Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression

Background: Gamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA) osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo. Methods: Established C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD) counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR. Results: GLA caused a significant decrease in tumour size (75 +/- 8.8%) and reduced MVD by 44 +/- 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF) (71 +/- 16%) and the VEGF receptor Flt1 (57 +/- 5.8%) but not Flk1. Expression of ERK1/2 was also reduced by 27 +/- 7.7% and 31 +/- 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2) was reduced by 35 +/- 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 +/- 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 +/- 18%) while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 +/- 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 +/- 7.3%) while p21 remained unchanged. The expression of p53 was increased (44 +/- 16%) by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 +/- 11%) of BrdU incorporation into the tumour in vivo. Conclusion: Overall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein expression of VEGF, Flt1, ERK1, ERK2, MMP2, Cyclin D1, pRb, p53 and p27. Combination therapy using drugs with other, complementary targets and GLA could lead to gains in treatment efficacy in this notoriously difficult to treat tumour.

Long-term oscillations in the sleep/wake cycle of infants

The development of circadian sleep-wakefulness rhythm was investigated by a longitudinal study of six normal infants. We propose an entropy based measure for the sleep/wake cycle fragmentation. Our results confirm that the sleep/wake cycle fragmentation and the sleep/wake ratio decrease, while the circadian power increases during the maturation process of infants. In addition to these expected linear trends in the variables devised to quantify sleep consolidation, circadian power and sleep/wake ratio, we found that they present infradian rhythms in the monthly range. (C) 2009 Elsevier B.V. All rights reserved.

Minimum cycle cover and Chinese postman problems on mixed graphs with bounded tree-width

Let M = (V, E, A) be a mixed graph with vertex set V, edge set E and arc set A. A cycle cover of M is a family C = {C(1), ... , C(k)} of cycles of M such that each edge/arc of M belongs to at least one cycle in C. The weight of C is Sigma(k)(i=1) vertical bar C(i)vertical bar. The minimum cycle cover problem is the following: given a strongly connected mixed graph M without bridges, find a cycle cover of M with weight as small as possible. The Chinese postman problem is: given a strongly connected mixed graph M, find a minimum length closed walk using all edges and arcs of M. These problems are NP-hard. We show that they can be solved in polynomial time if M has bounded tree-width. (C) 2008 Elsevier B.V. All rights reserved.

A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system

The aim of this study was to evaluate the anti-tumor activity of Amblyomin-X, a serine protease Kunitz-type inhibitor. Amblyomin-X induced tumor mass regression and decreased number of metastatic events in a B16F10 murine melanoma model. Alterations on expression of several genes related to cell cycle were observed when two tumor cell lines were treated with Amblyomin-X. PSMB2, which encodes a proteasome subunit, was differentially expressed, in agreement to inhibition of proteasomal activity in both cell lines. In conclusion, our results indicate that Amblyomin-X selectively acts on tumor cells by inducing apoptotic cell death, possibly by targeting the ubiquitin-proteasome system. (C) 2010 Elsevier Ltd. All rights reserved.

Thermoset matrix reinforced with sisal fibers: Effect of the cure cycle on the properties of the biobased composite

Thermoset phenolic composites reinforced with sisal fibers were prepared to optimize the cure step. In the present study, processing parameters such as pressure, temperature, and time interval were varied to control the vaporization of the water generated as a byproduct during the crosslinking reaction. These molecules can vaporize forming voids, which in turn affect the final material properties. The set of results on impact strength revealed that the application of higher pressure before the gel point of the phenolic matrix produced composites with better properties. The SEM images showed that the cure cycle corresponding to the application of higher values of molding pressure at the gel point of the phenolic resin led to the reduction of voids in the matrix. In addition, the increase in the molding pressure during the cure step increased the resin interdiffusion. Better filling of the fiber channels decreased the possibility of water molecules diffusing through the internal spaces of the fibers. These molecules then diffused mainly through the bulk of the thermoset matrix, which led to a decrease in the water diffusion coefficient (D) at all three temperatures (25, 55 and 70 degrees C) considered in the experiments. (C) 2009 Elsevier Ltd. All rights reserved.

Road Design for Future Maintenance : Life-cycle Cost Analyses for Road Barriers

The cost of a road construction over its service life is a function of design, quality of construction as well as maintenance strategies and operations. An optimal life-cycle cost for a road requires evaluations of the above mentioned components. Unfortunately, road designers often neglect a very important aspect, namely, the possibility to perform future maintenance activities. Focus is mainly directed towards other aspects such as investment costs, traffic safety, aesthetic appearance, regional development and environmental effects. This doctoral thesis presents the results of a research project aimed to increase consideration of road maintenance aspects in the planning and design process. The following subgoals were established: Identify the obstacles that prevent adequate consideration of future maintenance during the road planning and design process; and Examine optimisation of life-cycle costs as an approach towards increased efficiency during the road planning and design process. The research project started with a literature review aimed at evaluating the extent to which maintenance aspects are considered during road planning and design as an improvement potential for maintenance efficiency. Efforts made by road authorities to increase efficiency, especially maintenance efficiency, were evaluated. The results indicated that all the evaluated efforts had one thing in common, namely ignorance of the interrelationship between geometrical road design and maintenance as an effective tool to increase maintenance efficiency. Focus has mainly been on improving operating practises and maintenance procedures. This fact might also explain why some efforts to increase maintenance efficiency have been less successful. An investigation was conducted to identify the problems and difficulties, which obstruct due consideration of maintainability during the road planning and design process. A method called “Change Analysis” was used to analyse data collected during interviews with experts in road design and maintenance. The study indicated a complex combination of problems which result in inadequate consideration of maintenance aspects when planning and designing roads. The identified problems were classified into six categories: insufficient consulting, insufficient knowledge, regulations and specifications without consideration of maintenance aspects, insufficient planning and design activities, inadequate organisation and demands from other authorities. Several urgent needs for changes to eliminate these problems were identified. One of the problems identified in the above mentioned study as an obstacle for due consideration of maintenance aspects during road design was the absence of a model for calculating life-cycle costs for roads. Because of this lack of knowledge, the research project focused on implementing a new approach for calculating and analysing life-cycle costs for roads with emphasis on the relationship between road design and road maintainability. Road barriers were chosen as an example. The ambition is to develop this approach to cover other road components at a later stage. A study was conducted to quantify repair rates for barriers and associated repair costs as one of the major maintenance costs for road barriers. A method called “Case Study Research Method” was used to analyse the effect of several factors on barrier repairs costs, such as barrier type, road type, posted speed and seasonal effect. The analyses were based on documented data associated with 1625 repairs conducted in four different geographical regions in Sweden during 2006. A model for calculation of average repair costs per vehicle kilometres was created. Significant differences in the barrier repair costs were found between the studied barrier types. In another study, the injuries associated with road barrier collisions and the corresponding influencing factors were analysed. The analyses in this study were based on documented data from actual barrier collisions between 2005 and 2008 in Sweden. The result was used to calculate the cost for injuries associated with barrier collisions as a part of the socio-economic cost for road barriers. The results showed significant differences in the number of injuries associated with collisions with different barrier types. To calculate and analyse life-cycle costs for road barriers a new approach was developed based on a method called “Activity-based Life-cycle Costing”. By modelling uncertainties, the presented approach gives a possibility to identify and analyse factors crucial for optimising life-cycle costs. The study showed a great potential to increase road maintenance efficiency through road design. It also showed that road components with low investment costs might not be the best choice when including maintenance and socio-economic aspects. The difficulties and problems faced during the collection of data for calculating life-cycle costs for road barriers indicated a great need for improving current data collecting and archiving procedures. The research focused on Swedish road planning and design. However, the conclusions can be applied to other Nordic countries, where weather conditions and road design practices are similar. The general methodological approaches used in this research project may be applied also to other studies.

Decomposing Consumer Wealth Effects: Evidence on the Role of Real Estate Assets Following the Wealth Cycle of 1990-2002

During the period of 1990-2002 US households experienced a dramatic wealth cycle, induced by a 369% appreciation in the value of real per capita liquid stock market assets followed by a 55% decline. However, consumer spending in real terms continued to rise throughout this period. Using data from 1990-2005, traditional life-cycle approaches to estimating macroeconomic wealth effects confront two puzzles: (i) econometric evidence of a stable cointegrating relationship among consumption, income, and wealth is weak at best; and (ii) life-cycle models that rely on aggregate measures of wealth cannot explain why consumption did not collapse when the value of stock market assets declined so dramatically. We address both puzzles by decomposing wealth according to the liquidity of household assets. We find that the significant appreciation in the value of real estate assets that occurred after the peak of the wealth cycle helped sustain consumer spending from 2001 to 2005.

Cytotoxicity of Diepoxybutane and Epichlorohydrin in Relation to Stages of the Cell Cycle

Work conducted in the Millard Biochemistry Research Laboratory examines the dual nature of molecules as carcinogens and anti-tumor agents through the molecular mechanisms of duplex DNA damage by bifunctional alkylating agents. Diepoxybutane (DEB) and epichlorohydrin (ECH) are polar molecules that form covalent DNA interstrand lesions by cross-linking the N7 position of deoxyguanosine residues. A recent experiment indicated that ECH preferentially targets nuclear DNA over mitochondrial DNA, whereas DEB shows similar rates of lesion formation for both loci. It was concluded that preferential targeting of nuclear DNA results from relatively poor uptake of ECH across the mitochondrial membrane. The objective of my honors research was to determine if the cytotoxicities of DEB and ECH vary according to the presence of the nuclear envelope in 6C2 chicken erythro-progenitor cells. The cytotoxicity of DEB and ECH was compared between cells randomly distributed throughout the cell cycle (Go/G, and S » G2/M) and cells enriched in G2/M stages. Results indicated that ECH is more cytotoxic than DEB in both unsynchronized control 6C2 cells and synchronized 6C2 cells enriched in G2/M stages of the cell cycle. Treatment with either bifunctional alkylating agent induced greater cytotoxicity in 6C2 cells enriched in G2/M stages than in unsynchronized control 6C2 cells, suggesting that the presence of the nuclear envelope-or any plasma membrane-may inhibit the reactivity of DEB and ECH.

Business cycle and bank loan portfolio performance : empirical evidence from brazilian banks

Este trabalho estuda os efeitos do crescimento econômico e da taxas de juros sobre o desempenho de carteiras de empréstimo dos bancos comerciais brasileiros no período de 2000 a 2010. Os resultados empíricos mostram que o crescimento econômico é o principal "driver" para o desempenho da carteira de crédito. Não foram encontradas evidências estatísticas sginificativas de mudanças na taxa de juros sobre o desempenho das carteiras de empréstimos. Além disso, há evidências empíricas de que o impacto do crescimento econômico sobre o desempenho da carteria de crédito tem efeito defasado de 2 trimestres. Por fim, os resultados mostram que alterações de PIB impactam de forma mais significativa o desempenho da carteira de crédito dos bancos comerciais brasileiros maiores. Devido ao efeito multiplicador do mercado de crédito, quanto maior o banco, maior a expansão relativa de sua carteira de crédito e, conseqüentemente a taxa de inadimplência da carteira, que é agravada pela concentração do mercado de crédito no Brasil.

On the welfare costs of business-cycle fluctuations and economic-growth variation in the 20th century

Lucas (1987) has shown a surprising result in business-cycle research: the welfare cost of business cycles are very small. Our paper has several original contributions. First, in computing welfare costs, we propose a novel setup that separates the effects of uncertainty stemming from business-cycle fluctuations and economic-growth variation. Second, we extend the sample from which to compute the moments of consumption: the whole of the literature chose primarily to work with post-WWII data. For this period, actual consumption is already a result of counter-cyclical policies, and is potentially smoother than what it otherwise have been in their absence. So, we employ also pre-WWII data. Third, we take an econometric approach and compute explicitly the asymptotic standard deviation of welfare costs using the Delta Method. Estimates of welfare costs show major differences for the pre-WWII and the post-WWII era. They can reach up to 15 times for reasonable parameter values -β=0.985, and ∅=5. For example, in the pre-WWII period (1901-1941), welfare cost estimates are 0.31% of consumption if we consider only permanent shocks and 0.61% of consumption if we consider only transitory shocks. In comparison, the post-WWII era is much quieter: welfare costs of economic growth are 0.11% and welfare costs of business cycles are 0.037% - the latter being very close to the estimate in Lucas (0.040%). Estimates of marginal welfare costs are roughly twice the size of the total welfare costs. For the pre-WWII era, marginal welfare costs of economic-growth and business- cycle fluctuations are respectively 0.63% and 1.17% of per-capita consumption. The same figures for the post-WWII era are, respectively, 0.21% and 0.07% of per-capita consumption.

On the welfare costs of business-cycle fluctuations and economic-growth variation in the 20th century

Lucas(1987) has shown a surprising result in business-cycle research: the welfare cost of business cycles are very small. Our paper has several original contributions. First, in computing welfare costs, we propose a novel setup that separates the effects of uncertainty stemming from business-cycle uctuations and economic-growth variation. Second, we extend the sample from which to compute the moments of consumption: the whole of the literature chose primarily to work with post-WWII data. For this period, actual consumption is already a result of counter-cyclical policies, and is potentially smoother than what it otherwise have been in their absence. So, we employ also pre-WWII data. Third, we take an econometric approach and compute explicitly the asymptotic standard deviation of welfare costs using the Delta Method. Estimates of welfare costs show major diferences for the pre-WWII and the post-WWII era. They can reach up to 15 times for reasonable parameter values = 0:985, and = 5. For example, in the pre-WWII period (1901-1941), welfare cost estimates are 0.31% of consumption if we consider only permanent shocks and 0.61% of consumption if we consider only transitory shocks. In comparison, the post-WWII era is much quieter: welfare costs of economic growth are 0.11% and welfare costs of business cycles are 0.037% the latter being very close to the estimate in Lucas (0.040%). Estimates of marginal welfare costs are roughly twice the size of the total welfare costs. For the pre-WWII era, marginal welfare costs of economic-growth and business-cycle uctuations are respectively 0.63% and 1.17% of per-capita consumption. The same gures for the post-WWII era are, respectively, 0.21% and 0.07% of per-capita consumption.

Aggregate uncertainty, disappointment aversion and the business cycle

We investigate the eff ect of aggregate uncertainty shocks on real variables. More speci fically, we introduce a shock in the volatility of productivity in an RBC model with long-run volatility risk and preferences that exhibit generalised disappointment aversion. We find that, when combined with a negative productivity shock, a volatility shock leads to further decline in real variables, such as output, consumption, hours worked and investment. For instance, out of the 2% decrease in output as a result of both shocks, we attribute 0.25% to the e ffect of an increase in volatility. We also fi nd that this e ffect is the same as the one obtained in a model with Epstein-Zin- Weil preferences, but higher than that of a model with expected utility. Moreover, GDA preferences yield superior asset pricing results, when compared to both Epstein-Zin-Weil preferences and expected utility.

The exhaustion of the brazilian growth cycle

O Brasil recebeu muita atenção na última década, sua ascensão ao status de grande potência e uma das maiores economias mundiais tem sido enfatizada. No entanto, existem sinais de que essa prosperidade recente está chegando ao fim, sugerindo que houve um excesso de otimismo em relação ao aparente sucesso econômico do país e a possiblidade de crescimento contínuo. O Brasil focou na exportação de produtos primários e em um modelo de crescimento baseado no consumo, que se tornaram as locomotivas da economia. Uma pujante economia mundial demandando produtos primários e um amplo e inexplorado mercado interno ajudam a explicar o crescimento brasileiro na década passada. Não obstante, esse modelo apresenta diversas limitações. A inflação, mais uma vez, está em alta e os gargalos que impedem o desenvolvimento econômico não foram resolvidos. O objetivo desta dissertação é demonstrar que o atual ciclo de crescimento da economia brasileira está no fim. Dados de diversas fontes, nacionais e internacionais, serão usados para indicar que, novamente, o país teve um crescimento efêmero e não possui uma estrutura econômica adequada para promover o desenvolvimento de longo prazo. Uma breve análise dos fundamentos econômicos, clima de negócios e outros tópicos relacionados ao crescimento e desenvolvimento será apresentada, articulando dados e fatos para encontrar causas e explicações para a atual inversão de tendência econômica.