Interaction between primary alveolar macrophages and primary alveolar type II cells under basal conditions and after lipopolysaccharide or quartz exposure

Evidence suggests that hyperproduction of reactive oxidants and inflammatory mediators plays a critical role in adverse pulmonary responses to silica or lipopolysaccharide (LPS). The main objective of this study was to contribute to advancing the understanding of the role of AM\u27s and type II (TII) cells in the induction of pulmonary inflammation and injury in response to silica and LPS, and improve our understanding of the interaction between AM\u27s and TII cells which would occur in vivo. To reach this objective, three aims were put forth. (1) Determine the relative responsiveness of primary rat AM\u27s, primary rat TII cells and RLE-6TN, a rat TII cell line to silica and LPS under comparable conditions. (2) Determine if AM/TII intercellular interactions exist and under what conditions they can be demonstrated. (3) Attempt to identify the mediator(s) responsible for this interaction. The following findings were made: (1) although AM\u27s were generally found to release more inflammatory mediators than TII cells following LPS or silica exposures, primary TII cells clearly produced significant levels of mediators which could be capable of contributing considerably to lung inflammation and injury. (2) Since the RLE-6TN cell line responses to LPS and silica exposures were generally considerably less intense and required higher doses of stimulant than those measured in primary TII cells, RLE-6TN cells may not be a good substitute for primary TII cells in studying the pulmonary epithelium. (3) LPS was more potent than silica in inducing inflammatory cytokines from the three cell types. However, silica was found to be as potent as LPS or even slightly more potent as an inducer of cellular oxidants, especially from primary TII cells. (4) Surfactant appears to be an inhibitory mediator released from TII cells and acts on AM\u27s. (5) Basal transwell co-culture conditions are better than mixed co-culture conditions to study AM/TII cell interactions since the inhibitory effect of the surfactant in the transwell co-culture is minimized. (6) Oxidants, TNF-alpha, IL-1beta, prostaglandins and leukotrienes, probably do not directly affect the AM/TII intercellular interaction; instead, they (and especially TNF-alpha) appear to indirectly modulate the complex pathways of the AM/TII communication

Enhancement of Short Text Clustering by Iterative Classification

Short text clustering is a challenging task due to the lack of signal contained in such short texts. In this work, we propose iterative classification as a method to b o ost the clustering quality (e.g., accuracy) of short texts. Given a clustering of short texts obtained using an arbitrary clustering algorithm, iterative classification applies outlier removal to obtain outlier-free clusters. Then it trains a classification algorithm using the non-outliers based on their cluster distributions. Using the trained classification model, iterative classification reclassifies the outliers to obtain a new set of clusters. By repeating this several times, we obtain a much improved clustering of texts. Our experimental results show that the proposed clustering enhancement method not only improves the clustering quality of different clustering methods (e.g., k-means, k-means--, and hierarchical clustering) but also outperforms the state-of-the-art short text clustering methods on several short text datasets by a statistically significant margin.Comment: 30 pages, 2 figure

Light Spanners

A $t$-spanner of a weighted undirected graph $G=(V,E)$, is a subgraph $H$ such that $d_H(u,v)\le t\cdot d_G(u,v)$ for all $u,v\in V$. The sparseness of the spanner can be measured by its size (the number of edges) and weight (the sum of all edge weights), both being important measures of the spanner's quality -- in this work we focus on the latter. Specifically, it is shown that for any parameters $k\ge 1$ and $\epsilon>0$, any weighted graph $G$ on $n$ vertices admits a $(2k-1)\cdot(1+\epsilon)$-stretch spanner of weight at most $w(MST(G))\cdot O_\epsilon(kn^{1/k}/\log k)$, where $w(MST(G))$ is the weight of a minimum spanning tree of $G$. Our result is obtained via a novel analysis of the classic greedy algorithm, and improves previous work by a factor of $O(\log k)$.Comment: 10 pages, 1 figure, to appear in ICALP 201

Subset feedback vertex set is fixed parameter tractable

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

Folding and unfolding phylogenetic trees and networks

Phylogenetic networks are rooted, labelled directed acyclic graphs which are commonly used to represent reticulate evolution. There is a close relationship between phylogenetic networks and multi-labelled trees (MUL-trees). Indeed, any phylogenetic network $N$ can be "unfolded" to obtain a MUL-tree $U(N)$ and, conversely, a MUL-tree $T$ can in certain circumstances be "folded" to obtain a phylogenetic network $F(T)$ that exhibits $T$. In this paper, we study properties of the operations $U$ and $F$ in more detail. In particular, we introduce the class of stable networks, phylogenetic networks $N$ for which $F(U(N))$ is isomorphic to $N$, characterise such networks, and show that they are related to the well-known class of tree-sibling networks.We also explore how the concept of displaying a tree in a network $N$ can be related to displaying the tree in the MUL-tree $U(N)$. To do this, we develop a phylogenetic analogue of graph fibrations. This allows us to view $U(N)$ as the analogue of the universal cover of a digraph, and to establish a close connection between displaying trees in $U(N)$ and reconcilingphylogenetic trees with networks

Diagnostic stewardship in infectious diseases:a continuum of antimicrobial stewardship in the fight against antimicrobial resistance

Antimicrobial resistance (AMR) has been exacerbated by the inappropriate use of diagnostics, leading to excessive prescription of antimicrobials, and is an imminent threat to global health. Diagnostic stewardship (DS) is an auxiliary to antimicrobial stewardship (AMS) and comprises ordering the right tests, for the right patient, at the right time. It also promotes the judicious use of rapid and novel molecular diagnostic tools to enable the initiation of proper antibiotic therapy, while avoiding excessive use of broad-spectrum antibiotics. Proper interpretation of test results is crucial to avoid overdiagnosis and excessive healthcare costs. Although many rapid diagnostic tools have been developed with a high diagnostic yield, they are often limited by accessibility, cost, and lack of knowledge regarding their use. Careful consideration of clinical signs and symptoms with knowledge of the local epidemiology are essential for DS. This enables appropriate interpretation of microbiological results. Multidisciplinary teams that include well trained professionals should cooperate to promote DS. Challenges and barriers to the implementation of DS are mostly caused by scarcity of resources and lack of trained personnel and, most importantly, lack of knowledge. The lack of resources is often due to absence of awareness of the impact that good medical microbiology diagnostic facilities and expertise can have on the proper use of antibiotics.</p

Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.Scopu