The flexibility of myosin 7a

Myosin 7a is a molecular motor found in hair cells of the ear and the photoreceptor cells of the eye. Myosin 7a is comprised of an actin-binding motor domain, a lever; which is composed of 5 IQ motifs that can potentially bind 5 light chains followed by a single alpha helical (SAH) domain, and a tail composed of 2 MyTH4-FERM domains. The lever is an essential mechanical element in myosin 7a function, but an understanding of its mechanical properties and how these derive from its substructure is lacking. It has been observed in vitro that myosin 7a is able to regulate its activity through a head-tail interaction. How the flexibility of the sub-domains of the lever allows the molecule to fold up is not completely understood. To address this, the first aim of this study was to look for evidence of novel light chain binding partners in myosin 7a, which revealed calmodulin to be the preferred light chain. My second aim was to study the structure and flexibility of the lever of full-length myosin 7a using single-particle image processing of images from negative stain electron microscopy (EM). Image averaging revealed the lever to be much shorter than expected. Additionally, there was evidence of thermally-driven flexing at the motor-lever junction. A stiffness of 78 pN.nm.rad-2 for the flexing was inferred, which represents a significant compliance in the head. An investigation into lever bending analysis, by monitoring the decay of tangent-tangent correlations of the lever shapes, yielded a persistence length of 38 ± 3 nm. Finally, long time molecular dynamics (MD) simulations were compared with a novel coarse-grained (CG) simulation technique called Fluctuating Finite Element Analysis (FFEA), which treats proteins as visco-elastic continua subject to thermal noise to probe the flexibility of myosin 7a. FFEA allows sufficiently long time simulations that are computationally less expensive than corresponding all-atom MD simulations to allow myosin 7a to explore its full range of configurations. Extraction of flexibility data from all-atom MD simulations calculated the bending stiffness of the SAH domain to be 60.5 pN.nm2, with reasonable overlap of the major modes of motion between the all-atom and CG simulation types

Physics of Microswimmers - Single Particle Motion and Collective Behavior

Locomotion and transport of microorganisms in fluids is an essential aspect of life. Search for food, orientation toward light, spreading of off-spring, and the formation of colonies are only possible due to locomotion. Swimming at the microscale occurs at low Reynolds numbers, where fluid friction and viscosity dominates over inertia. Here, evolution achieved propulsion mechanisms, which overcome and even exploit drag. Prominent propulsion mechanisms are rotating helical flagella, exploited by many bacteria, and snake-like or whip-like motion of eukaryotic flagella, utilized by sperm and algae. For artificial microswimmers, alternative concepts to convert chemical energy or heat into directed motion can be employed, which are potentially more efficient. The dynamics of microswimmers comprises many facets, which are all required to achieve locomotion. In this article, we review the physics of locomotion of biological and synthetic microswimmers, and the collective behavior of their assemblies. Starting from individual microswimmers, we describe the various propulsion mechanism of biological and synthetic systems and address the hydrodynamic aspects of swimming. This comprises synchronization and the concerted beating of flagella and cilia. In addition, the swimming behavior next to surfaces is examined. Finally, collective and cooperate phenomena of various types of isotropic and anisotropic swimmers with and without hydrodynamic interactions are discussed.Comment: 54 pages, 59 figures, review article, Reports of Progress in Physics (to appear

Non-determinism in the narrative structure of video games

PhD ThesisAt the present time, computer games represent a finite interactive system. Even in their more experimental forms, the number of possible interactions between player and NPCs (non-player characters) and among NPCs and the game world has a finite number and is led by a deterministic system in which events can therefore be predicted. This implies that the story itself, seen as the series of events that will unfold during gameplay, is a closed system that can be predicted a priori. This study looks beyond this limitation, and identifies the elements needed for the emergence of a non-finite, emergent narrative structure. Two major contributions are offered through this research. The first contribution comes in the form of a clear categorization of the narrative structures embracing all video game production since the inception of the medium. In order to look for ways to generate a non-deterministic narrative in games, it is necessary to first gain a clear understanding of the current narrative structures implemented and how their impact on users’ experiencing of the story. While many studies have observed the storytelling aspect, no attempt has been made to systematically distinguish among the different ways designers decide how stories are told in games. The second contribution is guided by the following research question: Is it possible to incorporate non-determinism into the narrative structure of computer games? The hypothesis offered is that non-determinism can be incorporated by means of nonlinear dynamical systems in general and Cellular Automata in particular

Critical Market Crashes

This review is a partial synthesis of the book ``Why stock market crash'' (Princeton University Press, January 2003), which presents a general theory of financial crashes and of stock market instabilities that his co-workers and the author have developed over the past seven years. The study of the frequency distribution of drawdowns, or runs of successive losses shows that large financial crashes are ``outliers'': they form a class of their own as can be seen from their statistical signatures. If large financial crashes are ``outliers'', they are special and thus require a special explanation, a specific model, a theory of their own. In addition, their special properties may perhaps be used for their prediction. The main mechanisms leading to positive feedbacks, i.e., self-reinforcement, such as imitative behavior and herding between investors are reviewed with many references provided to the relevant literature outside the confine of Physics. Positive feedbacks provide the fuel for the development of speculative bubbles, preparing the instability for a major crash. We demonstrate several detailed mathematical models of speculative bubbles and crashes. The most important message is the discovery of robust and universal signatures of the approach to crashes. These precursory patterns have been documented for essentially all crashes on developed as well as emergent stock markets, on currency markets, on company stocks, and so on. The concept of an ``anti-bubble'' is also summarized, with two forward predictions on the Japanese stock market starting in 1999 and on the USA stock market still running. We conclude by presenting our view of the organization of financial markets.Comment: Latex 89 pages and 38 figures, in press in Physics Report

A comparison of processing techniques for producing prototype injection moulding inserts.

This project involves the investigation of processing techniques for producing low-cost moulding inserts used in the particulate injection moulding (PIM) process. Prototype moulds were made from both additive and subtractive processes as well as a combination of the two. The general motivation for this was to reduce the entry cost of users when considering PIM. PIM cavity inserts were first made by conventional machining from a polymer block using the pocket NC desktop mill. PIM cavity inserts were also made by fused filament deposition modelling using the Tiertime UP plus 3D printer. The injection moulding trials manifested in surface finish and part removal defects. The feedstock was a titanium metal blend which is brittle in comparison to commodity polymers. That in combination with the mesoscale features, small cross-sections and complex geometries were considered the main problems. For both processing methods, fixes were identified and made to test the theory. These consisted of a blended approach that saw a combination of both the additive and subtractive processes being used. The parts produced from the three processing methods are investigated and their respective merits and issues are discussed