Observaciones sobre las bellezas históricas del Antiguo Testamento /

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Report of the Indian statutory commission ...

Sir John Allsebrook Simon, chairman.

Report of the Indian statutory commission ...

Sir John Allsebrook Simon, chairman.

Studies on the mechanism of action on antitumour imidazotetrazinones

The imidazotetrazinones are clinically active antitumour agents, temozolomide currently proving successful in the treatment of melanomas and gliomas. The exact nature of the biological processes underlying response are as yet unclear.This thesis attempts to identify the cellular targets important to the cytotoxicity of imidazotetrazinones, to elucidate the pathways by which this damage leads to cell death, and to identify mechanisms by which tumour cells may circumvent this action. The levels of the DNA repair enzymes O6-alkylguanine-DNA-alkyltransferase (O6-AGAT) and 3-methyladenine-DNA-glycosylase (3MAG) have been examined in a range of murine and human cell lines with differential sensitivity to temozolomide. All the cell lines were proficient in 3MAG despite there being 40-fold difference in sensitivity to temozolomide. This suggests that while 3-methyladenine is a major product of temozolomide alkylation of DNA it is unlikely to be a cytotoxic lesion. In contrast, there was a 20-fold variation in O6-AGAT levels and the concentration of this repair enzyme correlated with variations in cytotoxicity. Furthermore, depletion of this enzyme in a resistant, O6-AGAT proficient cell line (Raji), by pre-treatment with the free base O6-methylguanine resulted in 54% sensitisation to the effects of temozolomide. These observations have been extended to 3 glioma cell lines; results that support the view that the cytotoxicity of temozolomide is related to alkylation at the O6-position of guanine and that resistance to this drug is determined by efficient repair of this lesion. It is clear, however, the other factors may influence tumour response since temozolomide showed little differential activity towards 3 established solid murine tumours in vivo, despite different tumour O6-AGAT levels. Unlike mitozolomide, temozolomide is incapable of cross-linking DNA and a mechanism by which O6-methylguanine may exert lethality is unclear. The cytotoxicity of the methyl group may be due to its disruption of DNA-protein interactions, or alternatively cell death may not be a direct result of the alkyl group itself, but manifested by DNA single-strand breaks. Enhanced alkaline elution rates were found for the DNA of Raji cells treated with temozolomide following alkyltransferase depletion, suggesting a relationship between O6-methylguanine and the induction single-strand breaks. Such breaks can activate poly(ADP-ribose) synthetase (ADPRT) an enzyme capable of rapid and lethal depletion of cellular NAD levels. However, at concentrations of temozolomlde relevant in vivo little change in adenine nucleotides was detected in cell lines, although this enzyme would appear important in modulating DNA repair since inhibition of ADPRT potentiated temozolomide cytotoxicity in Raji cells but not O6-AGAT deficient GM892A cells. Cell lines have been reported that are O6-AGAT deficient yet resistant to methylating agents. Thus, resistance to temozolomide may arise not only by removal of the methyl group from the O6-position of guanine, but also from another mechanism involving caffeine-sensitive post-replication repair or mismatch repair activity. A modification of the standard Maxam Gilbert sequencing technique was used to determine the sequence specificity of guanine-N7 alkylation. Temozolomide preferentially alkylated runs of guanines with the intensity of reaction increasing with the number of adjacent guanines in the DNA sequence. Comparable results were obtained with a polymerase-stop assay, although neither technique elucidates the sequence specificity of O6-guanine alkylation. The importance of such specificity to cytotoxicity is uncertain, although guanine-rich sequences are common to the promoter regions of oncogenes. Expression of a plasmid reporter gene under the control of the Ha-ras proto~oncogene promoter was inhibited by alkylation with temozolomide when transfected into cancer cell lines, However, this inhibition did not appear to be related to O6~guanine alkylation and therefore would seem unimportant to the chemotherapeutic activity of temozolomide.

Mode-locked semiconductor lasers with optical injection

We perform characterization of the pulse shape and noise properties of quantum dot passively mode-locked lasers (PMLLs). We propose a novel method to determine the RF linewidth and timing jitter, applicable to high repetition rate PMLLs, through the dependence of modal linewidth on the mode number. Complex electric field measurements show asymmetric pulses with parabolic phase close to threshold, with the appearance of waveform instabilities at higher currents. We demonstrate that the waveform instabilities can be overcome through optical injection-locking to the continues wave (CW) master laser, leading to time-bandwidth product (TBP) improvement, spectral narrowing, and spectral tunability. We discuss the benefits of single- and dual-tone master sources and demonstrate that dual-tone optical injection can additionally improve the noise properties of the slave laser with RF linewidth reduction below instrument limits (1 kHz) and integrated timing jitter values below 300 fs. Dual-tone injection allowed slave laser repetition rate control over a 25 MHz range with reduction of all modal optical linewidths to the master source linewidth, demonstrating phase-locking of all slave modes and coherence improvement.

(Table S1) Age determination of Atlantic Ocean sediment cores

Well-dated benthic foraminifer oxygen isotopic records (d18O) from different water depths and locations within the Atlantic Ocean exhibit distinct patterns and significant differences in timing over the last deglaciation. This has two implications: on the one hand, it confirms that benthic d18O cannot be used as a global correlation tool with millennial-scale precision, but on the other hand, the combination of benthic isotopic records with independent dating provides a wealth of information on past circulation changes. Comparing new South Atlantic benthic isotopic data with published benthic isotopic records, we show that (1) circulation changes first affected benthic d18O in the 1000-2200 m range, with marked decreases in benthic d18O taking place at ~17.5 cal. kyr B.P. (ka) due to the southward propagation of brine waters generated in the Nordic Seas during Heinrich Stadial 1 (HS1) cold period; (2) the arrival of d18O-depleted deglacial meltwater took place later at deeper North Atlantic sites; (3) hydrographic changes recorded in North Atlantic cores below 3000 m during HS1 do not correspond to simple alternations between northern- and southern-sourced water but likely reflect instead the incursion of brine-generated deep water of northern as well as southern origin; and (4) South Atlantic waters at ~44°S and ~3800 m depth remained isolated from better-ventilated northern-sourced water masses until after the resumption of North Atlantic Deep Water (NADW) formation at the onset of the Bølling-Allerod, which led to the propagation of NADW into the South Atlantic.

Marinetti y el modelo de artista moderno

El objetivo de este artículo es analizar la figura del artista a comienzos del siglo XX a través de los textos y las ideas del poeta italiano Filippo Tommaso Marinetti. Partiendo sus teorías de las bases del decadentismo, Marinetti genera un modelo de artista en el que ejercen gran influencia conceptos como el genio y la libertad artística, muy asociados al Romanticismo, pero al que añade nuevos elementos de gran relevancia para la coyuntura política y social de su época. Entre estos, estarían aquellos que vincularon al artista futurista con la política de su tiempo, con el fascismo y con los modos de comunicación con el cada vez más importante público de grandes masas. Obsesionado con la idea de progreso, Marinetti aspira a crear un nuevo artista capaz de generar un nuevo mundo que introdujera definitivamente a Italia en la modernidad.

Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia

RATIONALE: As more preterm infants recover from severe bronchopulmonary dysplasia (BPD), it is critical to understand the clinical consequences of this condition on the lung health of adult survivors.

OBJECTIVES: To assess structural and functional lung parameters in young adult BPD survivors and preterm and term controls Methods: Young adult survivors of BPD (mean age 24) underwent spirometry, lung volumes, transfer factor, lung clearance index and fractional exhaled nitric oxide measurements together with high-resolution chest tomographic (CT) imaging and cardiopulmonary exercise testing.

MEASUREMENTS AND MAIN RESULTS: 25 adult BPD survivors, (mean ± SD gestational age 26.8 ± 2.3 weeks; birth weight 866 ± 255 g), 24 adult prematurely born non-BPD controls (gestational age 30.6 ± 1.9 weeks; birth weight 1234 ± 207 g) and 25 adult term birth control subjects (gestational age 38.5 ± 0.9 weeks; and birth weight 3569 ± 2979 g) were studied. BPD subjects were more likely to be wakened by cough (OR 9.7, 95% CI: 1.8 to 52.6), p<0.01), wheeze and breathlessness (OR 12.2, 95%CI: 1.3 to 112), p<0.05) than term controls after adjusting for sex and current smoking. Preterm subjects had greater airways obstruction than term subjects. BPD subjects had significantly lower values for FEV1 and FEF25-75 (% predicted and z scores) than term controls (both p<0.001). Although non-BPD subjects also had lower spirometric values than term controls, none of the differences reached statistical significance. More BPD subjects (25%) had fixed airflow obstruction than non-BPD (12.5%) and term (0%) subjects (p=0.004). Both BPD and non-BPD subjects had significantly greater impairment in gas transfer (KCO % predicted) than term subjects (both p<0.05). Eighteen (37%) preterm participants were classified as small for gestational age (birth weight < 10th percentile for gestational age). These subjects had significantly greater impairment in FEV1 (% predicted and z scores) than those born appropriate for gestational age. BPD survivors had significantly more severe radiographic structural lung impairment than non-BPD subjects. Both preterm groups had impaired exercise capacity compared to term controls. There was a trend for greater limitation and leg discomfort in BPD survivors.

CONCLUSIONS: Adult preterm birth survivors, especially those who developed BPD, continue to experience respiratory symptoms and exhibit clinically important levels of pulmonary impairment.

ENTREVISTA CON FRANZ HINKELAMMERT

El 05 de abril de 2001, en sesión ordinaria del Consejo Universitario de la Universidad Nacional, éste órgano de la UNA tomó el acuerdo de otorgar al Dr. Franz J. Hinkelammert, científico social alemán radicado en Costa Rica desde hace más de veinte años y uno de los fundadores del Departamento Ecuménico de Investigaciones(DEI); el Doctorado Honoris Causa, “por su excepcional aporte a las ciencias sociales contemporáneas”. El acto público para la entrega oficial de tal distinción se realizó un mes después, y en ese mismo acto, se le solicitó al Dr.Hinkelammert la entrega de una obra reciente o en preparación de su autoría, para que fuera publicada por la Editorial de la UNA, como parte del reconocimiento a su labor intelectual. El borrador final de esa obra fue entregada a la EUNA a finales de 2001, y tratándose de más de 500 páginas, tomó casi un año de prolijo trabajo la tarea de corrección y edición. Se trata del libro que comentamos en la presente entrevista, EL SUJETO Y LA LEY. El retorno del Sujeto reprimido, Editorial Universidad Nacional,Heredia, Costa Rica, 2003.

Cambios en al investigación y acción en desarrollo rural y medio ambiente

Resumen En este trabajo se procuró rescatar las acciones de investigación y acción que incursionan en los senderos de reconstrucción de las relaciones humanas con el medio ambiente y sus procesos, bajo una axiología integrada de valores que constituyen las relaciones, basadas en una nueva ética y solidaridad para repensar las formas de ver las cosas, formular preguntas relevantes y buscar la lectura apropiada de las respuestas, desde su complejidad. Esto involucra cambios en el pensar de los actores del desarrollo: técnicos y técnicas, agricultores, agricultoras y sociedad en general, los cuales en encuentran en la urgencia de 1) Aprender a ser; 2) aprender a pensar haciéndolo comunitariamente; 3) aprender a aprender; 4) aprender a desaprender y reaprender y 5) aprender a emprender (Milla Villena, 1983). La evaluación retrospectiva de dos investigaciones en el desarrollo rural: 1) una sobre la introducción de cambios en el manejo de animales menores en huertos caseros y 2) otra sobre reforestación de tacotales, ejemplifican intentos de realizar un diálogo paralelo entre el medio ambiente y las necesidades alimentarias de las poblaciones indígenas en un esfuerzo por demostrar que “Conocer, proponer y lograr cambios trascendentes en la realidad comunal implica desarrollar la capacidad de filtrar esta realidad, en un proceso cognoscitivo, que va de la mano con el uso solidario de los recursos y el desarrollo conjunto de estrategias factibles y apropiadas para la sustentabilidad de la vida en la comunidad”…

Representações sobre a leitura e sua influência em práticas educativas: um estudo de caso no 1.º ciclo de Bolonha

É hoje amplamente reconhecida na literatura de especialidade a importância da leitura, no âmbito de uma reconstrução em pleno de um exercício de cidadania que se (re)quer crescentemente multidimensional. No que respeita aos estudantes do ensino superior, aumentam hodiernamente os desdobramentos da leitura, cruzando-se no seu quotidiano e na escola, em práticas cujas diversidade e funcionalidade adquirem considerável relevância. Nesse sentido, neste estudo procuramos indagar que representações sobre a leitura evidenciam estudantes futuros profissionais da Educação a frequentar um 1.º ciclo de estudos de Bolonha sobre: i) a sua motivação para a leitura; ii) o seu desempenho em compreensão na leitura; iii) os fatores que os influenciam; iv) estratégias didáticas orientadas para a motivação para a leitura e o desenvolvimento da compreensão na leitura no seu futuro público. Adicionalmente refletimos sobre as possíveis repercussões de tais representações nas suas práticas educativas futuras centradas: i) na motivação do seu futuro público para a leitura; ii) no desempenho da compreensão na leitura nesse mesmo público. Face aos objetivos delineados, considerámos adequada uma abordagem de natureza qualitativa, tendo como referencial metodológico o estudo de caso. Os participantes neste estudo foram 53 estudantes inscritos na unidade curricular de Iniciação à Leitura e à Escrita que integra o plano de estudos da licenciatura em Educação Básica na Escola Superior de Educação de Viseu (3.º ano, 1.º semestre do ano letivo 2012/2013). Foram utilizados os seguintes instrumentos de recolha e análise dos dados: um inquérito por questionário; duas reflexões escritas individuais; um depoimento escrito individual sobre o processo de seleção de um álbum/obra e um relatório escrito final com uma componente coletiva e outra individual. Concluímos que as representações sobre a leitura evidenciadas por estes estudantes eram um constructo complexo e multidimensional, existindo múltiplos fatores que as influenciariam. Tais representações teriam repercussões no modo como os estudantes encaravam as suas futuras práticas educativas e o seu futuro público. Face ao interesse de que se revestem representações sobre a leitura dos estudantes futuros profissionais da Educação, pela sua responsabilidade na formação de leitores, importará realizar mais estudos que permitam (re)descobrir a sua possível riqueza e diversidade.