Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide a promising source for cell therapy and drug screening. Several high-yield protocols exist for hESC-CM production; however, methods to significantly advance hESC-CM maturation are still lacking. Building on our previous experience with mouse ESC-CMs, we investigated the effects of 3-dimensional (3D) tissue-engineered culture environment and cardiomyocyte purity on structural and functional maturation of hESC-CMs. 2D monolayer and 3D fibrin-based cardiac patch cultures were generated using dissociated cells from differentiated Hes2 embryoid bodies containing varying percentage (48-90%) of CD172a (SIRPA)-positive cardiomyocytes. hESC-CMs within the patch were aligned uniformly by locally controlling the direction of passive tension. Compared to hESC-CMs in age (2 weeks) and purity (48-65%) matched 2D monolayers, hESC-CMs in 3D patches exhibited significantly higher conduction velocities (CVs), longer sarcomeres (2.09 ± 0.02 vs. 1.77 ± 0.01 μm), and enhanced expression of genes involved in cardiac contractile function, including cTnT, αMHC, CASQ2 and SERCA2. The CVs in cardiac patches increased with cardiomyocyte purity, reaching 25.1 cm/s in patches constructed with 90% hESC-CMs. Maximum contractile force amplitudes and active stresses of cardiac patches averaged to 3.0 ± 1.1 mN and 11.8 ± 4.5 mN/mm(2), respectively. Moreover, contractile force per input cardiomyocyte averaged to 5.7 ± 1.1 nN/cell and showed a negative correlation with hESC-CM purity. Finally, patches exhibited significant positive inotropy with isoproterenol administration (1.7 ± 0.3-fold force increase, EC50 = 95.1 nm). These results demonstrate highly advanced levels of hESC-CM maturation after 2 weeks of 3D cardiac patch culture and carry important implications for future drug development and cell therapy studies.

Sensitivity to switching rates in stochastically switched ODEs

We consider a stochastic process driven by a linear ordinary differential equation whose right-hand side switches at exponential times between a collection of different matrices. We construct planar examples that switch between two matrices where the individual matrices and the average of the two matrices are all Hurwitz (all eigenvalues have strictly negative real part), but nonetheless the process goes to infinity at large time for certain values of the switching rate. We further construct examples in higher dimensions where again the two individual matrices and their averages are all Hurwitz, but the process has arbitrarily many transitions between going to zero and going to infinity at large time as the switching rate varies. In order to construct these examples, we first prove in general that if each of the individual matrices is Hurwitz, then the process goes to zero at large time for sufficiently slow switching rate and if the average matrix is Hurwitz, then the process goes to zero at large time for sufficiently fast switching rate. We also give simple conditions that ensure the process goes to zero at large time for all switching rates. © 2014 International Press.

Development of a GEM Electronic Board (GEB) for triple-GEM detectors

Developed for use with triple GEM detectors, the GEM Electronic Board (GEB) forms a crucial part of the electronics readout system being developed as part of the CMS muon upgrade program. The objective of the GEB is threefold; to provide stable powering and ground for the VFAT3 front ends, to enable high-speed communication between 24 VFAT3 front ends and an optohybrid, and to shield the GEM detector from electromagnetic interference. The paper describes the concept and design of a large-size GEB in detail, highlighting the challenges in terms of design and feasibility of this deceptively difficult system component.

Measurement of the cross section and angular correlations for associated production of a Z boson with b hadrons in pp collisions at √s = 7 TeV

A study of proton-proton collisions in which two b hadrons are produced in association with a Z boson is reported. The collisions were recorded at a centre-of-mass energy of 7TeV with the CMS detector at the LHC, for an integrated luminosity of 5:2 fb-1. The b hadrons are identified by means of displaced secondary vertices, without the use of reconstructed jets, permitting the study of b-hadron pair production at small angular separation. Differential cross sections are presented as a function of the angular separation of the b hadrons and the Z boson. In addition, inclusive measurements are presented. For both the inclusive and differential studies, different ranges of Z boson momentum are considered, and each measurement is compared to the predictions from different event generators at leading-order and next-to-leading-order accuracy. Copyright CERN.

Androesterilidad en girasol y comportamiento de líneas endocriadas a la podredumbre blanca de capítulos

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SMARTFIRE: an intelligent CFD-based fire model

This paper describes a project aimed at making Computational Fluid Dynamics (CFD) based fire simulation accessible to members of the fire safety engineering community. Over the past few years, the practise of CFD based fire simulation has begun the transition from the confines of the research laboratory to the desk of the fire safety engineer. To a certain extent, this move has been driven by the demands of performance based building codes. However, while CFD modelling has many benefits over other forms of fire simulation, it requires a great deal of expertise on the user’s part to obtain reasonable simulation results. The project described in this paper, SMARTFIRE, aims to relieve some of this dependence on expertise so that users are less concerned with the details of CFD analysis and can concentrate on results. This aim is achieved by the use of an expert system component as part of the software suite which takes some of the expertise burden away from the user. SMARTFIRE also makes use of the latest developments in CFD technology in order to make the CFD analysis more efficient. This paper describes design considerations of the SMARTFIRE software, emphasising its open architecture, CFD engine and knowledge based systems.

The numerical simulation of aircraft evacuation and its application to aircraft design and certification

Computer based mathematical models describing the aircraft evacuation process have a vital role to play in the design and development of safer aircraft, in the implementation of safer and more rigorous certification criteria and in cabin crew training and post mortuum accident investigation. As the risk of personal injury and costs involved in performing large-scale evacuation experiments for the next generation `Ultra High Capacity Aircraft' (UHCA) are expected to be high, the development and use of these evacuation modelling tools may become essential if these aircraft are to prove a viable reality. This paper describes the capabilities and limitations of the airEXODUS evacuation model and some attempts at validation, including its successful application to the prediction of a recent certification trial, prior to the actual trial taking place, is described. Also described is a newly defined parameter known as OPS which can be used as a measure of evacuation trial optimality. In addition, sample evacuation simulations in the presence of fire atmospheres are described.

Further validation of the buildingEXODUS evacuation model using the Tsukuba dataset

In this paper, the buildingEXODUS (V1.1) evacuation model is described and discussed and attempts at qualitative and quantitative model validation are presented. The data set used for the validation is the Tsukuba pavilion evacuation data. This data set is of particular interest as the evacuation was influenced by external conditions, namely inclement weather. As part of the validation exercise, the sensitivity of the buildingEXODUS predictions to a range of variables and conditions is examined, including; exit flow capacity, occupant response times and the impact of external conditions on the developing evacuation. The buildingEXODUS evacuation model was found to be able to produce good qualitative and quantitative agreement with the experimental data.

Validation of the buildingEXODUS Evacuation Model

In this paper, the buildingEXODUS (V1.1) evacuation model is described and discussed and attempts at qualitative and quantitative model validation are presented. The data sets used for validation are the Stapelfeldt and Milburn House evacuation data. As part of the validation exercise, the sensitivity of the buildingEXODUS predictions to a range of variables is examined, including: occupant drive, occupant location, exit flow capacity, exit size, occupant response times and geometry definition. An important consideration that has been highlighted by this work is that any validation exercise must be scrutinised to identify both the results generated and the considerations and assumptions on which they are based. During the course of the validation exercise, both data sets were found to be less than ideal for the purpose of validating complex evacuation models. However, the buildingEXODUS evacuation model was found to be able to produce reasonable qualitative and quantitative agreement with the experimental data.

Fire field modelling using the SMARTFIRE automated dynamic solution control environment

SMARTFIRE is a fire field model based on an open architecture integrated CFD code and knowledge-based system. It makes use of the expert system to assist the user in setting up the problem specification and new computational techniques such as Group Solvers to reduce the computational effort involved in solving the equations. This paper concentrates on recent research into the use of artificial intelligence techniques to assist in dynamic solution control of fire scenarios being simulated using fire field modelling techniques. This is designed to improve the convergence capabilities of the software while further decreasing the computational overheads. The technique automatically controls solver relaxations using an integrated production rule engine with a blackboard to monitor and implement the required control changes during solution processing. Initial results for a two-dimensional fire simulation are presented that demonstrate the potential for considerable savings in simulation run-times when compared with control sets from various sources. Furthermore, the results demonstrate enhanced solution reliability due to obtaining acceptable convergence within each time step unlike some of the comparison simulations.

Adaptive decision-making in buildingEXODUS

Given the importance of occupant behaviour on evacuation efficiency, a new behavioural feature has been implemented into buildingEXODUS. This feature concerns the response of occupants to exit selection and re-direction. This behaviour is not simply pre-determined by the user as part of the initialisation process, but involves the occupant taking decisions based on their previous experiences and the information available to them. This information concerns the occupants prior knowledge of the enclosure and line-of-sight information concerning queues at neighbouring exits. This new feature is demonstrated and reviewed through several examples.