A general lower bound for collaborative tree exploration

We consider collaborative graph exploration with a set of $k$ agents. All agents start at a common vertex of an initially unknown graph and need to collectively visit all other vertices. We assume agents are deterministic, vertices are distinguishable, moves are simultaneous, and we allow agents to communicate globally. For this setting, we give the first non-trivial lower bounds that bridge the gap between small ($k \leq \sqrt n$) and large ($k \geq n$) teams of agents. Remarkably, our bounds tightly connect to existing results in both domains. First, we significantly extend a lower bound of $\Omega(\log k / \log\log k)$ by Dynia et al. on the competitive ratio of a collaborative tree exploration strategy to the range $k \leq n \log^c n$ for any $c \in \mathbb{N}$. Second, we provide a tight lower bound on the number of agents needed for any competitive exploration algorithm. In particular, we show that any collaborative tree exploration algorithm with $k = Dn^{1+o(1)}$ agents has a competitive ratio of $\omega(1)$, while Dereniowski et al. gave an algorithm with $k = Dn^{1+\varepsilon}$ agents and competitive ratio $O(1)$, for any $\varepsilon > 0$ and with $D$ denoting the diameter of the graph. Lastly, we show that, for any exploration algorithm using $k = n$ agents, there exist trees of arbitrarily large height $D$ that require $\Omega(D^2)$ rounds, and we provide a simple algorithm that matches this bound for all trees

Anonymous Graph Exploration with Binoculars

International audienceWe investigate the exploration of networks by a mobile agent. It is long known that, without global information about the graph, it is not possible to make the agent halts after the exploration except if the graph is a tree. We therefore endow the agent with binoculars, a sensing device that can show the local structure of the environment at a constant distance of the agent current location.We show that, with binoculars, it is possible to explore and halt in a large class of non-tree networks. We give a complete characterization of the class of networks that can be explored using binoculars using standard notions of discrete topology. This class is much larger than the class of trees: it contains in particular chordal graphs, plane triangulations and triangulations of the projective plane. Our characterization is constructive, we present an Exploration algorithm that is universal; this algorithm explores any network explorable with binoculars, and never halts in non-explorable networks

Comparison of Peptide Array Substrate Phosphorylation of c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8

Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to predict kinase substrate preferences from the primary structure, hampering the understanding of kinase function in physiology and prompting the development of technologies that allow easy assessment of kinase substrate consensus sequences. Hence, we decided to explore the usefulness of phosphorylation of peptide arrays comprising of 1176 different peptide substrates with recombinant kinases for determining kinase substrate preferences, based on the contribution of individual amino acids to total array phosphorylation. Employing this technology, we were able to determine the consensus peptide sequences for substrates of both c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8, two highly homologous kinases with distinct signalling roles in cellular physiology. The results show that although consensus sequences for these two kinases identified through our analysis share important chemical similarities, there is still some sequence specificity that could explain the different biological action of the two enzymes. Thus peptide arrays are a useful instrument for deducing substrate consensus sequences and highly homologous kinases can differ in their requirement for phosphorylation events

Mobile agent rendezvous: A survey

Abstract. Recent results on the problem of mobile agent rendezvous on distributed networks are surveyed with an emphasis on outlining the various approaches taken by researchers in the theoretical computer science community.

Evidence for a Minimal Eukaryotic Phosphoproteome?

BACKGROUND: Reversible phosphorylation catalysed by kinases is probably the most important regulatory mechanism in eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS: We studied the in vitro phosphorylation of peptide arrays exhibiting the majority of PhosphoBase-deposited protein sequences, by factors in cell lysates from representatives of various branches of the eukaryotic species. We derived a set of substrates from the PhosphoBase whose phosphorylation by cellular extracts is common to the divergent members of different kingdoms and thus may be considered a minimal eukaryotic phosphoproteome. The protein kinases (or kinome) responsible for phosphorylation of these substrates are involved in a variety of processes such as transcription, translation, and cytoskeletal reorganisation. CONCLUSIONS/SIGNIFICANCE: These results indicate that the divergence in eukaryotic kinases is not reflected at the level of substrate phosphorylation, revealing the presence of a limited common substrate space for kinases in eukaryotes and suggests the presence of a set of kinase substrates and regulatory mechanisms in an ancestral eukaryote that has since remained constant in eukaryotic life

Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

Ordering heuristics for parallel graph coloring

This paper introduces the largest-log-degree-first (LLF) and smallest-log-degree-last (SLL) ordering heuristics for paral-lel greedy graph-coloring algorithms, which are inspired by the largest-degree-first (LF) and smallest-degree-last (SL) serial heuristics, respectively. We show that although LF and SL, in prac-tice, generate colorings with relatively small numbers of colors, they are vulnerable to adversarial inputs for which any paralleliza-tion yields a poor parallel speedup. In contrast, LLF and SLL allow for provably good speedups on arbitrary inputs while, in practice, producing colorings of competitive quality to their serial analogs. We applied LLF and SLL to the parallel greedy coloring algo-rithm introduced by Jones and Plassmann, referred to here as JP. Jones and Plassman analyze the variant of JP that processes the ver-tices of a graph in a random order, and show that on an O(1)-degree graph G = (V,E), this JP-R variant has an expected parallel run-ning time of O(lgV / lg lgV) in a PRAM model. We improve this bound to show, using work-span analysis, that JP-R, augmented to handle arbitrary-degree graphs, colors a graph G = (V,E) with degree ∆ using Θ(V +E) work and O(lgV + lg ∆ ·min{√E,∆+ lg ∆ lgV / lg lgV}) expected span. We prove that JP-LLF and JP-SLL — JP using the LLF and SLL heuristics, respectively — execute with the same asymptotic work as JP-R and only logarith-mically more span while producing higher-quality colorings than JP-R in practice. We engineered an efficient implementation of JP for modern shared-memory multicore computers and evaluated its performance on a machine with 12 Intel Core-i7 (Nehalem) processor cores. Our implementation of JP-LLF achieves a geometric-mean speedup of 7.83 on eight real-world graphs and a geometric-mean speedup of 8.08 on ten synthetic graphs, while our implementation using SLL achieves a geometric-mean speedup of 5.36 on these real-world graphs and a geometric-mean speedup of 7.02 on these synthetic graphs. Furthermore, on one processor, JP-LLF is slightly faster than a well-engineered serial greedy algorithm using LF, and like-wise, JP-SLL is slightly faster than the greedy algorithm using SL

Mast cells disrupt the function of the esophageal epithelial barrier

Mast cells (MCs) accumulate in the epithelium of patients with eosinophilic esophagitis (EoE), an inflammatory disorder characterized by extensive esophageal eosinophilic infiltration. Esophageal barrier dysfunction plays an important role in the pathophysiology of EoE. We hypothesized that MCs contribute to the observed impaired esophageal epithelial barrier. Herein, we demonstrate that coculture of differentiated esophageal epithelial cells with immunoglobulin E-activated MCs significanly decreased epithelial resistance by 30% and increased permeability by 22% compared with non-activated MCs. These changes were associated with decreased messenger RNA expression of barrier proteins filaggrin, desmoglein-1 and involucrin, and antiprotease serine peptidase inhibitor kazal type 7. Using targeted proteomics, we detected various cytokines in coculture supernatants, most notably granulocyte-macrophage colony-stimulating factor and oncostatin M (OSM). OSM expression was increased by 12-fold in active EoE and associated with MC marker genes. Furthermore, OSM receptor-expressing esophageal epithelial cells were found in the esophageal tissue of patients with EoE, suggesting that the epithelial cells may respond to OSM. Stimulation of esophageal epithelial cells with OSM resulted in a dose-dependent decrease in barrier function and expression of filaggrin and desmoglein-1 and an increase in protease calpain-14. Taken together, these data suggest a role for MCs in decreasing esophageal epithelial barrier function in EoE, which may in part be mediated by OSM

Are Small GTPases Signal Hubs in Sugar-Mediated Induction of Fructan Biosynthesis?

External sugar initiates biosynthesis of the reserve carbohydrate fructan, but the molecular processes mediating this response remain obscure. Previously it was shown that a phosphatase and a general kinase inhibitor hamper fructan accumulation. We use various phosphorylation inhibitors both in barley and in Arabidopsis and show that the expression of fructan biosynthetic genes is dependent on PP2A and different kinases such as Tyr-kinases and PI3-kinases. To further characterize the phosphorylation events involved, comprehensive analysis of kinase activities in the cell was performed using a PepChip, an array of >1000 kinase consensus substrate peptide substrates spotted on a chip. Comparison of kinase activities in sugar-stimulated and mock(sorbitol)-treated Arabidopsis demonstrates the altered phosphorylation of many consensus substrates and documents the differences in plant kinase activity upon sucrose feeding. The different phosphorylation profiles obtained are consistent with sugar-mediated alterations in Tyr phosphorylation, cell cycling, and phosphoinositide signaling, and indicate cytoskeletal rearrangements. The results lead us to infer a central role for small GTPases in sugar signaling