Binding free energy differences in a TCR-peptide-MHC complex induced by a peptide mutation: a simulation analysis.

Recognition by the T-cell receptor (TCR) of immunogenic peptides presented by class I major histocompatibility complexes (MHCs) is the determining event in the specific cellular immune response against virus-infected cells or tumor cells. It is of great interest, therefore, to elucidate the molecular principles upon which the selectivity of a TCR is based. These principles can in turn be used to design therapeutic approaches, such as peptide-based immunotherapies of cancer. In this study, free energy simulation methods are used to analyze the binding free energy difference of a particular TCR (A6) for a wild-type peptide (Tax) and a mutant peptide (Tax P6A), both presented in HLA A2. The computed free energy difference is 2.9 kcal/mol, in good agreement with the experimental value. This makes possible the use of the simulation results for obtaining an understanding of the origin of the free energy difference which was not available from the experimental results. A free energy component analysis makes possible the decomposition of the free energy difference between the binding of the wild-type and mutant peptide into its components. Of particular interest is the fact that better solvation of the mutant peptide when bound to the MHC molecule is an important contribution to the greater affinity of the TCR for the latter. The results make possible identification of the residues of the TCR which are important for the selectivity. This provides an understanding of the molecular principles that govern the recognition. The possibility of using free energy simulations in designing peptide derivatives for cancer immunotherapy is briefly discussed.

Modelling spectral reflectance of open cork oak woodland: a simulation analysis of the effects of vegetation structure and background

This study analyses the influence of vegetation structure (i.e. leaf area index and canopy cover) and seasonal background changes on moderate-resolution imaging spectrometer (MODIS)-simulated reflectance data in open woodland. Approximately monthly spectral reflectance and transmittance field measurements (May 2011 to October 2013) of cork oak tree leaves (Quercus suber) and of the herbaceous understorey were recorded in the region of Ribatejo, Portugal. The geometric-optical and radiative transfer (GORT) model was used to simulate MODIS response (red, near-infrared) and to calculate vegetation indices, investigating their response to changes in the structure of the overstorey vegetation and to seasonal changes in the understorey using scenarios corresponding to contrasting phenological status (dry season vs. wet season). The performance of normalized difference vegetation index (NDVI), soil-adjusted vegetation index (SAVI), and enhanced vegetation index (EVI) is discussed. Results showed that SAVI and EVI were very sensitive to the emergence of background vegetation in the wet season compared to NDVI and that shading effects lead to an opposing trend in the vegetation indices. The information provided by this research can be useful to improve our understanding of the temporal dynamic of vegetation, monitored by vegetation indices.

Multiple structural change models:a simulation analysis

In a reccnt paper. Bai and Perron (1998) considcrccl theoretical issues relatec\ lo lhe limiting distriblltion of estimators and test. statist.ics in the linear model \\'ith multiplc struct ural changes. \Ve assess. via simulations, the adequacy of the \'arious I1Iethods suggested. These CO\'er the size and power of tests for structural changes. the cO\'erage rates of the confidence Íntervals for the break dates and the relat.Í\'e merits of methods to select the I1umber of breaks. The \'arious data generating processes considered alIo,,' for general conditions OIl the data and the errors including differellces across segmcll(s. Yarious practical recommendations are made.

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.

Winner-Take-All Contention of Innovation under Globalization: A Simulation Analysis and East Asia's Empirics

This paper sets out to examine how innovation enhances export competitiveness: The proposition that export volume becomes enhanced as more productivity-enhancing innovation is captured by the exporting economy is the focus of this study. From a Schumpeterian perspective, innovation can be characterized by continuous creation and subsequent diffusion of newer technologies on the basis of the exporters' existing capital stock. Then we highlight the theoretical possibility that concentration of innovative activities in a small group of "winner" economies would lead to larger shares of "winner" economies' exports of innovation-active commodities than those commodities for which technology involved is already mature. The world's export data corroborates this theoretical prediction overall, and a focus upon East Asia has revealed the region's increasing resort to technology-intensive commodity sectors, which has presumably been enabled through attracting technology-bearing inward foreign direct investment. Considering the overall gains from innovation, acceleration of full "cycle" of innovation and imitation might be a desirable option.

Geographical simulation analysis for logistics enhancement in Asia

This paper presents a simulation of the reduction of several components in trade cost for Asia and examines its impact on the economy. Our simulation model based on the new economic geography embraces seven sectors, including manufacturing and non-manufacturing sectors, and 1,715 regions in 18 countries/economies in Asia, in addition to the two economies of the US and the European Union. The geographical course of transactions among regions is modeled as determined based on firms’ modal choice. The model also includes estimates of some border cost measures such as tariff rates, non-tariff barriers, other border clearance costs, transshipment costs and so on. Our simulation analysis for Asia includes several scenarios involving the improvement/development of routes and the reduction of the above-mentioned border cost. We have shown that the contribution of physical and non-physical infrastructure improvements conducted together is larger than the sum of the contribution by each when conducted independently.

Is FTA/EPA effective for a developing country to attract FDI? : simulation analysis based on an extended knowledge-capital model

To prepare an answer to the question of how a developing country can attract FDI, this paper explored the factors and policies that may help bring FDI into a developing country by utilizing an extended version of the knowledge-capital model. With a special focus on the effects of FTAs/EPAs between market countries and developing countries, simulations with the model revealed the following: (1) Although FTA/EPA generally ends to increase FDI to a developing country, the possibility of improving welfare through increased demand for skilled and unskilled labor becomes higher as the size of the country declines; (2) Because the additional implementation of cost-saving policies to reduce firm-type/trade-link specific fixed costs ends to depreciate the price of skilled labor by saving its input, a developing country, which is extremely scarce in skilled labor, is better off avoiding the additional option; (3) If a country hopes to enjoy larger welfare gains with EPA, efforts to increase skilled labor in the country, such as investing in education, may be beneficial.

Comparing the economic impacts of Asian integration by computational simulation analysis

The Geographical Simulation Model developed by IDE-JETRO (IDE-GSM) is a computer simulation model based on spatial economics. IDE-GSM enables us to predict the economic impacts of various trade and transport facilitation measures. Here, we mainly compare the prioritized projects of the Master Plan on ASEAN Connectivity (MPAC) and the Comprehensive Asia Development Plan (CADP). MPAC focus on specific hard or soft infrastructure projects that connect one ASEAN member state to another while the CADP emphasizes the importance of economic corridors or linkages between a large cluster and another cluster. As compared with MPAC projects, the simulation analysis shows that CADP projects have much larger positive impacts on ASEAN countries.

Simulation analysis of the EU ELV/RoHS directives based on an applied general equilibrium model with Melitz-type trade specification

This paper explores the potential usefulness of an AGE model with the Melitz-type trade specification to assess economic effects of technical regulations, taking the case of the EU ELV/RoHS directives as an example. Simulation experiments reveal that: (1) raising the fixed exporting cost to make sales in the EU market brings results that exports of the targeted commodities (motor vehicles and parts for ELV and electronic equipment for RoHS) to the EU from outside regions/countries expand while the domestic trade in the EU shrinks when the importer's preference for variety (PfV) is not strong; (2) if the PfV is not strong, policy changes that may bring reduction in the number of firms enable survived producers with high productivity to expand production to be large-scale mass producers fully enjoying the fruit of economies of scale; and (3) When the strength of the importer's PfV is changed from zero to unity, there is the value that totally changes simulation results and their interpretations.

An analysis of the automobile market: modeling of the long-run determinants of the demand for automobiles. Volume II: simulation analysis using the Wharton E.F.A. Automobile Demand Model. Final report.

Transportation Department, Washington, D.C.

Simulation analysis of a network computer,

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Simulation analysis of a pay-for-priority scheme for the IBM 360/75 /

Thesis (M.S.) - University of Illinois at Urbana-Champaign.