Directing migration of endothelial progenitor cells with applied DC electric fields

Naturally-occurring, endogenous electric fields (EFs) have been detected at skin wounds, damaged tissue sites and vasculature. Applied EFs guide migration of many types of cells, including endothelial cells to migrate directionally. Homing of endothelial progenitor cells (EPCs) to an injury site is important for repair of vasculature and also for angiogenesis. However, it has not been reported whether EPCs respond to applied EFs. Aiming to explore the possibility to use electric stimulation to regulate the progenitor cells and angiogenesis, we tested the effects of direct-current (DC) EFs on EPCs. We first used immunofluorescence to confirm the expression of endothelial progenitor markers in three lines of EPCs. We then cultured the progenitor cells in EFs. Using time-lapse video microscopy, we demonstrated that an applied DC EF directs migration of the EPCs toward the cathode. The progenitor cells also align and elongate in an EF. Inhibition of vascular endothelial growth factor (VEGF) receptor signaling completely abolished the EF-induced directional migration of the progenitor cells. We conclude that EFs are an effective signal that guides EPC migration through VEGF receptor signaling in vitro. Applied EFs may be used to control behaviors of EPCs in tissue engineering, in homing of EPCs to wounds and to an injury site in the vasculature.

Pharmaceutical process optimisation of bulk lyophilisates:implications of powder handling

Lyophilisation or freeze drying is the preferred dehydrating method for pharmaceuticals liable to thermal degradation. Most biologics are unstable in aqueous solution and may use freeze drying to prolong their shelf life. Lyophilisation is however expensive and has seen lots of work aimed at reducing cost. This thesis is motivated by the potential cost savings foreseen with the adoption of a cost efficient bulk drying approach for large and small molecules. Initial studies identified ideal formulations that adapted well to bulk drying and further powder handling requirements downstream in production. Low cost techniques were used to disrupt large dried cakes into powder while the effects of carrier agent concentration were investigated for powder flowability using standard pharmacopoeia methods. This revealed superiority of crystalline mannitol over amorphous sucrose matrices and established that the cohesive and very poor flow nature of freeze dried powders were potential barriers to success. Studies from powder characterisation showed increased powder densification was mainly responsible for significant improvements in flow behaviour and an initial bulking agent concentration of 10-15 %w/v was recommended. Further optimisation studies evaluated the effects of freezing rates and thermal treatment on powder flow behaviour. Slow cooling (0.2 °C/min) with a -25°C annealing hold (2hrs) provided adequate mechanical strength and densification at 0.5-1 M mannitol concentrations. Stable bulk powders require powder transfer into either final vials or intermediate storage closures. The targeted dosing of powder formulations using volumetric and gravimetric powder dispensing systems where evaluated using Immunoglobulin G (IgG), Lactate Dehydrogenase (LDH) and Beta Galactosidase models. Final protein content uniformity in dosed vials was assessed using activity and protein recovery assays to draw conclusions from deviations and pharmacopeia acceptance values. A correlation between very poor flowability (p<0.05), solute concentration, dosing time and accuracy was revealed. LDH and IgG lyophilised in 0.5 M and 1 M mannitol passed Pharmacopeia acceptance values criteria with 0.1-4 while formulations with micro collapse showed the best dose accuracy (0.32-0.4% deviation). Bulk mannitol content above 0.5 M provided no additional benefits to dosing accuracy or content uniformity of dosed units. This study identified considerations which included the type of protein, annealing, cake disruption process, physical form of the phases present, humidity control and recommended gravimetric transfer as optimal for dispensing powder. Dosing lyophilised powders from bulk was demonstrated as practical, time efficient, economical and met regulatory requirements in cases. Finally the use of a new non-destructive technique, X-ray microcomputer tomography (MCT), was explored for cake and particle characterisation. Studies demonstrated good correlation with traditional gas porosimetry (R2 = 0.93) and morphology studies using microscopy. Flow characterisation from sample sizes of less than 1 mL was demonstrated using three dimensional X-ray quantitative image analyses. A platinum-mannitol dispersion model used revealed a relationship between freezing rate, ice nucleation sites and variations in homogeneity within the top to bottom segments of a formulation.

The factors affecting the international judgement of the Forint and Zloty in the light of the financial crisis of year 2008

The financial crisis of 2007-2009 has shaken both money and capital markets. Its consequences have not even left European markets untouched and divided spirits in the financial world. In some countries efforts by the monetary policy to protect the national currency throughout the crisis seemed to be ineffective. In the present paper we are investigating the effect of the most important macroeconomic and economic policy factors on the exchange rate of the forint and zloty in the last decade. For an analysis of exchange rates we are relying on some preceding research results based on equilibrium exchange rate theories.

Using the stated preference method for the calculation of social discount rate

The aim of this paper is to build the stated preference method into the social discount rate methodology. The first part of the paper presents the results of a survey about stated time preferences through pair-choice decision situations for various topics and time horizons. It is assumed that stated time preferences differ from calculated time preferences and that the extent of stated rates depends on the time period, and on how much respondents are financially and emotionally involved in the transactions. A significant question remains: how can the gap between the calculation and the results of surveys be resolved, and how can the real time preferences of individuals be interpreted using a social time preference rate. The second part of the paper estimates the social time preference rate for Hungary using the results of the survey, while paying special attention to the pure time preference component. The results suggest that the current method of calculation of the pure time preference rate does not reflect the real attitudes of individuals towards future generations.

On the fundamentals of research and development (R&D) spillovers in competitive markets

Rivals may voluntarily share Research and Development (R&D) results even in the absence of any binding agreements or collusion. In a model where rival firms engage in non-cooperative independent R&D process, we used optimization and game theory analysis to study the equilibrium strategy of the firms. Our work showed that, while minimal spillover is always equilibrium, there may be another equilibrium where firms may reciprocally choose high, sometimes perfect, spillover rates. The incentive for sharing R&D output is based on firms' expectations of learning from their rivals' R&D progress in the future. This leads to strategic complementarities between the firms' choices of spillover rates and thus policy implication follows. ^ Public research agencies can contribute more to social welfare by providing research as public goods. In a non-cooperative public-private research relationship where parallel R&D is conducted, by making its R&D results accessible, the public research agency can stimulate private spillovers, even if there exists rivalry among the private firms who can benefit from such spillovers. ^

The effects of school mobility in pre -assessment grade levels on student performance and school accountability in urban Title I schools

This study examined the effects of student mobility and educational enrollment experiences on academic achievement. The educational progress, school enrollments and transfers of inner-city elementary students were tracked over a four-year period. Student achievement was measured by criterion-referenced reading tests administered in the second semester of the third grade. It further analyzed the degree to which the switch to different basal reading textbooks interrupted the continuity of education thereby contributing to the detrimental effects of intra-district mobility. ^ Mobility histories of 2,913 third grade students were collected to evaluate the number of times each student entered or withdrew from a Miami-Dade County Public School beginning in August 2000 through March 2004, and distinguished between transfers that occurred during the academic school year and those that occurred during summer months. Data were analyzed using Pearson correlations and multiple regressions to determine if school mobility contributed to performance on the Florida Comprehensive Assessment Third Grade Reading Test (FCAT). Transferring from one school to another was found to have a significant negative impact on student test scores. Transfers within the academic school year were more detrimental than transfers that occurred during the summer months. Third grade students who transferred into schools that used the same reading textbook series were found to have significantly higher FCAT reading scores than third graders who transferred into schools that used different reading textbooks. ^ The effects of mobility rates on overall school performance were also examined. Data was collected on 124 Title I elementary schools to determine the degree to which mobility affected school accountability scores. Title I schools with high student mobility rates had significantly lower accountability scores than schools with lower student mobility rates. ^ The results of this study highlight the impact of education and housing policy and imply a need for programs and practices that promote stability in the early elementary years. ^

Evidence of the heterogeneous market hypothesis using wavelet multi -resolution analysis

In finance literature many economic theories and models have been proposed to explain and estimate the relationship between risk and return. Assuming risk averseness and rational behavior on part of the investor, the models are developed which are supposed to help in forming efficient portfolios that either maximize (minimize) the expected rate of return (risk) for a given level of risk (rates of return). One of the most used models to form these efficient portfolios is the Sharpe's Capital Asset Pricing Model (CAPM). In the development of this model it is assumed that the investors have homogeneous expectations about the future probability distribution of the rates of return. That is, every investor assumes the same values of the parameters of the probability distribution. Likewise financial volatility homogeneity is commonly assumed, where volatility is taken as investment risk which is usually measured by the variance of the rates of return. Typically the square root of the variance is used to define financial volatility, furthermore it is also often assumed that the data generating process is made of independent and identically distributed random variables. This again implies that financial volatility is measured from homogeneous time series with stationary parameters. In this dissertation, we investigate the assumptions of homogeneity of market agents and provide evidence for the case of heterogeneity in market participants' information, objectives, and expectations about the parameters of the probability distribution of prices as given by the differences in the empirical distributions corresponding to different time scales, which in this study are associated with different classes of investors, as well as demonstrate that statistical properties of the underlying data generating processes including the volatility in the rates of return are quite heterogeneous. In other words, we provide empirical evidence against the traditional views about homogeneity using non-parametric wavelet analysis on trading data, The results show heterogeneity of financial volatility at different time scales, and time-scale is one of the most important aspects in which trading behavior differs. In fact we conclude that heterogeneity as posited by the Heterogeneous Markets Hypothesis is the norm and not the exception.

Functional near infrared spectroscopy study of language, joint attention and motor skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

The Importance of Dissimilatory Nitrate Reduction to Ammonium (DNRA) in the Nitrogen Cycle of Coastal Ecosystems

Until recently, it was believed that biological assimilation and gaseous nitrogen (N) loss through denitrification were the two major fates of nitrate entering or produced within most coastal ecosystems. Denitrification is often viewed as an important ecosystem service that removes reactive N from the ecosystem. However, there is a competing nitrate reduction process, dissimilatory nitrate reduction to ammonium (DNRA), that conserves N within the ecosystem. The recent application of nitrogen stable isotopes as tracers has generated growing evidence that DNRA is a major nitrogen pathway that cannot be ignored. Measurements comparing the importance of denitrification vs. DNRA in 55 coastal sites found that DNRA accounted for more than 30% of the nitrate reduction at 26 sites. DNRA was the dominant pathway at more than one-third of the sites. Understanding what controls the relative importance of denitrification and DNRA, and how the balance changes with increased nitrogen loading, is of critical importance for predicting eutrophication trajectories. Recent improvements in methods for assessing rates of DNRA have helped refine our understanding of the rates and controls of this process, but accurate measurements in vegetated sediment still remain a challenge.

The Role of Agriculture and Food Consumption in Tropical Conservation

A growing human population, shifting human dietary habits, and climate change are negatively affecting global ecosystems on a massive scale. Expanding agricultural areas to feed a growing population drives extensive habitat loss, and climate change compounds stresses on both food security and ecosystems. Understanding the negative effects of human diet and climate change on agricultural and natural ecosystems provides a context within which potential technological and behavioral solutions can be proposed to help maximize conservation. The purpose of this research was to (1) examine the potential effects of climate change on the suitability of areas for commercial banana plantations in Latin America in the 2050s and how shifts in growing areas could affect protected areas; (2) test the ability of small unmanned aerial vehicles (UAVs) to map productivity of banana plantations as a potential tool for increasing yields and decreasing future plantation expansions; (3) project the effects on biodiversity of increasing rates of animal product consumption in developing megadiverse countries; and (4) estimate the capacity of global pasture biomass production and Fischer-Tropsch hydrocarbon synthesis (IGCC-FT) processing to meet electricity, gasoline and diesel needs. The results indicate that (1) the overall extent of areas suitable for conventional banana cultivation is predicted to decrease by 19% by 2050 because of a hotter and drier climate, but all current banana exporting countries are predicted to maintain some suitable areas with no effects on protected areas; (2) Spatial patterns of NDVI and ENDVI were significantly positively correlated with several metrics of fruit yield and quality, indicating that UAV systems can be used in banana plantations to map spatial patterns of fruit yield; (3) Livestock production is the single largest driver of habitat loss, and both livestock and feedstock production are increasing in developing biodiverse tropical countries. Reducing global animal product consumption should therefore be at the forefront of strategies aimed at reducing biodiversity loss; (4) Removing livestock from global pasture lands and instead utilizing the biomass production could produce enough energy to meet 100% of the electricity, gasoline, and diesel needs of over 40 countries with extensive grassland ecosystems, primarily in tropical developing countries.

Investigation of spatial patterns of ground-water exchange with lakes, using a three-dimensional numerical model

Hydrogeologic variables controlling groundwater exchange with inflow and flow-through lakes were simulated using a three-dimensional numerical model (MODFLOW) to investigate and quantify spatial patterns of lake bed seepage and hydraulic head distributions in the porous medium surrounding the lakes. Also, the total annual inflow and outflow were calculated as a percentage of lake volume for flow-through lake simulations. The general exponential decline of seepage rates with distance offshore was best demonstrated at lower anisotropy ratio (i.e., Kh/Kv = 1, 10), with increasing deviation from the exponential pattern as anisotropy was increased to 100 and 1000. 2-D vertical section models constructed for comparison with 3-D models showed that groundwater heads and seepages were higher in 3-D simulations. Addition of low conductivity lake sediments decreased seepage rates nearshore and increased seepage rates offshore in inflow lakes, and increased the area of groundwater inseepage on the beds of flow-through lakes. Introduction of heterogeneity into the medium decreased the water table and seepage ratesnearshore, and increased seepage rates offshore in inflow lakes. A laterally restricted aquifer located at the downgradient side of the flow-through lake increased the area of outseepage. Recharge rate, lake depth and lake bed slope had relatively little effect on the spatial patterns of seepage rates and groundwater exchange with lakes.

Seawater carbonate chemistry and biological processes during experiments with early life stages of the blue mussel Mytilus edulis, 2010

Several experiments have shown a decrease of growth and calcification of organisms at decreased pH levels. There is a growing interest to focus on early life stages that are believed to be more sensitive to environmental disturbances such as hypercapnia. Here, we present experimental data, acquired in a commercial hatchery, demonstrating that the growth of planktonic mussel (Mytilus edulis) larvae is significantly affected by a decrease of pH to a level expected for the end of the century. Even though there was no significant effect of a 0.25-0.34 pH unit decrease on hatching and mortality rates during the first 2 days of development nor during the following 13-day period prior to settlement, final shells were respectively 4.5±1.3 and 6.0±2.3% smaller at pHNBS~7.8 (pCO2~1100-1200 µatm) than at a control pHNBS of ~8.1 (pCO2~460-640 µatm). Moreover, a decrease of 12.0±5.4% of shell thickness was observed after 15d of development. More severe impacts were found with a decrease of ~0.5 pHNBS unit during the first 2 days of development which could be attributed to a decrease of calcification due to a slight undersaturation of seawater with respect to aragonite. Indeed, important effects on both hatching and D-veliger shell growth were found. Hatching rates were 24±4% lower while D-veliger shells were 12.7±0.9% smaller at pHNBS~7.6 (pCO2~1900 µatm) than at a control pHNBS of ~8.1 (pCO2~540 µatm). Although these results show that blue mussel larvae are still able to develop a shell in seawater undersaturated with respect to aragonite, the observed decreases of hatching rates and shell growth could lead to a significant decrease of the settlement success. As the environmental conditions considered in this study do not necessarily reflect the natural conditions experienced by this species at the time of spawning, future studies will need to consider the whole larval cycle (from fertilization to settlement) under environmentally relevant conditions in order to investigate the potential ecological and economical losses of a decrease of this species fitness in the field.

Radiocarbon age of bottom sediments from the Yenisei Gulf and the Kara Sea

Sedimentation rates and bottom sediment ages were determined by 14C method in the Kara Sea and the Yenisei River marginal filter. Age of carbon supplied by the Yenisei River is estimated to be 6.9 ka. As supplied carbon mixes with young biogenic carbon under influence of plankton and benthos young carbon flux (planktogenic) sharply diminishes. This has been inferred from studies of organic matter in sedimentary traps deployed along sections from the Yenisei River mouth to 76°N. The major part (70-80%) of organic carbon in bottom sediments of the Kara and Laptev Seas is ancient (Holocene). Planktogenic part comprises only 20-30%. In the Central Arctic Basin percentage of planktogenic organic matter in bottom sediments is still lower, the major part being associated with supply of ancient terrigenous organic material of low nutritional value for organisms. Determinations of sedimentation rates and recent matter fluxes from sedimentary traps served as a basis for locating a sedimentary depocenter in the Yenisei River both for present time and for geological past. Regularities of variations of sediment matter fluxes in the marginal filter were studied.

Averaged sedimentation rates in the Northwest Pacific and Bering Sea during the first and the second oxygen isotope stages

Isotope chronostratigraphy of Upper Quaternary sediments from the Northwest Pacific and the Bering Sea was established by oxygen isotope records in planktonic and benthic foraminifera. The main regularities of temporal variations of calcium carbonate, organic carbon and opal contents, as well as of magnetic susceptibility in sediments of the study region with regard to climatic variations and productivity were established by means of isotopic-geochemical and lithophysical analyses of bottom sediments. Correlation of volcanogenic interbeds in the sediments was carried out, and their stratigraphy and age were preliminarily ascertained. Correlation was accomplished of A.P. Jouse diatom horizons determined by an analysis of the main ecological variations in diatom assemblages in Upper Quaternary sediments of the Northwest Pacific, Bering and Okhotsk Seas, and their comparison with similar variations in sediment cores with standard oxygen isotope stages. Also variations in lithology and contents of biogenic components in sediments of the region and in the cores were taken into account. A ratio of abundance of "neritic" species to the sum of "neritic" and oceanic species abundance (coefficient Id) can be a criterion of ecological changes of diatom assemblages in the studied region. It is determined by climate variability and mostly by sea ice influence. Schemes of average sedimentation rates in the Northwest Pacific and Bering Sea for periods of the first and the second oxygen isotope stages (12.5-1 and 24-12.5 ka, respectively) were plotted on the basis of obtained results and correlation of diatom horizons and lithological units in early studied cores with the oxygen isotope stages. Closure of the Bering Strait and aeration of the north-eastern shelf of the Bering Sea during the second stage induced increase of sedimentation rates in the Bering Sea, as compared with the first stage, and suspended material transport from the Bering Sea through the Kamchatka Strait into the Northwest Pacific and its accumulation in the southeast direction.