The Silencing of N-myc Downstream-Regulated Gene-1 in an Orthotopic Pancreatic Cancer Model Leads to More Aggressive Tumor Growth and Metastases

BACKGROUND: The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence. METHODS: Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis. RESULTS: The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015). CONCLUSION: NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.

Growth for Europe – Is the Juncker Plan the answer? EPC Discussion Paper, 20 March 2015

Executive Summary. The euro area is still suffering from low growth and high unemployment. For the recovery to become a reality, there needs to be a balance between fiscal discipline, supply side improvements and actions aimed at stimulating demand and growth. Increasing investment, both private and public, are important components in overcoming the recession. This becomes especially clear when comparing investment dynamics during the crisis with pre-crisis levels. Total investment is still much lower than before the crisis and public investment is well below its pre-crisis peak as well. In late November 2014, European Commission President Jean-Claude Juncker submitted a long-awaited proposal for a European Investment Plan that aims to stimulate private investment. Apart from the creation of the new European Fund for Strategic Investment (EFSI), through which private investors will receive public guarantees, the investment plan also aims to provide project assistance and improve the Single Market by removing sector-specific or other financial barriers to investment. While generally perceived as a first positive step towards increasing private investment, some commentators have expressed reservations about the plan. These include, among others, the lack of fresh money for the initial contributions to EFSI. Since a substantial amount of these contributions is reshuffled from other places in the European budget, the question was raised whether EFSI can fund additional projects or just replicates investment projects that would have happened without the plan. Other criticism relates to the high estimate of the expected leverage ratio of 1:15, and to the risk that the plan will only have a limited impact on stressed economies. The Juncker Plan addresses private investment, but so far there really is no clear strategy to stimulate productive public investment on the European and national level. Countries with fiscal space are reluctant to engage in higher spending, while those willing and in need of it the most are restricted by the rules. Member States and the Commission should therefore discuss options for further improving the euro area's economic governance. In addition to urging countries with fiscal space to increase investing in national public goods, investment could be treated with budget flexibility. One could, for instance, upgrade the importance of public investment in the European Semester. Additional deficit granted for public investment purposes could be attached to certain Country-Specific Recommendations. Another solution would be to allow some form of budget flexibility, such as the formulation of a new Golden Rule for productive public investment becoming part of the Stability and Growth Pact's application. Besides relying on a larger amount of flexibility in the rules, the Financial Transaction Tax (FTT) could be another solution to fund investment in European public goods. It will also be necessary to overcome the mistrust among Member States that is preventing further action. The political bargain of stronger conditionality, such as through contractual arrangements, could improve the situation. Increased trust will also be an important condition for tackling long-reaching economic governance reforms such as the creation of a Fiscal Capacity, which could take the form of a macroeconomic shock insurance. Such a Fiscal Capacity could make a real difference in providing the necessary funding to maintain productive public investment, even in times of deep recessions. The proposals presented do not attempt to be conclusive, but shall rather be an input for a wider debate on how to increase growth and employment in Europe. The paper draws heavily on the discussion of a Workshop on Growth and Investment, which the European Policy Centre (EPC) hosted on 10 December 2014 under Chatham-House Rule, with a group of economists and representatives from the European institutions.

Effect of nitrogen supply on leaf appearance, leaf growth, leaf nitrogen economy and photosynthetic capacity in maize (Zea mays L.)

Leaf area growth and nitrogen concentration per unit leaf area, N-a (g m(-2) N) are two options plants can use to adapt to nitrogen limitation. Previous work indicated that potato (Solanum tuberosum L.) adapts the size of leaves to maintain Na and photosynthetic capacity per unit leaf area. This paper reports on the effect of N limitation on leaf area production and photosynthetic capacity in maize, a C4 cereal. Maize was grown in two experiments in pots in glasshouses with three (0.84-6.0 g N pot(-1)) and five rates (0.5-6.0 g pot(-1)) of N. Leaf tip and ligule appearance were monitored and final individual leaf area was determined. Changes with leaf age in leaf area, leaf N content and light-saturated photosynthetic capacity, P a,, were measured on two leaves per plant in each experiment. The final area of the largest leaf and total plant leaf area differed by 16 and 29% from the lowest to highest N supply, but leaf appearance rate and the duration of leaf expansion were unaffected. The N concentration of expanding leaves (N-a or %N in dry matter) differed by at least a factor 2 from the lowest to highest N supply. A hyperbolic function described the relation between P-max and N-a. The results confirm the 'maize strategy': leaf N content, photosynthetic capacity, and ultimately radiation use efficiency is more sensitive to nitrogen limitation than are leaf area expansion and light interception. The generality of the findings is discussed and it is suggested that at canopy level species showing the 'potato strategy' can be recognized from little effect of nitrogen supply on radiation use efficiency, while the reverse is true for species showing the 'maize strategy' for adaptation to N limitation. (c) 2004 Elsevier B.V. All rights reserved.

Use of farmer-prioritized vertisol management options for enhanced green gram and tomato production in central Kenya

Green grams (Phaseolus aures L.) and tomato (Solanum lycopersicum L) are widely grown in the vertisols of the Mwea Irrigation Scheme alongside the rice fields. Green grams can fix nitrogen (biological nitrogen fixation) and are grown for its highly nutritious and curative seeds while tomatoes are grown for its fruit rich in fibres, minerals and vitamins. The two can be prepared separately or together in a variety of ways including raw salads and/or cooked/fried. They together form significant delicacies consumed with rice which is the major cash crop grown in the black cotton soils. The crops can grow well in warm conditions but tomato is fairly adaptable except under excessive humidity and temperatures that reduce yields. Socio-economic prioritization by the farming community and on-farm demonstrations of soil management options were instituted to demonstrate enhanced green gram and tomato production in vertisol soils of lower parts of Kirinyaga County (Mwea East and Mwea West districts). Drainage management was recognized by the farming community as the best option although a reduced number of farmers used drainage and furrows/ridges, manure, fertilizer and shifting options with reducing order of importance. Unavailability of labour and/or financial cost for instituting these management options were indicated as major hindrances to adopt the yield enhancing options. Labour force was contributed to mainly by the family alongside hiring (64.2%) although 28% and 5.2% respectively used hired or family labour alone. The female role in farming activities dominated while the male role was minimal especially at weeding. The youth role remained excessively insignificant and altogether absent at marketing. Despite the need for labour at earlier activities (especially when management options needed to be instituted) it was at the marketing stage that this force was directed. Soils were considered infertile by 60% but 40% indicated that their farms had adequate fertility. Analysis showed that ridging and application of farm yard manure and fertilizer improved fertility, crop growth and income considerably. Phosphate and zinc enhancement reduced alkalinity and sodicity. Green gram and tomato yields increased under ridges and farm yard manure application by 17-25% which significantly enhanced household income.

Time domain decomposition for European options in financial modelling

Finance is one of the fastest growing areas in modern applied mathematics with real world applications. The interest of this branch of applied mathematics is best described by an example involving shares. Shareholders of a company receive dividends which come from the profit made by the company. The proceeds of the company, once it is taken over or wound up, will also be distributed to shareholders. Therefore shares have a value that reflects the views of investors about the likely dividend payments and capital growth of the company. Obviously such value will be quantified by the share price on stock exchanges. Therefore financial modelling serves to understand the correlations between asset and movements of buy/sell in order to reduce risk. Such activities depend on financial analysis tools being available to the trader with which he can make rapid and systematic evaluation of buy/sell contracts. There are other financial activities and it is not an intention of this paper to discuss all of these activities. The main concern of this paper is to propose a parallel algorithm for the numerical solution of an European option. This paper is organised as follows. First, a brief introduction is given of a simple mathematical model for European options and possible numerical schemes of solving such mathematical model. Second, Laplace transform is applied to the mathematical model which leads to a set of parametric equations where solutions of different parametric equations may be found concurrently. Numerical inverse Laplace transform is done by means of an inversion algorithm developed by Stehfast. The scalability of the algorithm in a distributed environment is demonstrated. Third, a performance analysis of the present algorithm is compared with a spatial domain decomposition developed particularly for time-dependent heat equation. Finally, a number of issues are discussed and future work suggested.

Bioeconomic modelling of woody regrowth carbon offset options in productive grazing systems

Agricultural land has been identified as a potential source of greenhouse gas emissions offsets through biosequestration in vegetation and soil. In the extensive grazing land of Australia, landholders may participate in the Australian Government’s Emissions Reduction Fund and create offsets by reducing woody vegetation clearing and allowing native woody plant regrowth to grow. This study used bioeconomic modelling to evaluate the trade-offs between an existing central Queensland grazing operation, which has been using repeated tree clearing to maintain pasture growth, and an alternative carbon and grazing enterprise in which tree clearing is reduced and the additional carbon sequestered in trees is sold. The results showed that ceasing clearing in favour of producing offsets produces a higher net present value over 20 years than the existing cattle enterprise at carbon prices, which are close to current (2015) market levels (~$13 t–1 CO2-e). However, by modifying key variables, relative profitability did change. Sensitivity analysis evaluated key variables, which determine the relative profitability of carbon and cattle. In order of importance these were: the carbon price, the gross margin of cattle production, the severity of the tree–grass relationship, the area of regrowth retained, the age of regrowth at the start of the project, and to a lesser extent the cost of carbon project administration, compliance and monitoring. Based on the analysis, retaining regrowth to generate carbon income may be worthwhile for cattle producers in Australia, but careful consideration needs to be given to the opportunity cost of reduced cattle income.

Growth of boehmite nanofibers by assembling nanoparticles with surfactant micelles

It is known that boehmite (AlOOH) nanofibers formed in the presence of nonionic poly(ethylene oxide) (PEO) surfactant at 373 K. A novel approach is proposed in this study for the growth of the boehmite nanofibers: when fresh aluminum hydrate precipitate was added at regular interval to initial mixture of boehmite and PEO surfactant at 373 K, the nanofibers grow from 40 to 50 nm long to over 100 nm. It is believed that the surfactant micelles play an important role in the nanofiber growth: directing the assembly of aluminum hydrate particles through hydrogen bonding with the hydroxyls on the surface of aluminum hydrate particles. Meanwhile a gradual improvement in the crystallinity of the fibers during growth is observed and attributed to the Ostwald ripening process. This approach allows us to precisely control the size and morphology of boehmite nanofibers using soft chemical methods and could be useful for low temperature, aqueous syntheses of other oxide nanomaterials with tailorable structural specificity such as size, dimension and morphology.