900 resultados para Davenport (Ia.)


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Mezzarane RA, Kohn AF, Couto-Roldan E, Martinez L, Flores A, Manjarrez E. Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats. J Neurophysiol 108: 1176-1185, 2012. First published June 6, 2012; doi:10.1152/jn.00831.2011.-Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L 7 ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.

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Context. The angular diameter distances toward galaxy clusters can be determined with measurements of Sunyaev-Zel'dovich effect and X-ray surface brightness combined with the validity of the distance-duality relation, D-L(z)(1 + z)(2)/D-A(z) = 1, where D-L(z) and D-A(z) are, respectively, the luminosity and angular diameter distances. This combination enables us to probe galaxy cluster physics or even to test the validity of the distance-duality relation itself. Aims. We explore these possibilities based on two different, but complementary approaches. Firstly, in order to constrain the possible galaxy cluster morphologies, the validity of the distance-duality relation (DD relation) is assumed in the Lambda CDM framework (WMAP7). Secondly, by adopting a cosmological-model-independent test, we directly confront the angular diameters from galaxy clusters with two supernovae Ia (SNe Ia) subsamples (carefully chosen to coincide with the cluster positions). The influence of the different SNe Ia light-curve fitters in the previous analysis are also discussed. Methods. We assumed that eta is a function of the redshift parametrized by two different relations: eta(z) = 1 +eta(0)z, and eta(z) = 1 + eta(0)z/(1 + z), where eta(0) is a constant parameter quantifying the possible departure from the strict validity of the DD relation. In order to determine the probability density function (PDF) of eta(0), we considered the angular diameter distances from galaxy clusters recently studied by two different groups by assuming elliptical and spherical isothermal beta models and spherical non-isothermal beta model. The strict validity of the DD relation will occur only if the maximum value of eta(0) PDF is centered on eta(0) = 0. Results. For both approaches we find that the elliptical beta model agrees with the distance-duality relation, whereas the non-isothermal spherical description is, in the best scenario, only marginally compatible. We find that the two-light curve fitters (SALT2 and MLCS2K2) present a statistically significant conflict, and a joint analysis involving the different approaches suggests that clusters are endowed with an elliptical geometry as previously assumed. Conclusions. The statistical analysis presented here provides new evidence that the true geometry of clusters is elliptical. In principle, it is remarkable that a local property such as the geometry of galaxy clusters might be constrained by a global argument like the one provided by the cosmological distance-duality relation.

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The existence of inhomogeneities in the observed Universe modifies the distance-redshift relations thereby affecting the results of cosmological tests in comparison to the ones derived assuming spatially uniform models. By modeling the inhomogeneities through a Zeldovich-Kantowski-Dyer-Roeder approach which is phenomenologically characterized by a smoothness parameter alpha, we rediscuss the constraints on the cosmic parameters based on type Ia supernovae (SNe Ia) and gamma-ray bursts (GRBs) data. The present analysis is restricted to a flat Lambda CDM model with the reasonable assumption that Lambda does not clump. A chi(2) analysis using 557 SNe Ia data from the Union2 compilation data (R. Amanullah et al., Astrophys. J. 716, 712 (2010).) constrains the pair of parameters (Omega(m), alpha) to Omega(m) = 0.27(-0.03)(+0.08) (2 sigma) and alpha >= 0.25. A similar analysis based only on 59 Hymnium GRBs (H. Wei, J. Cosmol. Astropart. Phys. 08 (2010) 020.) constrains the matter density parameter to be Omega(m) = 0.35(-0.24)(+0.62) (2 sigma) while all values for the smoothness parameter are allowed. By performing a joint analysis, it is found that Omega(m) = 0.27(-0.06)(+0.06) and alpha >= 0.52. As a general result, although considering that current GRB data alone cannot constrain the smoothness alpha parameter, our analysis provides an interesting cosmological probe for dark energy even in the presence of inhomogeneities.

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The use of type Ia supernovae as distance estimators has shown that about 75% of the energy content of the universe has a negative equation of state parameter and thus, drives the acceleration of the universe. Constraining the exact nature of this energy is one of the main goals in cosmology. As the statistics of observed high-redshift supernovae increases, systematic effects become the limiting factor to pursue such investigations, thus deeper understanding of the physical properties of SNe is of great importance. In this thesis we investigate spectral homogeneity and diversity of local and high redshift supernovae. Special emphasis has been given to the analysis of optical spectra of local peculiar supernovae 1999aa and 1999ac. The study of the spectra of SN 1999aa pointed out that this SN could be a link between the extreme peculiar SN 1991T and normal SNe. Moreover, the identification of a high velocity component of Ca II and possibly of a low velocity component of C III suggests some degree of asphericity in the ejecta of this supernova. Evidence for a deflagration of a C+O white dwarf was found in the early spectra of SN 1999ac. The spectral proprieties of a vast sample of local SNe are also studied by means of newly introduced spectral indicators. These were used to possibly improve the intrinsic spread of SN peak magnitudes to 0.15 mag, independently of light curve parameters. The first quantitative comparison between local and high redshift supernova is carried out. No evidence for extreme peculiar sub-luminous SNe was found in our data set including 13 SNe with redshift range z=0.279-0.912. Furthermore, SN2002fd (z=0.279) was found to show spectral characteristics similar to SN 1991T/SN 1999aa-like supernovae. We also present a feasibility study of the Hubble diagram in rest frame I-band up to z~0.5, and show the possibility to probe the presence of intergalactic dust, which could possibly mimic the effect of dark energy in the Hubble diagram.

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Type Ia supernovae have been successfully used as standardized candles to study the expansion history of the Universe. In the past few years, these studies led to the exciting result of an accelerated expansion caused by the repelling action of some sort of dark energy. This result has been confirmed by measurements of cosmic microwave background radiation, the large-scale structure, and the dynamics of galaxy clusters. The combination of all these experiments points to a “concordance model” of the Universe with flat large-scale geometry and a dominant component of dark energy. However, there are several points related to supernova measurements which need careful analysis in order to doubtlessly establish the validity of the concordance model. As the amount and quality of data increases, the need of controlling possible systematic effects which may bias the results becomes crucial. Also important is the improvement of our knowledge of the physics of supernovae events to assure and possibly refine their calibration as standardized candle. This thesis addresses some of those issues through the quantitative analysis of supernova spectra. The stress is put on a careful treatment of the data and on the definition of spectral measurement methods. The comparison of measurements for a large set of spectra from nearby supernovae is used to study the homogeneity and to search for spectral parameters which may further refine the calibration of the standardized candle. One such parameter is found to reduce the dispersion in the distance estimation of a sample of supernovae to below 6%, a precision which is comparable with the current lightcurve-based calibration, and is obtained in an independent manner. Finally, the comparison of spectral measurements from nearby and distant objects is used to test the possibility of evolution with cosmic time of the intrinsic brightness of type Ia supernovae.

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Il lavoro di tesi esamina i plausibili sistemi progenitori per le supernovae di tipo di Ia e analizza i principali modelli di esplosione studiati ed implementati dai gruppi di ricerca per le SNe Ia.

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L'informatica e le sue tecnologie nella società moderna si riassumono spesso in un assioma fuorviante: essa, infatti, è comunemente legata al concetto che ciò che le tecnologie ci offrono può essere accessibile da tutti e sfruttato, all'interno della propria quotidianità, in modi più o meno semplici. Anche se quello appena descritto è un obiettivo fondamentale del mondo high-tech, occorre chiarire subito una questione: l'informatica non è semplicemente tutto ciò che le tecnologie ci offrono, perchè questo pensiero sommario fa presagire ad un'informatica "generalizzante"; l'informatica invece si divide tra molteplici ambiti, toccando diversi mondi inter-disciplinari. L'importanza di queste tecnologie nella società moderna deve spingerci a porre domande, riflessioni sul perchè l'informatica, in tutte le sue sfaccettature, negli ultimi decenni, ha portato una vera e propria rivoluzione nelle nostre vite, nelle nostre abitudini, e non di meno importanza, nel nostro contesto lavorativo e aziendale, e non ha alcuna intenzione (per fortuna) di fermare le proprie possibilità di sviluppo. In questo trattato ci occuperemo di definire una particolare tecnica moderna relativa a una parte di quel mondo complesso che viene definito come "Intelligenza Artificiale". L'intelligenza Artificiale (IA) è una scienza che si è sviluppata proprio con il progresso tecnologico e dei suoi potenti strumenti, che non sono solo informatici, ma soprattutto teorico-matematici (probabilistici) e anche inerenti l'ambito Elettronico-TLC (basti pensare alla Robotica): ecco l'interdisciplinarità. Concetto che è fondamentale per poi affrontare il nocciolo del percorso presentato nel secondo capitolo del documento proposto: i due approcci possibili, semantico e probabilistico, verso l'elaborazione del linguaggio naturale(NLP), branca fondamentale di IA. Per quanto darò un buono spazio nella tesi a come le tecniche di NLP semantiche e statistiche si siano sviluppate nel tempo, verrà prestata attenzione soprattutto ai concetti fondamentali di questi ambiti, perché, come già detto sopra, anche se è fondamentale farsi delle basi e conoscere l'evoluzione di queste tecnologie nel tempo, l'obiettivo è quello a un certo punto di staccarsi e studiare il livello tecnologico moderno inerenti a questo mondo, con uno sguardo anche al domani: in questo caso, la Sentiment Analysis (capitolo 3). Sentiment Analysis (SA) è una tecnica di NLP che si sta definendo proprio ai giorni nostri, tecnica che si è sviluppata soprattutto in relazione all'esplosione del fenomeno Social Network, che viviamo e "tocchiamo" costantemente. L'approfondimento centrale della tesi verterà sulla presentazione di alcuni esempi moderni e modelli di SA che riguardano entrambi gli approcci (statistico e semantico), con particolare attenzione a modelli di SA che sono stati proposti per Twitter in questi ultimi anni, valutando quali sono gli scenari che propone questa tecnica moderna, e a quali conseguenze contestuali (e non) potrebbe portare questa particolare tecnica.

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The most common form of neutrophil death is apoptosis. In the present study, we report surprising differences in the molecular mechanisms used for caspase activation between FAS/CD95-stimulated and TNF receptor 1 (TNFR1)-stimulated neutrophils. Whereas FAS-induced apoptosis was followed by caspase-8 activation and required Bid to initiate the mitochondrial amplification loop, TNF-?-induced apoptosis involved class IA PI3Ks, which were activated by MAPK p38. TNF-?-induced PI3K activation resulted in the generation of reactive oxygen species, which activated caspase-3, a mechanism that did not operate in neutrophils without active NADPH oxidase. We conclude that in neutrophils, proapoptotic pathways after TNFR1 stimulation are initiated by p38 and PI3K, but not by caspase-8, a finding that should be considered in anti-inflammatory drug-development strategies.

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Glycoprotein Ia* (GPIa*), a very high molecular mass, platelet alpha-granule protein consisting of 167 kDa subunits disulphide-linked in a multimeric structure, was first described by Bienz and Clemetson in 1989 (J. Biol. Chem. 264, 507-514). In 1991 Hayward et al. (J. Biol. Chem. 266, 7114-7120) independently identified a platelet protein with multimeric structure. Despite strong similarities to GPIa* they concluded that it was a novel multimeric protein and named it first p-155 and later, multimerin. Multimerin has also been found in endothelial cells and has been cloned recently from an endothelial cell cDNA library. This has made it possible for us to clarify the relationship between GPIa* and multimerin. GPIa* was isolated from platelet releasate and the N-terminal sequence of 167 kDa and 155 kDa subunit species were determined. The N-terminal 15 amino acids of GPIa* were identical to the deduced amino acids 184-198 of endothelial multimerin. The N-terminal sequence of the 155 kDa protein was identical to the deduced amino acids 318-326 of multimerin. Thus, platelet GPIa* (167 kDa) is the main processed form of multimerin stored in platelet alpha-granules. The GPIa*/processed multimerin (167 kDa) still contains an RGDS sequence near its N-terminus as well as an EGF domain which may be involved in binding to the platelet surface after release. This sequence and domain are cleaved off in the p-155 form, described earlier as platelet multimerin, which is probably formed after release from alpha-granules.

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The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancer and plays a crucial role in glioblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K isoforms as a novel anti-tumor approach in glioblastoma. Consistent expression of the PI3K catalytic isoform PI3K p110α was detected in a panel of glioblastoma patient samples. In contrast, PI3K p110β expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110α/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p110α activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p110α or PI3K p110β also led to impaired anchorage-independent growth, a decreased migratory capacity of glioblastoma cells, and reduced the activation of the Akt/mTOR pathway. These effects were selective, because targeting of PI3K p110δ did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110α can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110α/p-S6.