Interstitial doping induced superconductivity at 15.3 K in Nb5Ge3 compound

It is reported superconductivity in Nb5Ge3C0.3, an interstitial carbide compound. The temperature dependence of the electrical resistivity, ac-susceptibility, and heat capacity (HC) indicate that a bulk type-II superconductivity appears at T-C - 15.3 K. Magneto-resistance measurements suggest an upper critical field of B-C2 similar to 10.6 T and a coherence length of xi similar to 55 angstrom at zero temperature. Neutron diffraction analyzes locate the carbon atoms at the interstitial 2b site of the Mn5Si3 type-structure. Heat capacity data below T-C are well described by BCS theory. The size of the jump at T-C is in good agreement with the superconducting volume fraction observed in susceptibility measurements. A Debye temperature and Sommerfeld constant were also extracted from heat capacity data as 343 K and 34 mJ/mol K-2, respectively. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4730611]

Crotamine Pharmacology Revisited: Novel Insights Based on the Inhibition of K-V Channels

Crotamine, a 5-kDa peptide, possesses a unique biological versatility. Not only has its cell-penetrating activity become of clinical interest but, moreover, its potential selective antitumor activity is of great pharmacological importance. In the past, several studies have attempted to elucidate the exact molecular target responsible for the crotamine-induced skeletal muscle spasm. The aim of this study was to investigate whether crotamine affects voltage-gated potassium (K-V) channels in an effort to explain its in vivo effects. Crotamine was studied on ion channel function using the two-electrode voltage clamp technique on 16 cloned ion channels (12 K-V channels and 4 Na-V channels), expressed in Xenopus laevis oocytes. Crotamine selectively inhibits K-V 1.1, K-V 1.2, and K-V 1.3 channels with an IC50 of similar to 300 nM, and the key amino acids responsible for this molecular interaction are suggested. Our results demonstrate for the first time that the symptoms, which are observed in the typical crotamine syndrome, may result from the inhibition of K-V channels. The ability of crotamine to inhibit the potassium current through K-V channels unravels it as the first snake peptide with the unique multifunctionality of cell-penetrating and antitumoral activity combined with K-V channel-inhibiting properties. This new property of crotamine might explain some experimental observations and opens new perspectives on pharmacological uses.

K-41(n, gamma)K-42 thermal and resonance integral cross section measurements

We measured the K-41 thermal neutron absorption and resonance integral cross sections after the irradiation of KNO3 samples near the core of the IEA-R1 IPEN pool-type research reactor. Bare and cadmium-covered targets were irradiated in pairs with Au-Al alloy flux-monitors. The residual activities were measured by gamma-ray spectroscopy with a HPGe detector, with special care to avoid the K-42 decay beta(-) emission effects on the spectra. The gamma-ray self-absorption was corrected with the help of MCNP simulations. We applied the Westcott formalism in the average neutron flux determination and calculated the depression coefficients for thermal and epithermal neutrons due to the sample thickness with analytical approximations. We obtained 1.57(4) and 1.02(4) b, for thermal and resonance integral cross sections, respectively, with correlation coefficient equal to 0.39.

Activation of the mitochondrial ATP-sensitive K+ channel reduces apoptosis of spleen mononuclear cells induced by hyperlipidemia

Background We have previously demonstrated that increased rates of superoxide generation by extra-mitochondrial enzymes induce the activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) in the livers of hypertriglyceridemic (HTG) mice. The resulting mild uncoupling mediated by mitoKATP protects mitochondria against oxidative damage. In this study, we investigate whether immune cells from HTG mice also present increased mitoKATP activity and evaluate the influence of this trait on cell redox state and viability. Methods Oxygen consumption (Clark-type electrode), reactive oxygen species production (dihydroethidium and H2-DCF-DA probes) and cell death (annexin V, cytocrome c release and Trypan blue exclusion) were determined in spleen mononuclear cells. Results HTG mice mononuclear cells displayed increased mitoKATP activity, as evidenced by higher resting respiration rates that were sensitive to mitoKATP antagonists. Whole cell superoxide production and apoptosis rates were increased in HTG cells. Inhibition of mitoKATP further increased the production of reactive oxygen species and apoptosis in these cells. Incubation with HTG serum induced apoptosis more strongly in WT cells than in HTG mononuclear cells. Cytochrome c release into the cytosol and caspase 8 activity were both increased in HTG cells, indicating that cell death signaling starts upstream of the mitochondria but does involve this organelle. Accordingly, a reduced number of blood circulating lymphocytes was found in HTG mice. Conclusions These results demonstrate that spleen mononuclear cells from hyperlipidemic mice have more active mitoKATP channels, which downregulate mitochondrial superoxide generation. The increased apoptosis rate observed in these cells is exacerbated by closing the mitoKATP channels. Thus, mitoKATP opening acts as a protective mechanism that reduces cell death induced by hyperlipidemia.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Chemical carcinogenesis by 7,12-dimethylbenzanthracene in balb/c mice

FAPESP

Adaptação cultural cruzada e validação da versão do Índice Funcional de Espondilite Anquilosante de Bath (BASFI) para o português do Brasil

OBJETIVO: Conduzir uma adaptação cultural cruzada do Índice Funcional de Espondilite Anquilosante de Bath (BASFI, Bath Ankylosing Spondylitis Functional Index) para o português do Brasil e avaliar suas propriedades de medição. MéTODOS: O BASFI foi traduzido por quatro reumatologistas e três professores de língua inglesa. O questionário traduzido foi aplicado a pacientes com espondilite anquilosante por observadores treinados e autoaplicado em três momentos, dias 1, 2 e 14. A validade foi estimada analisando-se a associação do BASFI e as medidas de capacidade funcional (rotação cervical, distância intermaleolar, teste de Schober e distância occipito-parede). A consistência interna foi testada pelo coeficiente α de Cronbach, e a confiabilidade pelo teste-reteste (coeficiente de correlação intraclasse [CCI]). RESULTADOS: Foram incluídos 60 pacientes com espondilite anquilosante: 85% do gênero masculino, com idade média de 47 ± 12 anos e duração média da doença de 20 ± 11 anos. A confiabilidade intraobservador no teste-reteste (intervalo de duas semanas) revelou alto ICC (0,999; 95% IC: 0,997-0,999), além de alta consistência interna (coeficiente α de Cronbach: 0,86; 95% IC: 0,80-0,90). Considerando-se a validade, os índices do BASFI foram correlacionados com a rotação cervical (0,53; P < 0,001) e a distância intermaleolar (0,50; P < 0,001). CONCLUSÃO: A versão do BASFI para o português do Brasil é confiável e válida para avaliação de pacientes com espondilite anquilosante.

Estratégias para uma eficaz utilizaçao das TIC no ensino pré-universitário em Portugal

[ES] Esta tesis tiene como objetivo principal conocer y diagnosticar la situación real de la informática y por extensión la de las tecnologías de la información y la comunicación (TIC) en el sistema educativo portugués, en los grados de la enseñanza preuniversitaria, teniendo como centro de atención los docentes y su perfil académico y profesional.

Pseudodifferential analysis in Psi*-algebras on transmission spaces, infinite solving ideal chains and K-theory for conformally compact spaces

The present thesis is a contribution to the theory of algebras of pseudodifferential operators on singular settings. In particular, we focus on the $b$-calculus and the calculus on conformally compact spaces in the sense of Mazzeo and Melrose in connection with the notion of spectral invariant transmission operator algebras. We summarize results given by Gramsch et. al. on the construction of $Psi_0$-and $Psi*$-algebras and the corresponding scales of generalized Sobolev spaces using commutators of certain closed operators and derivations. In the case of a manifold with corners $Z$ we construct a $Psi*$-completion $A_b(Z,{}^bOmega^{1/2})$ of the algebra of zero order $b$-pseudodifferential operators $Psi_{b,cl}(Z, {}^bOmega^{1/2})$ in the corresponding $C*$-closure $B(Z,{}^bOmega^{12})hookrightarrow L(L^2(Z,{}^bOmega^{1/2}))$. The construction will also provide that localised to the (smooth) interior of Z the operators in the $A_b(Z, {}^bOmega^{1/2})$ can be represented as ordinary pseudodifferential operators. In connection with the notion of solvable $C*$-algebras - introduced by Dynin - we calculate the length of the $C*$-closure of $Psi_{b,cl}^0(F,{}^bOmega^{1/2},R^{E(F)})$ in $B(F,{}^bOmega^{1/2}),R^{E(F)})$ by localizing $B(Z, {}^bOmega^{1/2})$ along the boundary face $F$ using the (extended) indical familiy $I^B_{FZ}$. Moreover, we discuss how one can localise a certain solving ideal chain of $B(Z, {}^bOmega^{1/2})$ in neighbourhoods $U_p$ of arbitrary points $pin Z$. This localisation process will recover the singular structure of $U_p$; further, the induced length function $l_p$ is shown to be upper semi-continuous. We give construction methods for $Psi*$- and $C*$-algebras admitting only infinite long solving ideal chains. These algebras will first be realized as unconnected direct sums of (solvable) $C*$-algebras and then refined such that the resulting algebras have arcwise connected spaces of one dimensional representations. In addition, we recall the notion of transmission algebras on manifolds with corners $(Z_i)_{iin N}$ following an idea of Ali Mehmeti, Gramsch et. al. Thereby, we connect the underlying $C^infty$-function spaces using point evaluations in the smooth parts of the $Z_i$ and use generalized Laplacians to generate an appropriate scale of Sobolev spaces. Moreover, it is possible to associate generalized (solving) ideal chains to these algebras, such that to every $ninN$ there exists an ideal chain of length $n$ within the algebra. Finally, we discuss the $K$-theory for algebras of pseudodifferential operators on conformally compact manifolds $X$ and give an index theorem for these operators. In addition, we prove that the Dirac-operator associated to the metric of a conformally compact manifold $X$ is not a Fredholm operator.

Capitoli della teoria delle funzioni di K. Weierstrass nell'interpretazione di A. Hurwitz e S. Pincherle

Ricostruzione della teoria delle funzioni affrontata nel corso "Einleitung in die Theorie der analytischen Funktionen" tenuto da K. Weierstrass attraverso l'analisi e il confronto dei saggi di due suoi studenti: A. Hurwitz e S. Pincherle.

Misura di asimmetria CP nei decadimenti: $D^0 \to K^+K^-$ e $D^0 \to \pi^+ \pi^-$ ad LHCb

La fisica del sapore è uno dei settori di ricerca più promettenti per realizzare misure di altissima precisione del Modello Standard e per osservare indirettamente, attraverso i decadimenti mediati dalle interazioni deboli nuove particelle. L'esperimento LHCb \`e stato progettato per realizzare misure di altissima precisione in questo settore. Grazie all'alta luminosità integrata disponibile (3 fb \ap{-1}) ed alla elevata sezione d’urto di produzione dei quark charm, LHCb \`e in grado di realizzare misure di una precisione mai raggiunta fino ad ora da altri esperimenti. In questo lavoro di tesi \`e stata realizzata una misura preliminare della simmetria di violazione di CP, realizzata mediante i decadimenti dei mesoni neutri $D^0$ negli stati finali $K^+K^-$ e $\pi^+\pi^-$. Per realizzare la misura sono stati selezionati i decadimenti $D^{*\pm} \to D^0(K^+K^-)\pi^\pm_s$ e $D^{*\pm} \to D^0(\pi^+\pi^-)\pi^\pm_s$ utilizzando i dati raccolti da LHCb durante il RUN-1 (2010-2012) ed \`e stato sviluppato un modello di adattamento ai dati in grado di misurare la differenza di asimmetria di CP integrate nel tempo nei decadimenti $D^0 \rightarrow K^+K^-$ e $D^0 \rightarrow \pi^+\pi^-$, $\Delta A_{CP}$. Il modello \`e stato sviluppato in modo da descrivere le distribuzioni di massa invariante del $D^0$ e del $D^{*\pm}$ sia per la componente di segnale sia per quelle di fondo ed \`e stato adattato ai dati, per sottrarne i fondi e misurare le asimmetrie $A_{RAW}(K^+K^-)$ e $A_{RAW}(\pi^+\pi^-)$, corrispondenti alla differenza tra il numero di eventi di segnale $D^{*+}$ e $D^{*-}$, diviso la loro somma. La differenza di queste asimmetrie corrisponde a $\Delta A_{CP}$, la cui misura, non ufficiale, \`e stata determinata essere $\Delta A_{CP}= (-0.12\pm 0.08)\% $. Questo risultato rappresenta la miglior misura al mondo mai realizzata da un singolo esperimento.

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.

Comparison of the binding and internalization properties of 12 DOTA-coupled and ¹¹¹In-labelled CCK2/gastrin receptor binding peptides: a collaborative project under COST Action BM0607

Specific overexpression of cholecystokinin 2 (CCK2)/gastrin receptors has been demonstrated in several tumours of neuroendocrine origin. In some of these cancer types, such as medullary thyroid cancer (MTC), a sensitive diagnostic modality is still unavailable and therapeutic options for inoperable lesions are needed. Peptide receptor radionuclide therapy (PRRT) may be a viable therapeutic strategy in the management of these patients. Several CCK2R-targeted radiopharmaceuticals have been described in recent years. As part of the European Union COST Action BM0607 we studied the in vitro and in vivo characteristics of 12 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CCK2R binding peptides. In the present study, we analysed binding and internalization characteristics. Stability, biodistribution and imaging studies have been performed in parallel by other centres involved in the project.