Smoothed Analysis of the Minimum-Mean Cycle Canceling Algorithm and the Network Simplex Algorithm

The minimum-cost flow (MCF) problem is a fundamental optimization problem with many applications and seems to be well understood. Over the last half century many algorithms have been developed to solve the MCF problem and these algorithms have varying worst-case bounds on their running time. However, these worst-case bounds are not always a good indication of the algorithms' performance in practice. The Network Simplex (NS) algorithm needs an exponential number of iterations for some instances, but it is considered the best algorithm in practice and performs best in experimental studies. On the other hand, the Minimum-Mean Cycle Canceling (MMCC) algorithm is strongly polynomial, but performs badly in experimental studies. To explain these differences in performance in practice we apply the framework of smoothed analysis. We show an upper bound of $O(mn^2\log(n)\log(\phi))$ for the number of iterations of the MMCC algorithm. Here $n$ is the number of nodes, $m$ is the number of edges, and $\phi$ is a parameter limiting the degree to which the edge costs are perturbed. We also show a lower bound of $\Omega(m\log(\phi))$ for the number of iterations of the MMCC algorithm, which can be strengthened to $\Omega(mn)$ when $\phi=\Theta(n^2)$. For the number of iterations of the NS algorithm we show a smoothed lower bound of $\Omega(m \cdot \min \{ n, \phi \} \cdot \phi)$.Comment: Extended abstract to appear in the proceedings of COCOON 201

Vertex-Coloring with Star-Defects

Defective coloring is a variant of traditional vertex-coloring, according to which adjacent vertices are allowed to have the same color, as long as the monochromatic components induced by the corresponding edges have a certain structure. Due to its important applications, as for example in the bipartisation of graphs, this type of coloring has been extensively studied, mainly with respect to the size, degree, and acyclicity of the monochromatic components. In this paper we focus on defective colorings in which the monochromatic components are acyclic and have small diameter, namely, they form stars. For outerplanar graphs, we give a linear-time algorithm to decide if such a defective coloring exists with two colors and, in the positive case, to construct one. Also, we prove that an outerpath (i.e., an outerplanar graph whose weak-dual is a path) always admits such a two-coloring. Finally, we present NP-completeness results for non-planar and planar graphs of bounded degree for the cases of two and three colors

On the geometry of C^3/D_27 and del Pezzo surfaces

We clarify some aspects of the geometry of a resolution of the orbifold X = C3/D_27, the noncompact complex manifold underlying the brane quiver standard model recently proposed by Verlinde and Wijnholt. We explicitly realize a map between X and the total space of the canonical bundle over a degree 1 quasi del Pezzo surface, thus defining a desingularization of X. Our analysis relys essentially on the relationship existing between the normalizer group of D_27 and the Hessian group and on the study of the behaviour of the Hesse pencil of plane cubic curves under the quotient.Comment: 23 pages, 5 figures, 2 tables. JHEP style. Added references. Corrected typos. Revised introduction, results unchanged

IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

Lack of HLA predominance and HLA shared epitopes in biliary Atresia

Biliary atresia (BA) is characterized by progressive inflammation and fibrosis of bile ducts. A theory of pathogenesis entails autoimmune-mediated injury targeting bile duct epithelia. One of the strongest genetic associations with autoimmunity is with HLA genes. In addition, apparently dissimilar HLA alleles may have similar antigen-binding sites, called shared epitopes, that overlap in their capacity to present antigens. In autoimmune disease, the incidence of the disease may be related to the presence of shared epitopes, not simply the HLA allelic association. Aim: To determine HLA allele frequency (high-resolution genotyping) and shared epitope associations in BA. Results: Analysis of every allele for HLA-A, -B, -C, -DRB1, -DPB1 and -DQB1 in 180 BA and 360 racially-matched controls did not identify any significant HLA association with BA. Furthermore, shared epitope analysis of greater than 10 million possible combinations of peptide sequences was not different between BA and controls. Conclusions: This study encompasses the largest HLA allele frequency analysis for BA in the United States and is the first study to perform shared epitope analysis. When controlling for multiple comparisons, no HLA allele or shared epitope association was identified in BA. Future studies of genetic links to BA that involve alterations of the immune response should include investigations into defects in regulatory T cells and non-HLA linked autoinflammatory diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-42) contains supplementary material, which is available to authorized users

Establishing a follow-up of the Swiss MONICA participants (1984-1993): record linkage with census and mortality data

BACKGROUND: To assess the feasibility and quality of an anonymous linkage of 1) MONICA (MONItoring of trends and determinants in CArdiovscular disease, three waves between 1984 and 1993) data with 2) census and mortality records of the Swiss National Cohort in order to establish a mortality follow-up until 2008. Many countries feature the defect of lacking general population cohorts because they have missed to provide for follow-up information of health surveys. METHODS: Record linkage procedures were used in a multi-step approach. Kaplan-Meier curves from our data were contrasted with the survival probabilities expected from life tables for the general population, age-standardized mortality rates from our data with those derived from official cross-sectional mortality data. Cox regression models were fit to investigate the influence of covariates on survival. RESULTS: 97.8% of the eligible 10,160 participants (25-74y at baseline) could be linked to a census (1990: 9,737; 2000: 8,749), mortality (1,526, 1984-2008) and/or emigration record (320, 1990-2008). Linkage success did not differ by any key study characteristic. Results of survival analyses were robust to linkage step or certainty of a correct link. Loss to follow-up between 1990 and 2000 amounted to 4.7%. MONICA participants had lower mortality than the general population, but similar mortality patterns, (e.g. variation by educational level, marital status or region). CONCLUSIONS: Using anonymized census and death records allowed an almost complete mortality follow-up of MONICA study participants of up to 25 years. Lower mortality compared to the general population was in line with a presumable 'healthy participant' selection in the original MONICA study. Apart from that, the derived data set reproduced known mortality patterns and showed only negligible potential for selection bias introduced by the linkage process. Anonymous record linkage was feasible and provided robust results. It can thus provide valuable information, when no cohort study is available

Emerging Concepts for Pelvic Organ Prolapse Surgery: What is Cure?

The objective of this review is to discuss emerging concepts in pelvic organ prolapse, in particular, “What is cure?” In a post-trial data analysis of the CARE (Colpopexy and Urinary Reduction Efforts) trial, treatment success varied tremendously depending on the definition used (19.2%–97.2%). Definitions that included the absence of vaginal bulge symptoms had the strongest relationships with the patients’ assessment of overall improvement and treatment success. As demonstrated by this study, there are several challenges in defining cure in prolapse surgery. Additionally, the symptoms of prolapse are variable. The degree of prolapse does not correlate directly with symptoms. There are many surgical approaches to pelvic organ prolapse. Multiple ways to quantify prolapse are used. There is a lack of standardized definition of cure. The data on prolapse surgery outcomes are heterogeneous. The goal of surgical repair is to return the pelvic organs to their original anatomic positions. Ideally, we have four main goals: no anatomic prolapse, no functional symptoms, patient satisfaction, and the avoidance of complications. The impact of transvaginal mesh requires thoughtful investigation. The driving force should be patient symptoms in defining cure of prolapse

HLA-DR Alpha 2 Mediates Negative Signalling via Binding to Tirc7 Leading to Anti-Inflammatory and Apoptotic Effects in Lymphocytes In Vitro and In Vivo

Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRα2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-ζ chain & ZAP70, and inhibition of IFN-γ and FasL expression. HLA-DRα2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRα2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway

A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

<p>Abstract</p> <p>Background</p> <p>The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes.</p> <p>Results</p> <p>To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4⁺cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, <it>IL7R</it>, was selected for further validation. The expression levels of <it>IL7R </it>in allergen challenged CD4⁺cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies.</p> <p>Conclusion</p> <p>We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.</p