Pancreatic cancer is nowadays one of the neoplasms with worst prognosis, so research towards the discovery of new molecular targets for therapy and diagnosis is more than urgent. In this direction, we have deeply evaluated the role of Galectin-1 (Gal-1) - a protein that is highly overexpressed in the tumor stroma- in pancreatic tumor progression. Interestingly, we have found that Gal-1 interacts with tissue plasminogen activator (tPA) and that this interplay seems to be involved both in pancreatic tumor epithelial cells and fibroblasts migration, Erk1/2 activation and invasion, suggesting its importance in the tumor/stroma crosstalk in vitro. We have also focused on the biochemical identification of tPA/Gal-1 interaction domains. Furthermore, we have studied Gal-1 role in pancreatic tumor progression in vivo, using murine (xenografts and transgenics) and zebrafish models. We have found that Gal-1 participates in proliferation, angiogenesis, stroma formation and necrosis in Ela-1-myc pancreatic tumors, as well as in the acinar to ductal metaplasia. Importantly, these effects result in an overall significant increase in the survival of Ela-1-myc mice with reduced Gal-1 levels. We have also analyzed Gal-1 role in mouse embryonic pancreatic development, finding interesting parallelisms with tumors. Finally, the molecular mechanisms involved in Gal-1 driving tumor pancreatic progression have been addressed through a transcriptome analysis. All together, our data support Gal-1 as a new molecular target to fight against pancreatic cancer. / Avui en dia, el càncer de pàncrees representa un dels tumors amb més elevats índex de mortalitat, per la qual cosa la recerca dirigida a la identificació de molècules per teràpia i diagnosi són més que necessàries. Amb aquest objectiu, hem avaluat el paper que juga Galectina-1 (Gal-1) - una proteïna altament sobreexpressada en l’estroma tumoral- en la progressió tumoral pancreàtica. Hem trobat que Gal-1 interactua amb l’activador tissular del plasminògen (tPA), participant en la migració, l’activació de Erk1/2 i la invasió, tant en cèl4lules tumorals pancreàtiques com en fibroblasts in vitro, suggerint una importància caudal d’aquesta interacció en la comunicació entre el tumor i l’estroma. Així mateix, ens hem centrat en la identificació bioquímica dels dominis d’interacció entre Gal-1 i tPA. A més, el paper de Gal-1 en la progressió tumoral pancreàtica ha estat adreçat in vivo, utilitzant models murins (xenografts i transgènics) i el peix zebra. Així doncs hem trobat que Gal-1 participa en la proliferació, angiogènesi, formació de l’estroma i la necrosi dels tumors pancreàtics dels ratolins Ela- 1-myc, així com en la metaplasia acinar-ductal. De forma significativa, aquests efectes es tradueixen en un increment important en la supervivència dels ratolins Ela-1-myc amb nivells reduïts de Gal-1. Hem també analitzat el paper que juga Gal-1 en el desenvolupament pancreàtic embrionari murí, trobant paral4lelismes interessants amb els tumors. Finalment, hem volgut ocupar-nos dels mecanismes moleculars involucrats en els efectes produïts per Gal-1 durant la progressió tumoral pancreàtica mitjançant microarrays. Les nostres dades presenten Gal-1 com una nova diana terapèutica per lluitar contra el càncer de pàncrees.

Les Andes de Mérida (Venezuela) est caractérisé par la présence de morphologie glaciaire bien préservée entre 2400-4978 m. Les études de ces morphologies glaciares font la contribution pour mieux comprendre et reconstruire la Dernière Glaciation aux Andes Vénézuéliennes. La reconstruction de la Dernière Glaciation (connue dans la région comme Glaciation Mérida) était limitée par la disponibilité de chronologie glaciaire. Cette thèse fait sa contribution à la reconstruction de la Dernière Glaciation et à la connaissance du paléoclimat depuis le Pléistocène Superieur. La méthodologie a involucré l´analyse géomorphologique et l´étude géochronologique. La morphologie glaciaire a été datée avec la technique de nucléides cosmogéniques produits in-situ (10Be). Cette technique est appropriée pour dater les matériels riches en quartz et la période d´intérêt. Les inférences des conditions paleoclimatiques ont été faites sur la base des analyses de la paléo ELA.Des différentes dynamiques glaciares ont été identifiées aux Andes centrales de Mérida. Dans les vallées de Mucubají et Mucuchache, la dynamique a été caractérisée par plusieurs étapes de avancé-arrêt des glaciaires dans un recul général de la glace. Dans les vallées de Gavidia et Mifafí, la disparition des glaciares a été très rapide avec la vitesse de recul plus haute (entre 4-7 km/ky). Divers caractéristiques morpho métriques comme la pente du fond de la vallée, la topographie de la zone d´accumulation (cirques glaciares avec les murs très incliné), des surfaces de la zone d´accumulation et son orientation ont aussi contrôlé les différents dynamiques glaciares.Les avancées des glaciares ont été identifiées entre 2500-4200 m. Les avancées glaciares pendant le MIS 3 ont été reconnues à Sierra Nevada. Ces avancées ont été liées aux hautes précipitations dans le nord de l´Amérique de Sud produites par l´activité de la Zone de Convergence Intertropical. Ces avancées ont été aussi reliées aux conditions plus chaudes et humides dans l´Hémisphère Nord (aussi ces conditions ont été identifiées aux Andes vénézuéliennes et sont connues comme l´Interstadío El Pedregal). Les avancées glaciares pendant le Dernière Maximum Glaciares ont été enregistrées en Sierra Nevada á Mucubají et Las Tapias entre 3100-3600 m. Principalement, les avancées glaciares MIS 2 sont arrivées pendant l´Oldest Dryas-El Caballo Estadío à 17 ka. Ces avancées glaciares ont été reliées aux températures froides dans l´Hémisphère Nord et les températures plus froides enregistrées dans les carottes de glaciares tropicaux.Mots clésDatation par cosmogéniques produits in-situ, morphologie glaciaire, Pléistocène, Dernière Glaciation, LGM, paléo ELA. / The central Mérida Andes (Venezuela) landscape is characterized by the presence of well-preserved glacial landforms located between 2400 and 4978 m a.s.l. Geomorphological studies of these glacial landforms significantly contribute to the Venezuelan Andes glaciations reconstructions. However, Last Glaciation (locally called Mérida Glaciation) was poorly reconstructed because of limited chronological data. This dissertation attempts to contribute to the Last Glaciation reconstruction and paleoclimate knowledge since the late Pleistocene. Accordance this necessity, the methodology involved geomorphological analysis and geochronological study. Glacial landforms were dated based on the Terrestrial Cosmogenic Nuclide dating (10Be). This method is suitable for date quartz-rich materials and for the period of interest. To deduce paleoclimate conditions an analysis based on paleo ELA was developed.In the central Mérida Andes different Late Pleistocene glacier dynamics were identified. In the Mucubají and the Mucuchache valleys, successive stages of glacier stop-advance were identified during an overall glacier withdrawal. In the Gavidia and Mifafí valleys, glacier withdrawal was rapid with the highest retreat rates (between 4-7 km/ky). Morphometric features as glaciers bottom valley slopes, accumulation zone topography (glaciers cirques with steep walls), areas and orientation controlled different glaciers dynamics.Glacier advances were evidenced between 2500-4200 m. MIS 3 glaciers advances has been recognized in the Sierra Nevada. These were related to the highest runoff in the north of South America produced by the Intertropical Convergence Zone (ITCZ) and the local warm and wet climate conditions (locally named El Pedregal Interstadial). LGM glacier advances were recorded in Sierra Nevada in the Mucubají and Las Tapias between 3100-3600 m. MIS 2 Glaciers advances mainly occurred during the Oldest Dryas- El Caballo Stadial at around 17 ka. These glaciers advances correlate to the cold temperatures in the North Hemisphere and the coldest temperatures recorded in tropical ice cores.KeywordsTerrestrial cosmogenic nuclides dating, TCN, cosmogenic dating, glacial landforms, Andes Mérida, Venezuela. Pleistocene, Last Glaciation, LGM, paleo ELA, tropic paleoclimate.

O bagaço de cana-de-açúcar é um resíduo gerado no processo de produção de açúcar e álcool pelas usinas. O histórico de uso desse material aponta para a queima visando à produção de vapor e energia para o processo. As necessidades ambientais e econômicas ligadas tanto à emissão de gases estufa quanto as áreas agricultáveis apontam para um melhor aproveitamento desse resíduo que é constituído de cerca de 50% de celulose, 28% de hemiceluloses (também chamadas polioses), 21% de lignina e 1% de inorgânicos. Dentro desse contexto este trabalho visou à utilização da celulose do bagaço para a obtenção de açúcares fermentescíveis para a produção de etanol de 2ª geração. O bagaço foi desmedulado e a fração fibra foi pré-hidrólisada visando eliminar as hemiceluloses. Em seguida a fração fibra pré-hidrolisada foi deslignificada através de polpação soda antraquinona (SAQ). A polpa celulósica da fração fibra do bagaço foi hidrolisada em ácido sulfúrico e ácido clorídrico através do método \"ELA\", extremely low acid. Esse método utiliza ácido mineral muito diluído, altas temperaturas e pressões. As temperaturas de hidrólise utilizadas compreenderam a faixa de 180 a 230°C e as concentrações de ácido sulfúrico e ácido clorídrico utilizadas foram 0,07%, 0,14% e 0,28% e 0,05%, 0,10% e 0,20%, respectivamente. A razão sólido-líquido empregada foi 1:20 (m/v) e os reatores utilizados foram de aço inox 316L. A perda de massa após os experimentos de hidrólise foi quantificada e a composição dos hidrolisados foi analisada por cromatografia líquida de alta eficiência (CLAE). Paralelamente um estudo de degradação de glicose em ácido sulfúrico e ácido clorídrico foi conduzido com o objetivo de minimizar a degradação de glicose e conseqüentemente aumentar o seu rendimento. Através desse estudo também foi possível comparar o efeito de cada ácido na cinética de degradação de glicose. A faixa de temperatura utilizada foi de 200 a 220°C e a faixa de concentração de ácido sulfúrico e ácido clorídrico foi a mesma empregada nos estudos de hidrólise ácida. As constantes de velocidade de ordem um obtidas através de regressões lineares dos dados de perda de massa foram utilizadas para calcular a energia de ativação de Arrhenius. As energias de ativação médias obtidas para a reação com H2SO4 e HCl foram 184.9 e 183.5 kJ/mol, respectivamente. O rendimento máximo de glicose para a hidrólise da polpa celulósica em H2SO4 foi 69,8% e em HCl foi 70,2%. As constantes de velocidade de ordem um obtidas através de regressões lineares dos dados de glicose residual para a degradação de glicose também foram utilizadas para calcular a energia de ativação de Arrhenius. As energias de ativação médias para a decomposição de glicose em H2SO4 e HCl foram 124.5 e 142.9 kJ/mol, respectivamente. Através dos estudos realizados foi possível concluir que HCl foi um catalisador mais efetivo que o H2SO4 com base no valor das constantes de velocidade determinadas e nos rendimentos máximos de glicose obtidos. Porém, o HCl é menos vantajoso economicamente que o H2SO4 e os íons cloreto são responsáveis por tornar esse ácido mais corrosivo que o H2SO4. / Sugarcane bagasse is a residue from sugar and alcohol production process. In the industry of sugar and alcohol this residue is burned to produce steam and energy for the process. The environmental and economic needs related to both emission of greenhouse gases and the increase of sugarcane planted area point to be a better utilization of the bagasse. The approximate composition of sugarcane bagasse is 50% cellulose, 28% hemicelluloses, 21% lignin and 1% inorganic compounds. From this view point, this work aimed to use cellulose from sugarcane bagasse to obtain fermentable sugars to produce second generation ethanol. Depithed bagasse was pre-hydrolyzed to remove hemicelluloses. Afterwards, pre-hydrolyzed depithed bagasse was pulped using soda-anthraquinone (SAQ) method to remove lignin. Cellulosic pulp was hydrolyzed employing the ELA conditions. Sulphuric acid and hydrochloric acid were chosen as hydrolysis catalysts. The ELA uses mineral acid in extremely low concentration, high temperatures and pressures. The temperature range chosen for kinetic study was from 180 to 230°C. The H2SO4 concentration was 0.07%, 0.14%, and 0.28% and HCl concentration was 0.05%, 0.10%, and 0.20%. In hydrolysis experiments the solid-liquid ratio employed was 1:20. Reactors resistant to acid corrosion made by 316L-stainless steel were used in the experiments. The weight loss after the hydrolysis experiments was determined and the hydrolysate composition was analyzed by high performance liquid chromatography (HPLC). A study of glucose decomposition in both acid catalysts was also carried out. The aim of this study was to minimize glucose degradation and acquire data to compare the effect of catalyst type on glucose degradation. The temperature range employed was from 200 to 220°C and the catalysts concentration was the same described above. First-order rate constants for hydrolysis of cellulosic pulp were obtained from linear regressions using data from weight loss. These rate constants were also used to calculate Arrhenius activation energy. The average activation energies for H2SO4 and HCl were 184.9 and 183.5 kJ/mol, respectively. The maximum glucose yields obtained in H2SO4 and HCl were 69.8% and 70.2%, respectively. First-order rate constants for glucose decomposition were also obtained from linear regressions and also used to calculate Arrhenius activation energy. The average activation energies for glucose decomposition in H2SO4 and HCl were 124.5 e 142.9 kJ/mol, respectively. From the results of kinetic studies was possible to conclude that HCl was a more efficient catalyst than H2SO4. Moreover, HCl is more expensive than H2SO4 and chloride ions are responsible for making HCl more corrosive than H2SO4.

Leave with ideas to build confidence and understanding about using hands-on activities and literacy strategies as tools to understand the nature of wave movement.

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A researched and standards-based approach for secondary students practicing reading and writing skills Product Features: Prompts students to write grade-aligned opinion paragraphs for nonfiction and fiction Improves reading comprehension and vocabulary development Use as a complement to Teaching to Standards: English Language Arts or a stand-alone program Also available as the Access Language Arts: WRITE iPad App

The rapid rate of global warming currently underway highlights the need for a deeper understanding of abrupt climate change. The Younger Dryas is a Late-Glacial climate event of widespread and unusually rapid change whose study can help us address this need for increased understanding. Reconstructions from the glacial record offer important contributions to our understanding of the Younger Dryas due to (among other things) the direct physical response of glaciers to even minor perturbations in climate. Because the glacier equilibrium line altitude (ELA) provides a more explicit comparison of climate than properties such as glacier length or area, ELA methods lend themselves well to paleoclimate applications and allow for more direct comparisons in space and time. Here we present a physically based ELA model for alpine paleoglacier climate reconstructions that accounts for differences in glacier width, glacier shape, bed topography and ice thickness, and includes error estimates using Monte Carlo simulations. We validate the ELA model with published mass balance measurements from 4 modern glaciers in the Swiss Alps. We then use the ELA model, combined with a temperature index model, to estimate the changes in temperature and precipitation between the Younger Dryas (constrained by 10Be surface exposure ages) and the present day for three glacier systems in the Graubünden Alps. Our results indicate an ELA depression in this area of 320 m ±51 m during the Younger Dryas relative to today. This ELA depression represents annual mean temperatures 2.29 °C ±1.32 °C cooler relative to today in the region, which corresponds to a decrease in mean summer temperatures of 1.47 °C ±0.73 °C. Our results indicate relatively small changes in summer temperature dominate over other climate changes for the Younger Dryas paleoglaciers in the Alps. This ELA-based paleoclimate reconstruction offers a simple, fast, and cost-effective alternative to many other paleoclimate reconstruction methods. Continued application of the ELA model to more regions will lead to an improved understanding of the Younger Dryas in the Alps, and by extension, of rapid climate events generally.

English learners (ELs) at a middle school in California were not meeting federal accountability requirements in English language arts (ELA). ELs lacking proficiency in ELA often drop out of high school and live in poverty as adults. The purpose of the study was to examine teachers' perceptions of their self-efficacy to implement effective pedagogical strategies to help ELs develop ELA proficiency. A case study design was used to investigate the problem through the lens of second language acquisition theory. The purposeful sample included 11 middle school language arts teachers. Participants completed an online anonymous survey, and responses were analyzed using open coding and analytical coding. The following 3 themes emerged from the data: teachers varied in their perceptions of their efficacy to support ELs, teachers perceived their teacher preparation and professional development experiences to be inadequate in preparing them to support ELs, and teachers blamed students and parents for the lack of proficiency in ELA. A professional development project was designed to address the findings and to help build teachers' pedagogical skills and self-efficacy in instructing ELs. Positive social change may be promoted by increasing teachers' ability to effectively instruct ELs, which will increase their efficacy with this population. ELs will benefit by possessing the reading, writing, and communication skills necessary for high school and postsecondary success and to be competitive in the workforce.

La activación glial es un proceso que se ha implicado en diversas patologías entre las que se incluyen diferentes enfermedades neurodegenerativas, como la enfermedad de Alzheimer o la Esclerosis Lateral Amiotrófica. Esto se debe a que durante la activación glial se producen mediadores proinflamatorios, como la ciclooxigenasa (COX-2), el óxido nítrico (NO), factor de necrosis tumoral (TNF-alfa), la interleuquina-1 (IL-1) o la interleuquina-6 (IL-6), que presentan un potencial neurotóxico.El grupo de factores de transcripción C/EBPs (CCAAT/enhancer binding proteins) pertenecen a la familia bZIP y está compuesta por seis miembros. C/EBP-alfa, C/EBP-beta y C/EBP-delta participan en procesos como la proliferación y diferenciación celular o el control del metabolismo. Además, estos factores de transcripción se encuentran implicados en procesos inflamatorios como la respuesta de fase aguda o la activación de macrófagos, donde regulan la transcripción de muchos mediadores proinflamatorios, que se han relacionado con los efectos más neurotóxicos de la activación glial. En este trabajo se ha caracterizado la expresión de C/EBP-alfa, C/EBP-beta y C/EBP-delta en los astrocitos y la microglía en condiciones basales y también durante la activación glial. En primer lugar, C/EBP-alfa se expresa principalmente en la microglía y sus niveles disminuyen de forma tiempo y concentración dependiente cuando las células se tratan con lipopolisacárido (LPS) como estímulo proinflamatorio. Además del LPS, que es un agonista del receptor TLR4, la activación de los receptores TLR2, TLR3 y TLR9 también produce la disminución de este factor de transcripción.La síntesis de C/EBP-delta tiene lugar tanto en astrocitos como en microglía durante la activación glial in vitro, cuando estas células se tratan con LPS. Los agonistas de los receptores TLR2, TLR3 y TLR9 producen un aumento similar al producido por el LPS en las células microgliales. Dicho aumento está mediado por la actividad del enzima ERK1/2 y supone un incremento de la unión de C/EBP-delta al promotor de COX-2. En la microglía activada, C/EBP-delta forma dímeros con otros factores de transcripción como p65 (un componente de NF-kB) y C/EBP-beta.Por su parte, C/EBP-beta se encuentra presente de una forma mayoritaria en las células microgliales, aunque también se encuentra en menor cantidad en los astrocitos. El tratamiento con LPS supone el aumento tiempo y concentración dependiente de los niveles nucleares de C/EBP-beta gracias a la síntesis del novo. Este aumento está mediado por la enzima JNK. Para estudiar la funcián de C/EBP-beta en la activación glial se han generado clones de la línea microglial BV2 que sobreexpresan LIP, una isoforma de C/EBP-beta que actúa como un dominante negativo y se han utilizado ratones deficientes en C/EBP-beta. La inhibición de C/EBP-beta supone una atenuación en la producción del ARNm de los mediadores proinflamatorios NOS-II, COX-2 e IL-6 cuando las células gliales se activan, y también en la producción de NO cuando las células se tratan con LPS e IFN-gamma.Los resultados de este trabajo sugieren la implicación de C/EBP-alfa, C/EBP-beta y C/EBP-gamma en la regulación de la síntesis de diversos mediadores proinflamatorios, y su importancia en la parte más neurotóxica de la activación glial.