Algebraic Approach to Interacting Quantum Systems

We present an algebraic framework for interacting extended quantum systems to study complex phenomena characterized by the coexistence and competition of different states of matter. We start by showing how to connect different (spin-particle-gauge) {\it languages} by means of exact mappings (isomorphisms) that we name {\it dictionaries} and prove a fundamental theorem establishing when two arbitrary languages can be connected. These mappings serve to unravel symmetries which are hidden in one representation but become manifest in another. In addition, we establish a formal link between seemingly unrelated physical phenomena by changing the language of our model description. This link leads to the idea of {\it universality} or equivalence. Moreover, we introduce the novel concept of {\it emergent symmetry} as another symmetry guiding principle. By introducing the notion of {\it hierarchical languages}, we determine the quantum phase diagram of lattice models (previously unsolved) and unveil hidden order parameters to explore new states of matter. Hierarchical languages also constitute an essential tool to provide a unified description of phases which compete and coexist. Overall, our framework provides a simple and systematic methodology to predict and discover new kinds of orders. Another aspect exploited by the present formalism is the relation between condensed matter and lattice gauge theories through quantum link models. We conclude discussing applications of these dictionaries to the area of quantum information and computation with emphasis in building new models of computation and quantum programming languages.Comment: 44 pages, 14 psfigures. Advances in Physics 53, 1 (2004

mTOR pathway in papillary thyroid carcinoma: Different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.Acknowledgments: This study was supported by FCT (“Portuguese Foundation for Science and Technology”) through PhD grants to Catarina Tavares (SFRH/BD/87887/2012), Ana Pestana (SFRH/BD/110617/2015), and Rui Batista (SFRH/BD/111321/2015) and by a CNPq PhD grant (“National Counsel of Technological and Scientific Development”, Brazil), Science without Borders, Process n# 237322/2012-9 for Luciana Ferreira. Miguel Melo received a grant from Genzyme for the research project “Molecular biomarkers of prognosis and response to therapy in differentiated thyroid carcinomas”. Further funding was obtained from FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project "Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and by the project “Advancing cancer research: from basic acknowledgement to application”; NORTE-01-0145-FEDER-000029; “Projetos Estruturados de I&D&I, funded by Norte 2020-Programa Operacional Regional do Norte. This work was also financed by Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo through a grant “Prof. E. Limbert Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo/Sanofi-Genzyme in thyroid pathology”

Freeze-dried jaboticaba peel powder rich in anthocyanins did not reduce weight gain and lipid content in mice and rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Jaboticaba, a native fruit from Brazilian Atlantic Forest, is an important source of anthocyanins. Anthocyanins have been recently identified as modulators of lipid metabolism and energy expenditure 'in vivo'. The purpose of this study was to evaluate the effect of the freeze-dried jaboticaba peel powder on obesity treatment in different experimental models. Obese Swiss mice and obese Sprague-Dawley rats were fed a high-fat diet supplemented with 1, 2 and 4% freeze-dried jaboticaba peel powder for 6 weeks. Energy intake, weight gain and body composition were determined, and the results were analyzed using variance and Tukey's tests (p<0.05). The energy intake was higher in mice groups supplemented with 2% and 4% of jaboticaba peel. In relation to weight gain, the mice supplemented with 2% of jaboticaba peel had higher total weight gain than the other experimental groups, while no significant difference in the fat mass accumulation was observed among the groups. The rats did not show significant differences in the evaluated parameters. These results suggest that the supplementation with freeze-dried jaboticaba peel powder, at concentrations of 1, 2 and 4%, was not effective in the reduction of energy intake, weight gain and body fat both in mice and in rats.6213743Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

In vivo activity of Sapindus saponaria against azole-susceptible and -resistant human vaginal Candida species

<p>Abstract</p> <p>Background</p> <p>Study of <it>in vivo </it>antifungal activity of the hydroalcoholic extract (HE) and n-BuOH extract (BUTE) of <it>Sapindus saponaria </it>against azole-susceptible and -resistant human vaginal <it>Candida </it>spp.</p> <p>Methods</p> <p>The <it>in vitro </it>antifungal activity of HE, BUTE, fluconazole (FLU), and itraconazole (ITRA) was determined by the broth microdilution method. We obtained values of minimal inhibitory concentration (MIC) and minimum fungicide concentration (MFC) for 46 strains of <it>C. albicans </it>and 10 of <it>C. glabrata </it>isolated from patients with vulvovaginal candidiasis (VVC). VVC was induced in hyperestrogenic Wistar rats with azole-susceptible <it>C. albicans </it>(SCA), azole-resistant <it>C. albicans </it>(RCA), and azole-resistant <it>C. glabrata </it>(RCG). The rats were treated intravaginally with 0.1 mL of HE or BUTE at concentrations of 1%, 2.5% and 5%; 100 μg/mL of FLU (treatment positive control); or distilled water (negative control) at 1, 24, and 48 h after induction of the infection, and the progress of VVC was monitored by culturing and scanning electron microscopy (SEM). The toxicity was evaluated in cervical cells of the HeLa cell line.</p> <p>Results</p> <p>The extracts showed <it>in vitro </it>inhibitory and fungicidal activity against all the isolates, and the MIC and MFC values for the <it>C. glabrata </it>isolates were slightly higher. <it>In vivo</it>, the SCA, RCA, and RCG infections were eliminated by 21 days post-infection, with up to 5% HE and BUTE, comparable to the activity of FLU. No cytotoxic action was observed for either extract.</p> <p>Conclusions</p> <p>Our results demonstrated that HE and BUTE from <it>S. saponaria </it>show inhibitory and fungicidal activity <it>in vitro</it>, in addition to <it>in vivo </it>activity against azole-resistant vaginal isolates of <it>C. glabrata </it>and azole-susceptible and resistant isolates of <it>C. albicans</it>. Also considering the lack of cytotoxicity and the low concentrations of the extracts necessary to eliminate the infection <it>in vivo</it>, HE and BUTE show promise for continued studies with purified antifungal substances in VVC yeast isolates.</p

NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features

Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the SLC5A5 gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied SLC5A5 expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, SLC5A5 expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring BRAFV600E mutation. Analysis of SLC5A5 expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/or distant metastases or harboring RAS, BRAF and/or TERT promoter (TERTp) mutations presented significantly less SLC5A5 expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for BRAF, NRAS and TERTp mutations. SLC5A5 mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving BRAF, RAS and TERTp. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. SLC5A5 mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.This study was supported by FCT (‘Portuguese Foundation for Science and Technology’) through PhD grants to Catarina Tavares (SFRH/BD/87887/2012), Ana Pestana (SFRH/BD/110617/2015), Rui Batista (SFRH/BD/111321/2015) and by a CNPq PhD grant (‘National Counsel of Technological and Scientific Development’, Brazil), Science without Borders, Process n# 237322/2012-9 for Luciana Ferreira. Miguel Melo received a grant from Genzyme for the research project ‘Molecular biomarkers of prognosis and response to therapy in differentiated thyroid carcinomas’. Further funding was obtained from FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ (POCI-01-0145-FEDER-007274) and by the project ‘Advancing cancer research: from basic knowledgement to application’; NORTE-01-0145-FEDER-000029; ‘Projetos Estruturados de I&D&I’, funded by Norte 2020-Programa Operacional Regional do Norte. This work was also financed by Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo through a grant ‘Prof. E Limbert Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo/Sanofi-Genzyme in thyroid pathology’

Measuring co-authorship and networking-adjusted scientific impact

Appraisal of the scientific impact of researchers, teams and institutions with productivity and citation metrics has major repercussions. Funding and promotion of individuals and survival of teams and institutions depend on publications and citations. In this competitive environment, the number of authors per paper is increasing and apparently some co-authors don't satisfy authorship criteria. Listing of individual contributions is still sporadic and also open to manipulation. Metrics are needed to measure the networking intensity for a single scientist or group of scientists accounting for patterns of co-authorship. Here, I define I1 for a single scientist as the number of authors who appear in at least I1 papers of the specific scientist. For a group of scientists or institution, In is defined as the number of authors who appear in at least In papers that bear the affiliation of the group or institution. I1 depends on the number of papers authored Np. The power exponent R of the relationship between I1 and Np categorizes scientists as solitary (R>2.5), nuclear (R=2.25-2.5), networked (R=2-2.25), extensively networked (R=1.75-2) or collaborators (R<1.75). R may be used to adjust for co-authorship networking the citation impact of a scientist. In similarly provides a simple measure of the effective networking size to adjust the citation impact of groups or institutions. Empirical data are provided for single scientists and institutions for the proposed metrics. Cautious adoption of adjustments for co-authorship and networking in scientific appraisals may offer incentives for more accountable co-authorship behaviour in published articles.Comment: 25 pages, 5 figure

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4&lt;sup&gt;+&lt;/sup&gt; T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system &lt;i&gt;in&lt;/i&gt; &lt;i&gt;vivo&lt;/i&gt;. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation