Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.

Integrative and systemic approaches for evaluating PPARβ/δ (PPARD) function.

The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of genes involved in cellular differentiation, development, metabolism and also tumorigenesis. Three PPAR isotypes (α, β/δ and γ) have been identified, among which PPARβ/δ is the most difficult to functionally examine due to its tissue-specific diversity in cell fate determination, energy metabolism and housekeeping activities. PPARβ/δ acts both in a ligand-dependent and -independent manner. The specific type of regulation, activation or repression, is determined by many factors, among which the type of ligand, the presence/absence of PPARβ/δ-interacting corepressor or coactivator complexes and PPARβ/δ protein post-translational modifications play major roles. Recently, new global approaches to the study of nuclear receptors have made it possible to evaluate their molecular activity in a more systemic fashion, rather than deeply digging into a single pathway/function. This systemic approach is ideally suited for studying PPARβ/δ, due to its ubiquitous expression in various organs and its overlapping and tissue-specific transcriptomic signatures. The aim of the present review is to present in detail the diversity of PPARβ/δ function, focusing on the different information gained at the systemic level, and describing the global and unbiased approaches that combine a systems view with molecular understanding.

Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis.

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

Manual para buenos directivos de PYMES que quieren innovar: Empresas 2.0

Estamos viviendo desde la entrada al siglo XXI una explosión acelerada de las tecnologías, de las TIC’s, las redes sociales en internet, etc. que están modificando enormemente los hábitos de consumo y los principios de la sociedad. A todo ello, hay que añadir la situación de crisis económica general que existe en el mundo, y que afecta enormemente a las empresas y al tejido empresarial de un país. En este entorno, las compañías deben basar sus estrategias en estar cerca del cliente y ser capaces de visualizar necesidades no cubiertas. Sobre todo, las empresas deben transformarse para crear organizaciones humanizadas capaces de generar innovación y adaptarse rápidamente a los nuevos entornos que van surgiendo. Para poder hacer frente a esta nueva situación las empresas deben poner en valor el talento de todas las personas que forman parte de la organización. El activo más importante y escaso, para poder desarrollar estrategias triunfadoras. El trabajo pretende resumir la situación actual para las empresas, recoger todas las ideas y nuevas tendencias que existen en cuanto a la gestión del talento, la organización del trabajo y la creación de estructuras que permitan innovar. A lo largo del trabajo se van desarrollando las diferentes herramientas, sistemas y disciplinas que están a disposición de las empresas para crear un entorno que favorezca la innovación, como camino para mantenerse en el mercado global.

Angio-RM das artérias carótidas e vertebrais: análise de diferentes técnicas de volume e diluição de contraste em aparelho de 1,0 t e gradiente de 15 mt/m

OBJETIVO: Avaliar as artérias cervicais (carótidas e vertebrais) por meio da angio-RM, utilizando-se diferentes dosagens e diluições de contraste paramagnético. MATERIAIS E MÉTODOS: Estudo prospectivo em 15 pacientes, com análise de 30 artérias carótidas comuns, 30 artérias carótidas internas, 30 artérias carótidas externas e 30 artérias vertebrais, utilizando-se diferentes volumes e dosagens de contraste paramagnético: grupo I - dose única (14 ml de Gd-DTPA); grupo II -dose dupla (28 ml de Gd-DTPA); grupo III - dose única e diluída a 50%. A injeção de contraste foi realizada com a utilização de bomba injetora e com velocidades de injeção de 2 ml/s (grupo I) e 3 ml/s (grupos II e III). Os segmentos arteriais foram analisados por três examinadores em consenso de forma subjetiva, avaliando-se o grau de visibilidade, intensidade de contrastação e definição de seus contornos. RESULTADOS: Em todos os itens analisados os pacientes do grupo II apresentaram melhor resultado (visibilização total, boa contrastação dos vasos e contornos bem definidos). No grupo I houve boa visibilização das artérias carótidas e vertebrais, porém a intensidade de contraste e a definição dos contornos apresentaram variabilidade qualitativa. O grupo III apresentou os piores resultados, com dificuldade de visibilização, intensidade de contrastação baixa e contornos mal definidos. CONCLUSÃO: Entre os grupos analisados, a técnica utilizando dose dupla de gadolínio é a que permite melhor avaliação das artérias cervicais. A utilização de contraste diluído prejudica a avaliação dos vasos do pescoço.

Investigating ferromagnetism and charge order in Bi1-xSrxMnO3(x<0.3)ceramic oxides.

The possible coexistence of ferromagnetism and charge/orbital order in Bi3/4Sr1/4MnO3 has been investigated. The manganite Bi0.75Sr0.25MnO3, with commensurate charge balance, undergoes an electronic transition at TCO~600 K that produces a longrange modulation with double periodicity along a and c axis, and unusual anisotropic evolution of the lattice parameters. The previously proposed ferromagnetic properties of this new ordered phase were studied by magnetometry and diffraction techniques. In zero field the magnetic structure is globally antiferromagnetic, ruling out the apparition of spontaneous ferromagnetism. However, the application of magnetic fields produces a continuous progressive canting of the moments, inducing a ferromagnetic phase even for relatively small fields (H<<1 T). Application of pulsed high fields produces a remarkable and reversible spin polarization (under 30 T, the ferromagnetic moment is ~3 ¿B/Mn, without any sign of charge order melting). The coexistence of ferromagnetism and charge order at low and very-high fields is a remarkable property of this system.

Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content

Polyphenols are a major class of bioactive phytochemicals whose consumption may play a role in the prevention of a number of chronic diseases such as cardiovascular diseases, type II diabetes and cancers. Phenol-Explorer, launched in 2009, is the only freely available web-based database on the content of polyphenols in food and their in vivo metabolism and pharmacokinetics. Here we report the third release of the database (Phenol-Explorer 3.0), which adds data on the effects of food processing on polyphenol contents in foods. Data on >100 foods, covering 161 polyphenols or groups of polyphenols before and after processing, were collected from 129 peer-reviewed publications and entered into new tables linked to the existing relational design. The effect of processing on polyphenol content is expressed in the form of retention factor coefficients, or the proportion of a given polyphenol retained after processing, adjusted for change in water content. The result is the first database on the effects of food processing on polyphenol content and, following the model initially defined for Phenol-Explorer, all data may be traced back to original sources. The new update will allow polyphenol scientists to more accurately estimate polyphenol exposure from dietary surveys. Database URL: http://www.phenol-explorer.eu

Pd-catalysed amidation of 2,6-dihalopurine nucleosides. Replacement of iodine at 0 ºC

Pd-catalysed reactions of 2-Cl, 2-Br and 2-I derivatives of a 6-chloropurine nucleoside with benzamide have been compared, using Pd2dba3, Xantphos and Cs2CO3 in toluene, between 20 and 80 °C. The reactivity order was 2-I > 2-Br > 6-Cl ≫ 2-Cl. The 2-I substituent could be replaced even at 0 °C, under conditions disclosed here for the first time. On the other hand, the replacement of the chlorine atom at position 2 (2-Cl) required 110 °C.

Bupivacaine 0.5 % versus articaine 4 % for the removal of lower third molars. A crossover randomized controlled trial

Objective: To compare the anesthetic action of 0.5% bupivacaine in relation to 4% articaine, both with 1:200,000 epinephrine, in the surgical removal of lower third molars. As a secondary objective hemodynamic changes using both anesthetics were analyzed. Study Design: Triple-blind crossover randomized clinical trial. Eighteen patients underwent bilateral removal of impacted lower third molars using 0.5% bupivacaine or 4% articaine in two different appointments. Preoperative, intraoperative and postoperative variables were recorded. Differences were assessed with McNemar tests and repeated measures ANOVA tests. Results: Both solutions exhibited similar latency times and intraoperative efficacy. Statistical significant lower pain levels were observed with bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia (p<0.05). Systolic blood pressure and heart rate values were significantly higher with articaine. Conclusions: Bupivacaine could be a valid alternative to articaine especially due to its early postoperative pain prevention ability.

Chest CT at a dose below 0.3 mSv : impact of iterative reconstruction on image quality and lung analysis

Le nombre d'examens tomodensitométriques (Computed Tomography, CT) effectués chaque année étant en constante augmentation, différentes techniques d'optimisation, dont les algorithmes de reconstruction itérative permettant de réduire le bruit tout en maintenant la résolution spatiale, ont étés développées afin de réduire les doses délivrées. Le but de cette étude était d'évaluer l'impact des algorithmes de reconstruction itérative sur la qualité image à des doses effectives inférieures à 0.3 mSv, comparables à celle d'une radiographie thoracique. Vingt CT thoraciques effectués à cette dose effective ont été reconstruits en variant trois paramètres: l'algorithme de reconstruction, rétroprojection filtrée versus reconstruction itérative iDose4; la matrice, 5122 versus 7682; et le filtre de résolution en densité (mou) versus spatiale (dur). Ainsi, 8 séries ont été reconstruites pour chacun des 20 CT thoraciques. La qualité d'image de ces 8 séries a d'abord été évaluée qualitativement par deux radiologues expérimentés en aveugle en se basant sur la netteté des parois bronchiques et de l'interface entre le parenchyme pulmonaire et les vaisseaux, puis quantitativement en utilisant une formule de merit, fréquemment utilisée dans le développement de nouveaux algorithmes et filtres de reconstruction. La performance diagnostique de la meilleure série acquise à une dose effective inférieure à 0.3 mSv a été comparée à celle d'un CT de référence effectué à doses standards en relevant les anomalies du parenchyme pulmonaire. Les résultats montrent que la meilleure qualité d'image, tant qualitativement que quantitativement a été obtenue en utilisant iDose4, la matrice 5122 et le filtre mou, avec une concordance parfaite entre les classements quantitatif et qualitatif des 8 séries. D'autre part, la détection des nodules pulmonaires de plus de 4mm étaient similaire sur la meilleure série acquise à une dose effective inférieure à 0.3 mSv et le CT de référence. En conclusion, les CT thoraciques effectués à une dose effective inférieure à 0.3 mSv reconstruits avec iDose4, la matrice 5122 et le filtre mou peuvent être utilisés avec confiance pour diagnostiquer les nodules pulmonaires de plus de 4mm.

Kulttuuritapahtumatuotanto 2.0 : verkkosovellukset modernin kulttuuritapahtumatuotannon projektinhallinnan apuvälineinä

Opinnäytetyö selvittää, minkälaisia verkkosovelluksia kulttuurialan tapahtumatuotanto-organisaatiot käyttävät projektinhallintansa apuvälineinä. Miten sovelluksia hyödynnetään ja minkälaisia haasteita niistä mahdollisesti aiheutuu käyttäjille? Työssä käydään myös läpi verkkosovellusten käytön ja muutenkin organisaatioiden verkottumisen myötä tulleita haasteita ja ratkaisumalleja. Verkkosovelluksista keskitytään vain kaikille vapaisiin ja ilmaisiin sovelluksiin. Esitellyt sovellukset ovat helppokäyttöisiä ja helposti muokattavissa moneen eri käyttötarkoitukseen. Web 2.0 -maailma on tuonut mukanaan monenlaisia monikäyttöisiä verkkosovelluksia. Kulttuuritapahtumatuotanto-organisaatiot ovat alkaneet ottaa sovelluksia käyttöön myös projektinhallintatehtävissään. Monet sovelluksista tarjoavat hyvän apuvälineen pienelle tai vähän suuremmallekin tapahtumatuotanto-organisaatiolle, jolla ei välttämättä riittäisi resursseja isompaan projektinhallintatyökaluohjelmistoon. Pääasiallisena aineistona on käytetty kahta kulttuuritapahtumatuotantoalan ammattilaisen haastattelua. Tapausesimerkeiksi valitut kaksi organisaatiota ovat keskenään hieman erilaisia. Toinen edustaa perinteisemmin toimivaa organisaatiota ja toinen kollaboratiivisemmin toimivaa, verkottuneempaa organisaatiota. Työ havainnollistaa, kuinka verkkosovelluksista on eri tavoin hyötyä molemmille organisaatiotyypeille. Haastattelujen tavoitteena oli saada syvempää tietoa kyseisten kulttuuritapahtumatuotanto-organisaation projektinhallinnasta yleensä ja verkkosovellusten roolista siinä. Verkkosovellusten mahdollistamat hyödyt eivät ole laajasti eri alojen ammattilaisten tiedossa. Molempien työssä esiteltyjen organisaatioiden työryhmät ovat levittäytyneet moniin eri kaupunkeihin tai maihin. Työssä esitellään organisaatioiden eri paikoissa olevien jäsenten toimintaa ja verkkosovellusten hyötyä työryhmän välisessä työskentelyssä. Verkkosovellusten kanssa työskennellessään organisaatiot kohtaavat mahdollisesti uudenlaisia henkilöstöhallinnallisia haasteita. Työryhmän motivointi ja osallistaminen ovat yksi muutenkin tärkeä haaste, joka verkottuneesti toimivien organisaatioiden työskentelyssä tulee entistä vahvemmin esille.

Study of D J meson decays to D +π-, D 0π+ and D ∗+π- final states in pp collisions

A study of D +π−, D 0π+ and D ∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D 1(2420)0 resonance is observed in the D ∗+π− final state and the D∗2(2460) resonance is observed in the D +π−, D 0π+ and D ∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D ∗+π−, D +π− and D 0π+ final states.

Proximidad 2.0, el nuevo reto de la policía como servicio público

Este informe pretende efectuar un estudio en el cual se establezca un catálogo básico de elementos referentes para los servicios de atención a la ciudadanía y proximidad que en un futuro las policías ofrecerán a través de las redes sociales. Unas bases de esta tipología no podemos asentarla si no se tienen en consideración reflexiones multidisciplinares como por ejemplo la sociología, la política y la tecnología. En los últimos dos años las Redes Sociales o Social Network Sites (término en inglés) han ido transformándose, cada día más, en una herramienta indispensable no solo a nivel particular y personal, sino también a nivel empresarial, institucional y de representación colectiva.

Dynamics of integrable birational maps preserving genus 0 foliations

Pòster presentat al congrés NPDDS2014

Oracle RAC 12.1.0.1 : Alta disponibilitat per a bases de dades

Estudi sobre les funcionalitats d'alta disponibilitat (Real Application Clusters) del programari gestor de bases de dades Oracle Database 12c.