Improving Strategies via SMT Solving

We consider the problem of computing numerical invariants of programs by abstract interpretation. Our method eschews two traditional sources of imprecision: (i) the use of widening operators for enforcing convergence within a finite number of iterations (ii) the use of merge operations (often, convex hulls) at the merge points of the control flow graph. It instead computes the least inductive invariant expressible in the domain at a restricted set of program points, and analyzes the rest of the code en bloc. We emphasize that we compute this inductive invariant precisely. For that we extend the strategy improvement algorithm of [Gawlitza and Seidl, 2007]. If we applied their method directly, we would have to solve an exponentially sized system of abstract semantic equations, resulting in memory exhaustion. Instead, we keep the system implicit and discover strategy improvements using SAT modulo real linear arithmetic (SMT). For evaluating strategies we use linear programming. Our algorithm has low polynomial space complexity and performs for contrived examples in the worst case exponentially many strategy improvement steps; this is unsurprising, since we show that the associated abstract reachability problem is Pi-p-2-complete

Molecular analysis of phosphoglycerate kinase in Trypanoplasma borreli and the evolution of this enzyme in kinetoplastida.

In the protozoan kinetoplastid organism Trypanoplasma borreli, phosphoglycerate kinase (PGK) activity was found in two different cell compartments: 80% in the cytosol and 20% in peroxisome-like organelles called glycosomes. However, only one functional pgk gene could be detected, in addition to a pseudo-pgk gene. No short-range linkage could be established between these two genes, although they are presumably present on the same chromosome. The intact gene codes for a polypeptide of 411 amino acids, with a C-terminal extension of four residues, -VAKF, a sequence with probably a low targeting efficiency for glycosomes. The calculated net charge and molecular mass of the encoded polypeptide are +13 and 44230Da, respectively. In other Kinetoplastida, different tandemly arranged genes code for distinct PGK isoenzymes in glycosomes and cytosol. By comparison of the pgk gene organization, and a phylogenetic analysis, we have traced a plausible scenario of the evolution of the PGK isoenzymes in these organisms and of the enzymes' intracellular compartmentation

Organization, sequence and stage-specific expression of the phosphoglycerate kinase genes of Leishmania mexicana mexicana

In Leishmania mexicana two genes were detected coding for different isoforms of the glycolytic enzyme phosphoglycerate kinase. This situation contrasts with that observed in other Trypanosomatidae (Trypanosoma brucei, Trypanosoma congolense, Crithidia fasciculata) analyzed previously, which all contain three different genes coding for isoenzymes A, B and C, respectively. All attempts to detect in L. mexicana a type A PGK, or a gene encoding it, proved unsuccesful. We have cloned and characterized the genes PGKB and PGKC. They code for polypeptides of 416 and 478 amino acids with a molecular mass of 45146 and 51318 Da, respectively. The two polypeptides are 99% identical. PGKC is characterized by a 62 residue C-terminal extension with alternating stretches of hydrophobic and charged, mainly positive amino acids. As in other Trypanosomatidae, PGKB is located in the cytosol, PGKC in the glycosomes. However, Leishmania mexicana distinguishes itself from other trypanosomatids by the simultaneous expression of these isoenzymes: approximately 80% of PGK activity is found in the cytosol and 20% in the glycosomes, both in promastigotes and in the amastigote-like form of the parasite

Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands

NK cells are regulated in part by killer Ig-like receptors (KIR) that interact with HLA molecules on potential target cells. KIR and HLA loci are highly polymorphic and certain KIR/HLA combinations were found to protect against HIV disease progression. We show in this study that KIR/HLA interactions also influence resistance to HIV transmission. HIV-exposed but seronegative female sex workers in Abidjan, Côte d'Ivoire, frequently possessed inhibitory KIR genes in the absence of their cognate HLA genes: KIR2DL2/KIR2DL3 heterozygosity in the absence of HLA-C1 and KIR3DL1 homozygosity in the absence of HLA-Bw4. HIV-seropositive female sex workers were characterized by corresponding inhibitory KIR/HLA pairings: KIR2DL3 homozygosity together with HLA-C1 and a trend toward KIR3DL1/HLA-Bw4 homozygosity. Absence of ligands for inhibitory KIR could lower the threshold for NK cell activation. In addition, exposed seronegatives more frequently possessed AB KIR genotypes, which contain more activating KIR. The data support an important role for NK cells and KIR/HLA interactions in antiviral immunity

Combining Zonotope Abstraction and Constraint Programming for Synthesizing Inductive Invariants

International audienceWe propose to extend an existing framework combining abstract interpretation and continuous constraint programming for numerical invariant synthesis, by using more expressive underlying abstract domains, such as zonotopes. The original method, which relies on iterative refinement, splitting and tightening a collection of abstract elements until reaching an inductive set, was initially presented in combination with simple underlying abstract elements: boxes and octagons. The novelty of our work is to use zonotopes, a sub-polyhedric domain that shows a good compromise between cost and precision. As zonotopes are not closed under intersection, we had to extend the existing framework, in addition to designing new operations on zonotopes, such as a novel splitting algorithm based on paving zonotopes by sub-zonotopes and parallelotopes. We implemented this method on top of the APRON library, and tested it on programs with non-linear loops that present complex, possibly non-convex, invariants. We present some results demonstrating both the interest of this splitting-based algorithm to synthesize invariants on such programs, and the good compromise presented by its use in combination with zonotopes with respect to its use with both simpler domains such as boxes and octagons, and more expressive domains such as polyhedra

Lack of effect of chemokine receptor CCR2b gene polymorphism on HIV-1 plasma RNA viral load and immune activation among HIV-1 seropositive female sex workers in Abidjan, Côte d'Ivoire

The prevalence of the CCR2b-V64I mutation among human immunodeficiency virus (HIV)-seropositive and -seronegative female workers and the potential effect of heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of immune activation were assessed. CCR2b-V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV-1 monitor assay and CD4(+) T-cell counts and markers of immune activation by standard three-color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b-V64I, and 8 (3%) were homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b-V64I mutation compared with 37 (23%) of the 161 HIV-seropositive FSW (P = 0.47). In a univariate analysis of viral load among HIV-seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log(10) copies/ml. After controlling for the effects of CD4(+) T-cell counts in a multivariate analysis, no significant difference was observed between the groups in viral load or in markers of immune activation. The data suggest that the presence of the CCR2b mutation has no effect on HIV-1 plasma viral load and markers of immune activation in our study population. The finding that the frequency of this mutation is similar in HIV-seropositive and -seronegative female workers suggests that its presence is not associated with increased risk of HIV infection

Table_1_Enabling effective maize seed system in low-income countries of West Africa: Insights from Benin.DOCX

IntroductionAccess to high-quality seeds remains a key constraint to the intensification of crop production in low-income countries. In this study, we analyzed maize seed production and distribution systems in Benin to identify leverage points for effective seed systems, a prerequisite for improving maize production.MethodsSemi-structured interviews were conducted with 81 seed producers selected in seven municipalities across the three phytogeographical zones of Benin. Key informant interviews were also conducted with ten public and private stakeholders involved in maize seed systems in Benin.Results and discussionFindings showed that the legal and institutional frameworks governing seed systems in Benin were recently reinforced with a national seed policy, the creation and operationalization of the National Committee of Plant Seeds and the existence of regulations and rules on the production, quality control, certification, trade, and packaging of seeds. In addition, enabling conditions to facilitate the involvement of the private sector have been greatly improved with the revision of modalities for obtaining approval for the production and distribution of seeds in Benin. While the seed sector is improving and both public and private stakeholders are involved in maize seed production and distribution, synergies among stakeholders need to be strengthened. Strengthening business and marketing skills of seed producers through training and promoting the comparative advantages of improved seeds in increasing yield and production among maize farmers could be a promising avenue. Connecting seed producers with maize farmers' organizations coupled with ICT-based agro-advisories could boost the development of the maize seed sector, and ultimately the maize value chain.</p