Platelet phospholipids are differentially protected against oxidative degradation by plasmalogens

The oxidative degradation of phospholipids in the presence and absence of plasmalogens (plasmenyl phosphatidylethanolamine: PPE) was followed by chemical analysis. Human platelet phospholipids, either intact or after removal of PPE by acid treatment, were oxidized with 28 mM 2,2′-azobis(2-amidinopropane di-HCl in Triton X-100 micelles (detergent/phospholipid 5∶1, mol/mol). PPE (12% of all phospholipids, mol/mol) disappeared about three times more rapidly than glycerophospholipids, whereas sphingomyelin remained unaltered and the lysophosphatidylethanolamine (lysoPE) generated became progressively more unsaturated. After 60 min oxidation, the FA compositions of PS, PC, and PI were similar in extracts with or without plasmalogens. In contrast, diacyl phosphatidylethanolamine (DPE) became more saturated in the absence of PPE. The rate of phospholipid destruction was always unique to each class, but for all phospholipids slowed down in the presence of PPE. This protective effect increased in the order DPE<PS<PC<PI and did not seem to be simply related to the class unsaturation. α-Tocopherol had no influence on the time courses of the quantities and compositions of the phospholipids, even at a molar ratio of α-tocopherol to phospholipids four times higher than in platelet membranes. Thus, PPE protected phospholipids efficiently but differentially against peroxidative attack, whereas the contribution of α-tocopherol appeared to be negligible even at a concentration four times greater than in platelet membranes.     

Tight binding of the antitumor drug ditercalinium to quadruplex DNA

The structural selectivity of the DNA-binding antitumor drug ditercalinium was investigated by competition dialysis with a series of nineteen different DNA substrates. The 7H-pyridocarbazole dimer was found to bind to double-stranded DNA with a preference for GC-rich species but can in addition form stable complexes with triplex and quadruplex structures. The preferential interaction of the drug with four-stranded DNA structures was independently confirmed by electrospray mass spectrometry and a detailed analysis of the binding reaction was performed by surface plasmon resonance (SPR) spectroscopy. The BIAcore SPR study showed that the kinetic parameters for the interaction of ditercalinium with the human telomeric quadruplex sequence are comparable to those measured with a duplex sequence. Slow association and dissociation were observed with both the quadruplex and duplex structures. The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG(3)[T(2)AG(3)](3)) provides new perspectives for the design of drugs that can bind to human telomeres.     

External Rewriting for Skeptical Proof Assistants

This paper presents the design, the implementation, and experiments of the integration of syntactic, conditional possibly associative-commutative term rewriting into proof assistants based on constructive type theory. Our approach is called external because it consists in performing term rewriting in a specific and efficient environment and checking the computations later in a proof assistant. Two typical systems are considered in this work: ELAN, based on the rewriting calculus, as the term rewriting-based environment, and Coq, based on the calculus of inductive constructions as the proof assistant. We first formalize the proof terms for deduction by rewriting and strategies in ELAN using the rewriting calculus with explicit substitutions. We then show how these proof terms can soundly be translated into Coq syntax where they can be directly type checked. For the method to be applicable for rewriting modulo associativity and commutativity, we provide an effective method to prove equalities modulo these axioms in Coq using ELAN. These results have been integrated into an ELAN-based rewriting tactic in Coq.     

TGV: theory, principles and algorithms

This paper presents the TGV tool, which allows for the automatic synthesis of conformance test cases from a formal specification of a (non-deterministic) reactive system. TGV was developed by Irisa Rennes and Verimag Grenoble, with the support of the Vasy team of Inria Rhônes-Alpes. The paper describes the main elements of the underlying testing theory, which is based on a model of transitions system which distinguishes inputs, outputs and internal actions, and is based on the concept of conformance relation. The principles of the test synthesis process, as well as the main algorithms, are explained. We then describe the main characteristics of the TGV tool and refer to some industrial experiments that have been conducted to validate the approach. As a conclusion, we describe some ongoing work on test synthesis.     

Towards Reduced Basis Approaches in ab initio Electronic Structure Computations

Due to the high dimensionality of the spaces where the problems are set, adapted discretization basis are often advocated in complex physical problems (Navier–Stokes equations, solid mecanics, ab initio electronic structure computations) to express the solution in terms of solution of similar (but easier to solve) problems. However, very few mathematical studies have been undertaken to asses the numerical properties of these approximations. Within this context, we will present in this paper an overview of the tools required to develop more rigorous reduced basis approaches for quantum chemistry: a posteriori numerical analysis and fast exponential decay of the n-width of the solution set.     

Study and experimental validation of the calculation of the ECT signal induced by a minute crack using a FEM–BIM combination

A combination of the boundary integral (BIM) and finite element (FEM) methods is presented for the calculation of the signal induced by small cracks. This approach—by preserving the attractive properties of both methods—allows considering a large variety of probe structures while the computation time remains low, especially if the signal of a complete scan is calculated. To validate the calculation results, experiments are carried out using a large number of minute cracks. The good agreement obtained between the measured and calculated data shows the applicability of the presented method.     

Mapping sky and surface luminance distribution using a flux mapper

A prototype, all-sky flux mapper has been developed at the Solar Energy Research Institute (SERI). The flux mapper is a video system which provides a rapid, real time processing of daylightning luminance data. The system uses an orthographic-projection fish-eye lens to project the entire image of a 180° field onto a vidicon target. The signal is then digitized and may be plotted as equal brightness comtours or recorded on tape for later analysis. The system has great potential for use in delineating illuminance distribution of the sky and of interior spaces.     

Radiosity for dynamic scenes in flatland with the visibility complex

The radiosity method is particularly suitable for global illumination calculations in static environments. Nonetheless, recent applications of image synthesis such as architectural simulation or lighting design require the ability to modify environments. Previous methods have attempted to deal with dynamic environments (environments where the geometry, the material properties, etc., can change)but still suffer some limitations in the case of moving objects. One of the main problems remaining is the efficient and accurate detection of which form factors must really be recomputed, since their calculation is the most time-consuming part of the radiosity method. To correctly understand and solve this problem, we start with a method in 2D for polygonal scenes using the visibility complex. It is a powerful data structure representing the visibility relationships between objects in the plane. We have developed and implemented an algorithm which uses this structure to efficiently compute the discontinuity mesh and the form factors for static scenes. We also propose an extension to our algorithm to efficiently update only the modified form factors when an object is moving. This approach enhances our understanding and will hopefully lead to efficient solutions in 3D.     

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aigu?s Myéloblastiques (GOELAM)

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.