Human atrial beta1L-adrenoceptor but not beta3-adrenoceptor activation increases force and Ca2+ current at physiological temperature

BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.

Geometric and force relationships for the development of a scaled model hydraulic excavator

Hydraulic excavators in the mining industry are widely used owing to the large payload capabilities these machines can achieve. However, there are very few optimisation studies for producing efficient hydraulic excavator backets. An efficient bucket can avoid unnecessary weight; greatly influence the payload and optimise the efficiency of hydraulic mining excavators. This paper presents a framework for the development of a scaled hydraulic excavator by examining the geometry and force relationships. A small hydraulic excavator was purchased and fitted with a broom scaled to a factor. Geometric and force relationships of the model were derived to assist computer instrumentation to retrieve necessary variable input for bucket design.

Effects of different practice task constraints on fluctuations of player heart rate in small-sided football games

This paper analyzes effects of different practice task constraints on heart rate (HR) variability during 4v4 smallsided football games. Participants were sixteen football players divided into two age groups (U13, Mean age: 12.4±0.5 yrs; U15: 14.6±0.5). The task consisted of a 4v4 sub-phase without goalkeepers, on a 25x15 m field, of 15 minutes duration with an active recovery period of 6 minutes between each condition. We recorded players’ heart rates using heart rate monitors (Polar Team System, Polar Electro, Kempele, Finland) as scoring mode was manipulated (line goal: scoring by dribbling past an extended line; double goal: scoring in either of two lateral goals; and central goal: scoring only in one goal). Subsequently, %HR reserve was calculated with the Karvonen formula. We performed a time-series analysis of HR for each individual in each condition. Mean data for intra-participant variability showed that autocorrelation function was associated with more short-range dependence processes in the “line goal” condition, compared to other conditions, demonstrating that the “line goal” constraint induced more randomness in HR response. Relative to inter-individual variability, line goal constraints demonstrated lower %CV and %RMSD (U13: 9% and 19%; U15: 10% and 19%) compared with double goal (U13: 12% and 21%; U15: 12% and 21%) and central goal (U13: 14% and 24%; U15: 13% and 24%) task constraints, respectively. Results suggested that line goal constraints imposed more randomness on cardiovascular stimulation of each individual and lower inter-individual variability than double goal and central goal constraints.

Examination of gaze behaviors under in situ and video simulation task constraints reveals differences in information pickup for perception and action

Gaze and movement behaviors of association football goalkeepers were compared under two video simulation conditions (i.e., verbal and joystick movement responses) and three in situ conditions (i.e., verbal, simplified body movement, and interceptive response). The results showed that the goalkeepers spent more time fixating on information from the penalty kick taker’s movements than ball location for all perceptual judgment conditions involving limited movement (i.e., verbal responses, joystick movement, and simplified body movement). In contrast, an equivalent amount of time was spent fixating on the penalty taker’s relative motions and the ball location for the in situ interception condition, which required the goalkeepers to attempt to make penalty saves. The data suggest that gaze and movement behaviors function differently, depending on the experimental task constraints selected for empirical investigations. These findings highlight the need for research on perceptual— motor behaviors to be conducted in representative experimental conditions to allow appropriate generalization of conclusions to performance environments.

Vibration of L-shaped plates under a deterministic force or moment excitation : a case of statistical energy analysis application

Analytical and closed form solutions are presented in this paper for the vibration response of an L-shaped plate under a point force or a moment excitation. Inter-relationships between wave components of the source and the receiving plates are clearly defined. Explicit expressions are given for the quadratic quantities such as input power, energy flow and kinetic energy distributions of the L-shaped plate. Applications of statistical energy analysis (SEA) formulation in the prediction of the vibration response of finite coupled plate structures under a single deterministic forcing are examined and quantified. It is found that the SEA method can be employed to predict the frequency averaged vibration response and energy flow of coupled plate structures under a deterministic force or moment excitation when the structural system satisfies the following conditions: (1) the coupling loss factors of the coupled subsystems are known; (2) the source location is more than a quarter of the plate bending wavelength away from the source plate edges in the point force excitation case, or is more than a quarter wavelength away from the pair of source plate edges perpendicular to the moment axis in the moment excitation case due to the directional characteristic of moment excitations. SEA overestimates the response of the L-shaped plate when the source location is less than a quarter bending wavelength away from the respective plate edges owing to wave coherence effect at the plate boundary

The effect of friction on indenter force and pile-up in numerical simulations of bone nanoindentation

Nanoindentation is a useful technique for probing the mechanical properties of bone, and finite element (FE) modeling of the indentation allows inverse determination of elasto-plastic constitutive properties. However, all but one FE study to date have assumed frictionless contact between indenter and bone. The aim of this study was to explore the effect of friction in simulations of bone nanoindentation. Two dimensional axisymmetric FE simulations were performed using a spheroconical indenter of tip radius 0.6 m and angle 90°. The coefficient of friction between indenter and bone was varied between 0.0 (frictionless) and 0.3. Isotropic linear elasticity was used in all simulations, with bone elastic modulus E=13.56GPa and Poisson‟s ratio f 0.3. Plasticity was incorporated using both Drucker-Prager and von Mises yield surfaces. Friction had a modest effect on the predicted force-indentation curve for both von Mises and Drucker-Prager plasticity, reducing maximum indenter displacement by 10% and 20% respectively as friction coefficient was increased from zero to 0.3 (at a maximum indenter force of 5mN). However, friction has a much greater effect on predicted pile-up after indentation, reducing predicted pile-up from 0.27 to 0.11 m with a von Mises model, and from 0.09 to 0.02 m with Drucker-Prager plasticity. We conclude that it is potentially important to include friction in nanoindentation simulations of bone if pile-up is used to compare simulation results with experiment.

Legal ethics in a post-Westphalian world : building the international rule of law and otehr tasks

The emergence of strong sovereign states after the Treaty of Westphalia turned two of the most cosmopolitan professions (law and arms) into two of the least cosmopolitan. Sovereign states determined the content of the law within their borders – including which, if any, ecclesiastical law was to be applied; what form of economic regulation was adopted; and what, if any, international law applied. Similarly, states sought to ensure that all military force was at their disposal in national armies. The erosion of sovereignty in a post-Westphalian world may significantly reverse these processes. The erosion of sovereignty is likely to have profound consequences for the legal profession and the ethics of how, and for what ends, it is practised. Lawyers have played a major role in the civilization of sovereign states through the articulation and institutionalisation of key governance values – starting with the rule of law. An increasingly global profession must take on similar tasks. The same could be said of the military. This essay will review the concept of an international rule of law and its relationship to domestic conceptions and outline the task of building the international rule of law and the role that lawyers can and should play in it.

Extending the task of diarization to speaker attribution

In this paper we extend the concept of speaker annotation within a single-recording, or speaker diarization, to a collection wide approach we call speaker attribution. Accordingly, speaker attribution is the task of clustering expectantly homogenous intersession clusters obtained using diarization according to common cross-recording identities. The result of attribution is a collection of spoken audio across multiple recordings attributed to speaker identities. In this paper, an attribution system is proposed using mean-only MAP adaptation of a combined-gender UBM to model clusters from a perfect diarization system, as well as a JFA-based system with session variability compensation. The normalized cross-likelihood ratio is calculated for each pair of clusters to construct an attribution matrix and the complete linkage algorithm is employed to conduct clustering of the inter-session clusters. A matched cluster purity and coverage of 87.1% was obtained on the NIST 2008 SRE corpus.

Professions without borders : global ethics and the international rule of law

The emergence of strong sovereign states after the Treaty of Westphalia turned two of the most cosmopolitan professions (law and arms) into two of the least cosmopolitan. Sovereign states determined the content of the law within their borders – including which, if any, ecclesiastical law was to be applied; what form of economic regulation was adopted; and what, if any, international law applied. Similarly, states sought to ensure that all military force was at their disposal in national armies. The erosion of sovereignty in a post-Westphalian world may significantly reverse these processes. The erosion of sovereignty is likely to have profound consequences for the legal profession and the ethics of how, and for what ends, it is practised. Lawyers have played a major role in the civilization of sovereign states through the articulation and institutionalisation of key governance values – starting with the rule of law. An increasingly global profession must take on similar tasks. The same could be said of the military. This essay will review the concept of an international rule of law and its relationship to domestic conceptions and outline the task of building the international rule of law and the role that lawyers can and should play in it.

Emergent task-specific object semantics through distributed experience networks

Autonomous development of sensorimotor coordination enables a robot to adapt and change its action choices to interact with the world throughout its lifetime. The Experience Network is a structure that rapidly learns coordination between visual and haptic inputs and motor action. This paper presents methods which handle the high dimensionality of the network state-space which occurs due to the simultaneous detection of multiple sensory features. The methods provide no significant increase in the complexity of the underlying representations and also allow emergent, task-specific, semantic information to inform action selection. Experimental results show rapid learning in a real robot, beginning with no sensorimotor mappings, to a mobile robot capable of wall avoidance and target acquisition.

Detecting gesture force peaks for intuitive interaction

With the release of the Nintendo Wii in 2006, the use of haptic force gestures has become a very popular form of input for interactive entertainment. However, current gesture recognition techniques utilised in Nintendo Wii games fall prey to a lack of control when it comes to recognising simple gestures. This paper presents a simple gesture recognition technique called Peak Testing which gives greater control over gesture interaction. This recognition technique locates force peaks in continuous force data (provided by a gesture device such as the Wiimote) and then cancels any peaks which are not meant for input. Peak Testing is therefore technically able to identify movements in any direction. This paper applies this recognition technique to control virtual instruments and investigates how users respond to this interaction. The technique is then explored as the basis for a robust way to navigate menus with a simple flick of the wrist. We propose that this flick-form of interaction could be a very intuitive way to navigate Nintendo Wii menus instead of the current pointer techniques implemented.

A Regularization Approach to Metrical Task Systems

We address the problem of constructing randomized online algorithms for the Metrical Task Systems (MTS) problem on a metric δ against an oblivious adversary. Restricting our attention to the class of “work-based” algorithms, we provide a framework for designing algorithms that uses the technique of regularization. For the case when δ is a uniform metric, we exhibit two algorithms that arise from this framework, and we prove a bound on the competitive ratio of each. We show that the second of these algorithms is ln n + O(loglogn) competitive, which is the current state-of-the art for the uniform MTS problem.

Effect of topic domain and task type on Web image searching

Many user studies in Web information searching have found the significant effect of task types on search strategies. However, little attention was given to Web image searching strategies, especially the query reformulation activity despite that this is a crucial part in Web image searching. In this study, we investigated the effects of topic domains and task types on user’s image searching behavior and query reformulation strategies. Some significant differences in user’s tasks specificity and initial concepts were identified among the task domains. Task types are also found to influence participant’s result reviewing behavior and query reformulation strategies.

Digital human modelling for vehicle design and manufacturing

Digital human modelling (DHM) has today matured from research into industrial application. In the automotive domain, DHM has become a commonly used tool in virtual prototyping and human-centred product design. While this generation of DHM supports the ergonomic evaluation of new vehicle design during early design stages of the product, by modelling anthropometry, posture, motion or predicting discomfort, the future of DHM will be dominated by CAE methods, realistic 3D design, and musculoskeletal and soft tissue modelling down to the micro-scale of molecular activity within single muscle fibres. As a driving force for DHM development, the automotive industry has traditionally used human models in the manufacturing sector (production ergonomics, e.g. assembly) and the engineering sector (product ergonomics, e.g. safety, packaging). In product ergonomics applications, DHM share many common characteristics, creating a unique subset of DHM. These models are optimised for a seated posture, interface to a vehicle seat through standardised methods and provide linkages to vehicle controls. As a tool, they need to interface with other analytic instruments and integrate into complex CAD/CAE environments. Important aspects of current DHM research are functional analysis, model integration and task simulation. Digital (virtual, analytic) prototypes or digital mock-ups (DMU) provide expanded support for testing and verification and consider task-dependent performance and motion. Beyond rigid body mechanics, soft tissue modelling is evolving to become standard in future DHM. When addressing advanced issues beyond the physical domain, for example anthropometry and biomechanics, modelling of human behaviours and skills is also integrated into DHM. Latest developments include a more comprehensive approach through implementing perceptual, cognitive and performance models, representing human behaviour on a non-physiologic level. Through integration of algorithms from the artificial intelligence domain, a vision of the virtual human is emerging.