Hardness results for approximate pure Horn CNF formulae minimization

We study the hardness of approximation of clause minimum and literal minimum representations of pure Horn functions in n Boolean variables. We show that unless P=NP, it is not possible to approximate in polynomial time the minimum number of clauses and the minimum number of literals of pure Horn CNF representations to within a factor of \(2^{\log^{1-o(1)} n}\) . This is the case even when the inputs are restricted to pure Horn 3-CNFs with O(n ^1+ε ) clauses, for some small positive constant ε. Furthermore, we show that even allowing sub-exponential time computation, it is still not possible to obtain constant factor approximations for such problems unless the Exponential Time Hypothesis turns out to be false.     

A recursive method for solving unconstrained tangentialinterpolation problems

An efficient recursive solution is presented for the one-sided unconstrained tangential interpolation problem. The method relies on the triangular factorization of a certain structured matrix that is implicitly defined by the interpolation data. The recursive procedure admits a physical interpretation in terms of discretized transmission lines. In this framework the generating system is constructed as a cascade of first-order sections. Singular steps occur only when the input data is contradictory, i.e., only when the interpolation problem does not have a solution. Various pivoting schemes can be used to improve numerical accuracy or to impose additional constraints on the interpolants. The algorithm also provides coprime factorizations for all rational interpolants and can be used to solve polynomial interpolation problems such as the general Hermite matrix interpolation problem. A recursive method is proposed to compute a column-reduced generating system that can be used to solve the minimal tangential interpolation problem     

Analysis of thermal stratification in the primary circuit of a VVER-440 reactor with the CFX code

The thermal stratification can lead an important role in the aging of the NPP piping because of the stresses caused by the temperature differences and the cyclic temperature changes. These stresses can limit the lifetime of the piping, or lead to penetrating cracks. For the stress analyses, the determination of the thermal hydraulic parameters of the stratified flow is necessary, which can be simulated by computational fluid dynamics (CFD) codes. The results of the simulation show the time development and the breaking up of the stratification and the temperature distribution of the stratified flow. The main difficulty of these CFD simulations is the uncertainty of the boundary conditions because of the unknown flow circumstances. In this paper, some results of CFX simulations are presented concerning the pressurizer surge line, and the injection pipe of the HPIS for VVER-440 type reactors.     

Processing of iridoid glycoside antirrinoside fromMaurandya antirrhiniflora (Scrophulariaceae) byMeris paradoxa (Geometridae) andLepipolys species (Noctuidae)

The iridoid glycoside antirrinoside was found to be sequestered by highly aposematic larvae of the geometrid mothMeris paradoxa and two noctuid mothLepipolys species feeding onMaurandya antirrhiniflora (Scrophulariaceae), a natural food plant from southern Arizona. The antirrinoside content of leaves and petioles being consumed, eariy-instar larvae, late-instar larvae, larval frass, regurgitant, reflex-bleeding emission (Meris paradoxa), cocoons, pupae, meconium emitted upon eclosion, and adult moths was determined. Larvae, other than the earliest instars, did not excrete antirrinoside in the frass, but sequestered it in amounts of 3–11 % of the dry weight. Small amounts of antirrinoside remained in various pupal or cocoon parts and some was emitted in the meconium upon eclosion. The total antirrinoside accounted for was, however, considerably below that expected based upon the remarkably high 20% content of the leaves and petioles being consumed. The adult cryptic moths of both species contained little or no antirrinoside. This is the first report of a natural food plant and larval stages forM. paradoxa and a previously undescribedLepipolys species. It is also the first report of antirrinoside sequestration and utilization by insects.Chemistry of the Scrophulariaceae. 20. Paper 19: Stermitz, F.R., Ianiro, T.T., Robinson, R.D., and Gardner, D.R. 1991.J. Nat. Prod. 54:626–628.     

Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation

This study investigates the significance of the glucose-6-phosphate dehydrogenase (G6PD) catalyzed oxidative and the transketolase (TK) catalyzed nonoxidative pentose cycle (PC) reactions in the tumor proliferation process by characterizing tumor growth patterns and synthesis of the RNA ribose moiety in the presence of respective inhibitors of G6PD and TK. Mass spectra analysis of 13C-labeled carbons revealed that these PC reactions contribute to over 85% of de novo ribose synthesis in RNA from [1,2-(13)C]glucose in cultured Mia pancreatic adenocarcinoma cells, with the fraction synthesized through the TK pathway predominating (85%). Five days of treatment with the TK inhibitor oxythiamine (OT) and the G6PD inhibitor dehydroepiandrosterone-sulfate (0.5 microM each) exerted a 39 and a 23% maximum inhibitory effect on cell proliferation in culture, which was increased to 60% when the two drugs were administered in combination. In vivo testing of 400 mg/kg OT or dehydroepiandrosterone-sulfate in C57BL/6 mice hosting Ehrlich's ascitic tumor cells revealed a 90.4 and a 46% decrease in the final tumor mass after 3 days of treatment. RNA ribose fractional synthesis through the TK reaction using metabolites directly from glycolysis declined by 9.1 and 23.9% after OT or the combined treatment, respectively. Nonoxidative PC reactions play a central regulating role in the carbon-recruiting process toward de novo nucleic acid ribose synthesis and cell proliferation in vitro and in vivo. Therefore, enzymes or substrates regulating the nonoxidative synthesis of ribose could also be the sites to preferentially target tumor cell proliferation by new anticancer drugs.     

The role of mast cells in mucosal permeability changes during ischemia-reperfusion injury of the small intestine

The ipsilateral primary motor cortex (M1) plays a role in voluntary movement. In our studies, we used repetitive transcranial magnetic stimulation (rTMS) to study the effects of transient disruption of the ipsilateral M1 on the performance of finger sequences in right-handed normal subjects. Stimulation of the M1 ipsilateral to the movement induced timing errors in both simple and complex sequences performed with either hand, but with complex sequences, the effects were more pronounced with the left-sided stimulation. Recent studies in both animals and humans have confirmed the traditional view that ipsilateral projections from M1 to the upper limb are mainly directed to truncal and proximal muscles, with little evidence for direct connections to distal muscles. The ipsilateral motor pathway appears to be an important mechanism for functional recovery after focal brain injury during infancy, but its role in functional recovery for older children and adults has not yet been clearly demonstrated. There is increasing evidence from studies using different methodologies such as rTMS, functional imaging and movement-related cortical potentials, that M1 is involved in ipsilateral hand movements, with greater involvement in more complex tasks and the left hemisphere playing a greater role than the right.     

Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage

Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa.     

hERG Optimization of Benzofuro−Pyridine and Pyrazino−Indole Derivatives as MCHR1 Antagonists

Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the antagonists of melanin concentrating hormone receptor 1 (MCHR1). The design, synthesis, and biological studies of novel MCHR1 antagonists based on benzofuro−pyridine and pyrazino−indole scaffold was performed. We confirmed that fine-tuning lipophilicity and basic pK_a by modifying the benzyl group and introducing different substituents on the aliphatic nitrogen sidechain decreases both hERG inhibition and metabolic clearance. We have succeeded to develop excellent in vitro parameters in the case of compounds 17 (4-[(5-chloropyridin-2-yl)methoxy]-1-[4-(2-hydroxyethyl)-8-oxa-4-azatricyclo[7.4.0.0²,⁷]trideca-1(13),2(7),9,11-tetraen-11-yl]-1,2-dihydropyridin-2-one monohydrochloride) and 23 g (4-[(5-chloropyridin-2-yl)methoxy]-1-(1,2,3,4-tetrahydropyrazino[1,2-a]indol-8-yl)pyridin-2(1H)-one monohydrochloride), which can be considered as valuable tools for further pharmacological investigation.