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Taking the advantage of high-throughput single nucleotide polymorphism (SNP) genotyping technology, large genome-wide association studies (GWASs) have been considered to hold promise for unraveling complex relationships between genotypes and phenotypes. Current multi-locus-based methods are insufficient to detect interactions with diverse genetic effects on multifarious diseases. Also, statistic tests for high-order epistasis ( ≥ 2 SNPs) raise huge computational and analytical challenges because the computation increases exponentially as the growth of the cardinality of SNPs combinations. In this paper, we provide a simple, fast and powerful method, named DAM, using Bayesian inference to detect genome-wide multi-locus epistatic interactions in multiple diseases. Experimental results on simulated data demonstrate that our method is powerful and efficient. We also apply DAM on two GWAS datasets from WTCCC, i.e., Rheumatoid Arthritis and Type 1 Diabetes, and identify some novel findings. Therefore, we believe that our method is suitable and efficient for the full-scale analysis of multi-disease-related interactions in GWASs.

This study aimed to reveal the genetic and epigenetic variations involved in a resynthesized Brassica napus (AACC) generated from a hybridization between a B. rapa (AA) landrace and B. alboglabra (CC). Amplified fragment length polymorphism (AFLP), methylation-sensitive amplified polymorphism, and the cDNA-AFLP technique were performed to detect changes between different generations at the genome, methylation, and transcription levels. We obtained 30 lines of resynthesized B. napus with a mean 1000-seed weight of over 7.50 g. All of the lines were self-compatible, probably because both parents were self-compatible. At the genome level, the S0 generation had the lowest frequency of variations (0.18%) and the S3 generation had the highest (6.07%). The main variation pattern was the elimination of amplified restriction fragments on the CC genome from the S0 to the S4 generations. At the methylation level, we found three loci that exhibited altered methylation patterns on the parental A genome; the variance rate was 1.35%. At the transcription level, we detected 43.77% reverse mutations and 37.56% deletion mutations that mainly occurred on the A and C genomes, respectively, in the S3 generation. Our results highlight the genetic variations that occur during the diploidization of resynthesized B. napus.

Aerosolization efficiency is the key characteristic of dry powder inhaler (DPI). However, lack of knowledge about powder dispersion and deposition is still a major obstacle to further improve inhaler. In the current work, both the in vitro deposition experiments and numerical simulations were employed to investigate the performance of three different DPI channel designs. The powder model was commercially available Seretide Accuhaler, which contains carrier lactose and drug mixture of fluticasone propionate (FP) and salmeterol xinafoate (SX). The in vitro results, such as the mass mediate aerodynamic diameter (MMAD), fine particle fraction (FPF) and fine particle dose (FPD), were obtained by the Next Generation Impactor (NGI). The values of MMAD were significantly (p<0.05) affected by channel design. However, based on the FPF result, the three channel designs had similar capabilities of aerosolization. It was demonstrated that particle-wall collision was the dominant mechanism for the detachment and de-agglomeration at these conditions. Furthermore, good linear correlations were found between the FPD values on the first 4 stages of NGI and the outlet velocities of their corresponding particles, which would be used for a potential on-line approach to the evaluation of DPI efficiency., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: We investigated cytokines and angiogenic factors (CAFs) in patients with metastatic renal cell carcinoma (mRCC) treated in a randomized phase II clinical trial of sorafenib versus sorafenib+ interferon-α (IFN-α) that yielded no differences in progression-free survival (PFS). We aimed to link the CAF profile to PFS and select candidate predictive and prognostic markers for further study., Methods: The concentrations of 52 plasma CAFs were measured pretreatment (n = 69), day 28, and day 56 using multiplex bead arrays and enzyme-linked immunosorbent assay. We investigated the association between baseline levels of CAFs with PFS and posttreatment changes., Results: Unsupervised CAF clustering analysis revealed two distinct mRCC patient groups with elevated proangiogenic or proinflammatory mediators. A six-marker baseline CAF signature [osteopontin, vascular endothelial growth factor (VEGF), carbonic anhydrase 9, collagen IV, VEGF receptor-2, and tumor necrosis factor-related apoptosis-inducing ligand] correlated with PFS benefit (hazard ratio 0.20 versus 2.25, signature negative versus positive, respectively; P = 0.0002). While changes in angiogenic factors were frequently attenuated by the sorafenib+ IFN combination, most key immunomodulatory mediators increased., Conclusions: Using CAF profiling, we identified two mRCC patient groups, a candidate plasma signature for predicting PFS benefit, and distinct marker changes occurring with each treatment. This platform may provide valuable insights into renal cell carcinoma biology and the molecular consequences of targeted therapies.

Purpose: There is an unmet need for biomarkers for identifying patients likely to benefit from anticancer treatments, selecting dose, and understanding mechanisms of resistance. Plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptor 2 (sVEGFR-2) are known to be modulated by VEGF pathway inhibitors. It is unknown whether chemotherapy or VEGFR inhibitor/chemotherapy combinations induce changes in these or other cytokines and angiogenic factors (CAFs) and whether such changes could be markers of benefit., Methods: Thirty-five plasma CAFs were analyzed using multiplexed bead arrays and enzyme-linked immunosorbent assays from 123 patients with non-small-cell lung cancer in a randomized phase II study who received vandetanib, a VEGFR and epidermal growth factor receptor inhibitor, monotherapy carboplatin and paclitaxel (CP), or the combination (VCP). Changes in CAFs at days 8, 22, and 43 from baseline were correlated with progression risk., Results: VEGF increased and sVEGFR-2 decreased by day 43 in the vandetanib arm, whereas a distinct pattern was observed in the CP and VCP arms, with significant decreases in interleukin (IL) -12, IL-1 receptor antagonist, and matrix metalloproteinase 9 (MMP-9) and increased macrophage chemoattractant protein 1. In each treatment arm, changes in different markers were associated with progression risk. For example, increases in IL-8 with VCP, MMP-9 with CP, and VEGF with vandetanib monotherapy were associated with increased progression risk, and increase in intercellular adhesion molecule 1 with vandetanib was associated with decreased risk., Conclusion: Vandetanib and chemotherapy treatment led to distinct patterns of CAF changes; the combination resembled chemotherapy alone. Changes in specific CAFs correlated with clinical outcome, but markers differed for each treatment arm. CAF profiling may provide insights into the biologic effects of treatment and identify drug-specific markers of activity and clinical benefit.

Pooling design is a very helpful tool for reducing the number of tests in DNA library screening, which is a key process to obtain high-quality DNA libraries for studying gene functions. Three basic problems in pooling design are, given an m x n binary matrix and a positive integer d, to decide whether the matrix is d-separable (d-separable, or d-disjunct). The three problems are all known to be coNP-complete. Since in most applications, d is a small integer compared to n, it is interesting to investigate whether there are efficient algorithms solving the above problems when the value of d is small. In this article, we give a negative answer to the above question by studying the parameterized complexity of these three problems, with d as the parameter. We show that the parameterized versions of all the three problems are co-W[2]-complete. An immediate implication of our results is that, given an m x n binary matrix and a positive integer d, a deterministic algorithm with running time f(d) x (mn)(O(1)) (where f is an arbitrary computable function) to decide whether the matrix is d-separable (d-separable, or d-disjunct) should not be expected.

The study of gene functions requires a DNA library of high quality, such a library is obtained from a large mount of testing and screening. Pooling design is a very helpful tool for reducing the number of tests for DNA library screening. In this paper, we present new one- and two-stage pooling designs, together with new probabilistic pooling designs. The approach in this paper works for both error-free and error-tolerance scenarios.

The study of gene functions requires a DNA library of high quality, such a library is obtained from a large mount of testing and screening. Pooling design is a very helpful tool for reducing the number of tests for DNA library screening. In this paper, we present two Las Vegas algorithms for efficient constructions of d-disjunct and (d ; z)-disjunct matrices respectively. These new constructions can be directly applied to construct error-free and error-tolerant pooling designs.

The study of gene functions requires the development of a DNA library of high quality through much of testing and screening. Pooling design is a mathematical tool to reduce the number of tests for DNA library screening. The transversal design is a special type of pooling design, which is good in implementation. In this paper, we present a new construction for transversal designs. We will also extend our construction to the error-tolerant case.

Thiobacillus denitrificans, a species of autotrophic facultative anaerobic bacterium, was found to be capable of oxidizing sulfide into elemental sulfur when nitrate was adopted as its electron acceptor and carbon dioxide as its sole carbon source under anoxic conditions. In this way, sulfur was accumulated extracellularly and nitrate was converted into nitrogen gas. Based on these special physiological characteristics, an innovative process of simultaneous desulfurization and denitrification (SDD) was developed to obtain sulfur from sulfide. A strain of T. denitrificans, named D(4), was isolated and used as sulfur producers in this study. The stoichiometric equations of SDD by T. denitrificans were also derived. The key factors affecting this process were investigated through continuous-flow and batch tests. The experimental results indicated that both the sulfide concentration and the ratio of S2-/NO3- in the influent are key factors. Their suitable levels are suggested to be controlled less than 300 mg/L and 5/3-5/2, respectively, to achieve a high sulfur conversion degree.

Farach et al. introduced the inhibitor model in pooling design, where existence of a single inhibitor clone in a pool dictates its outcome to be negative regardless of the existence of positive clones in the pool. Various sequential or multiround pooling designs have been given to identify all the positive clones under the inhibitor model. Recently, Hwang and Liu gave a (one round) pooling design for the inhibitor model which is error tolerant. More specifically, suppose the set of n clones to be screened contains up to d positive clones, up to r inhibitors and the pooling experiments can generate up to e errors, they show that a (d + r + 2e)-disjunct matrix does the job. In this paper, we give a pooling design for the case that among n clones exactly d are positive. We reduce the requirement of (d + r + 2e)-disjunctness to (d + r + e)-disjunctness, which would mean the saving of many pools. We also show how our design can be used to identify all positive clones when their number is, at most, d.

Continuous-flow experiment was conducted in an acidogenic sulfate-reducing reactor supplied with molasses as sole carbon resource and sulfate sodium as electron acceptor. The composition of Volatile fat acid(VFA) in terminal liquid products, the distribution of acetic acid, the existence of microbial populations and the interspecific relationship between sulfate-reducing bacteria (SRB) and acidogenic bacteria (AB) were investigated in different experimental stages when sulfate removal rate and gas production maintained at a relatively stable status. The experimental results showed that an acetic-acid type microbial metabolism pathway was formed based on the fact that the proportion of acetic acid in terminal liquid products was as high as 50% to 82%. It was also explained the formation of acetic-acid type microbial metabolism pathway was resulted from acetic acid accumulation in the terminal liquid products, which was subjected to the bio-chain cooperation relationship between populations of SRB and AB, and the incomplete-oxidation of organic substance in acidogenic-phase reactor of two-phase anaerobic treatment process. It was also presented that the formation of acetic-acid type microbial metabolism pathway depended on the capability of acetic-acid utilized-SRB (ASRB) population competing against other populations and its ability of acetic acid consumption. Furthermore, this kind of metabolism pathway could offer suitable carbon resource for methane producing reactor in the two-phase anaerobic treatment process, and has significant effect on the sulfate removal rate of the whole treatment system and its running stability.

Let P be a set of n points on the euclidean plane. Let Ls(P) and Lm(P) denote the lengths of the Steiner minimum tree and the minimum spanning tree on P, respectively. In 1968, Gilbert and Pollak conjectured that for any P, Ls(P) >/= (radical3/2)Lm(P). We provide an abridged proof for their conjecture in this paper.