GCA in 2d

We make a detailed study of the infinite dimensional Galilean Conformal Algebra (GCA) in the case of two spacetime dimensions. Classically, this algebra is precisely obtained from a contraction of the generators of the relativistic conformal symmetry in 2d. Here we find quantum mechanical realisations of the (centrally extended) GCA by considering scaling limits of certain 2d CFTs. These parent CFTs are non-unitary and have their left and right central charges become large in magnitude and opposite in sign. We therefore develop, in parallel to the usual machinery for 2d CFT, many of the tools for the analysis of the quantum mechanical GCA. These include the representation theory based on GCA primaries, Ward identities for their correlation functions and a nonrelativistic Kac table. In particular, the null vectors of the GCA lead to differential equations for the four point function. The solution to these equations in the simplest case is explicitly obtained and checked to be consistent with various requirements.Comment: 45 pages; v2: 47 pages. Restructured introduction, minor corrections, added references. Journal versio

Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation

BACKGROUND: Fas receptor-mediated eosinophil apoptosis is currently forwarded as a mechanism resolving asthma-like inflammation. This view is based on observations in vitro and in airway lumen with unknown translatability to airway tissues in vivo. In fact, apoptotic eosinophils have not been detected in human diseased airway tissues whereas cytolytic eosinophils abound and constitute a major mode of degranulation of these cells. Also, Fas receptor stimulation may bypass the apoptotic pathway and directly evoke cytolysis of non-apoptotic cells. We thus hypothesized that effects of anti-Fas mAb in vivo may include both apoptosis and cytolysis of eosinophils and, hence, that established eosinophilic inflammation may not resolve by this treatment. METHODS: Weeklong daily allergen challenges of sensitized mice were followed by airway administration of anti-Fas mAb. BAL was performed and airway-pulmonary tissues were examined using light and electron microscopy. Lung tissue analysis for CC-chemokines, apoptosis, mucus production and plasma exudation (fibrinogen) were performed. RESULTS: Anti-Fas mAb evoked apoptosis of 28% and cytolysis of 4% of eosinophils present in allergen-challenged airway tissues. Furthermore, a majority of the apoptotic eosinophils remained unengulfed and eventually exhibited secondary necrosis. A striking histopathology far beyond the allergic inflammation developed and included degranulated eosinophils, neutrophilia, epithelial derangement, plasma exudation, mucus-plasma plugs, and inducement of 6 CC-chemokines. In animals without eosinophilia anti-Fas evoked no inflammatory response. CONCLUSION: An efficient inducer of eosinophil apoptosis in airway tissues in vivo, anti-Fas mAb evoked unprecedented asthma-like inflammation in mouse allergic airways. This outcome may partly reflect the ability of anti-Fas to evoke direct cytolysis of non-apoptotic eosinophils in airway tissues. Additionally, since most apoptotic tissue eosinophils progressed into the pro-inflammatory cellular fate of secondary necrosis this may also explain the aggravated inflammation. Our data indicate that Fas receptor mediated eosinophil apoptosis in airway tissues in vivo may cause severe disease exacerbation due to direct cytolysis and secondary necrosis of eosinophils

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m−2 twice daily, days 1–14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m−2, (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m−2 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17–59%) with capecitabine (including three complete responses) and 26% (95% CI 9–51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand–foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a ⩾10% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patient-orientated therapy

Differential Patterns of Food Appreciation during Consumption of a Simple Food in Congenitally Anosmic Individuals: An Explorative Study

Food is evaluated for various attributes. One of the key food evaluation domains is hedonicity. As food is consumed, its hedonic valence decreases (due to prolonged sensory stimulation) and hedonic habituation results. The aim of the present study was to investigate changes in food pleasantness ratings during consumption of a simple food by individuals without olfactory experience with food as compared to normosmics. 15 congenital anosmics and 15 normosmic controls were each presented with ten 10 g banana slices. Each was visually inspected, then smelled and chewed for ten seconds and subsequently rated for hedonicity on a 21-point scale. There was a significant difference in pleasantness ratings between congenital anosmics and controls (F(1, 26) = 6.71, p = .02) with the anosmics exhibiting higher ratings than the controls, a significant main repeated-measures effect on the ratings (F(1.85, 48) = 12.15, p<.001), which showed a decreasing trend over the course of consumption, as well as a significant portion*group interaction (F(1.85, 48) = 3.54, p = .04), with the anosmic participants experiencing a less pronounced decline. The results of the present explorative study suggest that over the course of consumption of a simple food, congenitally anosmic individuals experience differential patterns of appreciation of food as compared to normosmics. In this particular case, the decrease of hedonic valence was less pronounced in congenital anosmics

Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia

BACKGROUND\ud \ud Levels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. It remains unclear whether CrP changes seen during malaria contribute to the development of anaemia, or result from an altered RBC age distribution due to suppressive effects of malaria on erythropoiesis.\ud \ud METHODS\ud \ud A cross sectional study was conducted in the north-east coast of Tanzania to investigate whether the changes in glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins (CD55 and CD59) contributes to malaria anaemia. Blood samples were collected from a cohort of children under intensive surveillance for Plasmodium falciparum parasitaemia and illness. Levels of CD55 and CD59 were measured by flow cytometer and compared between anaemic (8.08 g/dl) and non- anaemic children (11.42 g/dl).\ud \ud RESULTS\ud \ud Levels of CD55 and CD59 decreased with increased RBC age. CD55 levels were lower in anaemic children and the difference was seen in RBC of all ages. Levels of CD59 were lower in anaemic children, but these differences were not significant. CD55, but not CD59, levels correlated positively with the level of haemoglobin in anaemic children.\ud \ud CONCLUSION\ud \ud The extent of CD55 loss from RBC of all ages early in the course of malarial anaemia and the correlation of CD55 with haemoglobin levels support the hypothesis that CD55 may play a causal role in this disorder

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Molecular characterization and expression analysis of five different elongation factor 1 alpha genes in the flatfish Senegalese sole (Solea senegalensis Kaup): Differential gene expression and thyroid hormones dependence during metamorphosis

<p>Abstract</p> <p>Background</p> <p>Eukaryotic elongation factor 1 alpha (eEF1A) is one of the four subunits composing eukaryotic translation elongation factor 1. It catalyzes the binding of aminoacyl-tRNA to the A-site of the ribosome in a GTP-dependent manner during protein synthesis, although it also seems to play a role in other non-translational processes. Currently, little information is still available about its expression profile and regulation during flatfish metamorphosis. With regard to this, Senegalese sole (<it>Solea senegalensis</it>) is a commercially important flatfish in which <it>eEF1A </it>gene remains to be characterized.</p> <p>Results</p> <p>The development of large-scale genomics of Senegalese sole has facilitated the identification of five different <it>eEF1A </it>genes, referred to as <it>SseEF1A1</it>, <it>SseEF1A2</it>, <it>SseEF1A3</it>, <it>SseEF1A4</it>, and <it>Sse42Sp50</it>. Main characteristics and sequence identities with other fish and mammalian eEF1As are described. Phylogenetic and tissue expression analyses allowed for the identification of <it>SseEF1A1 </it>and <it>SseEF1A2 </it>as the Senegalese sole counterparts of mammalian <it>eEF1A1 </it>and <it>eEF1A2</it>, respectively, and of <it>Sse42Sp50 </it>as the ortholog of <it>Xenopus laevis </it>and teleost <it>42Sp50 </it>gene. The other two elongation factors, <it>SseEF1A3 </it>and <it>SseEF1A4</it>, represent novel genes that are mainly expressed in gills and skin. The expression profile of the five genes was also studied during larval development, revealing different behaviours. To study the possible regulation of <it>SseEF1A </it>gene expressions by thyroid hormones (THs), larvae were exposed to the goitrogen thiourea (TU). TU-treated larvae exhibited lower <it>SseEF1A4 </it>mRNA levels than untreated controls at both 11 and 15 days after treatment, whereas transcripts of the other four genes remained relatively unchanged. Moreover, addition of exogenous T4 hormone to TU-treated larvae increased significantly the steady-state levels of <it>SseEF1A4 </it>with respect to untreated controls, demonstrating that its expression is up-regulated by THs.</p> <p>Conclusion</p> <p>We have identified five different <it>eEF1A </it>genes in the Senegalese sole, referred to as <it>SseEF1A1</it>, <it>SseEF1A2</it>, <it>SseEF1A3</it>, <it>SseEF1A4</it>, and <it>Sse42Sp50</it>. The five genes exhibit different expression patterns in tissues and during larval development. TU and T4 treatments demonstrate that <it>SseEF1A4 </it>is up-regulated by THs, suggesting a role in the translational regulation of the factors involved in the dramatic changes that occurs during Senegalese sole metamorphosis.</p

A Comprehensive Benchmark of Kernel Methods to Extract Protein–Protein Interactions from Literature

The most important way of conveying new findings in biomedical research is scientific publication. Extraction of protein–protein interactions (PPIs) reported in scientific publications is one of the core topics of text mining in the life sciences. Recently, a new class of such methods has been proposed - convolution kernels that identify PPIs using deep parses of sentences. However, comparing published results of different PPI extraction methods is impossible due to the use of different evaluation corpora, different evaluation metrics, different tuning procedures, etc. In this paper, we study whether the reported performance metrics are robust across different corpora and learning settings and whether the use of deep parsing actually leads to an increase in extraction quality. Our ultimate goal is to identify the one method that performs best in real-life scenarios, where information extraction is performed on unseen text and not on specifically prepared evaluation data. We performed a comprehensive benchmarking of nine different methods for PPI extraction that use convolution kernels on rich linguistic information. Methods were evaluated on five different public corpora using cross-validation, cross-learning, and cross-corpus evaluation. Our study confirms that kernels using dependency trees generally outperform kernels based on syntax trees. However, our study also shows that only the best kernel methods can compete with a simple rule-based approach when the evaluation prevents information leakage between training and test corpora. Our results further reveal that the F-score of many approaches drops significantly if no corpus-specific parameter optimization is applied and that methods reaching a good AUC score often perform much worse in terms of F-score. We conclude that for most kernels no sensible estimation of PPI extraction performance on new text is possible, given the current heterogeneity in evaluation data. Nevertheless, our study shows that three kernels are clearly superior to the other methods