Molecular Dynamics Simulation of a Micellar System

We present the results of an atomistic molecular dynamics simulation based on the AMBER/OPLS force field applied to segments of isolated one-dimensional micelles, 2,3,6,7,10,11-Hexa-(1,4,7-Trioxaoctyl)-Triphenylene, in aqueous solution using the SPC/E water model. The quantities which we study include the intra-micellar monomer structure, e.g., the equilibrium monomer-monomer separation along the micelle, the micelle-water interface, which yields the effective micellar diameter, and the flexibility of the micelle in terms of its persistence length as a function of temperature. In addition, we determine the micelle size distribution at low concentration via the free enthalpy gain per monomer-monomer contact using a hydration shell model in combination with thermodynamic integration. Finally, we locate the isotropic-to-nematic transition by using our results as input for an analytical model.     

Agent-Based Analysis of Biomass Feedstock Production Dynamics

The success of the bioenergy sector based on lignocellulosic feedstock will require a sustainable and resilient transition from the current agricultural system focused on food crops to one also producing energy crops. The dynamics of this transition are not well understood. It will be driven significantly by the collective participation, behavior, and interaction of various stakeholders such as farmers within the production system. The objective of this work is to study the system dynamics through the development and application of an agent-based model using the theory of complex adaptive systems. Farmers and biorefinery, two key stakeholders in the system, are modeled as independent agents. The decision making of each agent as well as its interaction with other agents is modeled using a set of rules reflecting the economic, social, and personal attributes of the agent. These rules and model parameters are adapted from literature. Regulatory mechanisms such as Biomass Crop Assistance Program are embedded in the decision-making process. The model is then used to simulate the production of Miscanthus as an energy crop in Illinois. Particular focus has been given on understanding the dynamics of Miscanthus adaptation as an agricultural crop and its impact on biorefinery capacity and contractual agreements. Results showed that only 60% of the maximum regional production capacity could be reached, and it took up to 15 years to establish that capacity. A 25% reduction in the land opportunity cost led to a 63% increase in the steady- state productivity. Sensitivity analysis showed that higher initial conversion of land by farmers to grow energy crop led to faster growth in regional productivity.     

Single-Stranded DNA within Nanopores: Conformational Dynamics and Implications for Sequencing; a Molecular Dynamics Simulation Study

Engineered protein nanopores, such as those based on α-hemolysin from Staphylococcus aureus have shown great promise as components of next-generation DNA sequencing devices. However, before such protein nanopores can be used to their full potential, the conformational dynamics and translocation pathway of the DNA within them must be characterized at the individual molecule level. Here, we employ atomistic molecular dynamics simulations of single-stranded DNA movement through a model α-hemolysin pore under an applied electric field. The simulations enable characterization of the conformations adopted by single-stranded DNA, and allow exploration of how the conformations may impact on translocation within the wild-type model pore and a number of mutants. Our results show that specific interactions between the protein nanopore and the DNA can have a significant impact on the DNA conformation often leading to localized coiling, which in turn, can alter the order in which the DNA bases exit the nanopore. Thus, our simulations show that strategies to control the conformation of DNA within a protein nanopore would be a distinct advantage for the purposes of DNA sequencing.     

Dynamics Modeling and Simulation of a Bionic Swim Bladder System in Underwater Robotics

While considering that fish could suspend themselves under water and could enhance their mobility by adjusting its swim bladder, we have carried out research on a bionic swim bladder system in underwater robotics, which could amend the underwater robotics' static balance and controllability conditions even if the depth of water changes. First, this paper introduces the bio-swim bladder's structure and function. Second, it works out the dynamic model of the bionic swim bladder, and then it analyses the dynamic characteristic and effect of the bionic swim bladder system with the software Matlab/simulink. Finally, considering about the nonlinear relationship of the parameters in the model, this paper brings forward a dual-speed control method, which could make the effect of the bionic swim bladder non-coupling. The result of the simulation reveals that the bionic swim bladder could change the buoyancy and centroid distribution of the underwater robotics effectively and independently, bringing it into a balance state, under which the control and maneuverability could be enhanced.     

Comparing Stochastic Differential Equations and Agent-Based Modelling and Simulation for Early-Stage Cancer

There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm.     

Combining Computational Fluid Dynamics and Agent-Based Modeling: a new approach to evacuation planning

We introduce a novel hybrid of two fields-Computational Fluid Dynamics (CFD) and Agent-Based Modeling (ABM)-as a powerful new technique for urban evacuation planning. CFD is a predominant technique for modeling airborne transport of contaminants, while ABM is a powerful approach for modeling social dynamics in populations of adaptive individuals. The hybrid CFD-ABM method is capable of simulating how large, spatially-distributed populations might respond to a physically realistic contaminant plume. We demonstrate the overall feasibility of CFD-ABM evacuation design, using the case of a hypothetical aerosol release in Los Angeles to explore potential effectiveness of various policy regimes. We conclude by arguing that this new approach can be powerfully applied to arbitrary population centers, offering an unprecedented preparedness and catastrophic event response tool.     

Understanding the Dynamics of Violent Political Revolutions in an Agent-Based Framework

This paper develops an agent-based computational model of violent political revolutions in which a subjugated population of citizens and an armed revolutionary organisation attempt to overthrow a central authority and its loyal forces. The model replicates several patterns of rebellion consistent with major historical revolutions, and provides an explanation for the multiplicity of outcomes that can arise from an uprising. The relevance of the heterogeneity of scenarios predicted by the model can be understood by considering the recent experience of the Arab Spring involving several rebellions that arose in an apparently similar way, but resulted in completely different political outcomes: the successful revolution in Tunisia, the failed protests in Saudi Arabia and Bahrain, and civil war in Syria and Libya.     

Fostering Industrial Symbiosis With Agent-Based Simulation and Participatory Modeling

The sciences of industrial ecology, complex systems, and adaptive management are intimately related, since they deal with flows and dynamic interdependencies between system elements of various kinds. As such, the tool kit of complex systems science could enrich our understanding of how industrial ecosystems might evolve over time. In this article, I illustrate how an important tool of complex systems science— agent-based simulation —can help to identify those potential elements of an industrial ecosystem that could work together to achieve more eco-efficient outcomes. For example, I show how agent-based simulation can generate cost-efficient energy futures in which groups of firms behave more eco-efficiently by introducing strategically located clusters of renewable, low-emissions, distributed generation. I then explain how role-playing games and participatory modeling can build trust and reduce conflict about the sharing of common-pool resources such as water and energy among small clusters of evolving agents. Collective learning can encourage potential industrial partners to gradually cooperate by exchanging by-products and/or sharing common infrastructure by dint of their close proximity. This kind of coevolutionary learning, aided by participatory modeling, could help to bring about industrial symbiosis.     

The Experimental Evaluation and Molecular Dynamics Simulation of a Heat-Enhanced Transdermal Delivery System

Transdermal delivery systems are useful in cases where preferred routes such as the oral route are not available. However, low overall extent of delivery is seen due to the permeation barrier posed by the skin. Chemical penetration enhancers and invasive methods that disturb the structural barrier function of the skin can be used to improve transdermal drug delivery. However, for suitable drugs, a fast-releasing transdermal delivery system can be produced by incorporating a heating source into a transdermal patch. In this study, a molecular dynamics simulation showed that heat increased the diffusivity of the drug molecules, resulting in faster release from gels containing ketoprofen, diclofenac sodium, and lidocaine HCl. Simulations were confirmed by in vitro drug release studies through lipophilic membranes. These correlations could expand the application of heated transdermal delivery systems for use as fast-release-dosage forms.     

免疫衰老与老年人免疫

随着年龄的增加,人体免疫系统发生特征性的改变,"免疫衰老",从而导致传染病的发病率和严重程度增加及疫苗接种后保护不足。本文试图说明年龄依赖性的先天免疫和适应性免疫系统的缺陷。专门针对老年人的免疫系统,改进疫苗接种策略,研究新的佐剂和新的疫苗,将有助于克服免疫衰老的局限性,确保更好地保护脆弱的老年人口。     

Immunosenescence: potential causes and strategies for reversal

Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.     

Risk-Pooling and Herd Survival: An Agent-Based Model of a Maasai Gift-Giving System

We use agent-based modeling to study osotua, a gift giving system used by the Maasai of East Africa. Osotua’s literal meaning is “umbilical cord,” but it is used metaphorically to refer to a specific type of gift-giving relationship. Osotua relationships are characterized by respect, responsibility and restraint. Osotua partners ask each other for help only if they are in need and provide help only when asked and only if they are able. We hypothesize that under the ecologically volatile conditions in which Maasai pastoralists have traditionally lived, such a system is particularly suited to risk pooling. Here we explore whether osotua increases the viability of herds by comparing herd survivorship and stability under osotua rules to a) no exchange and b) probabilistic rules for requesting and giving livestock. Results from this model suggest that this gift-giving system can dramatically increase herd longevity through a limited pooling of risk.     

Heterogeneity in Thymic Emigrants: Implications for Thymectomy and Immunosenescence

The development of mature, antigen-inexperienced (naive) T cells begins in the thymus and continues after export into the periphery. Post-thymic maturation of naive T cells, in humans, coincides with the progressive loss of markers such as protein tyrosine kinase 7 (PTK7) and platelet endothelial cell adhesion molecule-1 (CD31). As a consequence, subpopulations of naive T cells can be recognised raising questions about the processes that give rise to the loss of these markers and their exact relationship to recent thymic emigrants (RTE). Here, we combine a mathematical survival analysis approach and data from healthy and thymectomised humans to understand the apparent persistence of populations of ‘veteran’ PTK7⁺T cells in thymectomised individuals. We show that a model of heterogeneity in rates of maturation, possibly linked to natural variation in TCR signalling thresholds or affinity for self-antigens, can explain the data. This model of maturation predicts that the average post-thymic age of PTK7⁺T cells will increase linearly with the age of the host suggesting that, despite the immature phenotype, PTK7⁺cells do not necessarily represent a population of RTE. Further, the model predicts an accelerated increase in the average post-thymic age of residual PTK7⁺T cells following thymectomy and may also explain in part the prematurely aged phenotype of the naive T cell pool in individuals thymectomised early in life.     

A Molecular Dynamics Simulation Study of Coaxial Stacking in RNA

Abstract

We report on unrestrained molecular dynamics simulations of an RNA tetramer binding to a tetra-nucleotide overhang at the 5′-end of an RNA hairpin (nicked structure) and of the corresponding continuous hairpin with Na⁺ as counterions. The simulations lead to stable structures and in this way a structural model for the coaxially stacked RNA hairpin is generated. The stacking interface in the coaxially stacked nicked hairpin structure is characterized by a reduced twist and shift and a slightly increased propeller twist as compared to the continuous system. This leads to an increased overlap between C22 and G23 in the stacking interface of the nicked structure. In the simulations the continuous RNA hairpin has an almost straight helical axis. On the other hand, the corresponding axis for the nicked structure exhibits a marked kink of 39°. The stacking interface exhibits no increased flexibility as compared to the corresponding base pair step in the continuous structure.     

The Effect of Increasing Water Temperatures on Schistosoma mansoni Transmission and Biomphalaria pfeifferi Population Dynamics: An Agent-Based Modelling Study

Introduction

There is increasing interest in the control and elimination of schistosomiasis. Little is known, however, about the likely effects of increasing water-body temperatures on transmission.

Methods

We have developed an agent-based model of the temperature-sensitive stages of the Schistosoma and intermediate host snail life-cycles, parameterised using data from S. mansoni and Biomphalaria pfeifferi laboratory and field-based observations. Infection risk is calculated as the number of cercariae in the model, adjusted for their probability of causing infection.

Results

The number of snails in the model is approximately constant between 15–31°C. Outside this range, snail numbers drop sharply, and the snail population cannot survive outside the range 14–32°C. Mean snail generation time decreases with increasing temperature from 176 days at 14°C to 46 days at 26°C. Human infection risk is highest between 16–18°C and 1 pm and 6–10 pm in calm water, and 20–25°C and 12–4 pm in flowing water. Infection risk increases sharply when temperatures increase above the minimum necessary for sustained transmission.

Conclusions

The model suggests that, in areas where S. mansoni is already endemic, warming of the water at transmission sites will have differential effects on both snails and parasites depending on abiotic properties of the water-body. Snail generation times will decrease in most areas, meaning that snail populations will recover faster from natural population reductions and from snail-control efforts. We suggest a link between the ecological properties of transmission sites and infection risk which could significantly affect the outcomes of interventions designed to alter water contact behaviour – proposing that such interventions are more likely to reduce infection levels at river locations than lakes, where infection risk remains high for longer. In cooler areas where snails are currently found, increasing temperatures may significantly increase infection risk, potentially leading to new, high-intensity foci of infection.     

Molecular Dynamics Simulation of Linear Polymers in a Solvent

This paper reports a series of simulations of a single linear polymer chain in solution. Both the monomer units and the solvent particles are represented by “beads” which interact via a purely repulsive shifted Lennard-Jones potential; the chains themselves are constructed by linking beads with relatively stiff elastic bonds. The chain lenghts range from 8 to 48 beads, and the total system size is between 1000 and 14000 beads. The static and dynamic properties of the polymer chains obtained from long simulations of these systems (over 10⁶ timesteps) are discussed, and the size and density dependence of the chain behavior examined.     

A Molecular Dynamics Simulation Study of Rigid and Non-rigid Hard Dumb-bells

Abstract

We present a comparative study, using molecular dynamics, of systems of diatomic, hard dumb-bell, molecules in which the interatomic distance is either constrained to a fixed value or is allowed to vary freely between preset limits. A significant improvement in simulation effciency can be attained by allowing the bond length to vary. We find that thermodynamic properties, and some time correlation functions, are only slightly affected by the removal of the rigid bond-length constraint. The atomic velocity correlation function responds dramatically at short times to changes in the degree of non-rigidity, but at long times these differences are much less important.     

Molecular Dynamics Simulation on a Parallel Computer

For the purpose of molecular dynamics simulations of large biopolymers we have built a parallel computer with a systolic loop architecture, based on Transputers as computational units, and have programmed it in occam II. The computational nodes of the computer are linked together in a systolic ring. The program based on this topology for large biopolymers increases its computational throughput nearly linearly with the number of computational nodes. The program developed is closely related to the simulation programs CHARMM and XPLOR, the input files required (force field, protein structure file, coordinates) and output files generated (sets of atomic coordinates representing dynamic trajectories and energies) are compatible with the corresponding files of these programs. Benchmark results of simulations of biopolymers comprising 66, 568, 3 634, 5 797 and 12 637 atoms are compared with XPLOR simulations on conventional computers (Cray, Convex, Vax). These results demonstrate that the software and hardware developed provide extremely cost effective biopolymer simulations. We present also a simulation (equilibrium of X-ray structure) of the complete photosynthetic reaction center of Rhodopseudomonas viridis (12 637 atoms). The simulation accounts for the Coulomb forces exactly, i.e. no cut-off had been assumed.     

Mitofusin-2 Independent Juxtaposition of Endoplasmic Reticulum and Mitochondria: An Ultrastructural Study

Besides its role in controlling the morphology of mitochondria, mitofusin-2 has been proposed to tether mitochondria to the endoplasmic reticulum (ER), based largely on light microscopic analysis. In this study we have examined by electron microscopy the organization of ER and mitochondria in cells expressing or not mitofusin-2. Contrary to previous studies, we observed that loss of mitofusin-2 increased ER-mitochondria juxtaposition. These results suggest that mitofusin-2 does not play a critical role in the juxtapostion of ER and mitochondria, and highlight the essential role of ultrastructural analysis to visualize and measure contact between two intracellular compartments.     

Temporal Dynamics of River Biofilm in Constant Flows: A Case Study in a Riverside Laboratory Flume

A 15‐week experiment was performed in a riverside laboratory flume (with diverted river water) to check variations of river biofilm structure (biomass, algal and bacterial compositions) and function (community gross primary production GPP and respiration) under constant flow while water quality went through natural temporal variations. One major suspended matter pulse coinciding with one river flood was recorded after 10 weeks of experiment. Epilithic biofilm first exhibited a 10‐week typical pattern of biomass accrual reaching 33 g ash‐free dry matter (AFDM) m^–2 and 487 mg chlorophyll‐a m^–2 and then, experienced a shift to dominance of loss processes (loss of 60% AFDM and 80% chlorophyll‐a) coinciding with the main suspended matter pulse. Algal diversity remained low and constant during the experiment: Fragilaria capucina and Encyonema minutum always contribute over 80% of cell counts. DGGE banding patterns discriminated between two groups that corresponded to samples before and after biomass loss, indicating major changes in the bacterial community composition. GPP/R remained high during the experiment, suggesting that photoautotrophic metabolism prevailed and detachment was not autogenic (i.e., due to algal senescence or driven by heterotrophic processes within the biofilm). Observational results suggested that silt deposition into the biofilm matrix could have triggered biomass loss. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)