Regulatory feedback on receptor and non-receptor synthesis for robust signaling.

Elaborate regulatory feedback processes are thought to make biological development robust, that is, resistant to changes induced by genetic or environmental perturbations. How this might be done is still not completely understood. Previous numerical simulations on reaction-diffusion models of Dpp gradients in Drosophila wing imaginal disc have showed that feedback (of the Hill function type) on (signaling) receptors and/or non-(signaling) receptors are of limited effectiveness in promoting robustness. Spatial nonuniformity of the feedback processes has also been shown theoretically to lead to serious shape distortion and a principal cause for ineffectiveness. Through mathematical modeling and analysis, the present article shows that spatially uniform nonlocal feedback mechanisms typically modify gradient shape through a shape parameter (that does not change with location). This in turn enables us to uncover new multi-feedback instrument for effective promotion of robust signaling gradients

An Evolutionary Algorithm to Generate Real Urban Traffic Flows

In this article we present a strategy based on an evolutionary algorithm to calculate the real vehicle ows in cities according to data from sensors placed in the streets. We have worked with a map imported from OpenStreetMap into the SUMO traffic simulator so that the resulting scenarios can be used to perform different optimizations with the confidence of being able to work with a traffic distribution close to reality. We have compared the results of our algorithm to other competitors and achieved results that replicate the real traffic distribution with a precision higher than 90%.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This research has been partially funded by project number 8.06/5.47.4142 in collaboration with the VSB-Technical University of Ostrava and Universidad de Málaga UMA/FEDER FC14-TIC36, programa de fortalecimiento de las capacidades de I+D+i en las universidades 2014-2015, de la Consejería de Economía, Innovación, Ciencia y Empleo, cofinanciado por el fondo europeo de desarrollo regional (FEDER). Also, partially funded by the Spanish MINECO project TIN2014-57341-R (http://moveon.lcc.uma.es). The authors would like to thank the FEDER of European Union for financial support via project Movilidad Inteligente: Wi-Fi, Rutas y Contaminación (maxCT) of the "Programa Operativo FEDER de Andalucía 2014-2020. We also thank all Agency of Public Works of Andalusia Regional Government staff and researchers for their dedication and professionalism. Daniel H. Stolfi is supported by a FPU grant (FPU13/00954) from the Spanish Ministry of Education, Culture and Sports

Tractable Pathfinding for the Stochastic On-Time Arrival Problem

We present a new and more efficient technique for computing the route that maximizes the probability of on-time arrival in stochastic networks, also known as the path-based stochastic on-time arrival (SOTA) problem. Our primary contribution is a pathfinding algorithm that uses the solution to the policy-based SOTA problem---which is of pseudo-polynomial-time complexity in the time budget of the journey---as a search heuristic for the optimal path. In particular, we show that this heuristic can be exceptionally efficient in practice, effectively making it possible to solve the path-based SOTA problem as quickly as the policy-based SOTA problem. Our secondary contribution is the extension of policy-based preprocessing to path-based preprocessing for the SOTA problem. In the process, we also introduce Arc-Potentials, a more efficient generalization of Stochastic Arc-Flags that can be used for both policy- and path-based SOTA. After developing the pathfinding and preprocessing algorithms, we evaluate their performance on two different real-world networks. To the best of our knowledge, these techniques provide the most efficient computation strategy for the path-based SOTA problem for general probability distributions, both with and without preprocessing.Comment: Submission accepted by the International Symposium on Experimental Algorithms 2016 and published by Springer in the Lecture Notes in Computer Science series on June 1, 2016. Includes typographical corrections and modifications to pre-processing made after the initial submission to SODA'15 (July 7, 2014

Internet addiction and its psychosocial risks (depression, anxiety, stress and loneliness) among Iranian adolescents and young adults: a structural equation model in a cross-sectional study

Internet addiction has become an increasingly researched area in many Westernized countries. However, there has been little research in developing countries such as Iran, and when research has been conducted, it has typically utilized small samples. This study investigated the relationship of Internet addiction with stress, depression, anxiety, and loneliness in 1,052 Iranian adolescents and young adults. The participants were randomly selected to complete a battery of psychometrically validated instruments including the Internet Addiction Test, Depression Anxiety Stress Scale, and the Loneliness Scale. Structural equation modeling and Pearson correlation coefficients were used to determine the relationship between Internet addiction and psychological impairments (depression, anxiety, stress and loneliness). Pearson correlation, path analysis, multivariate analysis of variance (MANOVA), and t-tests were used to analyze the data. Results showed that Internet addiction is a predictor of stress, depression, anxiety, and loneliness. Findings further indicated that addictive Internet use is gender sensitive and that the risk of Internet addiction is higher in males than in females. The results showed that male Internet addicts differed significantly from females in terms of depression, anxiety, stress, and loneliness. The implications of these results are discussed

A biologically inspired network design model

A network design problem is to select a subset of links in a transport network that satisfy passengers or cargo transportation demands while minimizing the overall costs of the transportation. We propose a mathematical model of the foraging behaviour of slime mould P. polycephalum to solve the network design problem and construct optimal transport networks. In our algorithm, a traffic flow between any two cities is estimated using a gravity model. The flow is imitated by the model of the slime mould. The algorithm model converges to a steady state, which represents a solution of the problem. We validate our approach on examples of major transport networks in Mexico and China. By comparing networks developed in our approach with the man-made highways, networks developed by the slime mould, and a cellular automata model inspired by slime mould, we demonstrate the flexibility and efficiency of our approach

Quantum-Dot Light-Emitting Diodes with Nitrogen-Doped Carbon Nanodot Hole Transport and Electronic Energy Transfer Layer

Electroluminescence efficiency is crucial for the application of quantum-dot light-emitting diodes (QD-LEDs) in practical devices. We demonstrate that nitrogen-doped carbon nanodot (N-CD) interlayer improves electrical and luminescent properties of QD-LEDs. The N-CDs were prepared by solution-based bottom up synthesis and were inserted as a hole transport layer (HTL) between other multilayer HTL heterojunction and the red-QD layer. The QD-LEDs with N-CD interlayer represented superior electrical rectification and electroluminescent efficiency than those without the N-CD interlayer. The insertion of N-CD layer was found to provoke the Forster resonance energy transfer (FRET) from N-CD to QD layer, as confirmed by time-integrated and - resolved photoluminescence spectroscopy. Moreover, hole-only devices (HODs) with N-CD interlayer presented high hole transport capability, and ultraviolet photoelectron spectroscopy also revealed that the N-CD interlayer reduced the highest hole barrier height. Thus, more balanced carrier injection with sufficient hole carrier transport feasibly lead to the superior electrical and electroluminescent properties of the QD-LEDs with N-CD interlayer. We further studied effect of N-CD interlayer thickness on electrical and luminescent performances for high-brightness QD-LEDs. The ability of the N-CD interlayer to improve both the electrical and luminescent characteristics of the QD-LEDs would be readily exploited as an emerging photoactive material for high-efficiency optoelectronic devices.ope

Repressive LTR Nucleosome Positioning by the BAF Complex Is Required for HIV Latency

The SWI/SNF BAF chromatin remodeling complex generates a repressive nucleosome structure at the HIV LTR conducive to establishment and maintenance of HIV latency, while PBAF augments HIV transcription

Association of Six Single Nucleotide Polymorphisms with Gestational Diabetes Mellitus in a Chinese Population

To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women.In this study, 1764 unrelated pregnant women were recruited, of which 725 women had GDM and 1039 served as controls. Six single nucleotide polymorphisms (rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK) were genotyped using TaqMan allelic discrimination assays. The genotype and allele distributions of each SNP between the GDM cases and controls and the combined effects of alleles for the risk of developing GDM were analyzed. We found that the rs4402960, rs2383208 and rs391300 were statistically associated with GDM (OR = 1.207, 95%CI = 1.029-1.417, p = 0.021; OR = 1.242, 95%CI = 1.077-1.432, p = 0.003; OR = 1.202, 95%CI = 1.020-1.416, P = 0.028, respectively). In addition, the effect was greater under a recessive model in rs391300 (OR = 1.820, 95%CI = 1.226-2.701, p = 0.003). Meanwhile, the joint effect of these three loci indicated an additive effect of multiple alleles on the risk of developing GDM with an OR of 1.196 per allele (p = 1.08×10(-4)). We also found that the risk alleles of rs2383208 (b = -0.085, p = 0.003), rs4402960 (b = -0.057, p = 0.046) and rs10830963 (b = -0.096, p = 0.001) were associated with HOMA-B, while rs7754840 was associated with decrease in insulin AUC during a 100 g OGTT given at the time of GDM diagnosis (b = -0.080, p = 0.007).Several risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. The effects of these SNPs on GDM might be through the impairment of beta cell function and these risk loci contributed additively to the disease

The GTPase Activating Rap/RanGAP Domain-Like 1 Gene Is Associated with Chicken Reproductive Traits

BACKGROUND: Abundant evidence indicates that chicken reproduction is strictly regulated by the hypothalamic-pituitary-gonad (HPG) axis, and the genes included in the HPG axis have been studied extensively. However, the question remains as to whether any other genes outside of the HPG system are involved in regulating chicken reproduction. The present study was aimed to identify, on a genome-wide level, novel genes associated with chicken reproductive traits. METHODOLOGY/PRINCIPAL FINDING: Suppressive subtractive hybridization (SSH), genome-wide association study (GWAS), and gene-centric GWAS were used to identify novel genes underlying chicken reproduction. Single marker-trait association analysis with a large population and allelic frequency spectrum analysis were used to confirm the effects of candidate genes. Using two full-sib Ningdu Sanhuang (NDH) chickens, GARNL1 was identified as a candidate gene involved in chicken broodiness by SSH analysis. Its expression levels in the hypothalamus and pituitary were significantly higher in brooding chickens than in non-brooding chickens. GWAS analysis with a NDH two tail sample showed that 2802 SNPs were significantly associated with egg number at 300 d of age (EN300). Among the 2802 SNPs, 2 SNPs composed a block overlapping the GARNL1 gene. The gene-centric GWAS analysis with another two tail sample of NDH showed that GARNL1 was strongly associated with EN300 and age at first egg (AFE). Single marker-trait association analysis in 1301 female NDH chickens confirmed that variation in this gene was related to EN300 and AFE. The allelic frequency spectrum of the SNP rs15700989 among 5 different populations supported the above associations. Western blotting, RT-PCR, and qPCR were used to analyze alternative splicing of the GARNL1 gene. RT-PCR detected 5 transcripts and revealed that the transcript, which has a 141 bp insertion, was expressed in a tissue-specific manner. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the GARNL1 gene contributes to chicken reproductive traits

Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response

<p>Abstract</p> <p>Background</p> <p>Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs). The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous - H), and TT (minor-allele homozygous - M). HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX^®- Amersham-Pharmacia, USA).</p> <p>Results</p> <p>Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in these patients.</p> <p>Conclusions</p> <p>The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.</p