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Showing papers by "University of Lisbon published in 2004"


Journal ArticleDOI
TL;DR: A new numerical method based on a combination of the classical shape derivative and of the level-set method for front propagation, which can easily handle topology changes and is strongly dependent on the initial guess.

2,176 citations


Journal ArticleDOI
TL;DR: In this paper, the authors reported high performance ZnO thin-film transistor (ZnO-TFT) fabricated by rf magnetron sputtering at room temperature with a bottom gate configuration.
Abstract: We report high-performance ZnO thin-film transistor (ZnO-TFT) fabricated by rf magnetron sputtering at room temperature with a bottom gate configuration. The ZnO-TFT operates in the enhancement mode with a threshold voltage of 19V, a saturation mobility of 27cm2∕Vs, a gate voltage swing of 1.39V∕decade and an on/off ratio of 3×105. The ZnO-TFT presents an average optical transmission (including the glass substrate) of 80% in the visible part of the spectrum. The combination of transparency, high mobility, and room-temperature processing makes the ZnO-TFT a very promising low-cost optoelectronic device for the next generation of invisible and flexible electronics.

1,499 citations


Journal ArticleDOI
TL;DR: The major constraints to carbon assimilation and the metabolic regulations that play a role in plant responses to water deficits, acting in isolation or in conjunction with other stresses, is reviewed.
Abstract: Drought is one of the greatest limitations to crop expansion outside the present-day agricultural areas. It will become increasingly important in regions of the globe where, in the past, the problem was negligible, due to the recognized changes in global climate. Today the concern is with improving cultural practices and crop genotypes for drought-prone areas; therefore, understanding the mechanisms behind drought resistance and the efficient use of water by the plants is fundamental for the achievement of those goals. In this paper, the major constraints to carbon assimilation and the metabolic regulations that play a role in plant responses to water deficits, acting in isolation or in conjunction with other stresses, is reviewed. The effects on carbon assimilation include increased resistance to diffusion by stomata and the mesophyll, as well as biochemical and photochemical adjustments. Oxidative stress is critical for crops that experience drought episodes. The role of detoxifying systems in preventing irreversible damage to photosynthetic machinery and of redox molecules as local or systemic signals is revised. Plant capacity to avoid or repair membrane damage during dehydration and rehydration processes is pivotal for the maintenance of membrane integrity, especially for those that embed functional proteins. Among such proteins are water transporters, whose role in the regulation of plant water status and transport of other metabolites is the subject of intense investigation. Long-distance chemical signalling, as an early response to drought, started to be unravelled more than a decade ago. The effects of those signals on carbon assimilation and partitioning of assimilates between reproductive and non-reproductive structures are revised and discussed in the context of novel management techniques. These applications are designed to combine increased crop water-use efficiency with sustained yield and improved quality of the products. Through an understanding of the mechanisms leading to successful adaptation to dehydration and rehydration, it has already been possible to identify key genes able to alter metabolism and increase plant tolerance to drought. An overview of the most important data on this topic, including engineering for osmotic adjustment or protection, water transporters, and C4 traits is presented in this paper. Emphasis is given to the most successful or promising cases of genetic engineering in crops, using functional or regulatory genes. as well as to promising technologies, such as the transfer of transcription factors.

1,197 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of the dual cholinesterase inhibitor rivastigmine in patients with mild-to-moderate dementia associated with Parkinson's disease were investigated.
Abstract: background Cholinergic deficits are prominent in patients who have dementia associated with Parkinson’s disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients. methods Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson’s disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and Alzheimer’s Disease Cooperative Study–Clinician’s Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer’s Disease Cooperative Study–Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini–Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test. results A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer’s disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01). conclusions In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson’s disease but also with higher rates of nausea, vomiting, and tremor.

1,082 citations


Journal ArticleDOI
TL;DR: In this paper, stellar parameters and metallicities for a large sample of 98 stars known to be orbited by planetary mass companions (almost all known targets), as well as for a volume-limited sample of 41 stars not known to host any planet were presented.
Abstract: We present stellar parameters and metallicities, obtained from a detailed spectroscopic analysis, for a large sample of 98 stars known to be orbited by planetary mass companions (almost all known targets), as well as for a volume-limited sample of 41 stars not known to host any planet. For most of the stars the stellar parameters are revised versions of the ones presented in our previous work. However, we also present parameters for 18 stars with planets not previously published, and a compilation of stellar parameters for the remaining 4 planet-hosts for which we could not obtain a spectrum. A comparison of our stellar parameters with values of T eff , log g, and [Fe/H] available in the literature shows a remarkable agreement. In particular, our spectroscopic log g values are now very close to trigonometric log g estimates based on Hipparcos parallaxes. The derived [Fe/H] values are then used to confirm the previously known result that planets are more prevalent around metal-rich stars. Furthermore, we confirm that the frequency of planets is a strongly rising function of the stellar metallicity, at least for stars with [Fe/H] > 0. While only about 3% of the solar metallicity stars in the CORALIE planet search sample were found to be orbited by a planet, this number increases to more than 25% for stars with [Fe/H] above +0.3. Curiously, our results also suggest that these percentages might remain relatively constant for values of [Fe/H] lower than about solar, increasing then linearly with the mass fraction of heavy elements. These results are discussed in the context of the theories of planetary formation.

1,022 citations


Journal ArticleDOI
TL;DR: In this paper, the impact of the North Atlantic oscillation (NAO) on winter precipitation and river flow regimes for the three main international Iberian river basins, namely the Douro (north), the Tejo (centre) and the Guadiana (south), was assessed in terms of total Spanish potential hydroelectricity production.
Abstract: The Iberian Peninsula precipitation and river flow regimes are characterized by large values of inter-annual variability, with large disparities between wet and dry years, especially in southern Iberia. This situation is a major problem for water resources management in general, and for the production of hydroelectricity in particular. Hydroelectric production represents, in an average year of precipitation, 20% of the total Spanish electricity production (and 35% for Portuguese production). Its absolute value, however, can vary by a factor of three between wet and dry years. We have assessed the impact of the North Atlantic oscillation (NAO) on winter precipitation and river flow regimes for the three main international Iberian river basins, namely the Douro (north), the Tejo (centre) and the Guadiana (south). Results show that the large inter-annual variability in the flows of these three rivers is largely modulated by the NAO phenomenon. Throughout most of the 20th century, the January-to-March river flow is better correlated with the December to February (DJF) NAO index than is the simultaneous (DJF) river flow. Correlation values for the period 1973-98 are highly significant (-0.76 for Douro, -0.77 for Tejo and -0.79 for Guadiana), being consistently of higher magnitude than those obtained over previous decades. This impact of the NAO on winter river flow was quantified in terms of total Spanish potential hydroelectricity production. The important control exerted by the NAO and the recent positive trend in the NAO index contribute to a significant decrease in the available flow. This reduction represents an important hazard for the two Iberian economies because of its negative impact on water-dependent resources, such as intensive agriculture and hydroelectric power production.

610 citations


Journal ArticleDOI
TL;DR: In this paper, customer loyalty can be explained to a substantial degree by customer satisfaction, trust, and communication, and shows the direct and indirect effects among those constructs and other constructs in an extension of the European Customer Satisfaction Index (ECSI) model.
Abstract: Loyalty has, over the past decade, become a crucial construct in marketing, and particularly in the burgeoning field of customer relationship management. This paper shows that customer loyalty can be explained to a substantial degree by customer satisfaction, trust, and communication, and shows the direct and indirect effects among those constructs and other constructs in an extension of the European Customer Satisfaction Index (ECSI) model. Both ECSI model and the extended model are estimated with data from a survey carried out among customers of the banking sector. Within the limitations of the study, the theoretical and managerial implications of these findings are discussed.

609 citations


Journal ArticleDOI
TL;DR: In this paper, cloud-resolving model (CRM) simulations and parallel single-column model (SCM) tests of the sensitivity of moist atmospheric convection to mid-tropospheric humidity are presented.
Abstract: As part of the EUROCS (EUROpean Cloud Systems study) project, cloud-resolving model (CRM) simulations and parallel single-column model (SCM) tests of the sensitivity of moist atmospheric convection to midtropospheric humidity are presented. This sensitivity is broadly supported by observations and some previous model studies, but is still poorly quantified. Mixing between clouds and environment is a key mechanism, central to many of the fundamental differences between convection schemes. Here, we define an idealized quasi-steady ‘testbed’, in which the large-scale environment is assumed to adjust the local mean profiles on a timescale of one hour. We then test sensitivity to the target profiles at heights above 2 km. Two independent CRMs agree reasonably well in their response to the different background profiles and both show strong deep precipitating convection in the more moist cases, but only shallow convection in the driest case. The CRM results also appear to be numerically robust. All the SCMs, most of which are one-dimensional versions of global climate models (GCMs), show sensitivity to humidity but differ in various ways from the CRMs. Some of the SCMs are improved in the light of these comparisons, with GCM improvements documented elsewhere. © Crown copyright, 2004.

455 citations


Journal ArticleDOI
TL;DR: In this paper, the authors developed a new measurement scale (the RELQUAL scale) to assess the degree of relationship quality between the exporting firm and the importer, which is presented as a high order concept.
Abstract: In this article the authors develop a new measurement scale (the RELQUAL scale) to assess the degree of relationship quality between the exporting firm and the importer. Relationship quality is presented as a high order concept. Findings reveal that a better quality of the relationship results in a greater 1) amount of information sharing, 2) communication quality, 3) long-term orientation, as well as 4) satisfaction with the relationship. The four multi-item scales show strong evidence of reliability as well as convergent, discriminant and nomological validity in a sample of British exporters. Findings also reveal that relationship quality is positively and significantly associated with export performance. Suggestions for applying the measure in future research are presented.

391 citations


Journal ArticleDOI
TL;DR: Liver injury in NASH and ASH is associated with increased hepatocyte apoptosis mediated by death receptors, and this potential mechanistic link might provide multiple interesting targets for therapeutic intervention.

371 citations


Journal ArticleDOI
TL;DR: In this article, the authors consider several effects of the matter wave dynamics which can be observed in Bose-Einstein condensates embedded into optical lattices and derive approximate evolution equations, the form of which depends on relation among the main spatial scales of the system.
Abstract: We consider several effects of the matter wave dynamics which can be observed in Bose–Einstein condensates embedded into optical lattices. For low-density condensates, we derive approximate evolution equations, the form of which depends on relation among the main spatial scales of the system. Reduction of the Gross–Pitaevskii equation to a lattice model (the tight-binding approximation) is also presented. Within the framework of the obtained models, we consider modulational instability of the condensate, solitary and periodic matter waves, paying special attention to different limits of the solutions, i.e. to smooth movable gap solitons and to strongly localized discrete modes. We also discuss how the Feshbach resonance, a linear force and lattice defects affect the nonlinear matter waves.

Journal ArticleDOI
TL;DR: The results suggest that the culture conditions used for axillary branching proliferation are appropriate for clonal propagation of almond clone VII, as they do not seem to interfere with the integrity of the regenerated plantlets.
Abstract: Almond shoots produced by axillary branching from clone VII derived from a seedling of cultivar Boa Casta were evaluated for somaclonal variation using randomly amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) analysis. To verify genetic stability we compared RAPD and ISSR patterns of plantlets obtained after 4 and 6 years of in vitro multiplication. A total of 64 RAPD and 10 ISSR primers gave 326 distinct and reproducible band classes, monomorphic across all 22 plantlets analysed. Thus, a total of 7,172 bands were generated, exhibiting homogeneous RAPD and ISSR patterns for the plantlets tested. These results suggest that the culture conditions used for axillary branching proliferation are appropriate for clonal propagation of almond clone VII, as they do not seem to interfere with the integrity of the regenerated plantlets. These results allowed us to establish the use of axillary branching plantlets (mother-plants) as internal controls for the analysis of somaclonal variation of shoots regenerated from other in vitro culture processes performed with clone VII (adventitious regeneration, regeneration from meristem culture, virus sanitation programs and genetic engineering).


Journal ArticleDOI
TL;DR: Although cancer stage was the major determinant of patients’ QoL globally, there were some diagnoses for which the impact of nutritional deterioration combined with deficiencies in nutritional intake may be more important than the stage of the disease process.
Abstract: The aims of this study were (1) to evaluate quality of life (QoL), nutritional status and dietary intake taking into account the stage of disease and therapeutic interventions, (2) to determine potential interrelationships, and (3) to quantify the relative contributions of the cancer, nutrition and treatments on QoL. In this prospective cross-sectional study conducted in 271 head and neck, oesophagus, stomach and colorectal cancer patients, the following aspects were evaluated: QoL (EORTC-QLQ C30), nutritional status (percent weight loss over the previous 6 months), usual diet (comprehensive diet history), current diet (24-h recall) and a range of clinical variables. Usual and current intakes differed according to the site of the tumour (P=0.02). Patients with stage III/IV disease showed a significant reduction from their usual energy/protein intake (P=0.001), while their current intakes were lower than in patients with stage I/II disease (P=0.0002). Weight loss was greater in patients with stage III/IV disease than in those with stage I/II disease (P=0.001). Estimates of effect size revealed that QoL function scores were determined in 30% by cancer location, in 20% by nutritional intake, in 30% by weight loss, in 10% by chemotherapy, in 6% by surgery, in 3% by disease duration and in 1% by stage of disease. Likewise in the case of symptom scales, 41% were attributed to cancer location, 22% to stage, 7% to nutritional intake, 7% to disease duration, 4% to surgery, 1% to weight loss and 0.01% to chemotherapy. Finally for single items, 30% were determined by stage, 20% by cancer location, 9% by intake, 4% by surgery, 3% by weight loss, 3% by disease duration and 1% by chemotherapy. Although cancer stage was the major determinant of patients’ QoL globally, there were some diagnoses for which the impact of nutritional deterioration combined with deficiencies in nutritional intake may be more important than the stage of the disease process.

Journal ArticleDOI
David P. Schmitt1, Lidia Alcalay2, Melissa Allensworth1, Jüri Allik3, Lara Ault4, Ivars Austers5, Kevin Bennett6, Gabriel Bianchi7, Fredrick Boholst8, Mary Ann Borg Cunen9, Johan Braeckman10, Edwin G. Brainerd11, Leo Gerard A. Caral8, Gabrielle Caron, María Martina Casullo12, Michael Cunningham4, Ikuo Daibo13, Charlotte J. S. De Backer10, Eros De Souza14, Rolando Díaz-Loving15, Glaucia Ribeiro Starling Diniz16, Kevin Durkin17, Marcela Echegaray18, Ekin Eremsoy19, Harald A. Euler20, Ruth Falzon9, Maryanne L. Fisher21, Dolores Foley22, Robert Fowler1, Douglas P. Fry23, Sirpa Fry23, M. Arif Ghayur24, Vijai N. Giri25, Debra L. Golden26, Karl Grammer, Liria Grimaldi27, Jamin Halberstadt28, Shamsul Haque29, Dora Herrera18, Janine Hertel30, Amanda Hitchell1, Heather Hoffmann31, Danica Hooper22, Zuzana Hradilekova32, Jasna Hudek-Kene-Evi33, Allen I. Huffcutt1, Jas Laile Suzana Binti Jaafar34, Margarita Jankauskaite35, Heidi Kabangu-Stahel, Igor Kardum33, Brigitte Khoury36, Hayrran Kwon37, Kaia Laidra3, Anton Laireiter38, Dustin Lakerveld39, Ada Lampert, Mary Anne Lauri9, Marguerite Lavallée, Suk-Jae Lee40, Luk Chung Leung41, Kenneth D. Locke42, Vance Locke17, Ivan Lukšík7, Ishmael Magaisa43, Dalia Marcinkeviciene35, André Mata44, Rui Mata44, Barry Mccarthy45, Michael E. Mills46, Nhlanhla Mkhize47, João Manuel Moreira44, Sérgio Moreira44, Miguel Moya48, M. Munyae49, Patricia Noller22, Hmoud Olimat50, Adrian Opre51, Alexia Panayiotou52, Nebojša Petrović53, Karolien Poels10, Miroslav Popper7, Maria Poulimenou54, Volodymyr P'Yatokha, Michel Raymond55, Ulf-Dietrich Reips56, Susan E. Reneau57, Sofía Rivera-Aragón15, Wade C. Rowatt58, Willibald Ruch59, Velko S. Rus60, Marilyn P. Safir61, Sonia Salas62, Fabio Sambataro27, Kenneth Sandnabba23, Rachel Schleeter1, Marion K. Schulmeyer, Astrid Schütz30, Tullio Scrimali27, Todd K. Shackelford63, Mithila B. Sharan25, Phillip R. Shaver64, Francis J Sichona65, Franco Simonetti2, Tilahun Sineshaw66, R. Sookdew47, Tom Speelman10, Spyros Spyrou67, H. Canan Sümer, Nebi Sümer68, Marianna Supekova7, Tomasz Szlendak, Robin Taylor69, Bert Timmermans70, William Tooke71, Ioannis Tsaousis72, F. S.K. Tungaraza65, Ashley Turner1, Griet Vandermassen10, Tim Vanhoomissen73, Frank Van Overwalle73, Ine Vanwesenbeeck, Paul L. Vasey74, João Veríssimo44, Martin Voracek75, Wendy W.N. Wan76, Ta-Wei Wang77, Peter Weiss78, Andik Wijaya, Liesbeth Woertman39, Gahyun Youn79, Agata Zupanèiè60 
Bradley University1, Pontifical Catholic University of Chile2, University of Tartu3, University of Louisville4, University of Latvia5, University of New Mexico6, Slovak Academy of Sciences7, University of San Carlos8, University of Malta9, Ghent University10, Clemson University11, University of Buenos Aires12, Osaka University13, Illinois State University14, National Autonomous University of Mexico15, University of Brasília16, University of Western Australia17, University of Lima18, Boğaziçi University19, University of Kassel20, University of York21, University of Queensland22, Åbo Akademi University23, Al Akhawayn University24, Indian Institute of Technology Kharagpur25, University of Hawaii at Manoa26, University of Catania27, University of Otago28, University of Dhaka29, Chemnitz University of Technology30, Knox College31, Comenius University in Bratislava32, University of Rijeka33, University of Malaya34, Vilnius University35, American University of Beirut36, Kwangju Health College37, University of Salzburg38, Utrecht University39, National Computerization Agency40, City University of Hong Kong41, University of Idaho42, University of Zimbabwe43, University of Lisbon44, University of Central Lancashire45, Loyola Marymount University46, University of Natal47, University of Granada48, University of Botswana49, University of Jordan50, Babeș-Bolyai University51, University of Cyprus52, University of Belgrade53, KPMG54, University of Montpellier55, University of Zurich56, University of Alabama57, Baylor University58, Queen's University Belfast59, University of Ljubljana60, University of Haifa61, University of La Serena62, Florida Atlantic University63, University of California, Davis64, University of Dar es Salaam65, Ramapo College66, Cyprus College67, Middle East Technical University68, University of the South Pacific69, VU University Amsterdam70, State University of New York System71, University of the Aegean72, Vrije Universiteit Brussel73, University of Lethbridge74, University of Vienna75, University of Hong Kong76, Yuan Ze University77, Charles University in Prague78, Chonnam National University79
TL;DR: In the International Sexuality Description Project, a total of 17,804 participants from 62 cultural regions completed the RelationshipQuestionnaire (RQ), a self-report measure of adult romantic attachment as discussed by the authors.
Abstract: As part of the International Sexuality Description Project, a total of 17,804 participants from 62 cultural regions completedthe RelationshipQuestionnaire(RQ), a self-reportmeasure of adult romanticattachment. Correlational analyses within each culture suggested that the Model of Self and the Model of Other scales of the RQ were psychometrically valid within most cultures. Contrary to expectations, the Model of Self and Model of Other dimensions of the RQ did not underlie the four-category model of attachment in the same way across all cultures. Analyses of specific attachment styles revealed that secure romantic attachment was normative in 79% of cultures and that preoccupied romantic attachment was particularly prevalent in East Asian cultures. Finally, the romantic attachment profiles of individual nations were correlated with sociocultural indicators in ways that supported evolutionary theories of romantic attachment and basic human mating strategies.


Journal ArticleDOI
TL;DR: The data indicate that the rate and orientation of pollen tube growth is regulated by NO levels at the pollen tube tip and suggest that this NO function is mediated by cGMP.
Abstract: Nitric oxide (NO) controls diverse functions in many cells and organs of animals. It is also produced in plants and has a variety of effects, but little is known about their underlying mechanisms. In the present study, we have discovered a role for NO in the regulation of pollen tube growth, a fast tip-growing cellular system. Pollen tubes must be precisely oriented inside the anatomically complex female ovary in order to deliver sperm. We hypothesized that NO could play a role in this guidance and tested this hypothesis by challenging the growth of pollen tubes with an external NO point source. When a critical concentration was sensed, the growth rate was reduced and the growth axis underwent a subsequent sharp reorientation, after which normal growth was attained. This response was abrogated in the presence of the NO scavenger CPTIO and affected by drugs interfering in the cGMP signaling pathway. The sensitivity threshold of the response was significantly augmented by sildenafil citrate (SC), an inhibitor of cGMP-specific phosphodiesterases in animals. NO distribution inside pollen tubes was investigated using DAF2-DA and was shown to occur mostly in peroxisomes. Peroxisomes are normally excluded from the tip of pollen tubes and little if any NO is found in the cytosol of that region. Our data indicate that the rate and orientation of pollen tube growth is regulated by NO levels at the pollen tube tip and suggest that this NO function is mediated by cGMP.

Journal ArticleDOI
TL;DR: In this article, the information gathered for 16 still unpublished exoplanet candidates discovered with the CORALIE echelle spectrograph mounted on the Euler Swiss telescope at La Silla Observatory is summarized.
Abstract: This paper summarizes the information gathered for 16 still unpublished exoplanet candidates discovered with the CORALIE echelle spectrograph mounted on the Euler Swiss telescope at La Silla Observatory. Amongst these new candidates, 10 are typical extrasolar Jupiter-like planets on intermediate- or long-period (100 ≤ 1350 d) and fairly eccentric (0.2 ≤ e ≤ 0.5) orbits (HD 19994, HD 65216, HD 92788, HD 111232, HD 114386, HD 142415, HD 147513, HD 196050, HD 216437, HD 216770). Two of these stars are in binary systems. The next 3 candidates are shorter-period planets (HD 6434, HD 121504) with lower eccentricities among which we find a hot Jupiter (HD 83443). More interesting cases are given by the multiple-planet systems HD 82943 and HD 169830. The former is a resonant = 2/1 system in which planet-planet interactions are influencing the system evolution. The latter is more hierarchically structured.

Journal ArticleDOI
TL;DR: PI3K is implicate as a major effector of IL-7–induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-all.
Abstract: Interleukin (IL)-7 is essential for normal T cell development. Previously, we have shown that IL-7 increases viability and proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells by up-regulating Bcl-2 and down-regulating the cyclin-dependent kinase inhibitor p27kip1. Here, we examined the signaling pathways via which IL-7 mediates these effects. We investigated mitogen-activated protein kinase (MEK)–extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)–Akt (protein kinase B) pathways, which have active roles in T cell expansion and have been implicated in tumorigenesis. IL-7 induced activation of the MEK–Erk pathway in T-ALL cells; however, inhibition of the MEK–Erk pathway by the use of the cell-permeable inhibitor PD98059, did not affect IL-7–mediated viability or cell cycle progression of leukemic cells. IL-7 induced PI3K-dependent phosphorylation of Akt and its downstream targets GSK-3, FOXO1, and FOXO3a. PI3K activation was mandatory for IL-7–mediated Bcl-2 up-regulation, p27kip1 down-regulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of T-ALL cells. PI3K signaling was also required for cell size increase, up-regulation of CD71, expression of the glucose transporter Glut1, uptake of glucose, and maintenance of mitochondrial integrity. Our results implicate PI3K as a major effector of IL-7–induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-ALL.

Journal ArticleDOI
TL;DR: A common 677C→T transition in the MTHFR gene is a well established genetic determinant of hyperhomocysteinaemia, and results in a thermolabile protein, with a decreased enzymatic activity.
Abstract: A growing body of evidence has highlighted the role of abnormal DNA methylation patterns on inappropriate gene expression and promotion of disease.1–3 DNA methylation patterns are maintained by DNA methyltransferases,4–7 using S-adenosylmethionine (AdoMet) as the methyl group donor; AdoMet is then converted to S-adenosylhomocysteine (AdoHcy). Intracellular homocysteine (Hcy) is derived from AdoHcy hydrolysis through the action of AdoHcy hydrolase, a reversible reaction with a dynamic equilibrium that strongly favours AdoHcy synthesis rather than hydrolysis.8 Thus, an efficient metabolic removal of Hcy is required to prevent AdoHcy accumulation. The toxicity of intracellular AdoHcy accumulation lies in its high affinity binding to the catalytic region of most AdoMet dependent methyltransferases (including DNA methyltransferases), acting as its inhibitor.9 Thereby, any disturbance in Hcy metabolism is likely to disturb cellular methylation processes, including DNA methylation patterns. 5,10-methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of Hcy metabolism that catalyses the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for the remethylation of Hcy to methionine. A common 677C→T transition in the MTHFR gene is a well established genetic determinant of hyperhomocysteinaemia, and results in a thermolabile protein, with a decreased enzymatic activity. The molecular basis of this thermolability is a missense mutation in the exon 4 of the MTHFR gene, a cytosine to thymine substitution at nucleotide 677, which converts an alanine to a valine codon in the N-terminal catalytic domain of the protein. The association between this MTHFR genotype and the total Hcy (tHcy) circulating levels is well known to be contingent on folate status.10,11 Recently, a second polymorphism associated with decreased enzymatic activity but not with thermolability was discovered in the MTHFR gene.12 This genetic variant corresponds to an adenosine to cytosine transversion at nucleotide 1298, in exon 7, leading to …

Journal ArticleDOI
TL;DR: In this paper, the integration of Poisson manifolds was studied in terms of variations of symplectic areas, and the existence of complete symplectic realizations was shown to exist.
Abstract: We discuss the integration of Poisson brackets, motivated by our recent solution to the integrability problem for general Lie brackets. We give the precise obstructions to integrating Poisson manifolds, describing the integration as a symplectic quotient, in the spirit of the Poisson sigma-model of Cattaneo and Felder. For regular Poisson manifolds we express the obstructions in terms of variations of symplectic areas, improving on results of Alcalde Cuesta and Hector. We apply our results (and our point of view) to decide about the existence of complete symplectic realizations, to the integrability of submanifolds of Poisson manifolds, and to the study of dual pairs, Morita equivalence and reduction.

Journal ArticleDOI
08 Jan 2004-Nature
TL;DR: A mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation is presented, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node.
Abstract: During vertebrate embryo development, the breaking of the initial bilateral symmetry is translated into asymmetric gene expression around the node and/or in the lateral plate mesoderm. The earliest conserved feature of this asymmetric gene expression cascade is the left-sided expression of Nodal, which depends on the activity of the Notch signalling pathway. Here we present a mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node. We identify the source of the asymmetric activation of Notch as a transient accumulation of extracellular calcium, which in turn depends on left-right differences in H+/K+-ATPase activity. Our results uncover a mechanism by which the Notch signalling pathway translates asymmetry in epigenetic factors into asymmetric gene expression around the node.

Journal ArticleDOI
TL;DR: In this paper, the effect of dopant concentration, heating treatment and annealing in reducing atmosphere on the microstructure as well as on the electrical and optical properties of the thin films is discussed.
Abstract: Transparent and conductive high preferential c-axis oriented ZnO thin films doped with Al have been prepared by sol–gel method using zinc acetate and aluminium chloride as cations source, 2-methoxiethanol as solvent and monoethanolamine as sol stabilizer. Film deposition was performed by dip-coating technique at a withdrawal rate of 1.5 cm min−1 on Corning 1737 glass substrate. The effect of dopant concentration, heating treatment and annealing in reducing atmosphere on the microstructure as well as on the electrical and optical properties of the thin films is discussed. The optical transmittance spectra of the films showed a very good transmittance, between 85 and 95%, within the visible wavelength region. The minimum resistivity of 1.3×10−3 Ω cm was obtained for the film doped with 2 wt.% Al, preheated at 400 °C and post-heated at 600 °C, after annealing under a reduced atmosphere of forming gas.

Journal ArticleDOI
TL;DR: In this article, the discovery of a very light planetary companion to the star mu Ara (HD160691) was presented, with a semi-amplitude of 4.1 m/s, the smallest Doppler amplitude detected so far.
Abstract: In this letter we present the discovery of a very light planetary companion to the star mu Ara (HD160691). The planet orbits its host once every 9.5days, and induces a sinusoidal radial velocity signal with a semi-amplitude of 4.1 m/s, the smallest Doppler amplitude detected so far. These values imply a mass of m2 sini = 14 earth-masses. This detection represents the discovery of a planet with a mass slightly smaller than that of Uranus, the smallest ``ice giant" in our Solar System. Whether this planet can be considered an ice giant or a super-earth planet is discussed in the context of the core-accretion and migration models.

Journal ArticleDOI
TL;DR: In this paper, the authors report the discovery of two new transiting planets with very short orbital periods: OGLE-TR-113 with m = 1.35 ± 0.13 RJup, P =1.69 days.
Abstract: As a result of a radial velocity follow-up of OGLE planetary transit candidates in Carina, we report the discovery of two new transiting planets with very short orbital periods: OGLE-TR-113 with m = 1.35 ± 0.22 MJup, r = 1.08 +0.07 −0.05 RJup, P = 1.43 days, and OGLE-TR-132 with m = 1.01 ± 0.31 MJup, r = 1.15 +0.80 −0.13 RJup, P = 1.69 days. These detections bring to three the number of known "very hot Jupiter" (Jovian exoplanets like OGLE-TR-56 with periods around 1.5 days). This indicates that the accumulation of periods around 3 days found in radial velocity surveys does not reflect an absolute limit.

Journal ArticleDOI
TL;DR: In this paper, the PUREX process is described from the viewpoint of the chemistry involved in the solvent extraction methods and other well-known technological approaches devoted to the reprocessing of irradiated uranium and thorium nuclear fuels and general radioactive wastes.
Abstract: After a brief description of the PUREX process as a starting point, this paper aims to point out some of its most recent developments, always from the viewpoint of the chemistry involved in the solvent extraction methods. In addition to PUREX, other well-known technological approaches devoted to the reprocessing of irradiated uranium and thorium nuclear fuels and general radioactive wastes — TRUEX, DIAMEX, TRPO, DIDPA and UNEX — are also presented and discussed.

Journal ArticleDOI
TL;DR: A new approximate FRAP model is presented that takes into account diffusion of highly mobile molecules during the bleach phase and shows that by the time the first postbleach image is acquired in a CLSM a significant fluorescence recovery of fast-moving molecules has already taken place.
Abstract: Fluorescence recovery after photobleaching (FRAP) is a widely used tool for estimating mobility parameters of fluorescently tagged molecules in cells Despite the widespread use of confocal laser scanning microscopes (CLSMs) to perform photobleaching experiments, quantitative data analysis has been limited by lack of appropriate practical models Here, we present a new approximate FRAP model for use on any standard CLSM The main novelty of the method is that it takes into account diffusion of highly mobile molecules during the bleach phase In fact, we show that by the time the first postbleach image is acquired in a CLSM a significant fluorescence recovery of fast-moving molecules has already taken place The model was tested by generating simulated FRAP recovery curves for a wide range of diffusion coefficients and immobile fractions The method was further validated by an experimental determination of the diffusion coefficient of fluorescent dextrans and green fluorescent protein The new FRAP method was used to compare the mobility rates of fluorescent dextrans of 20, 40, 70, and 500 kDa in aqueous solution and in the nucleus of living HeLa cells Diffusion coefficients were lower in the nucleoplasm, particularly for higher molecular weight dextrans This is most likely caused by a sterical hindrance effect imposed by nuclear components Decreasing the temperature from 37 to 22 degrees C reduces the dextran diffusion rates by approximately 30% in aqueous solution but has little effect on mobility in the nucleoplasm This suggests that spatial constraints to diffusion of dextrans inside the nucleus are insensitive to temperature

Journal ArticleDOI
TL;DR: Evidence that the Williams syndrome transcription factor (WSTF) is targeted to replication foci through direct interaction with the DNA clamp PCNA is provided and it is proposed that the WSTF–ISWI complex has a role in the maintenance of chromatin structures during DNA replication.
Abstract: The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci

Journal ArticleDOI
TL;DR: In this article, the authors derived zenith delay models from revised equations for the computation of the refractive index of the atmosphere, valid for a wide spectrum of optical wavelengths.
Abstract: [1] A major limitation in accuracy in modern satellite laser ranging is the modeling of atmospheric refraction. Recent improvements in this area include the development of mapping functions to project the atmospheric delay experienced in the zenith direction to a given elevation angle. In this paper, we derive zenith delay models from revised equations for the computation of the refractive index of the atmosphere, valid for a wide spectrum of optical wavelengths. The zenith total delay predicted with these models were tested against ray tracing through radiosonde data from a full year of data, for 180 stations distributed worldwide, and showed sub-millimeter accuracy for wavelengths ranging from 0.355 μm to 1.064 μm.

Journal ArticleDOI
01 Jan 2004
TL;DR: In this article, a hydrographic and ichthyoplanktonic survey was conducted on the western Iberia Peninsula shelf-slope, with the objective of assessing the influence of wind-driven flow on the transport and survival of sardine early life history stages.
Abstract: A hydrographic and ichthyoplanktonic survey was conducted on the western Iberia Peninsula shelf-slope, with the objective of assessing the influence of wind-driven flow on the transport and survival of sardine early life history stages. Measurements were taken during a 2-week period of an ‘upwelling-favourable’ wind event. An offshore displacement of the surface low salinity Western Iberia Buoyant Plume (WIBP) was observed well off the shelf break. Below the plume, the current was southward over the mid- and inner-shelf. Offshore, the flow was poleward in the northern part of the survey area and equatorward in the south. A convergence zone was detected along the outer shelf and upper slope where the buoyant plume was apparently trapped and deepened. In general, eggs and larvae were distributed according to the spreading of the low salinity surface waters, and also within the convergent band. Older larvae were retained within the latter feature. The role of wind forcing on the plume and its interaction with the slope flow were analysed. A mechanism of larvae retention was formulated based on simplified models of the observed shelf-slope circulation.