High-order collocation methods for differential equations with random inputs

Recently there has been a growing interest in designing efficient methods for the solution of ordinary/ partial differential equations with random inputs. To this end, stochastic Galerkin methods appear to be superior to other nonsampling methods and, in many cases, to several sampling methods. However, when the governing equations take complicated forms, numerical implementations of stochastic Galerkin methods can become nontrivial and care is needed to design robust and efficient solvers for the resulting equations. On the other hand, the traditional sampling methods, e. g., Monte Carlo methods, are straightforward to implement, but they do not offer convergence as fast as stochastic Galerkin methods. In this paper, a high-order stochastic collocation approach is proposed. Similar to stochastic Galerkin methods, the collocation methods take advantage of an assumption of smoothness of the solution in random space to achieve fast convergence. However, the numerical implementation of stochastic collocation is trivial, as it requires only repetitive runs of an existing deterministic solver, similar to Monte Carlo methods. The computational cost of the collocation methods depends on the choice of the collocation points, and we present several feasible constructions. One particular choice, based on sparse grids, depends weakly on the dimensionality of the random space and is more suitable for highly accurate computations of practical applications with large dimensional random inputs. Numerical examples are presented to demonstrate the accuracy and efficiency of the stochastic collocation methods

Physical losses could partially explain modest carotenoid retention in dried food products from biofortified cassava

Gari, a fermented and dried semolina made from cassava, is one of the most common foods in West Africa. Recently introduced biofortified yellow cassava containing provitamin A carotenoids could help tackle vitamin A deficiency prevalent in those areas. However there are concerns because of the low retention of carotenoids during gari processing compared to other processes (e.g. boiling). The aim of the study was to assess the levels of true retention in trans–β-carotene during gari processing and investigate the causes of low retention. Influence of processing step, processor (3 commercial processors) and variety (TMS 01/ 1371; 01/1368 and 01/1412) were assessed. It was shown that low true retention (46% on average) during gari processing may be explained by not only chemical losses (i.e. due to roasting temperature) but also by physical losses (i.e. due to leaching of carotenoids in discarded liquids): true retention in the liquid lost from grating negatively correlated with true retention retained in the mash (R = -0.914). Moreover, true retention followed the same pattern as lost water at the different processing steps (i.e. for the commercial processors). Variety had a significant influence on true retention, carotenoid content, and trans-cis isomerisation but the processor type had little effect. It is the first time that the importance of physical carotenoid losses was demonstrated during processing of biofortified crops

Effect of Anti-Obesity Drug on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45) for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17) for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12) for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04) for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40) for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58) for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. CONCLUSION/SIGNIFICANCE: We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors

Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors

Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders

Extremely Low Genetic Diversity Indicating the Endangered Status of Ranodon sibiricus (Amphibia: Caudata) and Implications for Phylogeography

Background: The Siberian salamander (Ranodon sibiricus), distributed in geographically isolated areas of Central Asia, is an ideal alpine species for studies of conservation and phylogeography. However, there are few data regarding the genetic diversity in R. sibiricus populations. Methodology/Principal Findings: We used two genetic markers (mtDNA and microsatellites) to survey all six populations of R. sibiricus in China. Both of the markers revealed extreme genetic uniformity among these populations. There were only three haplotypes in the mtDNA, and the overall nucleotide diversity in the mtDNA was 0.00064, ranging from 0.00000 to 0.00091 for the six populations. Although we recovered 70 sequences containing microsatellite repeats, there were only two loci that displayed polymorphism. We used the approximate Bayesian computation (ABC) method to study the demographic history of the populations. This analysis suggested that the extant populations diverged from the ancestral population approximately 120 years ago and that the historical population size was much larger than the present population size; i.e., R. sibiricus has experienced dramatic population declines. Conclusion/Significance: Our findings suggest that the genetic diversity in the R. sibiricus populations is the lowest among all investigated amphibians. We conclude that the isolation of R. sibiricus populations occurred recently and was a result of recent human activity and/or climatic changes. The Pleistocene glaciation oscillations may have facilitated intraspecie

New Insight into the History of Domesticated Apple: Secondary Contribution of the European Wild Apple to the Genome of Cultivated Varieties

The apple is the most common and culturally important fruit crop of temperate areas. The elucidation of its origin and domestication history is therefore of great interest. The wild Central Asian species Malus sieversii has previously been identified as the main contributor to the genome of the cultivated apple (Malus domestica), on the basis of morphological, molecular, and historical evidence. The possible contribution of other wild species present along the Silk Route running from Asia to Western Europe remains a matter of debate, particularly with respect to the contribution of the European wild apple. We used microsatellite markers and an unprecedented large sampling of five Malus species throughout Eurasia (839 accessions from China to Spain) to show that multiple species have contributed to the genetic makeup of domesticated apples. The wild European crabapple M. sylvestris, in particular, was a major secondary contributor. Bidirectional gene flow between the domesticated apple and the European crabapple resulted in the current M. domestica being genetically more closely related to this species than to its Central Asian progenitor, M. sieversii. We found no evidence of a domestication bottleneck or clonal population structure in apples, despite the use of vegetative propagation by grafting. We show that the evolution of domesticated apples occurred over a long time period and involved more than one wild species. Our results support the view that self-incompatibility, a long lifespan, and cultural practices such as selection from open-pollinated seeds have facilitated introgression from wild relatives and the maintenance of genetic variation during domestication. This combination of processes may account for the diversification of several long-lived perennial crops, yielding domestication patterns different from those observed for annual species