Estimating Mutual Information

We present two classes of improved estimators for mutual information $M(X,Y)$, from samples of random points distributed according to some joint probability density $\mu(x,y)$. In contrast to conventional estimators based on binnings, they are based on entropy estimates from $k$-nearest neighbour distances. This means that they are data efficient (with $k=1$ we resolve structures down to the smallest possible scales), adaptive (the resolution is higher where data are more numerous), and have minimal bias. Indeed, the bias of the underlying entropy estimates is mainly due to non-uniformity of the density at the smallest resolved scale, giving typically systematic errors which scale as functions of $k/N$ for $N$ points. Numerically, we find that both families become {\it exact} for independent distributions, i.e. the estimator $\hat M(X,Y)$ vanishes (up to statistical fluctuations) if $\mu(x,y) = \mu(x) \mu(y)$. This holds for all tested marginal distributions and for all dimensions of $x$ and $y$. In addition, we give estimators for redundancies between more than 2 random variables. We compare our algorithms in detail with existing algorithms. Finally, we demonstrate the usefulness of our estimators for assessing the actual independence of components obtained from independent component analysis (ICA), for improving ICA, and for estimating the reliability of blind source separation.Comment: 16 pages, including 18 figure

Cognitive appraisal of environmental stimuli induces emotion-like states in fish

The occurrence of emotions in non-human animals has been the focus of debate over the years. Recently, an interest in expanding this debate to non-tetrapod vertebrates and to invertebrates has emerged. Within vertebrates, the study of emotion in teleosts is particularly interesting since they represent a divergent evolutionary radiation from that of tetrapods, and thus they provide an insight into the evolution of the biological mechanisms of emotion. We report that Sea Bream exposed to stimuli that vary according to valence (positive, negative) and salience (predictable, unpredictable) exhibit different behavioural, physiological and neuromolecular states. Since according to the dimensional theory of emotion valence and salience define a two-dimensional affective space, our data can be interpreted as evidence for the occurrence of distinctive affective states in fish corresponding to each the four quadrants of the core affective space. Moreover, the fact that the same stimuli presented in a predictable vs. unpredictable way elicited different behavioural, physiological and neuromolecular states, suggests that stimulus appraisal by the individual, rather than an intrinsic characteristic of the stimulus, has triggered the observed responses. Therefore, our data supports the occurrence of emotion-like states in fish that are regulated by the individual's perception of environmental stimuli.European Commission [265957 Copewell]; Fundacao para a Ciencia e Tecnologia [SFRH/BD/80029/2011, SFRH/BPD/72952/2010]info:eu-repo/semantics/publishedVersio

A temática pastoral em Teócrito: os Idílios I, III, VI, VII, XI

This study proposes the translation with explanatory notes of the pastoral Idyls I, III, VI, VII and XI of the Hellenistic poet Theocritus (3rd century b. C.). In the introductory chapters the main characteristics of his poetry are presented, as well as the history of their transmission, preservation and the establishment of his poetic corpus. The selected poems highlight the bucolic gender of which the poet is usually considered the founder, having also composed some of the most admired works until today. As its main subjects we propose the shepherds' characterization, love's disturbing interference and its interaction with the locus amoenus. As a counterpoint to bucolic poetry we add at the end a translation of the pattern poem The Syrinx.Este trabalho propõe a tradução com notas explicativas dos Idílios pastorais I, III, VI, VII e XI do poeta helenístico Teócrito (séc. III a. C.). Nos capítulos introdutórios são apresentadas as principais características de sua poesia e a história da transmissão, manutenção e estabelecimento do seu corpus poético. O corpus selecionado valoriza o gênero bucólico de que o poeta é tradicionalmente considerado o fundador, tendo também composto alguns dos mais admirados exemplares até hoje. Como principais temas destacamos a caracterização dos pastores, a presença perturbadora do amor e sua interação com o locus amoenus. Como contraponto à poesia bucólica, acrescentamos ao final uma tradução do poema em figura A Siringe

Expanding the knowledge about Leishmania species in wild mammals and dogs in the Brazilian savannah

Background: Wild, synanthropic and domestic mammals act as hosts and/or reservoirs of several Leishmania spp. Studies on possible reservoirs of Leishmania in different areas are fundamental to understand host-parasite interactions and develop strategies for the surveillance and control of leishmaniasis. In the present study, we evaluated the Leishmania spp. occurrence in mammals in two conservation units and their surroundings in Brasília, Federal District (FD), Brazil. Methods: Small mammals were captured in Brasília National Park (BNP) and Contagem Biological Reserve (CBR) and dogs were sampled in residential areas in their vicinity. Skin and blood samples were evaluated by PCR using different molecular markers (D7 24Sα rRNA and rDNA ITS1). Leishmania species were identified by sequencing of PCR products. Dog blood samples were subjected to the rapid immunochromatographic test (DPP) for detection of anti-Leishmania infantum antibodies. Results: 179 wild mammals were studied and 20.1% had Leishmania DNA successfully detected in at least one sample. Six mammal species were considered infected: Clyomys laticeps, Necromys lasiurus, Nectomys rattus, Rhipidomys macrurus, Didelphis albiventris and Gracilinanus agilis. No significant difference, comparing the proportion of individuals with Leishmania spp., was observed between the sampled areas and wild mammal species. Most of the positive samples were collected from the rodent N. lasiurus, infected by L. amazonensis or L. braziliensis. Moreover, infections by Trypanosoma spp. were detected in N. lasiurus and G. agilis. All 19 dog samples were positive by DPP; however, only three (15.8%) were confirmed by PCR assays. DNA sequences of ITS1 dog amplicons showed 100% identity with L. infantum sequence. Conclusions: The results suggest the participation of six species of wild mammals in the enzootic transmission of Leishmania spp. in FD. This is the first report of L. amazonensis in N. lasiurus

Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation

Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young

Planck intermediate results. XXI. Comparison of polarized thermal emission from Galactic dust at 353 GHz with interstellar polarization in the visible

The Planck survey provides unprecedented full-sky coverage of the submillimetre polarized emission from Galactic dust. In addition to the information on the direction of the Galactic magnetic field, this also brings new constraints on the properties of dust. The dust grains that emit the radiation seen by Planck in the submillimetre also extinguish and polarize starlight in the visible. Comparison of the polarization of the emission and of the interstellar polarization on selected lines of sight probed by stars provides unique new diagnostics of the emission and light scattering properties of dust, and therefore of the important dust model parameters, composition, size, and shape. Using ancillary catalogues of interstellar polarization and extinction of starlight, we obtain the degree of polarization, p(V), and the optical depth in the V band to the star, tau(V). Toward these stars we measure the submillimetre polarized intensity, P-S, and total intensity, I-S,I- in the Planck 353 GHz channel. We compare the column density measure in the visible, E(B - V), with that inferred from the Planck product map of the submillimetre dust optical depth and compare the polarization direction (position angle) in the visible with that in the submillimetre. For those lines of sight through the di ff use interstellar medium with comparable values of the estimated column density and polarization directions close to orthogonal, we correlate properties in the submillimetre and visible to find two ratios, R-S/V = (P-S/I-S) = (p(V)/tau(V)) and R-P/p = P-S/p(V), the latter focusing directly on the polarization properties of the aligned grain population alone. We find R-S/V = 4.2, with statistical and systematic uncertainties 0.2 and 0.3, respectively, and R-P/p = 5.4 MJy sr(-1), with uncertainties 0.2 and 0.3 MJy sr(-1), respectively. Our estimate of R-S/V is compatible with predictions based on a range of polarizing dust models that have been developed for the di ff use interstellar medium. This estimate provides new empirical validation of many of the common underlying assumptions of the models, but is not yet very discriminating among them. However, our estimate of R-P/p is not compatible with predictions, which are too low by a factor of about 2.5. This more discriminating diagnostic, R-P/p, indicates that changes to the optical properties in the models of the aligned grain population are required. These new diagnostics, together with the spectral dependence in the submillimetre from Planck, will be important for constraining and understanding the full complexity of the grain models, and for interpreting the Planck thermal dust polarization and refinement of the separation of this contamination of the cosmic microwave background.Peer reviewe

Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP

Several epidemiological changes have occurred in the pattern of nosocomial and community acquired infectious diseases during the past 25 years. Social and demographic changes possibly related to this phenomenon include a rapid population growth, the increase in urban migration and movement across international borders by tourists and immigrants, alterations in the habitats of animals and arthropods that transmit disease, as well as the raise of patients with impaired host defense abilities. Continuous surveillance programs of emergent pathogens and antimicrobial resistance are warranted for detecting in real time new pathogens, as well as to characterize molecular mechanisms of resistance. In order to become more effective, surveillance programs of emergent pathogens should be organized as a multicenter laboratory network connected to the main public and private infection control centers. Microbiological data should be integrated to guide therapy, adapting therapy to local ecology and resistance patterns. This paper presents an overview of data generated by the Division of Infectious Diseases, Federal University of São Paulo, along with its participation in different surveillance programs of nosocomial and community acquired infectious diseases.Várias alterações epidemiológicas ocorreram no perfil das doenças infecciosas hospitalares e comunitárias nos últimos 25 anos. Mudanças sociais e demográficas possivelmente relacionadas com esse fenômeno incluem o rápido crescimento populacional, o aumento da migração urbana e deslocamento através de fronteiras internacionais por turistas e imigrantes, alterações nos habitats de animais e artrópodes que transmitem doença assim como o aumento no número de pacientes com deficiências nas respostas de defesa. Os programas contínuos de vigilância de patógenos emergentes e resistência antimicrobiana são necessários para a detecção em tempo real de novos patógenos assim como para caracterizar mecanismos moleculares de resistência. Para serem mais efetivos, os programasde vigilância dos patógenos emergentes devem ser organizados em uma rede de laboratórios multicêntricos ligados aos principais centros de controle de infecções, públicos e privados. Os dados microbiológicos devem ser integrados a guias terapêuticos adaptando práticas terapêuticas à ecologia local eaos padrões de resistência. O artigo apresenta uma revisão dos dados gerados pela Disciplina de Infectologia, Universidade Federal de São Paulo (UNIFESP), contemplando sua participação nos diferentes programas de vigilância de doenças infecciosas hospitalares e adquiridas na comunidade.Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina Divisão de Doenças InfecciosasUniversidade Federal de São Paulo (UNIFESP) Departamento de Microbiologia, Imunologia e ParasitologiaUNIFESP, Depto. de Medicina Divisão de Doenças InfecciosasUNIFESP, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL