Construction and optimization of a CC49-based scFv-beta-lactamase fusion protein for ADEPT

CC49 is a clinically validated antibody with specificity for TAG-72, a carbohydrate epitope that is over-expressed and exposed on a large fraction of solid malignancies. We constructed a single chain fragment (scFv) based on CC49 and fused it to beta-lactamase. The first generation fusion protein, TAB2.4, was expressed at low levels in Escherichia coli and significant degradation was observed during production. We optimized the scFv domain of TAB2.4 by Combinatorial Consensus Mutagenesis (CCM). An improved variant TAB2.5 was identified that resulted in an almost 4-fold improved expression and 2.5 degrees higher thermostability relative to its parent molecule. Soluble TAB2.5 can be manufactured in low-density E.coli cultures at 120 mg/l. Our studies suggest that CCM is a rapid and efficient method to generate antibody fragments with improved stability and expression. The fusion protein TAB2.5 can be used for antibody directed enzyme prodrug therapy (ADEPT).     

Maternal separation alters social odor preference development in infant mice (Mus musculus).

This study examined whether daily periods of maternal separation during the first two weeks of life would decrease attraction to familiar nest odors in CD-1 mice 10 and 14 days old. We also investigated whether placing a group of mice (Mus musculus) in nest shavings during the 180-min separation period would mitigate possible separation-induced deficits. The maternal separation procedure has been widely used as a rodent model for the effects of inconsistent or inadequate early caretaking on human development. From postnatal day (PND) 1 to 14, litters were separated from the dam, but not littermates for either 15 or 180 min, or were facility-reared controls. Control, facility-reared mice preferred home-cage nest to clean familiar shaving odors on PND 10, but not PND 14. In contrast, home-cage nest odors attracted maternally separated mice on both test days. Our results suggest that maternal separation maintains the olfactory tether to the nest in a period when the attraction normally begins to weaken. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simulation of salinity effects on past, present, and future soil organic carbon stocks

Soil organic carbon (SOC) models are used to predict changes in SOC stocks and carbon dioxide (CO(2)) emissions from soils, and have been successfully validated for non-saline soils. However, SOC models have not been developed to simulate SOC turnover in saline soils. Due to the large extent of salt-affected areas in the world, it is important to correctly predict SOC dynamics in salt-affected soils. To close this knowledge gap, we modified the Rothamsted Carbon Model (RothC) to simulate SOC turnover in salt-affected soils, using data from non-salt-affected and salt-affected soils in two agricultural regions in India (120 soils) and in Australia (160 soils). Recently we developed a decomposition rate modifier based on an incubation study of a subset of these soils. In the present study, we introduce a new method to estimate the past losses of SOC due to salinity and show how salinity affects future SOC stocks on a regional scale. Because salinity decreases decomposition rates, simulations using the decomposition rate modifier for salinity suggest an accumulation of SOC. However, if the plant inputs are also adjusted to reflect reduced plant growth under saline conditions, the simulations show a significant loss of soil carbon in the past due to salinization, with a higher average loss of SOC in Australian soils (55 t C ha(-1)) than in Indian soils (31 t C ha(-1)). There was a significant negative correlation (p < 0.05) between SOC loss and osmotic potential. Simulations of future SOC stocks with the decomposition rate modifier and the plant input modifier indicate a greater decrease in SOC in saline than in non-saline soils under future climate. The simulations of past losses of SOC due to salinity were repeated using either measured charcoal-C or the inert organic matter predicted by the Falloon et al. equation to determine how much deviation from the Falloon et al. equation affects the amount of plant inputs generated by the model for the soils used in this study. Both sets of results suggest that saline soils have lost carbon and will continue to lose carbon under future climate. This demonstrates the importance of both reduced decomposition and reduced plant input in simulations of future changes in SOC stocks in saline soils.     

A Model for Understanding Electromigration-Induced Void Evolution in Dual-Inlaid Cu Interconnect Structures

Electromigration-induced void evolution in various dual-inlaid copper (Cu) interconnect structures was simulated by applying a phenomenological model assisted by Monte Carlo-based simulations, considering the redistribution of heterogeneously nucleated voids and/or pre-existing vacancy clusters at the Cu/dielectric cap interface during electromigration. The results indicate that this model can qualitatively explain the electromigration-induced void evolution observed during experimental in situ secondary-electron microscopy (SEM) investigations as well as in various other reported studies. The electromigration mechanism in Cu interconnect structures and differences in the peculiar electromigration-induced void evolution in various dual-inlaid Cu interconnect structures can be clearly understood based on this model. These findings warrant reinvestigation of technologically important electromigration mechanisms by developing rigorous models based on similar concepts.     

Intraphase Microstructure–Understanding the Impact on Organic Solar Cell Performance

A comprehensive study of the effect of intraphase microstructure on organic photovoltaic (OPV) device performance is undertaken. Utilizing a bilayer device architecture, a small molecule donor (TIPS‐DBC) is deposited by both spin‐coating and by thermal evaporation in vacuum. The devices are then completed by thermal evaporation of C₆₀, an exciton blocking layer and the cathode. This bilayer approach enables a direct comparison of device performance for donor layers in which the same material exhibits subtle differences in microstructure. The electrical performance is shown to differ considerably for the two devices. The bulk and interfacial properties of the donor layers are compared by examination with photoelectron spectroscopy in air (PESA), optical absorption spectroscopy, charge extraction of photo‐generated charge carriers by linearly increasing voltage (photo‐CELIV), time‐resolved photoluminescence measurements, X‐ray reflectometry (XR), and analysis of dark current behavior. The observed differences in device performance are shown to be influenced by changes to energy levels and charge transport properties resulting from differences in the microstructure of the donor layers. Importantly, this work demonstrates that in addition to the donor/acceptor microstructure, the intraphase microstructure can influence critical parameters and can therefore have a significant impact on OPV performance.     

Energy intensities and greenhouse gas emission mitigation in global agriculture

Energy efficiency and greenhouse gas emissions are closely linked. This paper reviews agricultural options to reduce energy intensities and their impacts, discusses important accounting issues related to system boundaries, land scarcity, and measurement units and compares agricultural energy intensities and improvement potentials on an international level. Agricultural development in recent decades, while increasing yields, has led to lower average energy efficiencies when comparing the 1960s and the mid 1980s. In the two decades thereafter, energy intensities in developed countries increased, but with little impact on greenhouse gas emissions. Efficiency differences across countries in the year 2000 suggest a maximum improvement potential of 500 million tons of CO₂ annually. If only below average countries would increase their energy efficiency to average levels of the year 2000, the resulting emission reductions would be below 200 million tons of CO₂ annually.

基于满足Tier4排放法规的低颗粒排放燃烧系统开发的喷油策略研究

在一台非道路用中型发动机上展开了燃油喷射系统、进气系统以及废气再循环(EGR)系统控制策略的研究、开发.该方案旨在采用高压共轨燃油喷射系统,通过优化喷油嘴参数将发动机的颗粒(PM)排放控制在0.02g/kW·h以下.为了寻求NOx,PM排放及燃油经济性之间的最佳均衡关系,该燃油喷射系统具有较高的控制柔性,最高喷射压力可达200 MPa.阐明了该系统结合采用特殊特性的喷油嘴和燃烧室结构对降低PM排放的潜力.还阐明了控制机油消耗对于避免PM中含有大量可溶性有机组分的重要性.这种技术配置不但可以减少CO2排放和溶解到机油中的碳炯,而且从寿命周期费用角度考虑对用户来说也是非常有利的.     

Enhancing the carbon sink in European agricultural soils: including trace gas fluxes in estimates of carbon mitigation potential

The possibility that the carbon sink in agricultural soils can be enhanced has taken on great political significance since the Kyoto Protocol was finalised in December 1997. The Kyoto Protocol allows carbon emissions to be offset by demonstrable removal of carbon from the atmosphere. Thus, forestry activities (Article 3.3) and changes in the use of agricultural soils (Article 3.4) that are shown to reduce atmospheric CO₂levels may be included in the Kyoto emission reduction targets. The European Union is committed to a reduction in CO₂ emissions to 92% of baseline (1990) levels during the first commitment period (2008–2012). We have shown recently that there are a number of agricultural land-management changes that show some potential to increase the carbon sink in agricultural soils and others that allow alternative forms of carbon mitigation (i.e. through fossil fuel substitution), but the options differ greatly in their potential for carbon mitigation. The changes examined were, (a) switching all animal manure use to arable land, (b) applying all sewage sludge to arable land, (c) incorporating all surplus cereal straw, (d) conversion to no-till agriculture, (e) use of surplus arable land to de-intensify 1/3 of current intensive crop production (through use of 1/3 grass/arable rotations), (f) use of surplus arable land to allow natural woodland regeneration, and (g) use of surplus arable land for bioenergy crop production. In this paper, we attempt for the first time to assess other (non-CO₂) effects of these land-management changes on (a) the emission of the other important agricultural greenhouse gases, methane and nitrous oxide, and (b) other aspects of the ecology of the agroecosystems. We find that the relative importance of trace gas fluxes varies enormously among the scenarios. In some such as the sewage sludge, woodland regeneration and bioenergy production scenarios, the inclusion of trace gases makes only a small (<10%) difference to the CO₂-C mitigation potential. In other cases, for example the no-till, animal manure and agricultural de-intensification scenarios, trace gases have a large impact, sometimes halving or more than doubling the CO₂-C mitigation potential. The scenarios showing the greatest increase when including trace gases are those in which manure management changes significantly. In the one scenario (no-till) where the carbon mitigation potential was reduced greatly, a small increase in methane oxidation was outweighed by a sharp increase in N₂O emissions. When these land-management options are combined to examine the whole agricultural land area of Europe, most of the changes in mitigation potential are small, but depending upon assumptions for the animal manure scenario, the total mitigation potential either increases by about 20% or decreases by about 10%, shifting the mitigation potential of the scenario from just above the EU's 8% Kyoto emission reduction target (98.9 Tg C y⁻¹) to just below it. Our results suggest that (a) trace gas fluxes may change the mitigation potential of a land management option significantly and should always be considered alongside CO₂-C mitigation potentials and (b) agricultural management options show considerable potential for carbon mitigation even after accounting for trace gas fluxes. This revised version was published online in August 2006 with corrections to the Cover Date.