The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected β-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead β-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and β-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.

M-L band x-rays (3-3.5 KeV) from palladium coated targets for isochoric radiative heating of thin foil samples

We describe experiments designed to produce a bright M-L band x-ray source in the 3-3.5 keV region. Palladium targets irradiated with a 10(15) W cm(-2) laser pulse have previously been shown to convert up to similar to 2% of the laser energy into M-L band x-rays with similar pulse duration to that of the incident laser. This x-ray emission is further characterized here, including pulse duration and source size measurements, and a higher conversion efficiency than previously achieved is demonstrated (similar to 4%) using more energetic and longer duration laser pulses (200 ps). The emission near the aluminium K-edge (1.465-1.550 keV) is also reported for similar conditions, along with the successful suppression of such lower band x-rays using a CH coating on the rear side of the target. The possibility of using the source to radiatively heat a thin aluminium foil sample to uniform warm dense matter conditions is discussed.

Fasciola hepatica from naturally infected sheep and cattle in Great Britain are diploid

Diploid (2n = 2x = 20) and triploid (2n = 3x = 30) Fasciola hepatica have been reported in the UK, and in Asia diploid, triploid and mixoploid (2x/3x) Fasciola spp. exist but there is little information to indicate how common triploidy is, particularly in UK fluke. Here the ploidy of 565 adult F. hepatica from 66 naturally infected British sheep and 150 adult F. hepatica from 35 naturally infected British cattle was determined. All 715 of these parasites were diploid, based on observation of 10 bivalent chromosomes and sperm (n = 335) or, since triploids are aspermic, sperm alone (n = 380). This constitutes the first extensive analysis of the ploidy of F. hepatica field isolates from Great Britain and shows that most F. hepatica isolated from cattle and sheep are diploid and have the capacity to sexually reproduce. These data suggest that triploidy, and by extension parthenogenesis, is rare or non-existent in wild British F. hepatica populations. Given that F. hepatica is the only species of Fasciola present in Britain our results indicate that the parasite is predominantly diploid in areas where F. hepatica exists in isolation and suggests that triploidy may only originate in natural populations where co-infection of F. hepatica and its sister species Fasciola gigantica commonly occurs.

Zero-Reflectance Metafilms for Optimal Plasmonic Sensing

An ultrathin layer of metasurface that almost completely annihilates the reflection of light (>99.5%) over a wide range of incident angles (>80°) is experimentally demonstrated. Such zero-reflectance metafilms exhibit optimal performance for plasmonic sensing, since their sensitivity to changes of local refractive index is far superior to films of nonzero reflectance. Since both main detection mechanisms tracking intensity changes and wavelength shifts are improved, zero-reflectance metafilms are optimal for localized surface plasmon resonance molecular sensing. Such nanostructures have significant opportunities in many areas, including enhanced light harvesting as well as in developing high-performance molecular sensors for a wide range of chemical and biomedical applications.

Pupillary threshold as an index of population vitamin A status among children in India

Two hundred seven vitamin A-deficient southern Indian children aged 1-7 y (mean age: 56.9 mo) underwent testing of dark-adapted visual and pupillary thresholds in their village setting according to a previously reported protocol. One hundred thirty (62.8%) of the children also underwent serum retinol testing, and 178 (86.0%) participated in a randomized, placebo-controlled vitamin A dosing trial with pre- and postdose testing of dark-adaptation threshold. Most subjects (184 of 207, 88.9%) were able to complete pupillary testing, an objective sign requiring minimal cooperation, including a high proportion of the youngest children (72.2% of subjects aged 2 y). The proportion of children completing visual threshold testing, which requires greater understanding and cooperation, was significantly smaller than that able to complete pupillary testing (131 of 207, 63.3%; P < 0.0001, chi square). At baseline (predosing), the mean serum retinol concentration declined in linear fashion with a higher pupillary threshold (0.73 mumol/L with a score < or = 4; 0.47 mumol/L with a score > or = 8; P < 0.01). The mean pupillary threshold for these highly vitamin A-deficient Indian children (-0.622 log cd/m2) was significantly higher than that for 136 more moderately deficient Indonesian children (-0.985 log cd/m2; P < 0.001, two-sample t test) and 56 normal American children (-1.335 log cd/m2; P < 0.0001, two-sample t test). The improvement in pupillary dark-adaptation testing was not significant for children receiving vitamin A or placebo, though there was a nonsignificant trend toward greater improvement in children receiving vitamin A (P = 0.2, two-sample t test). Pupillary threshold testing represents a new, noninvasive, practical, and seemingly valid approach to assessing the vitamin A status of a moderately to severely deficient preschool population.

Envolvimento dos estudantes na escola e perceção de suporte social: um estudo com alunos dos 2º e 3º ciclos do ensino básico

O envolvimento dos estudantes na escola tem ganho relevância no âmbito da comunidade científica. Apesar de não existir um consenso face à sua definição, todas apontam para o facto do envolvimento se relacionar com a forma como os estudantes se identificam e valorizam os resultados escolares, bem como, a sua participação em atividades escolares curriculares e extracurriculares. O suporte social visto como a perceção que o indivíduo tem de ser valorizado e aceite pelos outros contidos na sua rede social. A investigação tem demonstrado a relação existente entre estes dois conceitos. A existência de suporte social, mais especificamente o estabelecimento de relações positivas com o grupo de pares parece estar relacionada com um maior envolvimento dos estudantes na escola. O objetivo do presente estudo é compreender a relação entre o envolvimento dos estudantes na escola e a perceção de suporte social. O mesmo foi realizado numa escola em Évora, com alunos do 2º e 3º ciclos do ensino básico (335 alunos). Foram utilizados dois questionários: o QEEE – Questionário acerca do Envolvimento dos Estudantes na Escola e o QPSS – Questionário de Percepção de Suporte Social. Os resultados do presente estudo apontam para correlações estatisticamente significativas entre o suporte social e o envolvimento dos estudantes na escola, corroborando assim investigações já realizadas; ABSTRACT: Students engagement with school has won relevance within the scientific community. Although there is no consensus over its definition, all point to the fact that the engagement relate to how the students to identify and value the school results as well as their participation in curricular and extracurricular activities. The social support seen as the perception that the individual must be valued and accepted by others contained in your social network. The research has demonstrated the relationship between these both. The existence of social support, specifically the establishment of good relations with the peer group seems to be related to greater student engagement with school. The aim of this study is to understand the link between student engagement with school and perceived social support. It was conducted in a school in Évora, with students from 2nd and 3th cycles of middle school (335 students). We used two questionnaires: QEEE – Questionnaire about the Student Engagement with School and QPSS – Questionnaire for Perceived Social Support. The results of this study show statistically significant correlations between social support and students engagement with school, thus confirming previous research.

Maus-tratos entre iguais e percepção de suporte social: um estudo com alunos dos 2º e 3º ciclos do ensino básico

O bullying e o suporte social, apesar de conceptualmente distintos, interagem entre si. O bullying é um subgrupo do comportamento agressivo, que ocorre intencional e repetidamente, numa relação assimétrica de poder entre pares. O suporte social envolve o apoio recebido pelas fontes de suporte da rede social. O principal objetivo deste estudo é analisar a relação entre bullying e perceção de suporte social. O mesmo realizou-se numa escola básica de Évora, com 335 alunos dos 2° e 3° ciclos do ensino básico, sendo utilizados o Questionário de Violência Escolar e Isolamento Social e o Questionário de Percepção de Suporte Social. Os resultados obtidos indicam baixos níveis de incidência de comportamentos de bullying. Verificou-se que uma fraca perceção de suporte social associa-se a um maior envolvimento no bullying, o que aponta para a perceção de suporte social como um fator protetor para o envolvimento em situações de vitimação e de agressão; ABSTRACT: Bullying and social support, although conceptually distinct, interact between itself. Bullying is a sub-group of the aggressive behavior that occurs repeatedly and intentionally, in an asymmetrical power relationship between peers. Social Support involves the support received by the sources of social support networks. The aim of this study is to analise the relationship between bullying and perceived social support. The aim was done in a basic school of Évora, with 335 students of 2nd and 3th cycles of basic education. The used questionnaires had been the Questionnaire for School Violence and Social isolation and the Questionnaire for Perceived Social Support. The results indicate low levels of incidence of bullying behavior. lt was found that a low perception of social support is associated with an increased involvement in bullying, which points to the social support as a protective for involvement in situations of victimization and agression.

La síntesis fenomeno-lógica. Aspectos metódicos de la apropiación heideggeriana de la fenomenología de Husserl

Sabemos que la relación filosófica entre la obra de Edmund Husserl y Martin Heidegger no es un asunto sencillo de abordar. Con facilidad se inclina la balanza hacia uno u otro autor.1 Eso por sí no sería grave, excepto por el hecho de que múltiples interpretaciones de entrada impiden cualquier posibilidad de acercamiento.2 De esa forma uno estaría obligado a tomar posición a favor de uno y en contra del otro. Ese camino evidentemente empobrece la discusión filosófica. Sin embargo, al intentar abordar una posible relación nos encontramos con ciertas interpretaciones de Heidegger que parecen colocar algo en donde todavía no había tal propuesta en su momento. Ante este panorama quisiera intentar destacar algunos aspectos que den luz sobre la relación fenomenológica entre Husserl y Heidegger tomando como hilo conductor las aseveraciones enfáticas de Heidegger en torno al papel que desempeñaron las Investigaciones lógicas (IL) de Husserl en la conformación de su pensar. Evidentemente con este retorno a las IL buscamos poner a prueba la propia interpretación de Heidegger. De esta forma se verá al final si los señalamientos de Heidegger proporcionan el espacio para llevar a cabo un diálogo fructífero que supere posiciones cerradas.

The LOICZ biogeochemical budget approach applied to Ria Formosa lagoon, - Algarve, South Portugal

Dissertação mest., Gestão da Água e da Costa, Universidade do Algarve, 2007

A Morgadinha de Valflor: a esperança de um sonho. Para uma leitura comparativa do drama de Pinheiro Chagas

Dissertação mest., Literatura, Universidade do Algarve, 2006

L'implication des parents dans l'orientation de leurs enfants

L'approche orientante qui est présentement implantée dans les écoles du Québec vise à favoriser l'implication des parents dans l'orientation de leurs enfants. La Suisse a pour sa part des méthodes qui répondent déjà à cet objectif. Afin de fournir une liste d'activités à privilégier pour la mise en oeuvre de l'approche orientante au Québec, 335 questionnaires ont été distribués à des parents du canton de Fribourg (Suisse). Ces derniers devaient indiquer les activités qui leur avaient été proposées au cours des études secondaires de leurs enfants, en plus de fournir leur degré de satisfaction à l'égard de celles-ci. Les résultats observés traduisent plusieurs suggestions d'activités permettant d'informer et d'impliquer davantage les parents dans l'orientation de leurs enfants.

Distributional Similarity of Words with Different Frequencies

Distributional semantics tries to characterize the meaning of words by the contexts in which they occur. Similarity of words hence can be derived from the similarity of contexts. Contexts of a word are usually vectors of words appearing near to that word in a corpus. It was observed in previous research that similarity measures for the context vectors of two words depend on the frequency of these words. In the present paper we investigate this dependency in more detail for one similarity measure, the Jensen-Shannon divergence. We give an empirical model of this dependency and propose the deviation of the observed Jensen-Shannon divergence from the divergence expected on the basis of the frequencies of the words as an alternative similarity measure. We show that this new similarity measure is superior to both the Jensen-Shannon divergence and the cosine similarity in a task, in which pairs of words, taken from Wordnet, have to be classified as being synonyms or not.