Targeting lactate transport suppresses in vivo breast tumour growth.

BACKGROUND Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. RESULTS The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. CONCLUSIONS This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

Surface phenomena and hydrodynamic effects on the deposition of Pseudomonas fluorescens

Biofilm adhesion to metals (copper, aluminium and brass) was studied at two different velocities and pH values of 7 and 9. Both bacteria and metals showed negative surface charges at those values of pH, which tends to slow down adhesion. Film densities increased with the fluid velocity and were also affected by the pH and by the growth rate of the bacteria. Long duration tests based on heat transfer measurements were run at five different fluid velocities and at pH = 7, showing in general an asymptotic behaviour and a control of deposition by adhesion and growth phenomena.

Avaliação de desempenho das organizações desportivas sem fins lucrativos através do Balanced Scorecard : estudo de caso do Conselho de Arbitragem da Federação Portuguesa de Futebol

A realização deste estudo junta duas áreas distintas: a arbitragem de futsal e o Balanced Scorecard (BSC). Nos últimos anos, devido ao crescimento acentuado da modalidade de Futsal, a mesma tem sido alvo de várias mudanças, nomeadamente no número de competições realizadas ao longo de uma época desportiva. Inerente ao elevado nível de competitividade alcançado, surge a necessidade de melhorar a gestão de uma área fundamental do jogo de futsal, a arbitragem. A arbitragem de futsal a nível nacional é gerida pelo Conselho de Arbitragem da Federação Portuguesa de Futebol (FPF). O Balanced Scorecard é uma metodologia de gestão estratégica, desenvolvida por Robert Kaplan e David Norton em 1992, que pode ser aplicada quer em organizações com fins lucrativos quer em organizações sem fins lucrativos, como é o caso do Conselho de Arbitragem da FPF. Desta forma, para colmatar a necessidade de melhorar a gestão da arbitragem de futsal, o presente estudo propõem-se aplicar a metodologia Balanced Scorecar ao Conselho de Arbitragem da Federação Portuguesa de Futebol na vertente futsal. Assim, irá ser apresentada uma análise do ambiente externo e interno, a definição de posicionamento e planeamento estratégico, o mapa estratégico e os objetivos definidos para cada perspetiva. Por fim, será feita uma reflexão quanto ao problema e aos objetivos do estudo, bem como, uma apresentação de algumas recomendações para futuros estudos.

Interactions between fiscal and monetary policy

Mestrado em Economia Monetária e Financeira

An assessment of biological and population parameters of the Common whelk, Buccinum undatum (L.) in the region of the North West Irish whelk fishery

The Common whelk, Buccinum undatum (L.) is a conspicuous benthic scavenger in Irish waters, and is a valuable fisheries resource in South East Ireland. B. undatum is fished in many parts of its range, and previous studies have shown that certain life history parameters, which vary with location, make this species vulnerable to overexploitation. This makes research into each exploited stock essential to ensure sustainable fisheries management of the species. In 2003, interest in B. undatum as a complementary species in the inshore fishery east of the Inishowen Peninsula, North West Ireland, initiated investigation into fisheries related biological and population aspects of the species in this region. The current study presents estimates of spatial variation and density of the stock, size at age and growth rates, size and age at onset of sexual maturity, and timing of reproductive events in the region of the North West Irish whelk fishery for the period of June 2003 to May 2004. Analysis of variance of the total shell length of whelk landings to the fishery was conducted over spatial scales of fishing pot, fishing string and landings to vessels. Landings varied significantly in shell length at the spatial scale at which whelks are attracted to baited pots, but did not vary significantly over larger spatial scales. Depletion estimates of stock density from fisheries derived Catch per Unit Effort data and a mark re-capture experiment estimate 0.134 - 0.227 whelks per m2. Two independent methods of age determination found similar growth logistics functions for B. undatum.Modal analysis of length frequency distribution of landings to the fishery estimated symptotic length, Leo = 151.64 mm and Brody growth coefficient, K = 0.04. Analysis of the striae in individual opercula, where each stria was found to represent annual growth, estimated Loo = 137.73 mm and K = 0.12. Common whelks in the region of the North West Irish whelk fishery grow slowly and are long-lived, with 19 opercula striae recorded in one individual. Onset of sexual maturity is late, and no sex-specific differences in size or age at maturity were determined in the present study. Males were found to achieve sexual maturity at 83.30 ± 10.77 mm, and 8.9 - 11.1 years of age, and females at 82.62 ± 10.68 mm and 8.8 to 11.1 years of age. Systematic observations of reproductive events, including histological changes to the female ovary and male testis, and changes in the size and mass of body components, suggest that breeding occurred between the autumn and winter months of October and December 2003. Biological aspects of B. undatum in the study region are compared with previous studies from other regions, and discussed in relation to sustainable management of the fishery.

Effects of nutrient foliar sprays containing growth regulators on productivity of peanut (Arachis hypogaea L. cv. Tatu-53)

The effects of the application of a macronutrient foliar spray combined with micronutrients and growth regulators (Unifol) on peanut grown in a soil with high fertility were investigated. A control without fertilizer and a soil fertilization (250 kg/ha) with NPK 9-30-16 were also established. Other treatments were as follows: Unifol fertilizer (18-12 16) applied 23 days after germination: Unifol (18-12-6) applied at the beginning of flowering; Unifol (18-12-6) applied during flowering, and Unifol (18-12-6) applied 23 days after germination plus Unifol (7-23-7) at the beginning of flowering. No significant differences were found amongst treatments, but certain treatments showed higher productivity e given Unifol fertilizer (18-12-6) applied 23 days after germination plus Unifol (7-23-7) at the flower anthesis. In this treatment, the number of pods, weight of seeds and production of seeds were higher. Best production of forage occurred in the treatment receiving soil fertilization.

Thermal biology, activity, and population parameters of Cnemidophorus vacariensis (Squamata, Teiidae), a lizard endemic to southern Brazil

We investigated the following aspects of the biology of a population of Cnemidophorus vacariensis Feltrim & Lema, 2000 during the four seasons: thermal biology, relationship with the thermal environment, daily and seasonal activity, population structure and growth rate. Cnemidophorus vacariensis is restricted to rocky outcrops of the "campos de cima da serra" grasslands on the Araucaria Plateau, southern Brazil, and is currently listed as regionally and nationally threatened with extinction. Data were collected from October 2004 through September 2007 in the state of Rio Grande do Sul. Sampling was conducted randomly from 08:00 a.m. to 6:00 p.m. The capture-mark-recapture method was employed. The lizards were captured by hand, and their cloacal temperature, sex, snout-ventral length (SVL), mass, and the temperature of their microhabitat (substrate temperature and air temperature) were recorded. Individuals were then marked by toe-clipping and released at the site of capture. Body temperatures were obtained for 175 individuals, activity data for 96 individuals, and data on population structure and growth for 59 individuals. All data were obtained monthly, at different times of the day. Cnemidophorus vacariensis average body temperature was 23.84ºC, ranging between 9.6 and 38.2ºC. Temperatures ranged between 21 and 29ºC. The correlation between external heat sources, substrate and air were positive and significant and there was a greater correlation between lizard's temperature and the temperature of the substrate (tigmothermic species). The relatively low body temperatures of individuals are associated with the climate of their environment (altitude up to 1,400 m), with large variations in temperature throughout the day and the year, and low temperatures in winter. The average body temperature observed for C. vacariensis was low when compared with that of phylogenetically related species, suggesting that the thermal biology of this species reflects adaptations to the temperate region where it lives. The monthly rates of activity of lizards were related to monthly variations in the ambient temperatures. Our data suggest that the daily and seasonal activity of C. vacariensis result from the interaction between two factors: changes in the environment temperature and the relationship between individuals and their thermal environment. The population structure of C. vacariensis varied throughout the study period, with maximum biomass in January and maximum density in February (recruitment period). The sex ratio diverged from the expected 1:1. The growth analysis showed a negative relationship between the growth rate of individuals and the SVL, revealing that young individuals grow faster than adults, a typical pattern for short-lived species. The population studied showed a seasonal and cyclical variation associated with the reproductive cycle. The life strategy of C. vacariensis seems to include adaptations to the seasonal variations in temperature, typical of its environment.

Olympic cities and communication

Article published in Greek in the special issue "The Olympic Games: the mega sports and media event" of the National and Kapodistrian University of Athens journal Communication Issues (2004, no.1), discussing the need for establishing a communication model for city-games relations.

Estudi de l'evolució del sòl urbà a la Vall d'Àneu

Aquest treball té com a principal objectiu analitzar l’evolució del sòl urbà als pobles de la Vall d’Àneu, dins l’àmbit del Parc Natural de l’Alt Pirineu. La Vall d’Àneu, situada en el Pirineu axial català, està formda pels municipis de l’Alt Àneu, Espot, Esterri d’Àneu i La Guingueta d’Àneu, i amb un total de 24 poblacions, totes elles per sota la cota de 1500 m. A mitjans del segle passat, el conjunt de pobles de la Vall mostraven una homogeneïtat envers la seva grandaria i distribució, on l’alçada no era un factor determinant. En les darreres dècades, la Vall d’Àneu ha experimentat un creixement demogràfic i econòmic, basat en el sector serveis (estacions d’esquí, turisme rural, esports d’aventura, etc.). Aquest gir econòmic ha desencadenat un creixmenet de les poblacions, accentuat en els últims anys. Aquest no ha estat homogeni, sinó que s’ha focalitzat en determinades zones segons el període. Així, en els darrers anys, aquest creixement s’ha centrat en els pobles propers a les pistes d’esquí i segons les previsions del PTPAPiA per l’any 2026, la tendència seguirà sent la mateixa.

An 40Ar/39Ar, Rb/Sr, and stable isotope study of micas in low-grade fold-and-thrust belt: An example from the Swiss Helvetic Alps

White micas in carbonate-rich tectonites and a few other rock types of large thrusts in the Swiss Helvetic fold-and-thrust belt have been analyzed by Ar-40/Ar-39 and Rb/Sr techniques to better constrain the timing of Alpine deformation for this region. Incremental Ar-40/Ar-39 heating experiments of 25 weakly metamorphosed (anchizone to low greenschist) samples yield plateau and staircase spectra. We interpret most of the staircase release spectra result from variable mixtures of syntectonic (neoformed) and detrital micas. The range in dates obtained within individual spectra depends primarily on the duration of mica nucleation and growth, and relative proportions of neoformed and detrital mica. Rb/Sr analyses of 12 samples yield dates of ca. 10-39 Ma (excluding one anomalously young sample). These dates are slightly younger than the Ar-40/Ar-39 total gas dates obtained for the same samples. The Rb/ Sr dates were calculated using initial Sr-87/Sr-86 ratios obtained from the carbonate-dominated host rocks, which are higher than normal Mesozoic carbonate values due to exchange with fluids of higher Sr-87/Sr-86 ratios (and lower O-18/O-16 ratios). Model dates calculated using Sr-87/Sr-86 values typical of Mesozoic marine carbonates more closely approximate the Ar-40/Ar-39 total gas dates for most of the samples. The similarities of Rb/Sr and Ar-40/Ar-39 total gas dates are consistent with limited amounts of detrital mica in the samples. The delta(18)O values range from 24-15%. (VSMOW) for 2-6 mum micas and 27-16parts per thousand for the carbonate host rocks. The carbonate values are significantly lower than their protolith values due to localized fluid-rock interaction and fluid flow along most thrust surfaces. Although most calcite-mica pairs are not in oxygen isotope equilibrium at temperatures of ca. 200-400 degreesC, their isotopic fractionations are indicative of either 1) partial exchange between the minerals and a common external fluid, or 2) growth or isotopic exchange of the mica with the carbonate after the carbonate had isotopically exchanged with an external fluid. The geological significance of these results is not easily or uniquely determined, and exemplifies the difficulties inherent in dating very fine-grained micas of highly deformed tectonites in low-grade metamorphic terranes. Two generalizations can be made regarding the dates obtained from the Helvetic thrusts: 1) samples from the two highest thrusts (Mt. Gond and Sublage) have all of their Ar-40/Ar-39 steps above 20 Ma, and 2) most samples from the deepest Helvetic thrusts have steps (often accounting for more than 80% of Ar-39 release) between 15 and 25 Ma. These dates are consistent with the order of thrusting in the foreland-imbricating system and increase proportions of neoformed to detrital mica in the more metamorphosed hinterland and deeply buried portions of the nappe pile. Individual thrusts accommodated the majority of their displacement during their initial incorporation into the foreland-imbricating system, and some thrusts remained active or were reactivated down to 15 Ma.

Anti-doping testing at the 2008 European football championship.

Big sports events like the 2008 European Football Championship are a challenge for anti-doping activities, particularly when the sports event is hosted by two different countries and there are two laboratories accredited by the World Anti-Doping Agency. This challenges the logistics of sample collection as well as the chemical analyses, which must be carried out timeously. The following paper discusses the handling of whereabouts information for each athlete and the therapeutic use exemption system, experiences in sample collection and transportation of blood and urine samples, and the results of the chemical analysis in two different accredited laboratories. An overview of the analytical results of blood profiling and growth hormone testing in comparison with the distribution of the normal population is also presented.

Waddlia chondrophila Infects and Multiplies in Ovine Trophoblast Cells Stimulating an Inflammatory Immune Response.

BACKGROUND: Waddlia chondrophila (W. chondrophila) is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus). This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity. METHODOLOGY/PRINCIPAL FINDINGS: Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i.) and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways. CONCLUSIONS/SIGNIFICANCE: W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

Threshold Effects of Dismissal Protection Regulation and the Emergence of Temporary Work Agencies

Labour market regulations aimed at enhancing job-security are dominant in several OECD countries. These regulations seek to reduce dismissals of workers and fluctuations in employment. The main theoretical contribution is to gauge the effects of such regulations on labour demand across establishment sizes. In order to achieve this, we investigate an optimising model of labour demand under uncertainty through the application of real option theory. We also consider other forms of employment which increase the flexibility of the labour market. In particular, we are modelling the contribution of temporary employment agencies (Zeitarbeit) allowing for quick personnel adjustments in client firms. The calibration results indicate that labour market rigidities may be crucial for understanding sluggishness in firms´ labour demand and the emergence and growth of temporary work.