Time dependency of molecular rate estimates and systematic overestimation of recent divergence times

Studies of molecular evolutionary rates have yielded a wide range of rate estimates for various genes and taxa. Recent studies based on population-level and pedigree data have produced remarkably high estimates of mutation rate, which strongly contrast with substitution rates inferred in phylogenetic (species-level) studies. Using Bayesian analysis with a relaxed-clock model, we estimated rates for three groups of mitochondrial data: avian protein-coding genes, primate protein-coding genes, and primate d-loop sequences. In all three cases, we found a measurable transition between the high, short-term (<1–2 Myr) mutation rate and the low, long-term substitution rate. The relationship between the age of the calibration and the rate of change can be described by a vertically translated exponential decay curve, which may be used for correcting molecular date estimates. The phylogenetic substitution rates in mitochondria are approximately 0.5% per million years for avian protein-coding sequences and 1.5% per million years for primate protein-coding and d-loop sequences. Further analyses showed that purifying selection offers the most convincing explanation for the observed relationship between the estimated rate and the depth of the calibration. We rule out the possibility that it is a spurious result arising from sequence errors, and find it unlikely that the apparent decline in rates over time is caused by mutational saturation. Using a rate curve estimated from the d-loop data, several dates for last common ancestors were calculated: modern humans and Neandertals (354 ka; 222–705 ka), Neandertals (108 ka; 70–156 ka), and modern humans (76 ka; 47–110 ka). If the rate curve for a particular taxonomic group can be accurately estimated, it can be a useful tool for correcting divergence date estimates by taking the rate decay into account. Our results show that it is invalid to extrapolate molecular rates of change across different evolutionary timescales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.

Evidence for time dependency of molecular rate estimates

Long-term changes in the genetic composition of a population occur by the fixation of new mutations, a process known as substitution. The rate at which mutations arise in a population and the rate at which they are fixed are expected to be equal under neutral conditions (Kimura, 1968). Between the appearance of a new mutation and its eventual fate of fixation or loss, there will be a period in which it exists as a transient polymorphism in the population (Kimura and Ohta, 1971). If the majority of mutations are deleterious (and nonlethal), the fixation probabilities of these transient polymorphisms are reduced and the mutation rate will exceed the substitution rate (Kimura, 1983). Consequently, different apparent rates may be observed on different time scales of the molecular evolutionary process (Penny, 2005; Penny and Holmes, 2001). The substitution rate of the mitochondrial protein-coding genes of birds and mammals has been traditionally recognized to be about 0.01 substitutions/site/million years (Myr) (Brown et al., 1979; Ho, 2007; Irwin et al., 1991; Shields and Wilson, 1987), with the noncoding D-loop evolving several times more quickly (e.g., Pesole et al., 1992; Quinn, 1992). Over the past decade, there has been mounting evidence that instantaneous mutation rates substantially exceed substitution rates, in a range of organisms (e.g., Denver et al., 2000; Howell et al., 2003; Lambert et al., 2002; Mao et al., 2006; Mumm et al., 1997; Parsons et al., 1997; Santos et al., 2005). The immediate reaction to the first of these findings was that the polymorphisms generated by the elevated mutation rate are short-lived, perhaps extending back only a few hundred years (Gibbons, 1998; Macaulay et al., 1997). That is, purifying selection was thought to remove these polymorphisms very rapidly.

Storytelling; safeguarding; treatment; and responsibility; attributes of recovery in psychiatric intensive care units

Background and aim In recent years policy in Australia has endorsed recovery-oriented mental health services underpinned by the needs, rights and values of people with lived experience of mental illness. This paper critically reviews the idea of recovery understood by nurses at the frontline of services for people experiencing acute psychiatric distress. Method Data gathered from focus groups held with nurses from two hospitals were used to ascertain their use of terminology, understanding of attributes and current practices that support recovery for people experiencing acute psychiatric distress. A review of literature further examined current nurse based evidence and nurse knowledge of recovery approaches specific to psychiatric intensive care settings. Results Four defining attributes of recovery based on nurses’ perspectives are shared to identify and describe strategies that may help underpin recovery specific to psychiatric intensive care settings. Conclusion The four attributes described in this paper provide a pragmatic framework with which nurses can reinforce their clinical decision-making and negotiate the dynamic and often incongruous challenges they experience to embed recovery-oriented culture in acute psychiatric settings.

A brush with the real world : the future of inertial motion capture in live performance

3D Motion capture is a medium that plots motion, typically human motion, converting it into a form that can be represented digitally. It is a fast evolving field and recent inertial technology may provide new artistic possibilities for its use in live performance. Although not often used in this context, motion capture has a combination of attributes that can provide unique forms of collaboration with performance arts. The inertial motion capture suit used for this study has orientation sensors placed at strategic points on the body to map body motion. Its portability, real-time performance, ease of use, and its immunity from line-of-sight problems inherent in optical systems suggest it would work well as a live performance technology. Many animation techniques can be used in real-time. This research examines a broad cross-section of these techniques using four practice-led cases to assess the suitability of inertial motion capture to live performance. Although each case explores different visual possibilities, all make use of the performativity of the medium, using either an improvisational format or interactivity among stage, audience and screen that would be difficult to emulate any other way. A real-time environment is not capable of reproducing the depth and sophistication of animation people have come to expect through media. These environments take many hours to render. In time the combination of what can be produced in real-time and the tools available in a 3D environment will no doubt create their own tree of aesthetic directions in live performance. The case study looks at the potential of interactivity that this technology offers.

Attractiveness of venture ideas : a conjoint study

Principal Topic : According to Shane & Venkataraman (2000) entrepreneurship consists of the recognition and exploitation of venture ideas - or opportunities as they often called - to create future goods and services. This definition puts venture ideas is at the heart of entrepreneurship research. Substantial research has been done on venture ideas in order to enhance our understanding of this phenomenon (e.g. Choi & Shepherd, 2004; Shane, 2000; Shepherd & DeTienne, 2005). However, we are yet to learn what factors drive entrepreneurs' perceptions of the relative attractiveness of venture ideas, and how important different idea characteristics are for such assessments. Ruef (2002) recognized that there is an uneven distribution of venture ideas undertaken by entrepreneurs in the USA. A majority introduce either a new product/service or access a new market or market segment. A smaller percentage of entrepreneurs introduce a new method of production, organizing, or distribution. This implies that some forms of venture ideas are perceived by entrepreneurs as more important or valuable than others. However, Ruef does not provide any information regarding why some forms of venture ideas are more common than others among entrepreneurs. Therefore, this study empirically investigates what factors affect the attractiveness of venture ideas as well as their relative importance. Based on two key characteristics of venture ideas, namely venture idea newness and relatedness, our study investigates how different types and degrees of newness and relatedness of venture ideas affect their attractiveness as perceived by expert entrepreneurs. Methodology/Key : Propositions According to Schumpeter (1934) entrepreneurs introduce different types of venture ideas such as new products/services, new method of production, enter into new markets/customer and new method of promotion. Further, according to Schumpeter (1934) and Kirzner (1973) venture ideas introduced to the market range along a continuum of innovative to imitative ideas. The distinction between these two extremes of venture idea highlights an important property of venture idea, namely their newness. Entrepreneurs, in order to gain competitive advantage or above average returns introduce their venture ideas which may be either new to the world, new to the market that they seek to enter, substantially improved from current offerings and an imitative form of existing offerings. Expert entrepreneurs may be more attracted to venture ideas that exhibit high degree of newness because of the higher newness is coupled with increased market potential (Drucker, 1985) Moreover, certain individual characteristics also affect the attractiveness of venture idea. According to Shane (2000), individual's prior knowledge is closely associated with the recognition of venture ideas. Sarasvathy's (2001) Effectuation theory proposes a high degree of relatedness between venture ideas and the resource position of the individual. Thus, entrepreneurs may be more attracted to venture ideas that are closely aligned with the knowledge and/or resources they already possess. On the other hand, the potential financial gain (Shepherd & DeTienne, 2005) may be larger for ideas that are not close to the entrepreneurs' home turf. Therefore, potential financial gain is a stimulus that has to be considered separately. We aim to examine how entrepreneurs weigh considerations of different forms of newness and relatedness as well as potential financial gain in assessing the attractiveness of venture ideas. We use conjoint analysis to determine how expert entrepreneurs develop preferences for venture ideas which involved with different degrees of newness, relatedness and potential gain. This analytical method paves way to measure the trade-offs they make when choosing a particular venture idea. The conjoint analysis estimates respondents' preferences in terms of utilities (or part-worth) for each level of newness, relatedness and potential gain of venture ideas. A sample of 50 expert entrepreneurs who were awarded young entrepreneurship awards in Sri Lanka in 2007 is used for interviews. Each respondent is interviewed providing with 32 scenarios which explicate different combinations of possible profiles open them into consideration. Conjoint software (SPSS) is used to analyse data. Results and Implications : The data collection of this study is still underway. However, results of this study will provide information regarding the attractiveness of each level of newness, relatedness and potential gain of venture idea and their relative importance in a business model. Additionally, these results provide important implications for entrepreneurs, consultants and other stakeholders as regards the importance of different of attributes of venture idea coupled with different levels. Entrepreneurs, consultants and other stakeholders could make decisions accordingly.

Attribute exclusion strategies in airline choice : accounting for exogenous information on decision maker processing strategies in models of discrete choice

We examine the impact of individual-specific information processing strategies (IPSs) on the inclusion/exclusion of attributes on the parameter estimates and behavioural outputs of models of discrete choice. Current practice assumes that individuals employ a homogenous IPS with regards to how they process attributes of stated choice (SC) experiments. We show how information collected exogenous of the SC experiment on whether respondents either ignored or considered each attribute may be used in the estimation process, and how such information provides outputs that are IPS segment specific. We contend that accounting the inclusion/exclusion of attributes will result in behaviourally richer population parameter estimates.

Flexural and torsional rigidity of colonoscope at room and body temperatures

A series of experiments have been conducted to determine the flexural, EI, and torsional, GJ, rigidity of an Olympus colonoscope CF‐140S and torsional rigidity of a Pentax colonoscope EC‐3870 and the dependency of these properties on temperature and on the presence of loops. Along the length of the colonoscope, the Olympus colonoscope flexural rigidity varied between 260 and 400 Ncm2 and torsional rigidity varied between 68 and 88 Ncm2/deg, with an average of 76 Ncm2/deg for tests involving 0.86 Nm of anti‐clockwise torque. Results show a significant decrease of 10% in torsional rigidity between clockwise and anti‐clockwise torque. For the Pentax colonoscope flexural rigidity was not tested; its torsional rigidity varied between 34 and 76 Ncm2/deg, with an average of 46 Ncm2/deg for tests involving 0.43 Nm of anti‐clockwise torque. An increase in temperature of the Olympus colonoscope from 24°C to 37°C reduces EI by an average of 17% and GJ by an average of 7%. A right‐handed loop caused a significant increase in flexural rigidity, but other looping configurations had no significant influence.

Application of machine learning in fault diagnostics of mechanical systems

A diagnostic method based on Bayesian Networks (probabilistic graphical models) is presented. Unlike conventional diagnostic approaches, in this method instead of focusing on system residuals at one or a few operating points, diagnosis is done by analyzing system behavior patterns over a window of operation. It is shown how this approach can loosen the dependency of diagnostic methods on precise system modeling while maintaining the desired characteristics of fault detection and diagnosis (FDD) tools (fault isolation, robustness, adaptability, and scalability) at a satisfactory level. As an example, the method is applied to fault diagnosis in HVAC systems, an area with considerable modeling and sensor network constraints.

An analytical and experimental study of the vibration response of a clamped ribbed plate

An analytical solution is presented in this paper for the vibration response of a ribbed plate clamped on all its boundary edges by employing a travelling wave solution. A clamped ribbed plate test rig is also assembled in this study for the experimental investigation of the ribbed plate response and to provide verification results to the analytical solution. The dynamic characteristics and mode shapes of the ribbed plate are measured and compared to those obtained from the analytical solution and from finite element analysis (FEA). General good agreements are found between the results. Discrepancies between the computational and experimental results at low and high frequencies are also discussed. Explanations are offered in the study to disclose the mechanism causing the discrepancies. The dependency of the dynamic response of the ribbed plate on the distance between the excitation force and the rib is also investigated experimentally. It confirms the findings disclosed in a previous analytical study [T. R. Lin and J. Pan, A closed form solution for the dynamic response of finite ribbed plates. Journal of the Acoustical Society of America 119 (2006) 917-925] that the vibration response of a clamped ribbed plate due to a point force excitation is controlled by the plate stiffness when the source is more than a quarter plate bending wavelength away from the rib and from the plate boundary. The response is largely affected by the rib stiffness when the source location is less than a quarter bending wavelength away from the rib.

Prandtl number scaling of natural convection of an inclined flat plate due to uniform surface heat flux

A new scaling analysis has been performed for the unsteady natural convection boundary layer under a downward facing inclined plate with uniform heat flux. The development of the thermal or viscous boundary layers may be classified into three distinct stages including a start-up stage, a transitional stage and a steady stage, which can be clearly identified in the analytical as well as numerical results. Earlier scaling shows that the existing scaling laws of the boundary layer thickness, velocity and steady state time scale for the natural convection flow on a heated plate of uniform heat flux provide a very poor prediction of the Prandtl number dependency of the flow. However, those scalings performed very well with Rayleigh number and aspect ratio dependency. In this study, a new Prandtl number scaling has been developed using a triple-layer integral approach for Pr > 1. It is seen that in comparison to the direct numerical simulations, the new scaling performs considerably better than the previous scaling.

Scaling for the Prandtl number of the natural convection boundary layer of an inclined flat plate under uniform surface heat flux

An improved scaling analysis and direct numerical simulations are performed for the unsteady natural convection boundary layer adjacent to a downward facing inclined plate with uniform heat flux. The development of the thermal or viscous boundary layers may be classified into three distinct stages: a start-up stage, a transitional stage and a steady stage, which can be clearly identified in the analytical as well as the numerical results. Previous scaling shows that the existing scaling laws of the boundary layer thickness, velocity and steady state time scale for the natural convection flow on a heated plate of uniform heat flux provide a very poor prediction of the Prandtl number dependency of the flow. However, those scalings perform very well with Rayleigh number and aspect ratio dependency. In this study, a modified Prandtl number scaling is developed using a triple layer integral approach for Pr > 1. It is seen that in comparison to the direct numerical simulations, the modified scaling performs considerably better than the previous scaling.

Prandtl number scaling of the unsteady natural convection boundary layer adjacent to a vertical flat plate for Pr > 1 subject to ramp surface heat flux

It is found in the literature that the existing scaling results for the boundary layer thickness, velocity and steady state time for the natural convection flow over an evenly heated plate provide a very poor prediction of the Prandtl number dependency of the flow. However, those scalings provide a good prediction of two other governing parameters’ dependency, the Rayleigh number and the aspect ratio. Therefore, an improved scaling analysis using a triple-layer integral approach and direct numerical simulations have been performed for the natural convection boundary layer along a semi-infinite flat plate with uniform surface heat flux. This heat flux is a ramp function of time, where the temperature gradient on the surface increases with time up to some specific time and then remains constant. The growth of the boundary layer strongly depends on the ramp time. If the ramp time is sufficiently long, the boundary layer reaches a quasi steady mode before the growth of the temperature gradient is completed. In this mode, the thermal boundary layer at first grows in thickness and then contracts with increasing time. However, if the ramp time is sufficiently short, the boundary layer develops differently, but after the wall temperature gradient growth is completed, the boundary layer develops as though the startup had been instantaneous.

Simulation-based comparison of pull-push system in motorcycle assembly line

To investigate the effects of adopting a pull system in assembly lines in contrast to a push system, simulation software called “ARENA” is used as a tool in order to present numerical results from both systems. Simulation scenarios are created to evaluate the effects of attributes changing in assembly systems, with influential factors including the change of manufacturing system (push system to pull system) and variation of demand. Moreover, pull system manufacturing consists of the addition attribute, which is the number of buffer storage. This paper will provide an analysis based on a previous case study, hence process time and workflow refer to the journal name “Optimising and simulating the assembly line balancing problem in a motorcycle manufacturing company: a case study” [2]. The implementation of the pull system mechanism is to produce a system improvement in terms of the number of Work-In-Process (WIP), total time of products in the system, and the number of finished product inventory, while retaining the same throughput.

Travel context : development of a model to measure destination brand performance across different travel situations

Purpose: There is a lack of theory relating to destination brand performance measurement in the destination branding literature, which emerged in the late 1990s (see for example Dosen, Vransevic, & Prebezac, 1998). Additionally, there is a lack of research about the importance of travel context in consumers’ destination decision making (Hu & Ritchie, 1993). This study develops a structural model to measure destination brand performance across different travel situations. The theory of planned behaviour (TpB) was utilised as a framework to underpin the consumer-based brand equity (CBBE) hierarchy to develop a model of destination brand performance. Research approach: A proposed model of destination brand performance was developed through a review of the literature. The first study was used to identify destination image attributes (the core construct) using an analysis of the literature, a document analysis, and personal interviews using the Repertory Test qualitative technique. Underpinned by Personal Construct Theory (PCT), the Repertory Test enables the elicitation of attributes consumers use to evaluate destinations when considering travel. Data was examined in the first study to i) identify any attribute differences in travel contexts and ii) create a scale for use in a questionnaire. A second study was conducted to test the proposed model using a questionnaire with eight groups of participants to assess four destinations across two travel contexts. The model was tested utilising structural equation modelling. Findings: The first study resulted in a list of 29 destination image attributes for use in a scale index. Attributes were assessed across travel contexts and few differences were identified. The second study assessed the congruence of destination brand identity (the destination marketing organisation’s desired image) and destination brand image (the actual perceptions held by consumers) using importance-performance analyses. Finally, the proposed model of destination brand performance was tested. Overall the data supported the model of destination brand performance across travel contexts and destinations. Additionally, this was compared to consumers’ decision sets, further supporting the model. Value: This research provides a contribution to the destination marketing literature through the development of a measurement of destination brand performance underpinned by TpB. Practically; it will provide destination marketing organisations with a tool to track destination brand performance, relative to key competing places, over time. This is important given the development of a destination brand is a long term endeavour.

Ingenuity pathways analysis of urine metabonomics phenotypes toxicity of gentamicin in multiple organs

We introduce the use of Ingenuity Pathway Analysis to analyzing global metabonomics in order to characterize phenotypically biochemical perturbations and the potential mechanisms of the gentamicin-induced toxicity in multiple organs. A single dose of gentamicin was administered to Sprague Dawley rats (200 mg/kg, n = 6) and urine samples were collected at -24-0 h pre-dosage, 0-24, 24-48, 48-72 and 72-96 h post-dosage of gentamicin. The urine metabonomics analysis was performed by UPLC/MS, and the mass spectra signals of the detected metabolites were systematically deconvoluted and analyzed by pattern recognition analyses (Heatmap, PCA and PLS-DA), revealing a time-dependency of the biochemical perturbations induced by gentamicin toxicity. As result, the holistic metabolome change induced by gentamicin toxicity in the animal's organisms was characterized. Several metabolites involved in amino acid metabolism were identified in urine, and it was confirmed that gentamicin biochemical perturbations can be foreseen from these biomarkers. Notoriously, it was found that gentamicin induced toxicity in multiple organs system in the laboratory rats. The proof-of-knowledge based Ingenuity Pathway Analysis revealed gentamicin induced liver and heart toxicity, along with the previously known toxicity in kidney. The metabolites creatine, nicotinic acid, prostaglandin E2, and cholic acid were identified and validated as phenotypic biomarkers of gentamicin induced toxicity. Altogether, the significance of the use of metabonomics analyses in the assessment of drug toxicity is highlighted once more; furthermore, this work demonstrated the powerful predictive potential of the Ingenuity Pathway Analysis to study of drug toxicity and its valuable complementation for metabonomics based assessment of the drug toxicity.