A Novel Approach for Ellipsoidal Outer-Approximation of the Intersection Region of Ellipses in the Plane

In this paper, a novel technique for tight outer-approximation of the intersection region of a finite number of ellipses in 2-dimensional (2D) space is proposed. First, the vertices of a tight polygon that contains the convex intersection of the ellipses are found in an efficient manner. To do so, the intersection points of the ellipses that fall on the boundary of the intersection region are determined, and a set of points is generated on the elliptic arcs connecting every two neighbouring intersection points. By finding the tangent lines to the ellipses at the extended set of points, a set of half-planes is obtained, whose intersection forms a polygon. To find the polygon more efficiently, the points are given an order and the intersection of the half-planes corresponding to every two neighbouring points is calculated. If the polygon is convex and bounded, these calculated points together with the initially obtained intersection points will form its vertices. If the polygon is non-convex or unbounded, we can detect this situation and then generate additional discrete points only on the elliptical arc segment causing the issue, and restart the algorithm to obtain a bounded and convex polygon. Finally, the smallest area ellipse that contains the vertices of the polygon is obtained by solving a convex optimization problem. Through numerical experiments, it is illustrated that the proposed technique returns a tighter outer-approximation of the intersection of multiple ellipses, compared to conventional techniques, with only slightly higher computational cost

Behavior of eigenvalues in a region of broken PT symmetry

PT-symmetric quantum mechanics began with a study of the Hamiltonian H=p2+x2(ix)ɛ. When ɛ≥0, the eigenvalues of this non-Hermitian Hamiltonian are discrete, real, and positive. This portion of parameter space is known as the region of unbroken PT symmetry. In the region of broken PT symmetry, ɛ<0, only a finite number of eigenvalues are real and the remaining eigenvalues appear as complex-conjugate pairs. The region of unbroken PT symmetry has been studied but the region of broken PT symmetry has thus far been unexplored. This paper presents a detailed numerical and analytical examination of the behavior of the eigenvalues for −4<ɛ<0. In particular, it reports the discovery of an infinite-order exceptional point at ɛ=−1, a transition from a discrete spectrum to a partially continuous spectrum at ɛ=−2, a transition at the Coulomb value ɛ=−3, and the behavior of the eigenvalues as ɛ approaches the conformal limit ɛ=−4

Robust Detection of Hierarchical Communities from Escherichia coli Gene Expression Data

Determining the functional structure of biological networks is a central goal of systems biology. One approach is to analyze gene expression data to infer a network of gene interactions on the basis of their correlated responses to environmental and genetic perturbations. The inferred network can then be analyzed to identify functional communities. However, commonly used algorithms can yield unreliable results due to experimental noise, algorithmic stochasticity, and the influence of arbitrarily chosen parameter values. Furthermore, the results obtained typically provide only a simplistic view of the network partitioned into disjoint communities and provide no information of the relationship between communities. Here, we present methods to robustly detect coregulated and functionally enriched gene communities and demonstrate their application and validity for Escherichia coli gene expression data. Applying a recently developed community detection algorithm to the network of interactions identified with the context likelihood of relatedness (CLR) method, we show that a hierarchy of network communities can be identified. These communities significantly enrich for gene ontology (GO) terms, consistent with them representing biologically meaningful groups. Further, analysis of the most significantly enriched communities identified several candidate new regulatory interactions. The robustness of our methods is demonstrated by showing that a core set of functional communities is reliably found when artificial noise, modeling experimental noise, is added to the data. We find that noise mainly acts conservatively, increasing the relatedness required for a network link to be reliably assigned and decreasing the size of the core communities, rather than causing association of genes into new communities.Comment: Due to appear in PLoS Computational Biology. Supplementary Figure S1 was not uploaded but is available by contacting the author. 27 pages, 5 figures, 15 supplementary file

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

The evaluation of a Taiwanese training program in smoking cessation and the trainees' adherence to a practice guideline

<p>Abstract</p> <p>Background</p> <p>The Taiwanese government began reimbursement for smoking cessation in 2002. Certification from a training program was required for physicians who wanted reimbursement. The program certified 6,009 physicians till 2007. The objective of this study is to evaluate the short- and long term efficacy of the training program.</p> <p>Methods</p> <p>For short term evaluation, all trainees in 2007 were recruited. For long term evaluation, computer randomly selected 2,000 trainees who received training from 2002 to 2006 were recruited. Course satisfaction, knowledge, confidence in providing smoking cessation services and the adherence to a practice guideline were evaluated by questionnaires.</p> <p>Results</p> <p>Trainees reported high satisfaction with the training program. There was significant difference between pre- and post-test scores in knowledge. Confidence in providing services was lower in the long term evaluation compared to short term evaluation. For adherence to a practice guideline, 86% asked the status of smoking, 88% advised the smokers to quit, 76% assessed the smoker's willingness to quit, 59% assisted the smokers to quit, and 60% arranged follow-up visits for smokers. The incentive of reimbursement was the most significant factor affecting confidence and adherence.</p> <p>Conclusions</p> <p>The training program was satisfactory and effective. Adherence to a practice guideline in our study was better than studies without physician training in other countries.</p

Genetic polymorphisms of DNA double strand break gene Ku70 and gastric cancer in Taiwan

<p>Abstract</p> <p>Background and aim</p> <p>The DNA repair gene <it>Ku70</it>, an important member of non-homologous end-joining repair system, is thought to play an important role in the repairing of DNA double strand breaks. It is known that defects in double strand break repair capacity can lead to irreversible genomic instability. However, the polymorphic variants of <it>Ku70</it>, have never been reported about their association with gastric cancer susceptibility.</p> <p>Methods</p> <p>In this hospital-based case-control study, the associations of <it>Ku70 </it>promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms with gastric cancer risk in a Taiwanese population were investigated. In total, 136 patients with gastric cancer and 560 age- and gender-matched healthy controls recruited from the China Medical Hospital in Taiwan were genotyped.</p> <p>Results</p> <p>As for <it>Ku70 </it>promoter T-991C, the ORs after adjusted by age and gender of the people carrying TC and CC genotypes were 2.41 (95% CI = 1.53-3.88) and 3.21 (95% CI = 0.96-9.41) respectively, compared to those carrying TT wild-type genotype. The <it>P </it>for trend was significant (<it>P </it>< 0.0001). In the dominant model (TC plus CC versus TT), the association between <it>Ku70 </it>promoter T-991C polymorphism and the risk for gastric cancer was also significant (adjusted OR = 2.48, 95% CI = 1.74-3.92). When stratified by age and gender, the association was restricted to those at the age of 55 or elder of age (TC vs TT: adjusted OR = 2.52, 95% CI = 1.37-4.68, <it>P </it>= 0.0139) and male (TC vs TT: adjusted OR = 2.58, 95% CI = 1.33-4.47, <it>P </it>= 0.0085). As for the other three polymorphisms, there was no difference between both groups in the distributions of their genotype frequencies.</p> <p>Conclusion</p> <p>In conclusion, the <it>Ku70 </it>promoter T-991C (rs5751129), but not the <it>Ku70 </it>promoter C-57G (rs2267437), promoter A-31G (rs132770) or intron 3 (rs132774), is associated with gastric cancer susceptibility. This polymorphism may be a novel useful marker for gastric carcinogenesis.</p

Changes over time in the "healthy soldier effect"

Background: Death rates in military populations outside of combat are often lower than those in the general population. This study considers how this "healthy soldier effect" changes over time.Methods: Standardized mortality ratios were used to compare changes in death rates relative to the Australian population in two large studies of Australian servicemen of the Korean War (n = 17,381) and the Vietnam War era (n = 83,908).Results: The healthy soldier effect was most consistently observed in deaths from circulatory diseases. A large deficit in these deaths in the initial follow-up period (10-20 years) was observed before rates tended to rise to the level seen in the general population. There was no healthy soldier effect in deaths from external causes in enlisted personnel, and these death rates were significantly higher than expected in the initial follow-up period among Korean War veterans and regular Army veterans of the Vietnam War. Those selected for national service during the Vietnam War exhibited the strongest healthy soldier effect of all cohorts assessed.Conclusions: Patterns of the healthy soldier effect over time varied markedly by study cohort and by cause of death studied. In a number of analyses, the healthy soldier effect was still apparent after more than 30 years of follow-up

The addition of a pH-sensitive gel improves microemulsion stability for the targeted removal of colonic ammonia

<p>Abstract</p> <p>Background</p> <p>We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA).</p> <p>Methods</p> <p>MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA.</p> <p>Results</p> <p>MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine.</p> <p>Conclusions</p> <p>MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies.</p

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses