Combinatorial formulas for Kazhdan-Lusztig polynomials with respect to W-graph ideals

In \cite{y1} Yin generalized the definition of $W$-graph ideal $E_J$ in weighted Coxeter groups and introduced the weighted Kazhdan-Lusztig polynomials $\left \{ P_{x,y} \mid x,y\in E_J\right \}$, where $J$ is a subset of simple generators $S$. In this paper, we study the combinatorial formulas for those polynomials, which extend the results of Deodhar \cite{v3} and Tagawa \cite{h1}.Comment: 16 page

Paradiplomacy of Regions: Cases of Burgundy and Central Bohemia Region

Diploma thesis "Paradiplomacy of regions, cases of Burgundy and Central Bohemia Region" deals with "foreign policy of non-central actors" and the possibilities for regions how to enforce their interest on international level. Key research questions are: What makes regions act abroad, what are the reasons for activities abroad? What is the role of Europeanization and internationalization in the process of development of local actors involved in regional foreign activities? Who is engaged in formulation of regional interests and who is responsible for implementation of regional international strategy? Is there a broader consensus among regional actors on the way how to develop foreign activities? Is the main motor of activity local administration or private sphere? What are the possibilities for action on international level with regard to regional competencies? First, there are examined main features of foreign strategies of regions in question. Then we analyze tools developed for implementation of those strategies. How are the strategies implemented, are they successful? Finally we define main future challenges for action of regions abroad. Powered by TCPDF (www.tcpdf.org

The number of genes differentially expressed as a result of infection with <i>F</i>. <i>hepatica</i> metacercariae.

<p>(A) A Venn diagram representing the differentially expressed genes obtained from statistical analyses of two groups (t7 <i>vs</i> t21 and t0 <i>vs</i> t21; Significant Analysis of Microarrays SAM test, false discovery rate at 5%). The figure represents the numbers of probe sets that are differently expressed between the three groups (untreated controls t0, infected and sacrificed at 7 days p.i (t7), and infected and sacrificed at 21 days p.i (t21)) and shared among the analyses (t7 <i>vs</i> t21, and t0 <i>vs</i> t21). (B) Down-regulated genes. (C) Up-regulated genes. Down-regulated genes are represented as green bars and up-regulated genes as red bars.</p

The most representative pathways and the associated differentially expressed genes in two stages of the infection.

<p>(A) Comparison between t7 (seven days post-infection) vs t21 (21 days post-infection). (B). Comparison between t0 (Uninfected) vs t21 (21 days post-infection). The fold change of each gene is shown in parentheses. Red squares represent the genes that are up-regulated, belonging to each signaling pathway, green squares represent genes that are down-regulated, whereas gray squares indicate the absence of those genes in that pathway.</p

The microarray was validated with PCR reactions.

<p>(A) PCR amplification from liver RNA samples for the selected genes at time t0 (before any treatment). (B) PCR amplification at t21 (21 days after oral infection of mice with <i>F</i>. <i>hepatica</i> metacercariae). Three up-regulated genes and three down-regulated genes were randomly chosen for PCR amplification. The corresponding PCR for each gene was performed using each biological sample obtained at t0 and t21. The results are representative of three individual experiments. MWM: molecular weight marker.</p

Gene networks associated with hepatic damage.

<p>The Ingenuity Pathway Analysis tool was used to identify significant genes that are related to hepatic damage as well as to build up interaction networks amongst them with the most significant associated-functions related to hepatic damage. Solid lines denote direct interactions and dotted-arrows predict activation pathways. The color red indicates up-regulation. The data used for such network construction were the comparison between t0 (uninfected) and t21 (21 days post-infection), which is where the most significant differential expression of genes occurs.</p

Inhibition of Granulomatous Inflammation and Prophylactic Treatment of Schistosomiasis with a Combination of Edelfosine and Praziquantel

<div><p>Background</p><p>Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus <i>Schistosoma</i>. This parasitic disease is due to immunologic reactions to <i>Schistosoma</i> eggs trapped in tissues. Egg-released antigens stimulate tissue-destructive inflammatory and granulomatous reactions, involving different immune cell populations, including T cells and granulocytes. Granulomas lead to collagen fibers deposition and fibrosis, resulting in organ damage. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult <i>Schistosoma</i> worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis.</p><p>Methodology/Principal Findings</p><p>Using <i>in vitro</i> and <i>in vivo</i> approaches, we have found that the alkylphospholipid analog edelfosine kills schistosomula, and displays anti-inflammatory activity. The combined treatment of PZQ and edelfosine during a few days before and after cercariae infection in a schistosomiasis mouse model, simulating a prophylactic treatment, led to seven major effects: a) killing of <i>Schistosoma</i> parasites at early and late development stages; b) reduction of hepatomegaly; c) granuloma size reduction; d) down-regulation of Th1, Th2 and Th17 responses at late post-infection times, thus inhibiting granuloma formation; e) upregulation of IL-10 at early post-infection times, thus potentiating anti-inflammatory actions; f) down-regulation of IL-10 at late post-infection times, thus favoring resistance to re-infection; g) reduction in the number of blood granulocytes in late post-infection times as compared to infected untreated animals.</p><p>Conclusions/Significance</p><p>Taken together, these data suggest that the combined treatment of PZQ and edelfosine promotes a high decrease in granuloma formation, as well as in the cellular immune response that underlies granuloma development, with changes in the cytokine patterns, and may provide a promising and effective strategy for a prophylactic treatment of schistosomiasis.</p></div

Granulocyte analysis in drug treated- and untreated-mice.

<p>Blood samples were analyzed for neutrophil, eosinophil and basophil counts in uninfected-untreated naive mice, infected untreated (<i>untreated</i>) mice and infected mice treated with PZQ, EDLF or PZQ+EDLF. Samples were taken at weeks 3 (A) and 8 (B) p.i. Data are shown as means ± SEM of eight mice. Asterisks represent statistical significance with respect to the infected untreated group. (*) <i>p</i><0.05; (**) <i>p</i><0.01; (***) <i>p</i><0.001.</p

Genes involved in causing damage and liver necrosis according to the Ingenuity Pathway Analysis tool.

<p>The fold change and significance of each gene are also shown. Regulated genes correspond to the comparison between t0 (uninfected mice) <i>vs</i> t21 (mice infected and necropsied at 21 days post-infection).</p><p>Genes involved in causing damage and liver necrosis according to the Ingenuity Pathway Analysis tool.</p

Gene Expression Profile in the Liver of BALB/c Mice Infected with <i>Fasciola hepatica</i>

<div><p>Background</p><p><i>Fasciola hepatica</i> infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by <i>Fasciola hepatica</i>, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with <i>F</i>. <i>hepatica</i> metacercariae using a microarray-based methodology.</p><p>Methodology</p><p>A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven <i>F</i>. <i>hepatica</i> metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21).</p><p>Results</p><p>We found that <i>F</i>. <i>hepatica</i> infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death.</p><p>Conclusion</p><p>The present study provides us insights at the molecular level about the underlying mechanisms used by <i>F</i>. <i>hepatica</i>, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with <i>F</i>. <i>hepatica</i> and cholangiocarcinoma. However, more studies should be performed to confirm this hypothesis.</p></div