Elastic response of [111]-tunneling impurities

We study the dynamic response of a [111] quantum impurity, such as lithium or cyanide in alkali halides, with respect to an external field coupling to the elastic quadrupole moment. Because of the particular level structure of a eight-state system on a cubic site, the elastic response function shows a biexponential relaxation feature and a van Vleck type contribution with a resonance frequency that is twice the tunnel frequency $\Delta/\hbar$. This basically differs from the dielectric response that does not show relaxation. Moreover, we show that the elastic response of a [111] impurity cannot be reduced to that of a two-level system. In the experimental part, we report on recent sound velocity and internal friction measurements on KCl doped with cyanide at various concentrations. At low doping (45 ppm) we find the dynamics of a single [111] impurity, whereas at higher concentrations (4700 ppm) the elastic response rather indicates strongly correlated defects. Our theoretical model provides a good description of the temperature dependence of $\delta v/v$ and $Q^{-1}$ at low doping, in particular the relaxation peaks, the absolute values of the amplitude, and the resonant contributions. From our fits we obtain the value of the elastic deformation potential $\gamma_t=0.192$ eV.Comment: 19 pages, 5 figure

Aggregation Prediction in Therapeutic Protein Formulations for Excipient Design

Computational Infrastructure & Informatics Poster SessionA major concern in the development therapeutic protein formulations is protein aggregation. Proteins can interact to form bound groups of protein molecules or aggregates. Aggregates in protein formulations reduce effectiveness and can lead to severe immune responses in patients. Excipients are additive molecules that are not therapeutically active, but can increase the stability of protein formulations. An ideal excipient binds with aggregation prone regions on the protein to limit interaction of that region with another protein molecule. The goal of this project is to predict aggregation prone regions and design excipients to interact with these regions. Several tools exist to predict which regions on a protein will be most likely to initiate aggregation. Aggrescan (http://bioinf.uab.es/aggrescan/) and SAP (Spatial Aggregation Potential) were used to predict aggregation prone regions on proteins and the results were compared. Aggrescan uses experimental data to assign each amino acid an aggregation propensity score. An aggregation prone region is identified by a sequence of amino acids with high propensities. The three-dimensional structure is not used in the aggregation prediction. SAP uses molecular simulation to determine regions that are hydrophobic and solvent accessible. Each residue is scored and the results are mapped to the three-dimensional protein structure. A successful prediction tool must use parameters that correlate with aggregation potential for a folded protein. The aggregation prone regions predicted by Aggrescan and SAP were compared to experimental data on protein aggregation. Proteins with a high number of predicted regions or large predicted regions were found to have higher experimental percent aggregation. With the regions identified, molecular simulations were performed for protein-excipient systems. A protein and small molecule docking algorithm was used to determine which regions of the protein certain excipients interacted with. Trehalose, poly(vinylpyrrolidone), and guanadine hydrochloride were used. For an excipient to successfully stabilize a protein and prevent aggregation, the excipient should interact with the aggregation prone regions predicted by Aggrescan and SAP. The predicted regions were compared to the regions where the excipient docks in the molecular simulation. The simulation results were compared to experimental data on the percent aggregation observed in several protein-excipient formulations. The excipients that were found to interact with the predicted aggregation prone regions in simulations should also experimentally prohibit aggregation, leading to lower percent aggregation. Hydrogen-deuterium swapping along with FTIR analysis will be performed experimentally to determine exposed regions on the protein. Proteins with a high number of exposed regions are less stable. The exposed regions will be compared to the aggregation prone regions predicted by Aggrescan and SAP

Soft Interaction Between Dissolved Dendrimers: Theory and Experiment

Using small-angle neutron scattering and liquid integral equation theory, we relate the structure factor of flexible dendrimers of 4th generation to their average shape. The shape is measured as a radial density profile of monomers belonging to a single dendrimer. From that, we derive an effective interaction of Gaussian form between pairs of dendrimers and compute the structure factor using the hypernetted chain approximation. Excellent agreement with the corresponding experimental results is obtained, without the use of adjustable parameters. The present analysis thus strongly supports the previous finding that flexible dendrimers of low generation present fluctuating structures akin to star polymers.Comment: 20 pages, 4 figures, submitted to Macromolecules on July 24, 200

Internal Friction of Amorphous Silicon in a Magnetic Field

The internal friction of e-beam amorphous silicon was measured in a magnetic field between 0 and 6 T, from 1.5-20 K, and was found to be independent of the field to better than 8%. It is concluded that the low energy excitations observed in this experiment are predominantly atomic in nature.Comment: 4 pages, 4 figures, REVTe

Low temperature acoustic properties of amorphous silica and the Tunneling Model

Internal friction and speed of sound of a-SiO(2) was measured above 6 mK using a torsional oscillator at 90 kHz, controlling for thermal decoupling, non-linear effects, and clamping losses. Strain amplitudes e(A) = 10^{-8} mark the transition between the linear and non-linear regime. In the linear regime, excellent agreement with the Tunneling Model was observed for both the internal friction and speed of sound, with a cut-off energy of E(min) = 6.6 mK. In the non-linear regime, two different behaviors were observed. Above 10 mK the behavior was typical for non-linear harmonic oscillators, while below 10 mK a different behavior was found. Its origin is not understood.Comment: 1 tex file, 6 figure

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Multi-Scale Simulation Modeling for Prevention and Public Health Management of Diabetes in Pregnancy and Sequelae

Diabetes in pregnancy (DIP) is an increasing public health priority in the Australian Capital Territory, particularly due to its impact on risk for developing Type 2 diabetes. While earlier diagnostic screening results in greater capacity for early detection and treatment, such benefits must be balanced with the greater demands this imposes on public health services. To address such planning challenges, a multi-scale hybrid simulation model of DIP was built to explore the interaction of risk factors and capture the dynamics underlying the development of DIP. The impact of interventions on health outcomes at the physiological, health service and population level is measured. Of particular central significance in the model is a compartmental model representing the underlying physiological regulation of glycemic status based on beta-cell dynamics and insulin resistance. The model also simulated the dynamics of continuous BMI evolution, glycemic status change during pregnancy and diabetes classification driven by the individual-level physiological model. We further modeled public health service pathways providing diagnosis and care for DIP to explore the optimization of resource use during service delivery. The model was extensively calibrated against empirical data.Comment: 10 pages, SBP-BRiMS 201

Using legume-based mixtures to enhance the nitrogen use efficiency and economic viability of cropping systems - Final report (LK09106/HGCA3447)

As costs for mineral fertilisers rise, legume-based leys are recognised as a potential alternative nitrogen source for crops. Here we demonstrate that including species-rich legume-based leys in rotations helps to maximise synergies between agricultural productivity and other ecosystem services. By using functionally diverse plant species mixtures, these services can be optimised and fine-tuned to regional and farm-specific needs. Replicated field experiments were conducted over three years at multiple locations, testing the performance of 12 legume species and 4 grass species sown in monocultures, as well as in a mixture of 10 of the legumes and all 4 grasses (called the All Species Mix, ASM). In addition, we compared this complex mixture to farmer-chosen ley mixtures on 34 sites across the UK. The trials showed that there is a large degree of functional complementarity among the legume species. No single species scored high on all evaluation criteria. In particular, the currently most frequently used species, white clover, is outscored by other legume species on a number of parameters such as early development and resistance to decomposition. Further complementarity emerged from the different responses of legume species to environmental variables, with soil pH and grazing or cutting regime being among the more important factors. For example, while large birdsfoot trefoil showed better performance on more acidic soils, the opposite was true for sainfoin, lucerne and black medic. In comparison with the monocultures, the ASM showed increased ground cover, increased above-ground biomass and reduced weed biomass. Benefits of mixing species with regard to productivity increased over time. In addition, the stability of biomass production across sites was greater in the ASM than in the legume monocultures. Within the on-farm trials, we further found that on soils low in organic matter the biomass advantage of the ASM over the Control ley was more marked than on the soils with higher organic matter content. Ecological modelling revealed that the three best multifunctional mixtures all contained black medic, lucerne and red clover. Within the long term New Farming Systems (NFS) rotational study, the use of a clover bi-crop showed improvement to soil characteristics compared to current practice (e.g. bulk density and water infiltration rate). Improvements in wheat yield were also noted with respect to the inclusion of a clover bi-crop in 2010, but there was evidence of a decline in response as the N dose was increased. Cumulatively, over both the wheat crop and the spring oilseed rape crop, the clover bi-crop improved margin over N. The highest average yield response (~9%) was associated with the ASM legume species mix cover cropping approach

Developing a nationally appropriate mitigation measure from the greenhouse gas abatement potential from livestock production in the Brazilian Cerrado.

Brazil is one of the first major developing countries to commit to a national greenhouse gas (GHG) emissions target that requires a reduction of between 36.1% and 38.9% relative to baseline emissions by 2020. The country intends to submit to agricultural emissions reductions as part of this target with livestock production identified as offering significant abatement potentia