Use of dynamic mechanical analysis (DMA) to determine critical transition temperatures in frozen biomaterials intended for lyophilization

Dynamic mechanical analysis is widely used to determine glass transitions in solid state materials. However, here we demonstrate the application of DMA for the determination of glass transitions (Tg’) in the frozen liquid state by means of a steel sample pocket. The use of the pocket allows frozen material to be analysed and glass transition events demonstrated. In addition, it allows weak glass transitions to be detected clearly in some complex formulations where they can be obscured by eutectic and other strong thermal events when other methods such as DSC or DTA are used. Classical excipients (trehalose, lactose, dextran) were analysed and shown to give reproducible Tg’ values, though with values slightly higher than those obtained by DSC. Finally, several complex real biological materials, typical of those encountered when freeze drying biological and biopharmaceutical materials, were analysed and the potential value of DMA demonstrated to determine the relevant glass transition temperatures for use in cryobiology and freeze drying.     

Study of kinetics of thermal aggregation of mitochondrial aspartate aminotransferase by dynamic light scattering: protective effect of α-crystallin

Thermal aggregation of aspartate aminotransferase from pig heart mitochondria (mAAT) has been studied at various temperatures and various protein concentrations by dynamic light scattering. The character of the dependence of protein aggregate size on time indicates that aggregation of mAAT proceeds in the regime of diffusion-limited cluster–cluster aggregation. Suppression of mAAT aggregation by α-crystallin is due to transition of the aggregation process into the regime of reaction-limited cluster–cluster aggregation. Realization of this regime of aggregation means that the sticking probability for the colliding particles is less than unity.     

The influence of contraction type,prior performance of a maximal voluntary contraction and measurement duration on fine-wire EMG amplitude

We aimed to investigate the impact of time on fine-wire (fw) electromyography (EMG) signal amplitude, and to determine whether any attenuation is confounded by task type. Twenty healthy participants were instrumented with fw and surface (s) EMG electrodes at the biceps brachii bilaterally. Participants held a weight statically with one arm and with the other arm either repeated the same task following a maximum voluntary contraction (MVC) or repeated dynamic elbow flexion/extension contractions. Each task was repeated for 30 s every five minutes over two hours. EMG amplitude was smoothed and normalized to time = 0. Stable median power frequency of the s-EMG ruled out the confounding influence of fatigue. Repeated-measures ANCOVAs determined the effect of electrode type and time (covariate) on EMG amplitude and the confounding impact of task type. During the isometric protocol, fw-EMG amplitude reduced over time (p = 0.002), while s-EMG amplitude (p = 0.895) and MPF (p > 0.05) did not change. Fw-EMG amplitude attenuated faster during the dynamic than the isometric protocol (p = 0.008) and there was evidence that the MVC preceding the isometric protocol impacted the rate of decline (p = 0.001). We conclude that systematic signal attenuation of fw-EMG occurs over time and is more pronounced during dynamic tasks.     

Old age takes its toll: Long-run projections of health-related public expenditure in Luxembourg

This paper simulates long-term trends in Luxembourg’s public expenditure on healthcare and on long-term care. We combine population projections with micro-simulations of individuals’ health status that account for their demographic, socio-economic characteristics and their childhood circumstances. Model equations estimated on data from the SHARE survey and from several branches of Social Security provide a rich framework to study policy-relevant applications. We simulate public expenditure on healthcare and long-term care under different scenarios to evaluate the separate contributions of population ageing, costs of producing health-related services, and the distribution of health status across age cohorts. Results suggest that rising per capita expenditure on healthcare will mostly result from production costs, while rising expenditure on long-term care will mostly reflect population ageing.     

On open access and optimal landings tax

This paper develops two types of simple models on the dynamic interaction between the stock of fish and the effort expended by fishers: continuous-time/discrete-time models in which a landings tax is incorporated as a control variable available to the management authority. The continuous-time model can describe several ideal options of the optimal tax program; however, unfortunately, it is incapable of choosing the best option. Hence, using the alternative tractable discrete-time model and a computational method, the remaining task of determining a unique optimal tax program is accomplished. The fishery thus managed exhibits a regulated open access.     

Distributed moment histogram: A neurophysiology based method of agonist and antagonist trunk muscle activity prediction

A neurocortical-based technique of muscle recruitment is presented to solve the muscle indeterminacy problem for lumbar torso modeling. Cortical recordings from behaving primates have established motor cortex cells that respond to a wide range of task directions, but are tuned to a preferred direction. A characteristic activity pattern of these neurons seems to be associated with effort direction. It was hypothesized that a model which recruits muscles based on a similar distribution would predict antagonistic muscle activity with greater realism than a widely referenced optimization formulation. The predictions of the Distributed Moment Histogram (DMH) method were evaluated under common speed (<30^os⁻¹) sagittal plane lifting conditions using five subjects. The predicted forces showed high correspondence with agonist and antagonist myoelectric patterns. The mean coefficient of determination for the erector spinae was r²=0.91, and 0.41 for the latissimus. For the antagonistic muscles, the rectus abdominus was found to be electrically silent (<3% MVC) and no activity was predicted by the method. The external oblique muscle was observed to be minimally active (<16% MVC), and the DMH method predicted its mostly constant activity with a mean standard error of 1.6% MVC. The realistic antagonistic predictions supported the hypothesis and justify this cortical based technique as an alternative for muscle tension estimation in biomechanical torso modeling. A primary advantage of this method is its computational simplicity and direct physiologic analogy     

Dynamic control in metabolic engineering: Theories,tools, and applications

Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically encoded metabolic control systems which allow cells to autonomously adjust their flux in response to their external and internal metabolic state. This review first discusses theoretical works which provide mechanistic insights and design choices for dynamic control systems including two-stage, continuous, and population behavior control strategies. Next, we summarize molecular mechanisms for various sensors and actuators which enable dynamic metabolic control in microbial systems. Finally, important applications of dynamic control to the production of several metabolite products are highlighted, including fatty acids, aromatics, and terpene compounds. Altogether, this review provides a comprehensive overview of the progress, advances, and prospects in the design of dynamic control systems for improved titer, rate, and yield metrics in metabolic engineering.     

Predators and mutualists influence the exclusion of aphid species from natural communities

We investigated why two species of aphids (Aphis jacobaeae and Brachycaudus cardui) were very rare in a study site despite their abundance in the surrounding area. The study site contained many common species of aphid and we tested the hypothesis that the community of aphid predators in the field excluded the missing species. Colonies of the two aphid species were artificially initiated in the experimental site and allocated to one of four treatments: control; ground predator exclusion; total predator exclusion, and provision of mutualist ants. Two measures of colony performance were analysed: longevity and cumulative aphid density. Colonies decline naturally in late summer but control colonies disappeared very quickly while colonies protected from all predators survived the longest. The performance of colonies protected from just ground predators was intermediate. We failed to persuade ants to tend A. jacobaeae. Colonies of B. cardui attended by ants performed better than controls and those with ground predators excluded, but not as well as those with all predators excluded. We conclude that the absence of the two species of aphid in the study site is influenced by the resident predator community, and by the availability of mutualists. Received: 27 April 1998 / Accepted: 30 November 1998     

Adaptive bolus-chasing computed tomography angiography in the cases of symmetric and asymmetric arterial flows in peripheral arteries

Synchronization of the contrast bolus peak and CT imaging aperture is a crucial issue for computed tomography angiography (CTA). It affects the CTA image quality and the amount of contrast dose. A whole-body CTA procedure means to scan from the abdominal aorta to pedal arteries. In this context, the synchronization is much more difficult with the asymmetric arterial flow in lower extremities than in the case of symmetric arterial flow. In this paper, we propose an adaptive optimal controller to chase the contrast bolus peak while it propagates in the aorta and lower extremities with symmetric flow. In the case of asymmetric flow after the contrast bolus splitting into two lower limbs, we propose a dynamic programming approach to cover the lower limbs optimally. Simulation and experimental results show that the proposed methods outperform the current constant-speed method substantially.