Combinatorial Bounds for Conflict-free Coloring on Open Neighborhoods

In an undirected graph $G$, a conflict-free coloring with respect to open neighborhoods (denoted by CFON coloring) is an assignment of colors to the vertices such that every vertex has a uniquely colored vertex in its open neighborhood. The minimum number of colors required for a CFON coloring of $G$ is the CFON chromatic number of $G$, denoted by $\chi_{ON}(G)$. The decision problem that asks whether $\chi_{ON}(G) \leq k$ is NP-complete. We obtain the following results: * Bodlaender, Kolay and Pieterse [WADS 2019] showed the upper bound $\chi_{ON}(G)\leq {\sf fvs}(G)+3$, where ${\sf fvs}(G)$ denotes the size of a minimum feedback vertex set of $G$. We show the improved bound of $\chi_{ON}(G)\leq {\sf fvs}(G)+2$, which is tight, thereby answering an open question in the above paper. * We study the relation between $\chi_{ON}(G)$ and the pathwidth of the graph $G$, denoted ${\sf pw}(G)$. The above paper from WADS 2019 showed the upper bound $\chi_{ON}(G) \leq 2{\sf tw}(G)+1$ where ${\sf tw}(G)$ stands for the treewidth of $G$. This implies an upper bound of $\chi_{ON}(G) \leq 2{\sf pw}(G)+1$. We show an improved bound of $\chi_{ON}(G) \leq \lfloor \frac{5}{3}({\sf pw}(G)+1) \rfloor$. * We prove new bounds for $\chi_{ON}(G)$ with respect to the structural parameters neighborhood diversity and distance to cluster, improving existing results. * We also study the partial coloring variant of the CFON coloring problem, which allows vertices to be left uncolored. Let $\chi^*_{ON}(G)$ denote the minimum number of colors required to color $G$ as per this variant. Abel et. al. [SIDMA 2018] showed that $\chi^*_{ON}(G) \leq 8$ when $G$ is planar. They asked if fewer colors would suffice for planar graphs. We answer this question by showing that $\chi^*_{ON}(G) \leq 5$ for all planar $G$. All our bounds are a result of constructive algorithmic procedures.Comment: 30 page

Etk/Bmx Regulates Proteinase-Activated-Receptor1 (PAR1) in Breast Cancer Invasion: Signaling Partners, Hierarchy and Physiological Significance

BACKGROUND: While protease-activated-receptor 1 (PAR(1)) plays a central role in tumor progression, little is known about the cell signaling involved. METHODOLOGY/PRINCIPAL FINDINGS: We show here the impact of PAR(1) cellular activities using both an orthotopic mouse mammary xenograft and a colorectal-liver metastasis model in vivo, with biochemical analyses in vitro. Large and highly vascularized tumors were generated by cells over-expressing wt hPar1, Y397Z hPar1, with persistent signaling, or Y381A hPar1 mutant constructs. In contrast, cells over-expressing the truncated form of hPar1, which lacks the cytoplasmic tail, developed small or no tumors, similar to cells expressing empty vector or control untreated cells. Antibody array membranes revealed essential hPar1 partners including Etk/Bmx and Shc. PAR(1) activation induces Etk/Bmx and Shc binding to the receptor C-tail to form a complex. Y/A mutations in the PAR(1) C-tail did not prevent Shc-PAR(1) association, but enhanced the number of liver metastases compared with the already increased metastases obtained with wt hPar1. We found that Etk/Bmx first binds via the PH domain to a region of seven residues, located between C378-S384 in PAR(1) C-tail, enabling subsequent Shc association. Importantly, expression of the hPar1-7A mutant form (substituted A, residues 378-384), which is incapable of binding Etk/Bmx, resulted in inhibition of invasion through Matrigel-coated membranes. Similarly, knocking down Etk/Bmx inhibited PAR(1)-induced MDA-MB-435 cell migration. In addition, intact spheroid morphogenesis of MCF10A cells is markedly disrupted by the ectopic expression of wt hPar1. In contrast, the forced expression of the hPar1-7A mutant results in normal ball-shaped spheroids. Thus, by preventing binding of Etk/Bmx to PAR(1) -C-tail, hPar1 oncogenic properties are abrogated. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration that a cytoplasmic portion of the PAR(1) C-tail functions as a scaffold site. We identify here essential signaling partners, determine the hierarchy of binding and provide a platform for therapeutic vehicles via definition of the critical PAR(1)-associating region in the breast cancer signaling niche

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis

Development of a 3D Collagen Model for the In Vitro Evaluation of Magnetic-assisted Osteogenesis

Abstract Magnetic stimulation has been applied to bone regeneration, however, the cellular and molecular mechanisms of repair still require a better understanding. A three-dimensional (3D) collagen model was developed using plastic compression, which produces dense, cellular, mechanically strong native collagen structures. Osteoblast cells (MG-63) and magnetic iron oxide nanoparticles (IONPs) were incorporated into collagen gels to produce a range of cell-laden models. A magnetic bio-reactor to support cell growth under static magnetic fields (SMFs) was designed and fabricated by 3D printing. The influences of SMFs on cell proliferation, differentiation, extracellular matrix production, mineralisation and gene expression were evaluated. Polymerase chain reaction (PCR) further determined the effects of SMFs on the expression of runt-related transcription factor 2 (Runx2), osteonectin (ON), and bone morphogenic proteins 2 and 4 (BMP-2 and BMP-4). Results demonstrate that SMFs, IONPs and the collagen matrix can stimulate the proliferation, alkaline phosphatase production and mineralisation of MG-63 cells, by influencing matrix/cell interactions and encouraging the expression of Runx2, ON, BMP-2 and BMP-4. Therefore, the collagen model developed here not only offers a novel 3D bone model to better understand the effect of magnetic stimulation on osteogenesis, but also paves the way for further applications in tissue engineering and regenerative medicine

Towards Efficient and Scalable Data-Intensive Content Delivery: State-of-the-Art, Issues and Challenges

This chapter presents the authors’ work for the Case Study entitled “Delivering Social Media with Scalability” within the framework of High-Performance Modelling and Simulation for Big Data Applications (cHiPSet) COST Action 1406. We identify some core research areas and give an outline of the publications we came up within the framework of the aforementioned action. The ease of user content generation within social media platforms, e.g. check-in information, multimedia data, etc., along with the proliferation of Global Positioning System (GPS)-enabled, always-connected capture devices lead to data streams of unprecedented amount and a radical change in information sharing. Social data streams raise a variety of practical challenges: derivation of real-time meaningful insights from effectively gathered social information, a paradigm shift for content distribution with the leverage of contextual data associated with user preferences, geographical characteristics and devices in general, etc. In this article we present the methodology we followed, the results of our work and the outline of a comprehensive survey, that depicts the state-of-the-art situation and organizes challenges concerning social media streams and the infrastructure of the data centers supporting the efficient access to data streams in terms of content distribution, data diffusion, data replication, energy efficiency and network infrastructure. The challenges of enabling better provisioning of social media data have been identified and they were based on the context of users accessing these resources. The existing literature has been systematized and the main research points and industrial efforts in the area were identified and analyzed. In our works, in the framework of the Action, we came up with potential solutions addressing the problems of the area and described how these fit in the general ecosystem