Translating Clojure to ACL2 for Verification

Software spends a significant portion of its life-cycle in the maintenance phase and over 20\% of the maintenance effort is fixing defects. Formal methods, including verification, can reduce the number of defects in software and lower corrective maintenance, but their industrial adoption has been underwhelming. A significant barrier to adoption is the overhead of converting imperative programming languages, which are common in industry, into the declarative programming languages that are used by formal methods tools. In comparison, the verification of software written in declarative programming languages is much easier because the conversion into a formal methods tool is easier. The growing popularity of declarative programming --- evident from the rise of multi-paradigm languages such as Javascript, Ruby, and Scala --- affords us the opportunity to verify the correctness of software more easily. Clojure is a declarative language released in 2007 that compiles to bytecode that executes on the Java Virtual Machine (JVM). Despite being a newer, declarative programming language, several companies have already used it to develop commercial products. Clojure shares a Lisp syntax with ACL2, an interactive theorem prover that is used to verify the correctness of software. Since both languages are based on Lisp, code written in either Clojure or ACL2 is easily converted to the other. Therefore, Clojure can conceivably be verified by ACL2 with limited overhead assuming that the underlying behavior of Clojure code matches that of ACL2. ACL2 has been previously used to reason about Java programs through the use of formal models of the JVM. Since Clojure compiles to JVM bytecode, a similar approach is taken in this dissertation to verify the underlying implementation of Clojure. The research presented in this dissertation advances techniques to verify Clojure code in ACL2. Clojure and ACL2 are declarative, but they are specifically functional programming languages so the research focuses on two important concepts in functional programming and verification: arbitrary-precision numbers ("bignums") and lists. For bignums, the correctness of a model of addition is verified that addresses issues that arise from the unique representation of bignums in Clojure. Lists, in Clojure, are implemented as a type of sequence. This dissertation demonstrates an abstraction that equates Clojure sequences to ACL2 lists. In support of the research, an existing ACL2 model of the JVM is modified to address specific aspects of compiled Clojure code and the new model is used to verify the correctness of core Clojure functions with respect to corresponding ACL2 functions. The results support the ideas that ACL2 can be used to reason about Clojure code and that formal methods can be integrated more easily in industrial software development when the implementation corresponds semantically to the verification model

Attribution of Responsibility after Failures within Platform Ecosystems

Increasingly, new hardware and software are embedded within ecosystems that include a platform and modules. Ideally these ecosystems perform reliably. However, if an ambiguously sourced failure occurs within one of these ecosystems, users are left to distribute blame across the various components of the ecosystem. The actual distribution of this blame, however, can be difficult to predict. This study investigates attribution of blame and discontinuance recommendations for ecosystem components after an ambiguously sourced failure. To extend platform ecosystems and attribution theory, we conducted a scenario-based experiment investigating the negative consequences of failure for platform and module components and the contingent effects from design elements (border strength) and contextual factors (task goal directedness, disruption severity). Results demonstrated a diffusion of negative consequences for failure across ecosystem components, but ecosystem modules (apps) received the majority of the blame and highest discontinuance recommendations. High border strength shifted negative consequences for failure away from the OS to the device. Low goal-directedness resulted in users taking more of the blame for the failure, and higher disruption severity resulted in higher discontinuance recommendations for the OS and device. Importantly, the amount of blame attributed to one component in an ecosystem predicted discontinuance recommendations for other components

Eye of the Blamestorm: An Exploration of User Blame Assessment within Compound Digital Platforms

More and more IS-enabled technologies are being used within the context of ecosystems that include both hardware and software components that act together as a central platform; we term these ecosystems digital compound platform ecosystems. However, given the interconnectedness of components within these platforms, if an ambiguously sourced failure occurs within one of these ecosystems, users may blame and/or take action against components in the ecosystem that were not actually at fault. This study considers antecedents of both blame and discontinuance intent within such ecosystems given a system failure of ambiguous origins. We test manipulations for border strength, goal directedness, and resolution duration to understand their impact. We find that all three of these manipulations have an effect on user assessment of blame and discontinuance intent. Further, we establish that blame is not a required condition for discontinuance intent to occur

Lobar pneumonia caused by Ralstonia pickettii in a sixty-five-year-old Han Chinese man: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Ralstonia pickettii </it>is a gram-negative, oxidase-positive bacillus and is an emerging pathogen found in infections described in hospital settings. The cases reported in the literature mostly are nosocomial infections due to contaminated blood products, sterile water, saline, treatment fluids and venous catheters. Human infection unrelated to contaminated solutions is rare. We report a case of lobar pneumonia and pulmonary abscess caused by <it>Ralstonia pickettii </it>in an older patient.</p> <p>Case presentation</p> <p>A sixty-five-year old Han Chinese man presented having had cough, expectoration, chest pain and fever lasting for twenty days. His medical history was notable for hypertension over the previous ten years, and the habit of smoking for forty years. A thoracic computed tomography scan supported the diagnosis of right-sided lobar pneumonia. A lung biopsy was done and pathological analysis confirmed lobar pneumonia. Two lung biopsy specimens from separate sites grew <it>Ralstonia pickettii</it>. After six days, a repeat thoracic scan revealed a right-sided abscess. A thoracentesis was performed and the purulent fluid grew <it>Ralstonia pickettii</it>. The chest tube remained inserted to rinse the cavity with sterile sodium chloride. He received an antibiotic course of intravenous cefoperazone sodium-sulbactam sodium for eighteen days and imipenem-cilastatin for twelve days. A repeat chest X-ray revealed resolution of the pulmonary abscess and improvement of pneumonia. He remained afebrile and free of respiratory symptoms after treatments.</p> <p>Conclusion</p> <p>This case demonstrates a <it>Ralstonia pickettii </it>infection in the absence of an obvious nosocomial source. It is possible that such cases will become common in the future. Therefore, further studies are needed to evaluate its sensitivity to common antibiotics.</p

Fetal Programming of Adult Glucose Homeostasis in Mice

BACKGROUND: Emerging evidence suggests that dietary soy and phytoestrogens can have beneficial effects on lipid and glucose metabolism. We have previously shown that male mice fed from conception to adulthood with a high soy-containing diet had reduced body weight, adiposity and a decrease in glucose intolerance, an early marker of insulin resistance and diabetes. OBJECTIVES: The purpose of this study was to identify the precise periods of exposure during which phytoestrogens and dietary soy improve lipid and glucose metabolism. Since intrauterine position (IUP) has been shown to alter sensitivity to endocrine disruptors, we also investigated whether the combination of IUP and fetal exposure to dietary phytoestrogens could potentially affect adult metabolic parameters. METHODS: Male outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet either during gestation, lactation or after weaning. Adiposity and bone mass density was assessed by dual x-ray absorptiometry. Glucose tolerance was assessed by a glucose tolerance test. Blood pressure was examined by the tail-cuff system. RESULTS: Here we show that metabolic improvements are dependent on precise windows of exposure during life. The beneficial effects of dietary soy and phytoestrogens on adiposity were apparent only in animals fed post-natally, while the improvements in glucose tolerance are restricted to animals with fetal exposure to soy. Interestingly, we observed that IUP influenced adult glucose tolerance, but not adiposity. Similar IUP trends were observed for other estrogen-related metabolic parameters such as blood pressure and bone mass density. CONCLUSION: Our results suggest that IUP and fetal exposure to estrogenic environmental disrupting compounds, such as dietary phytoestrogens, could alter metabolic and cardiovascular parameters in adult individuals independently of adipose gain

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.

OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism

Assessment of gene-by-sex interaction effect on bone mineral density

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015