Atomistic Insights into Rhodopsin Activation from a Dynamic Model

Rhodopsin, the light sensitive receptor responsible for blue-green vision, serves as a prototypical G protein-coupled receptor (GPCR). Upon light absorption, it undergoes a series of conformational changes that lead to the active form, metarhodopsin II (META II), initiating a signaling cascade through binding to the G protein transducin (G(t)). Here, we first develop a structural model of META II by applying experimental distance restraints to the structure of lumi-rhodopsin (LUMI), an earlier intermediate. The restraints are imposed by using a combination of biased molecular dynamics simulations and perturbations to an elastic network model. We characterize the motions of the transmembrane helices in the LUMI-to-META II transition and the rearrangement of interhelical hydrogen bonds. We then simulate rhodopsin activation in a dynamic model to study the path leading from LUMI to our META II model for wild-type rhodopsin and a series of mutants. The simulations show a strong correlation between the transition dynamics and the pharmacological phenotypes of the mutants. These results help identify the molecular mechanisms of activation in both wild type and mutant rhodopsin. While static models can provide insights into the mechanisms of ligand recognition and predict ligand affinity, a dynamic model of activation could be applicable to study the pharmacology of other GPCRs and their ligands, offering a key to predictions of basal activity and ligand efficacy.

Validation of the CDC Biofilm Reactor as a Dynamic Model for Assessment of Encrustation Formation on Urological Device Materials

Contemporary medical science is reliant upon the rational selection and utilization of devices, and therefore, an increasing need has developed for in vitro systems aimed at replicating the conditions to which urological devices will be subjected to during their use in vivo. We report the development and validation of a novel continuous flow encrustation model based on the commercially available CDC biofilm reactor. Proteus mirabilis-induced encrustation formation on test biomaterial sections under varying experimental parameters was analyzed by X-ray diffraction, infrared- and Raman spectroscopy and by scanning electron microscopy. The model system produced encrusted deposits similar to those observed in archived clinical samples. Results obtained for the system are highly reproducible with encrustation being rapidly deposited on test biomaterial sections. This model will have utility in the rapid screening of encrustation behavior of biomaterials for use in urological applications. (C) 2010 Wiley Periodicals. Inc. J Biomed Mater Res Part B: Appl Biomater 93B: 128-140, 2010

Accounting, Regulation and Profitability: The Case of PFI Hospital Refinancing

The refinancing of PFI (Private Finance Initiative) projects represents one of the most contentious aspects of Public Private Partnerships (PPPs) in the UK. The negative publicity associated with UK PFI refinancing deals is associated with several factors, including, evidence of massive private sector profit making, the failure of private sector financiers to share refinancing profits and, lastly, private sector frustration of adequate regulatory intervention in this area. Utilising a dynamic model of capital market and state interaction, this paper explains these outcomes as a function of effective private sector lobbying of bureaucratic state agencies to alter the structure of accounting, accountability and regulation with the goal of securing favourable profit and risk outcomes. These dynamics are illustrated with reference to the history of UK PFI refinancing and a case study of one of the projects where these gains reached extreme levels.

COLREGs-based collision avoidance strategies for unmanned surface vehicles

The aim of this paper is to report the preliminary development of an automatic collision avoidance technique for unmanned marine craft based on standardised rules, COLREGs, defined by the International Maritime Organisation. It is noted that all marine surface vessels are required to adhere to COLREGs at all times in order to minimise or eliminate the risk of collisions. The approach presented is essentially a reactive path planning algorithm which provides feedback to the autopilot of an unmanned vessel or the human captain of a manned ship for steering the craft safely. The proposed strategy consists of waypoint guidance by line-of-sight coupled with a manual biasing scheme. This is applied to the dynamic model of an unmanned surface vehicle. A simple PID autopilot is incorporated to ensure that the vessel adheres to the generated seaway. It is shown through simulations that the resulting scheme is able to generate viable trajectories in the presence of both stationary and dynamic obstacles. Rules 8 and 14 of the COLREGs, which apply to the amount of manoeuvre and to a head-on scenario respectively are simulated. A comparison is also made with an offline or deliberative grid-based path planning algorithm which has been modified to generate COLREGs-compliant routes.

A qualitative enquiry into the appropriation of mobile telephony at the bottom of the pyramid

Purpose: The paper aims to analyse Bottom of the Pyramid (BoP) customers’ (e.g. Bangladeshi farmers) use and appropriation of mobile telephony and to critically identify a suitable research strategy for such investigation.

Design/methodology/approach: Concentrated ethnographic immersion was combined with both methodological and investigator triangulation during a four-month period of fieldwork conducted in Bangladeshi villages to obtain more robust findings. Concentrated immersion was required to achieve relatively speedier engagement owing to the difficulty in engaging with respondents on a long-term basis.

Findings: The farmers’ use of mobile telephony went beyond the initial adoption, as they appropriated it through social and institutional support, inventive means and/or changes in their own lifestyle. The paper argues that technology appropriation, being a result of the mutual shaping of technology, human skills and abilities and macro-environmental factors, enables users to achieve desired outcomes which may not always be the ones envisaged by the original designers.

Research limitations/implications: The paper contributes to two major areas: first, it identifies technology appropriation as an important and emerging concept in international marketing research; second, it suggests a concentrated form of ethnographic engagement for studying technology appropriation in a developing country context.

Practical implications: A good understanding of the dynamic interplay between users’ skills and abilities, social contexts and technological artefacts/applications is required in order for businesses to serve BoP customers profitably.

Originality/value: The paper presents a dynamic model of technology appropriation based on findings collected through a pragmatic approach by combining concentrated ethnographic immersion with methodological and investigator triangulation

Strategies of actin reorganisation in plant cells

Spatial-temporal flexibility of the actin filament network (F-actin) is essential for all basic cellular functions and is governed by a stochastic dynamic model. In this model, actin filaments that randomly polymerise from a pool of free actin are bundled with other filaments and severed by ADF/cofilin. The fate of the severed fragments is not known. It has been proposed that the fragments are disassembled and the monomeric actin recycled for the polymerisation of new filaments. Here, we have generated tobacco cell lines and Arabidopsis plants expressing the actin marker Lifeact to address the mechanisms of F-actin reorganisation in vivo. We found that F-actin is more dynamic in isotropically expanding cells and that the density of the network changes with a periodicity of 70 seconds. The depolymerisation rate, but not the polymerisation rate, of F-actin increases when microtubules are destabilised. New filaments can be assembled from shorter free cytoplasmic fragments, from the products of F-actin severing and by polymerisation from the ends of extant filaments. Thus, remodelling of F-actin might not require bulk depolymerisation of the entire network, but could occur via severing and end-joining of existing polymers.

Performance management systems and Public Value Strategy: a case study

Purpose
This article aims to analyze the role of performance management systems (PMS) in supporting public value strategies.

Design/methodology/approach
This article draws on the public value dynamic model by Horner and Hutton (2010). It presents the results of a case study of implementation of a PMS model, the ‘Value Pyramid’ (VP).

Findings
The results stress the need for an improved conceptualization of PMS within public value strategy. Through experimentation using the VP, the case site was able to measure and visualize what it considered public value and reflect on the internal/external causes of both creation and destruction of public value.

Research limitations/implication
This article is limited to just one case study, although in-depth and longitudinal.

Originality/value
This article is one of the first attempting to understand the role of PMS within the public value strategy framework, answering the call of Benington and Moore (2010) to consider public value from an accounting perspective.

Characterisation of pavement profile heights using accelerometer readings and a combinatorial optimisation technique

Pavement surface profiles induce dynamic ride responses in vehicles which can potentially be used to classify road surface roughness. A novel method is proposed for the characterisation of pavement roughness through an analysis of vehicle accelerations. A combinatorial optimisation technique is applied to the determination of pavement profile heights based on measured accelerations at and above the vehicle axle. Such an approach, using low-cost inertial sensors, would provide an inexpensive alternative to the costly laser-based profile measurement vehicles. The concept is numerically validated using a half-car roll dynamic model to infer measurements of road profiles in both the left and right wheel paths.

Dynamic pricing model and algorithm for perishable products with fuzzy demand (ABS 2* Journal)

This paper studies the dynamic pricing problem of selling fixed stock of perishable items over a finite horizon, where the decision maker does not have the necessary historic data to estimate the distribution of uncertain demand, but has imprecise information about the quantity demand. We model this uncertainty using fuzzy variables. The dynamic pricing problem based on credibility theory is formulated using three fuzzy programming models, viz.: the fuzzy expected revenue maximization model, a-optimistic revenue maximization model, and credibility maximization model. Fuzzy simulations for functions with fuzzy parameters are given and embedded into a genetic algorithm to design a hybrid intelligent algorithm to solve these three models. Finally, a real-world example is presented to highlight the effectiveness of the developed model and algorithm.