452 research outputs found

    Subset feedback vertex set is fixed parameter tractable

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    The classical Feedback Vertex Set problem asks, for a given undirected graph G and an integer k, to find a set of at most k vertices that hits all the cycles in the graph G. Feedback Vertex Set has attracted a large amount of research in the parameterized setting, and subsequent kernelization and fixed-parameter algorithms have been a rich source of ideas in the field. In this paper we consider a more general and difficult version of the problem, named Subset Feedback Vertex Set (SUBSET-FVS in short) where an instance comes additionally with a set S ? V of vertices, and we ask for a set of at most k vertices that hits all simple cycles passing through S. Because of its applications in circuit testing and genetic linkage analysis SUBSET-FVS was studied from the approximation algorithms perspective by Even et al. [SICOMP'00, SIDMA'00]. The question whether the SUBSET-FVS problem is fixed-parameter tractable was posed independently by Kawarabayashi and Saurabh in 2009. We answer this question affirmatively. We begin by showing that this problem is fixed-parameter tractable when parametrized by |S|. Next we present an algorithm which reduces the given instance to 2^k n^O(1) instances with the size of S bounded by O(k^3), using kernelization techniques such as the 2-Expansion Lemma, Menger's theorem and Gallai's theorem. These two facts allow us to give a 2^O(k log k) n^O(1) time algorithm solving the Subset Feedback Vertex Set problem, proving that it is indeed fixed-parameter tractable.Comment: full version of a paper presented at ICALP'1

    Conflict-Free Coloring Made Stronger

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    In FOCS 2002, Even et al. showed that any set of nn discs in the plane can be Conflict-Free colored with a total of at most O(logn)O(\log n) colors. That is, it can be colored with O(logn)O(\log n) colors such that for any (covered) point pp there is some disc whose color is distinct from all other colors of discs containing pp. They also showed that this bound is asymptotically tight. In this paper we prove the following stronger results: \begin{enumerate} \item [(i)] Any set of nn discs in the plane can be colored with a total of at most O(klogn)O(k \log n) colors such that (a) for any point pp that is covered by at least kk discs, there are at least kk distinct discs each of which is colored by a color distinct from all other discs containing pp and (b) for any point pp covered by at most kk discs, all discs covering pp are colored distinctively. We call such a coloring a {\em kk-Strong Conflict-Free} coloring. We extend this result to pseudo-discs and arbitrary regions with linear union-complexity. \item [(ii)] More generally, for families of nn simple closed Jordan regions with union-complexity bounded by O(n1+α)O(n^{1+\alpha}), we prove that there exists a kk-Strong Conflict-Free coloring with at most O(knα)O(k n^\alpha) colors. \item [(iii)] We prove that any set of nn axis-parallel rectangles can be kk-Strong Conflict-Free colored with at most O(klog2n)O(k \log^2 n) colors. \item [(iv)] We provide a general framework for kk-Strong Conflict-Free coloring arbitrary hypergraphs. This framework relates the notion of kk-Strong Conflict-Free coloring and the recently studied notion of kk-colorful coloring. \end{enumerate} All of our proofs are constructive. That is, there exist polynomial time algorithms for computing such colorings

    Tight Security Analysis of 3-Round Key-Alternating Cipher with A Single Permutation

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    The tight security bound of the Key-Alternating Cipher (KAC) construction whose round permutations are independent from each other has been well studied. Then a natural question is how the security bound will change when we use fewer permutations in a KAC construction. In CRYPTO 2014, Chen et al. proved that 2-round KAC with a single permutation (2KACSP) has the same security level as the classic one (i.e., 2-round KAC). But we still know little about the security bound of incompletely-independent KAC constructions with more than 2 rounds. In this paper,we will show that a similar result also holds for 3-round case. More concretely, we prove that 3-round KAC with a single permutation (3KACSP) is secure up to Θ(23n4)\varTheta(2^{\frac{3n}{4}}) queries, which also caps the security of 3-round KAC. To avoid the cumbersome graphical illustration used in Chen et al.\u27s work, a new representation is introduced to characterize the underlying combinatorial problem. Benefited from it, we can handle the knotty dependence in a modular way, and also show a plausible way to study the security of rrKACSP. Technically, we abstract a type of problems capturing the intrinsic randomness of rrKACSP construction, and then propose a high-level framework to handle such problems. Furthermore, our proof techniques show some evidence that for any rr, rrKACSP has the same security level as the classic rr-round KAC in random permutation model

    Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

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    Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H2O2) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.

    BBB Secure Nonce Based MAC Using Public Permutations

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    In the recent trend of CAESAR competition and NIST light-weight competition, cryptographic community have witnessed the submissions of several cryptographic schemes that are build on public random permutations. Recently, in CRYPTO 2019, Chen et al. have initiated an interesting research direction in designing beyond birthday bound PRFs from public random permutations and they proposed two instances of such PRFs. In this work, we extend this research direction by proposing a nonce-based MAC build from public random permutations. We show that our proposed MAC achieves 2n/32n/3 bit security (with respect to the state size of the permutation) and the bound is essentially tight. Moreover, the security of the MAC degrades gracefully with the repetition of the nonce

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

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    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

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    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
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