hence, variants of these steroid hormone receptor genes appear to act synergistically to increase the risk of migraine by a factor of three.

A typical migraine susceptibility region localizes to chromosome 1q31

Migraine (with and without aura) is a prevalent neurovascular disease that shows strong familial aggregation, although the number of genes involved and the mode of inheritance is not clear. Some insight into the disease has been gained from genetic studies into a rare and very severe migraine subtype known as familial hemiplegic migraine (FHM). In this study, we took a family-based linkage and association approach to investigate the FHM susceptibility region on chromosome 1q31 for involvement in typical migraine susceptibility in affected Australian pedigrees. Initial multipoint ALLEGRO analysis provided strong evidence for linkage of Chrlq31 markers to typical migraine in a large multigenerational pedigree. The 1-LOD* unit support interval for suggestive linkage spanned approximately 18 cM with a maximum allele sharing LOD* score of 3.36 obtained for marker D1S2782 (P=0.00004). Subsequent analysis of an independent sample of 82 affected pedigrees added support to the initial findings with a maximum LOD* of 1.24 (P=0.008). Utilising the independent sample of 82 pedigrees, we also performed a family-based association test. Results of this analysis indicated distortion of allele transmission at marker D1S249 [global chi2 (5) of 15.00, P=0.010] in these pedigrees. These positive linkage and association results will need further confirmation by independent researchers. However, overall they provide good evidence for the existence of a typical migraine locus near these markers on Chrlq3l, and reinforce the idea that an FHM gene in this genomic region may also contribute to susceptibility to the more common forms of migraine.