A QUANTIFIER-ELIMINATION BASED HEURISTIC FOR AUTOMATICALLY GENERATING INDUCTIVE ASSERTIONS FOR PROGRAMS

A method using quantifier-elimination is proposed for automatically generating programinvariants/inductive assertions.Given a program,inductive assertions,hypothesized as parameterizedformulas in a theory,are associated with program locations.Parameters in inductive assertions arediscovered by generating constraints on parameters by ensuring that an inductive assertion is indeedpreserved by all execution paths leading to the associated location of the program.The method can beused to discover loop invariants-properties of variables that remain invariant at the entry of a loop.Theparameterized formula can be successively refined by considering execution paths one by one;heuristicscan be developed for determining the order in which the paths are considered.Initialization of programvariables as well as the precondition and postcondition,if available,can also be used to further refinethe hypothesized invariant.The method does not depend on the availability of the precondition andpostcondition of a program.Constraints on parameters generated in this way are solved for possiblevalues of parameters.If no solution is possible,this means that an invariant of the hypothesizedform is not likely to exist for the loop under the assumptions/approximations made to generate theassociated verification condition.Otherwise,if the parametric constraints are solvable,then undercertain conditions on methods for generating these constraints,the strongest possible invariant of thehypothesized form can be generated from most general solutions of the parametric constraints.Theapproach is illustrated using the logical languages of conjunction of polynomial equations as well asPresburger arithmetic for expressing assertions.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.     

Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair

Heart disease is a leading cause of death in newborn children and in adults. Efforts to promote cardiac repair through the use of stem cells hold promise but typically involve isolation and introduction of progenitor cells. Here, we show that the G-actin sequestering peptide thymosin beta4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin beta4. We found that thymosin beta4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt (also known as protein kinase B). After coronary artery ligation in mice, thymosin beta4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function. These findings suggest that thymosin beta4 promotes cardiomyocyte migration, survival and repair and the pathway it regulates may be a new therapeutic target in the setting of acute myocardial damage.     

Genome sequencing and analysis of Aspergillus oryzae

The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.     

Enhanced photocatalytic activity of electrochemically synthesized aluminum oxide nanoparticles

In this study, aluminum oxide (Al₂O₃) nanoparticles (NPs) were synthesized via an electrochemical method. The effects of reaction parameters such as supporting electrolytes, solvent, current and electrolysis time on the shape and size of the resulting NPs were investigated. The Al₂O₃ NPs were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, thermogravimetric analysis/differential thermal analysis, energy-dispersive X-ray analysis, and ultraviolet–visible spectroscopy. Moreover, the Al₂O₃ NPs were explored for photocatalytic degradation of malachite green (MG) dye under sunlight irradiation via two processes: adsorption followed by photocatalysis; coupled adsorption and photocatalysis. The coupled process exhibited a higher photodegradation efficiency (45%) compared to adsorption followed by photocatalysis (32%). The obtained kinetic data was well fitted using a pseudo-first-order model for MG degradation.     

On invariant checking

Checking whether a given formula is an invariant at a given program location (especially, inside a loop) can be quite nontrivial even for simple loop programs, given that it is in general an undecidable property. This is especially the case if the given formula is not an inductive loop invariant, as most automated techniques can only check or generate inductive loop invariants. In this paper, conditions are identified on simple loops and formulas when this check can be performed automatically. A general theorem is proved which gives a necessary and sufficient condition for a formula to be an invariant under certain restrictions on a loop. As a byproduct of this analysis, a new kind of loop invariant inside the loop body, called inside-loop invariant, is proposed. Such an invariant is more general than an inductive loop invariant typically used in the Floyd-Hoare axiomatic approach to program verification. The use of such invariants for program debugging is explored; it is shown that such invariants can be more useful than traditional inductive loop invariants especially when one is interested in checking extreme/side conditions such as underflow, accessing array/collection data structures outside the range, divide by zero, etc.     

Conditional Congruence Closure over Uninterpreted and Interpreted Symbols

A framework for generating congruence closure and conditional congruence closure of ground terms over uninterpreted as well as interpreted symbols satisfying various properties is proposed. It is based on some of the key concepts from Kapur’s congruence closure algorithm (RTA97) for ground equations based on introducing new symbols for all nonconstant subterms appearing in the equation set and using ground completion on uninterpreted constants and purified equalities over interpreted symbols belonging to different theories. In the original signature, the resulting rewrite systems may be nonterminating but they still generate canonical forms. A byproduct of this framework is a constant Horn completion algorithm using which ground canonical Horn rewrite systems can be generated for conditional ground theories.

New efficient algorithms for generating congruence closure of conditional and unconditional equations on ground terms over uninterpreted symbols are presented. The complexity of the conditional congruence closure is shown to be O(n*log(n)), which is the same as for unconditional ground equations. The proposed algorithm is motivated by our attempts to generate efficient and succinct interpolants for the quantifier-free theory of equality over uninterpreted function symbols which are often a conjunction of conditional equations and need additional simplification. A completion algorithm to generate a canonical conditional rewrite system from ground conditional equations is also presented. The framework is general and flexible and is used later to develop congruence closure algorithms for cases when function symbols satisfy simple properties such as commutativity, nilpotency, idempotency and identity as well as their combinations. Interesting outcomes include algorithms for canonical rewrite systems for ground equational and conditional theories on uninterpreted and interpreted symbols leading to generation of canonical forms for ground terms, constrained terms and Horn equations.

     

Solutions for a cultivated planet

Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.