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BackgroundCurrently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima’s D, Fay and Wu’s H and Fu and Li’s D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution.ResultsOur tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies.ConclusionsWe identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will be necessary to carry out association and functional studies to demonstrate the implication of these genes in normal pigmentation variation.

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Background: Fructose, a monosaccharide, has gained wide applications in food, pharmaceutical and medical industries because of its favourable properties and health benefits. Biocatalytic production of fructose from inulin employing inulinase is the most promising alternative for fructose production. For commercial production, use of immobilized inulinase is advantageous as it offers reutilization of enzyme and increase in stability. In order to meet the demand of concentrated fructose syrup, inulin hydrolysis at high substrate loading is essential. Results: Inulinase was immobilized on chitosan particles and employed for fructose production by inulin hydrolysis. Fourier transform infrared spectroscopy (FTIR) analysis confirmed linkage of inulinase with chitosan particles. Immobilized biocatalyst displayed significant increase in thermostability at 60 and 65°C. Statistical model was proposed with an objective of optimizing enzymatic inulin hydrolytic process. At high substrate loading (17.5 % inulin), using 9.9 U/g immobilized inulinase at 60°C in 12 h, maximum sugar yield was 171.1 ± 0.3 mg/ml and productivity was 14.25 g/l/h. Immobilized enzyme was reused for ten cycles. Raw inulin from chicory and asparagus was extracted and supplied in 17.5 % for enzymatic hydrolysis as a replacement of pure inulin. More than 70 % chicory inulin and 85 % asparagus inulin were hydrolyzed under optimized parameters at 60°C. Results of high performance liquid chromatography confirmed the release of fructose after inulin hydrolysis. Conclusions: The present findings prove potentiality of immobilized thermostable inulinase from Aspergillus tubingensis CR16 for efficient production of fructose syrup. Successful immobilization of inulinase on chitosan increased its stability and provided the benefit of enzyme reutilization. Box-Behnken design gave a significant model for inulin hydrolysis. Extraction of raw inulin from chicory and asparagus and their enzymatic hydrolysis using immobilized inulinase suggested that it can be a remarkable cost-effective process for large-scale fructose production.

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We consider black-box optimization in which only an extremely limited number of function evaluations, on the order of around 100, are affordable and the function evaluations must be performed in even fewer batches of a limited number of parallel trials. This is a typical scenario when optimizing variable settings that are very costly to evaluate, for example in the context of simulation-based optimization or machine learning hyperparameterization. We propose an original method that uses established approaches to propose a set of points for each batch and then down-selects from these candidate points to the number of trials that can be run in parallel. The key novelty of our approach lies in the introduction of a hyperparameterized method for down-selecting the number of candidates to the allowed batch-size, which is optimized offline using automated algorithm configuration. We tune this method for black box optimization and then evaluate on classical black box optimization benchmarks. Our results show that it is possible to learn how to combine evaluation points suggested by highly diverse black box optimization methods conditioned on the progress of the optimization. Compared with the state of the art in black box minimization and various other methods specifically geared towards few-shot minimization, we achieve an average reduction of 50% of normalized cost, which is a highly significant improvement in performance.

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Mapping constitutes a very important step in network-on-chip (NoC)-based implementation of an application. An application is often represented in the form of an application core graph. The cores of the core graph communicate between themselves using the underlying network. This paper presents a constructive heuristic to statically map applications on two-dimensional mesh-connected NoC. The approach corresponds to a design time decision of attachment of cores to the routers. The mapping results, in terms of overall communication cost metric, have been compared with many well-known techniques reported in the literature and also with an exact method built around integer linear programming (ILP). A thorough complexity analysis of the algorithm has been performed. For smaller benchmarks, the results obtained are same as those for the ILP generated solutions. For benchmarks containing 64 and higher number of cores, the mapping solutions are better than the existing ones. Dynamic performances of the mapped solutions have been compared with respect to synthetically generated self-similar traffic. In many cases, our approach requires less latency and energy per packet than the existing methods while providing higher throughput.