Detachment, Futile Cycling and Nucleotide Pocket Collapse in Myosin-V Stepping

Myosin-V is a highly processive dimeric protein that walks with 36nm steps along actin tracks, powered by coordinated ATP hydrolysis reactions in the two myosin heads. No previous theoretical models of the myosin-V walk reproduce all the observed trends of velocity and run-length with [ADP], [ATP] and external forcing. In particular, a result that has eluded all theoretical studies based upon rigorous physical chemistry is that run length decreases with both increasing [ADP] and [ATP]. We systematically analyse which mechanisms in existing models reproduce which experimental trends and use this information to guide the development of models that can reproduce them all. We formulate models as reaction networks between distinct mechanochemical states with energetically determined transition rates. For each network architecture, we compare predictions for velocity and run length to a subset of experimentally measured values, and fit unknown parameters using a bespoke MCSA optimization routine. Finally we determine which experimental trends are replicated by the best-fit model for each architecture. Only two models capture them all: one involving [ADP]-dependent mechanical detachment, and another including [ADP]-dependent futile cycling and nucleotide pocket collapse. Comparing model-predicted and experimentally observed kinetic transition rates favors the latter.Comment: 11 pages, 5 figures, 6 table

Entrepreneurial Inclination Among Business Students: a Malaysian Study

Entrepreneurship has been the fundamental topics of discussion among the politicians, economists, and academics. Business creation is especially critical in developing countries to stimulate economic growth. The present study attempts to examine entrepreneurial inclination among students who are a potential source of entrepreneurs. The fi ndings of the present research study indicate that majority of our business students are not entrepreneurial-inclined. They do not seem to possess strong entrepreneurial characteristics and entrepreneurial skills, and they are not keen in starting a new business. The roles of higher institutes of education and the government in promoting entrepreneurship are discussed

Surface coatings and catalyst production by electrodeposition

Electrodeposition and electrocodeposition in low gravity are discussed. The goal is to provide a better understanding of the role of convection and buoyancy in the mechanisms of formation of some electrodeposited surfaces, fluid flow in the vicinity of electrodepositing surfaces, the influence of a moving medium upon codeposition, the effect of gravity upon the dispersion (coagulation) of neutral particles that are desired for codeposition and preparation of improved surface coatings and metal catalysts

Doing the Work of Medicine? Medical Television Programmes and Patient Behaviour

This article explores the contribution of television programmes to shaping the doctor-patient relationship in Britain in the Sixties and beyond. Our core proposition is that TV programmes on medicine ascribe a specifi c position as patients to viewers. This is what we call the ‘Inscribed Patient’. In this article we discuss a number of BBC programmes centred on medicine, from the 1958 ‘On Call to a Nation’; to the 1985 ‘A Prize Discovery’, to examine how television accompanied the development of desired patient behaviour during the transition to what was dubbed “Modern Medicine” in early 1970s Britain. To support our argument about the “Inscribed Patient”, we draw a comparison with natural history programmes from the early 1960s, which similarly prescribed specifi c agencies to viewers as potential participants in wildlife fi lmmaking. We conclude that a ‘patient position’ is inscribed in biomedical television programmes, which advance propositions to laypeople about how to submit themselves to medical expertise. Inscribed patient; doctor-patient relationship; biomedical television programmes; wildlife television; documentary television; BBC Horizo

A customer relationship management case study : critical success factors in action

Critical success factors (CSFs) are seen as a way of identifying those elements of an information systems project that are critical for the success of that project. However, existing research about CSFs has been largely derivative in nature. Many researchers use the existing literature to derive their lists of CSFs for industries, IS domains (such as: EIS, ERP, CRM) and case studies. Moreover, these lists have come from only one targeted group of people, senior management. There is a need for a new perspective and fresh primary sources. This paper argues that after 27 years of CSF method application little theoretical development has occurred Firstly, CSFs are not easily deciphered or compiled; and secondly, hierarchical (multiple) lists of CSFs may present a better representation of the position. Using a case study in CRM adoption and implementation, this paper discusses research undertaken to determine the nature of CSFs and highlights the issues, and problems in CSFs thinking over the past two decades, while providing a new interpretation of CSFs in use

Observations of 3-D transverse dispersion and dilution in natural consolidated rock by X-ray tomography

Recent studies have demonstrated the importance of transverse dispersion for dilution and mixing of solutes but most observations have remained limited to two-dimensional sand-box models. We present a new core-flood test to characterize solute transport in 3-D natural-rock media. A device consisting of three annular regions was used for fluid injection into a cylindrical rock core. Pure water was injected into the center and outer region and a NaI solution into the middle region. Steady state transverse dispersion of NaI was visualized with an X-ray medical CT-scanner for a range of Peclét numbers. Three methods were used to calculate Dt: (1) fitting an analytical solution, (2) analyzing the second-central moment, and (3) analyzing the dilution index and reactor ratio. Transverse dispersion decreased with distance due to flow focusing. Furthermore, Dt in the power-law regime showed sub-linear behavior. Overall, the reactor ratios were high confirming the homogeneity of Berea sandstone

Heavy metal bioaccumulation by the important food plant, olea europaea L., in an ancient metalliferous polluted area of Cyprus

Aspects of the bioaccumulation of heavy metals are reviewed and possible evidence of homeostasis is highlighted. Examination and analysis of olive (Olea europaea L.) trees growing in close proximity to a copper dominated spoil tip dating from at least 2000 years BP, on the island of Cyprus, revealed both bioaccumulation and partitioning of copper, lead and zinc in various parts of the tree. A factor to quantify the degree of accumulation is illustrated and a possible seed protective mechanism suggested

A repulsive reference potential reproducing the dynamics of a liquid with attractions

A well-known result of liquid state theory is that the structure of dense fluids is mainly determined by repulsive forces. The WCA potential, which cuts intermolecular potentials at their minima, is therefore often used as a reference. However, this reference gives quite wrong results for the viscous dynamics of the Kob-Andersen binary Lennard-Jones liquid [Berthier and Tarjus, Phys. Rev. Lett. 103, 170601 (2009)]. We show that repulsive inverse-power law potentials provide a useful reference for this liquid by reproducing its structure, dynamics, and isochoric heat capacity

Exact dynamic properties of molecular motors

Molecular motors play important roles within a biological cell, performing functions such as intracellular transport and gene transcription. Recent experimental work suggests that there are many plausible biochemical mechanisms that molecules such as myosin-V could use to achieve motion. To account for the abundance of possible discrete-stochastic frameworks that can arise when modeling molecular motor walks, a generalized and straightforward graphical method for calculating their dynamic properties is presented. It allows the calculation of the velocity, dispersion, and randomness ratio for any proposed system through analysis of its structure. This article extends work of King and Altman ["A schematic method of deriving the rate laws of enzyme-catalyzed reactions," J. Phys. Chem. 60, 1375-1378 (1956)] on networks of enzymatic reactions by calculating additional dynamic properties for spatially hopping systems. Results for n-state systems are presented: single chain, parallel pathway, divided pathway, and divided pathway with a chain. A novel technique for combining multiple system architectures coupled at a reference state is also demonstrated. Four-state examples illustrate the effectiveness and simplicity of these methods

Thermodiffusion in model nanofluids by molecular dynamics simulations

In this work, a new algorithm is proposed to compute single particle (infinite dilution) thermodiffusion using Non-Equilibrium Molecular Dynamics simulations through the estimation of the thermophoretic force that applies on a solute particle. This scheme is shown to provide consistent results for simple Lennard-Jones fluids and for model nanofluids (spherical non-metallic nanoparticles + Lennard-Jones fluid) where it appears that thermodiffusion amplitude, as well as thermal conductivity, decrease with nanoparticles concentration. Then, in nanofluids in the liquid state, by changing the nature of the nanoparticle (size, mass and internal stiffness) and of the solvent (quality and viscosity) various trends are exhibited. In all cases the single particle thermodiffusion is positive, i.e. the nanoparticle tends to migrate toward the cold area. The single particle thermal diffusion 2 coefficient is shown to be independent of the size of the nanoparticle (diameter of 0.8 to 4 nm), whereas it increases with the quality of the solvent and is inversely proportional to the viscosity of the fluid. In addition, this coefficient is shown to be independent of the mass of the nanoparticle and to increase with the stiffness of the nanoparticle internal bonds. Besides, for these configurations, the mass diffusion coefficient behavior appears to be consistent with a Stokes-Einstein like law