On Lattice-Free Orbit Polytopes

Given a permutation group acting on coordinates of $\mathbb{R}^n$, we consider lattice-free polytopes that are the convex hull of an orbit of one integral vector. The vertices of such polytopes are called \emph{core points} and they play a key role in a recent approach to exploit symmetry in integer convex optimization problems. Here, naturally the question arises, for which groups the number of core points is finite up to translations by vectors fixed by the group. In this paper we consider transitive permutation groups and prove this type of finiteness for the $2$-homogeneous ones. We provide tools for practical computations of core points and obtain a complete list of representatives for all $2$-homogeneous groups up to degree twelve. For transitive groups that are not $2$-homogeneous we conjecture that there exist infinitely many core points up to translations by the all-ones-vector. We prove our conjecture for two large classes of groups: For imprimitive groups and groups that have an irrational invariant subspace.Comment: 27 pages, 2 figures; with minor adaptions according to referee comments; to appear in Discrete and Computational Geometr

Algorithms for highly symmetric linear and integer programs

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)This paper deals with exploiting symmetry for solving linear and integer programming problems. Basic properties of linear representations of finite groups can be used to reduce symmetric linear programming to solving linear programs of lower dimension. Combining this approach with knowledge of the geometry of feasible integer solutions yields an algorithm for solving highly symmetric integer linear programs which only takes time which is linear in the number of constraints and quadratic in the dimension

Algorithms for highly symmetric linear and integer programs

This paper deals with exploiting symmetry for solving linear and integer programming problems. Basic properties of linear representations of finite groups can be used to reduce symmetric linear programming to solving linear programs of lower dimension. Combining this approach with knowledge of the geometry of feasible integer solutions yields an algorithm for solving highly symmetric integer linear programs which only takes time which is linear in the number of constraints and quadratic in the dimensio

Study of glucose transporters in C. elegans

The calorie restriction (CR) and insulin/IGF-I-like signalling (IIS) are two pathways regulating the lifespan of C. elegans. Recent studies showed that glucose restriction extends the lifespan of C. elegans while excessive glucose shortens the lifespan of the worms. The first step of the glucose metabolism is the transport of glucose across the plasma membrane by the glucose transporters. The work described in this thesis aims to identify glucose transporters in C. elegans and to provide a primary investigation of the in vitro and in vivo function of the identified glucose transporter. Nine putative transporters have been cloned and expressed. Out of the nice cloned putative transporters in the C. elegans genome, H17B01.1 (H17) only is identified as a fully functional glucose transporter using an oocyte expression system in which glucose transport activity is directly measured. The two transcripts of H17 are both capable of transporting glucose with high affinity, as well as transporting trehalose. Heterologous expression of H17 in mammalian CHO-T cells suggests that the protein is localised both on the plasma membrane and in the cytosol. In vitro studies of H17 show that the protein does not respond to insulin stimulation when expressed in mammalian CHO-T cell and rat primary adipocyte systems. In vivo functional studies using H17 RNAi indicate that the worm’s lifespan is not affected by the H17 knockdown. However, glucose metabolism of C. elegans (as measured by glucose oxidation to CO2 and incorporation into fat reserves) is influenced by the decreased expression of H17, especially in the daf-2 mutant strain, e1370. However, the increase of glucose metabolism caused by H17 knockdown observed in daf-2 mutant is inhibited in the age-1 and akt-1 mutant strains. The findings reported in this thesis suggest that the H17 glucose transporter may play an important role glucose metabolism in C. elegans and that this transport and metabolism is influenced by insulin receptor activity and serine kinase cascades.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Algorithms for Highly Symmetric Linear and Integer Programs

This paper deals with exploiting symmetry for solving linear and integer programming problems. Basic properties of linear representations of finite groups can be used to reduce symmetric linear programming to solving linear programs of lower dimension. Combining this approach with knowledge of the geometry of feasible integer solutions yields an algorithm for solving highly symmetric integer linear programs which only takes time which is linear in the number of constraints and quadratic in the dimension.Comment: 21 pages, 1 figure; some references and further comments added, title slightly change

Exploiting Symmetry in Integer Convex Optimization using Core Points

We consider convex programming problems with integrality constraints that are invariant under a linear symmetry group. To decompose such problems we introduce the new concept of core points, i.e., integral points whose orbit polytopes are lattice-free. For symmetric integer linear programs we describe two algorithms based on this decomposition. Using a characterization of core points for direct products of symmetric groups, we show that prototype implementations can compete with state-of-the-art commercial solvers, and solve an open MIPLIB problem.Comment: 15 pages; small changes according to suggestions of a referee; to appear in Operations Research Letter

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon (R)) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo

Topical Diclofenac Reprograms Metabolism and Immune Cell Infiltration in Actinic Keratosis

Background: Melanoma and squamous cell carcinoma of the skin are characterized by an altered glucose metabolism, but little is known about metabolic changes in precancerous skin lesions such as actinic keratosis (AK). Here, we studied the central carbon metabolism and immune cell infiltrate of actinic keratosis lesions before, under, and 4 weeks after treatment with topical diclofenac (Solaraze (R)). Methods: This study was designed as a prospective, randomized, controlled, monocentric investigation (ClinicalTrials.gov Identifier: NCT01935531). Myeloid and T cell infiltration was analyzed in skin biopsies from 28 patients by immunohistochemistry. Furthermore, immune cell activation was determined via quantitative real-time PCR (IFN-gamma, IL-10, CSF1 , TGF-beta, IL-6). Glucose, amino acid and Krebs' cycle metabolism was studied by mass spectrometry prior, during and after treatment with topical diclofenac. Biopsies from sun-exposed, untreated, healthy skin served as controls. Results: Increased lactate and decreased glucose levels suggested accelerated glycolysis in pre-treatment AK. Further, levels of Krebs' cycle intermediates other than citrate and amino acids were elevated. Analysis of the immune infiltrate revealed less epidermal CD1a+ cells but increased frequencies of dermal CD8+ T cells in AK. Treatment with diclofenac reduced lactate and amino acid levels in AK, especially in responding lesions, and induced an infiltration of dermal CD8+ T cells accompanied by high IFN-gamma mRNA expression, suggesting improved T cell function. Discussion: Our study clearly demonstrated that not only cancers but also pre-malignant skin lesions, like AK, exhibit profound changes in metabolism, correlating with an altered immune infiltrate. Diclofenac normalizes metabolism, immune cell infiltration and function in AK lesions, suggesting a novel mechanism of action