Pi release from myosin: a simulation analysis of possible pathways

The release of phosphate (Pi) is an important element in actomyosin function and has been shown to be accelerated by the binding of myosin to actin. To provide information about the structural elements important for Pi release, possible escape pathways from various isolated myosin II structures have been determined by molecular dynamics simulations designed for studying such slow processes. The residues forming the pathways were identified and their role was evaluated by mutant simulations. Pi release is slow in the pre-powerstroke structure, an important element in preventing the powerstroke prior to actin binding, and is much more rapid for Pi modeled into the post-rigor and rigor-like structures. The previously proposed backdoor route is dominant in the pre-powerstroke and post-rigor states, whereas a different path is most important in the rigor-like state. This finding suggests a mechanism for the actin-activated acceleration of Pi release.

High-resolution dynamic computer simulation analysis of the behavior of sample components with pI values outside the pH gradient established by carrier ampholyte CIEF

The behavior of sample components whose pI values are outside the pH gradient established by 101 hypothetical biprotic carrier ampholytes covering a pH 6-8 range was investigated by computer simulation under constant current conditions with concomitant constant electroosmosis toward the cathode. Data obtained with the sample being applied between zones of carrier ampholytes and on the anodic side of the carrier ampholytes were studied and found to evolve into zone structures comprising three regions between anolyte and catholyte. The focusing region with the pH gradient is bracketed by two isotachopheretic zone structures comprising selected sample and carrier components as isotachophoretic zones. The isotachophoretic structures electrophoretically migrate in opposite direction and their lengths increase with time due to the gradual isotachophoretic decay at the pH gradient edges. Due to electroosmosis, however, the overall pattern is being transported toward the cathode. Sample components whose pI values are outside the established pH gradient are demonstrated to form isotachophoretic zones behind the leading cation of the catholyte (components with pI values larger than 8) and the leading anion of the anolyte (components with pI values smaller than 6). Amphoteric compounds with appropriate pI values or nonamphoteric components can act as isotachophoretic spacer compounds between sample compounds or between the leader and the sample with the highest mobility. The simulation data obtained provide for the first time insight into the dynamics of amphoteric sample components that do not focus within the established pH gradient.

The Potential of Tariff Policy for Climate Change Mitigation: Legal and Economic Analysis

This paper addresses a potential role that tariffs and tariff policy can play in encouraging countries to take part in a multilateral effort to mitigate climate change. It begins by assessing whether increasing tariffs on products from energy intensive or polluting industries amounts to a violation of WTO rules and whether protectionism in this case can be differentiated from genuine environmental concerns. It then argues that while lowering tariffs for environmental goods can serve as a carrot to promote dissemination of cleaner technologies, tariff deconsolidation is a legitimate stick to encourage polluting countries to move towards an international climate agreement. The paper further explores this view by undertaking a partialequilibrium simulation analysis to examine the impact of a unilateral unit increase in tariffs on the imports of the most carbon-intensive products from countries not committed to climate polices. Our results suggest that the committed importing countries would have to raise their tariffs only slightly to effect a significant decline in the imports of these products from the non-committed countries. For instance, a unit increase in the simple average applied tariffs on the imports of these carbon-intensive products in 2005 from our sample of non-committed exporting countries would reduce the imports of these products by an average 32.6% in Australia, 178% in Canada, 195% in the EU, 271% in Japan and 62% in the US, therebysuggesting the effectiveness of such a measure in pushing countries towards a global climate policy.

Simulation-based cost-utility analysis of population screening-based alendronate use in Switzerland

A simulation model adopting a health system perspective showed population-based screening with DXA, followed by alendronate treatment of persons with osteoporosis, or with anamnestic fracture and osteopenia, to be cost-effective in Swiss postmenopausal women from age 70, but not in men. INTRODUCTION: We assessed the cost-effectiveness of a population-based screen-and-treat strategy for osteoporosis (DXA followed by alendronate treatment if osteoporotic, or osteopenic in the presence of fracture), compared to no intervention, from the perspective of the Swiss health care system. METHODS: A published Markov model assessed by first-order Monte Carlo simulation was refined to reflect the diagnostic process and treatment effects. Women and men entered the model at age 50. Main screening ages were 65, 75, and 85 years. Age at bone densitometry was flexible for persons fracturing before the main screening age. Realistic assumptions were made with respect to persistence with intended 5 years of alendronate treatment. The main outcome was cost per quality-adjusted life year (QALY) gained. RESULTS: In women, costs per QALY were Swiss francs (CHF) 71,000, CHF 35,000, and CHF 28,000 for the main screening ages of 65, 75, and 85 years. The threshold of CHF 50,000 per QALY was reached between main screening ages 65 and 75 years. Population-based screening was not cost-effective in men. CONCLUSION: Population-based DXA screening, followed by alendronate treatment in the presence of osteoporosis, or of fracture and osteopenia, is a cost-effective option in Swiss postmenopausal women after age 70.

Space debris attitude simulation - ιOTA (In-Orbit Tumbling Analysis)

Today, there is little knowledge on the attitude state of decommissioned intact objects in Earth orbit. Observational means have advanced in the past years, but are still limited with respect to an accurate estimate of motion vector orientations and magnitude. Especially for the preparation of Active Debris Removal (ADR) missions as planned by ESA’s Clean Space initiative or contingency scenarios for ESA spacecraft like ENVISAT, such knowledge is needed. ESA's “Debris Attitude Motion Measurements and Modelling” project (ESA Contract No. 40000112447), led by the Astronomical Institute of the University of Bern (AIUB), addresses this problem. The goal of the project is to achieve a good understanding of the attitude evolution and the considerable internal and external effects which occur. To characterize the attitude state of selected targets in LEO and GTO, multiple observation methods are combined. Optical observations are carried out by AIUB, Satellite Laser Ranging (SLR) is performed by the Space Research Institute of the Austrian Academy of Sciences (IWF) and radar measurements and signal level determination are provided by the Fraunhofer Institute for High Frequency Physics and Radar Techniques (FHR). The In-Orbit Tumbling Analysis tool (ιOTA) is a prototype software, currently in development by Hyperschall Technologie Göttingen GmbH (HTG) within the framework of the project. ιOTA will be a highly modular software tool to perform short-(days), medium-(months) and long-term (years) propagation of the orbit and attitude motion (six degrees-of-freedom) of spacecraft in Earth orbit. The simulation takes into account all relevant acting forces and torques, including aerodynamic drag, solar radiation pressure, gravitational influences of Earth, Sun and Moon, eddy current damping, impulse and momentum transfer from space debris or micro meteoroid impact, as well as the optional definition of particular spacecraft specific influences like tank sloshing, reaction wheel behaviour, magnetic torquer activity and thruster firing. The purpose of ιOTA is to provide high accuracy short-term simulations to support observers and potential ADR missions, as well as medium-and long-term simulations to study the significance of the particular internal and external influences on the attitude, especially damping factors and momentum transfer. The simulation will also enable the investigation of the altitude dependency of the particular external influences. ιOTA's post-processing modules will generate synthetic measurements for observers and for software validation. The validation of the software will be done by cross-calibration with observations and measurements acquired by the project partners.

Teeth restored using fiber-reinforced posts: in vitro fracture tests and finite element analysis

In dentistry the restoration of decayed teeth is challenging and makes great demands on both the dentist and the materials. Hence, fiber-reinforced posts have been introduced. The effects of different variables on the ultimate load on teeth restored using fiber-reinforced posts is controversial, maybe because the results are mostly based on non-standardized in vitro tests and, therefore, give inhomogeneous results. This study combines the advantages of in vitro tests and finite element analysis (FEA) to clarify the effects of ferrule height, post length and cementation technique used for restoration. Sixty-four single rooted premolars were decoronated (ferrule height 1 or 2 mm), endodontically treated and restored using fiber posts (length 2 or 7 mm), composite fillings and metal crowns (resin bonded or cemented). After thermocycling and chewing simulation the samples were loaded until fracture, recording first damage events. Using UNIANOVA to analyze recorded fracture loads, ferrule height and cementation technique were found to be significant, i.e. increased ferrule height and resin bonding of the crown resulted in higher fracture loads. Post length had no significant effect. All conventionally cemented crowns with a 1-mm ferrule height failed during artificial ageing, in contrast to resin-bonded crowns (75% survival rate). FEA confirmed these results and provided information about stress and force distribution within the restoration. Based on the findings of in vitro tests and computations we concluded that crowns, especially those with a small ferrule height, should be resin bonded. Finally, centrally positioned fiber-reinforced posts did not contribute to load transfer as long as the bond between the tooth and composite core was intact.

Multi-Scale Modeling for Image Analysis of Brain Tumor Studies

Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multi-scale, multi-physics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlasbased segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression.

LTE uplink scheduling - flow level analysis

Long Term Evolution (LTE) is a cellular technology foreseen to extend the capacity and improve the performance of current 3G cellular networks. A key mechanism in the LTE traffic handling is the packet scheduler, which is in charge of allocating resources to active flows in both the frequency and time dimension. In this paper we present a performance comparison of three distinct scheduling schemes for LTE uplink with main focus on the impact of flow-level dynamics resulting from the random user behaviour. We apply a combined analytical/simulation approach which enables fast evaluation of flow-level performance measures. The results show that by considering flow-level dynamics we are able to observe performance trends that would otherwise stay hidden if only packet-level analysis is performed.