Program Verification Using Polynomials Over Modular Arithmetic

As program verification has matured as a discipline, so distinct topics have emerged and then developed into thriving sub-disciplines, each with their own language and focus. In Satisfiability Modulo Theories (SMT) solving the focus is on deciding the satisfiability of formulae over predicates (constraints) drawn from a background theory. If a SMT formula encodes the existence of a problematic path through a program, then a model of the formula will expose a fault as demonstrated with a counter-example. In abstract interpretation, on the other hand, the objective is typically to infer invariants for a program so as to demonstrate the absence of a fault. These complementary sub-disciplines do not exist in silos completing against one another: one sub-discipline informs the other. This thesis illustrates how these sub-disciplines cross-fertilise in both directions: presenting a new abstract domain that draws on techniques from SMT solving, namely solving systems of symbolic equations (theory solving). One fundamental operation used in the domain construction applies a propagation technique that suggests how the satisfiability the SMT formulae can be reduced to that of deciding the satisfiability of a compact SAT instance. This leads to a new technique for SMT solving. Although developed in tandem, for sake of presentation the thesis first addresses the satisfiability of systems of polynomial equations over bit-vectors. Instead of conventional bit-blasting, we exploit word-level inference to translate these systems into non-linear pseudo-boolean constraints. We derive the pseudo-booleans by simulating bit assignments through the addition of (linear) polynomials and applying a strong form of propagation by computing Gröbner bases, which provide an analog of a triangular form for systems of polynomials. By handling bit assignments symbolically, the number of Gröbner basis calculations, along with the number of assignments, is reduced. The final Gröbner basis yields an assignment to the bit-vectors, expressed parametrically in terms of the symbolic bits, together with non-linear pseudo-boolean constraints on the symbolic variables, modulo a power of two. The pseudo-booleans can be solved by translation into classical linear pseudo-boolean constraints (without a modulo) or by encoding them as propositional formulae, for which a novel translation process is described. This aspect of the thesis has a practical bias. The dual theme of the thesis on abstract domain construction has a theoretical bias. The thesis presents MPAD, the modulo polynomial abstract domain, whose invariants are systems of polynomial equations that hold modulo 2 to the power of ω, where ω is bit-width. MPAD systems over d variables symbolically represent sets of points in d-dimensional space as their solutions, and provide a way of representing and inferring polynomial invariants in the presence of wrap-around arithmetic. The domain operations of MPAD are computed using Gröbner bases, but are founded on a closure operation, mirroring a construction familiar in numeric abstraction. Given an input system of polynomials, and their associated solutions, closure derives a finite polynomial representation of all polynomials that satisfy these solutions. Closure is necessary for faithfully computing join and projection, operations that preserve it. Meet does not maintain closure, hence the need for an algorithm for computing it. Unlike convention polynomial abstraction, MPAD satisfies the ascending chain condition, finessing the need for widening. It also remedies the disparity in handling of equality but not disequality in guards, normally found in numeric abstraction: the structure of MPAD allowing the addition of a single polynomial disequality to be reexpressed using closure and join. We demonstrate that MPAD can derive invariants necessary for verifying the correctness of algorithms which exploit integrality, that were previously out of reach. As a whole, the thesis makes contributions to SMT solving and abstract interpretation, two complementary themes of program verification, both of which draw on common techniques from algebraic computation, namely Gröbner bases

Brief Note Surface Charge Determination of Proteus Mirabilis Exposed to Carbenicillin

Author Institution: Division of Infectious Diseases, Department of Medicine, The Ohio State University College of Medicin

The microbiome in patients with atopic dermatitis.

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Biomarkers of Radiosensitivity in A-Bomb Survivors Pregnant at the Time of Bombings in Hiroshima and Nagasaki

Purpose. There is evidence in the literature of increased maternal radiosensitivity during pregnancy. Materials and Methods. We tested this hypothesis using information from the atomic-bomb survivor cohort, that is, the Adult Health Study database at the Radiation Effects Research Foundation, which contains data from a cohort of women who were pregnant at the time of the bombings of Hiroshima and Nagasaki. Previous evaluation has demonstrated long-term radiation dose-response effects. Results/Conclusions. Data on approximately 250 women were available to assess dose-response rates for serum cholesterol, white blood cell count, erythrocyte sedimentation rate, and serum hemoglobin, and on approximately 85 women for stable chromosome aberrations, glycophorin A locus mutations, and naïve CD4 T-cell counts. Although there is no statistically significant evidence of increased radiosensitivity in pregnant women, the increased slope of the linear trend line in the third trimester with respect to stable chromosome aberrations is suggestive of an increased radiosensitivity

Between reality and fiction : hybrid forms as a border crossing on the German television

Die vorliegende Arbeit befasst sich mit hybriden Formen des Fernsehens. Dabei wird der Forschungsfrage nach Risiken und Potenzialen bestimmter Genres und ob diese von Rezipienten als Grenzüberschreitung wahrgenommen werden, nachgegangen. Ziel der Thesis ist es mit Hilfe eines Experteninterviews herausgearbeitete Aspekte zu de-mentieren oder bestätigen. Ausgewählte Hybridformen werden anhand verschiedener Kriterien untersucht und zu einem Ergebnis zusammengefügt

Targeting Extracellular Vesicles to the Arthritic Joint using a Damaged Cartilage Specific Antibody

The targeted delivery of therapies to diseased tissues offers a safe opportunity to achieve optimal efficacy whilst limiting systemic exposure. These considerations apply to many disease indications, but are especially relevant for rheumatoid arthritis (RA), as RA is a systemic autoimmune disease which affects multiple joints. We have identified an antibody that is specific to damaged arthritic cartilage (anti-ROS-CII) that can be used to deliver treatments specifically to arthritic joints, yielding augmented efficacy in experimental arthritis. In the current study, we demonstrate that scaffold enriched with bioactive payloads can be delivered precisely to an inflamed joint and achieve superior efficacy outcomes consistent with the pharmacological properties of these payloads. As a scaffold, we have used extracellular vesicles (EV) prepared from human neutrophils (PMN), which possess intrinsic anti-inflammatory properties and the ability to penetrate inflamed arthritic cartilage. EV fortified with anti-ROS-CII (EV/anti-ROS-CII) retained anti-ROS-CII specificity and bound exclusively to the damaged cartilage. Following systemic administration EV/anti-ROS-CII: a) exhibited the ability to localise specifically in the arthritic joint in vivo and b) was able to specifically target single (viral IL-10 or anti-TNF) or combined (viral IL-10 and anti-TNF) anti-inflammatory treatments to the arthritic joint, which accelerated attenuation of clinical and synovial inflammation. Overall, this study demonstrates the attainability of targeting a pro-resolving biological scaffold to the arthritic joint. The potential of targeting scaffolds such as EV, nanoparticles or combination thereof alongside combined therapeutics is paramount for designing systemically administered broad-spectrum of anti-inflammatory treatments