Ionic Mechanisms of Action Potential Rate Dependence, Conduction and Block in Normal Epicardium and in Remodeled Epicardium Post-Infarction

In this work, detailed computational models are used to study the electrophysiology of normal epicardium and the arrhythmogenic effects of epicardial cell remodeling post-infarction. The canine epicardial myocyte model described here reproduces a wide range of experimentally observed rate dependent phenomena in cell and tissue. Model behavior depends on updated formulations for the 4-AP sensitive transient outward current: Ito1), the slow component of the delayed rectifier potassium current: IKs), the L-type Ca2+ channel: ICa,L) and the sodium-potassium pump: INaK) fit to data from canine ventricular myocytes. The model shows that Ito1 plays a limited role in potentiating peak ICa,L and Ca2+ release for propagated action potentials: APs), but modulates the time course of action potential duration: APD) restitution. IKs plays an important role in APD shortening at short diastolic intervals but a limited role in AP repolarization at longer cycle lengths. In addition, simulations demonstrate that ICa,L, INaK and [Na+]i play critical roles in APD accommodation and the rate dependence of APD restitution. Starting from the ionic model of a normal epicardial cell described above, an epicardial border zone: EBZ) model was developed based on available remodeling data. Ionic models of normal zone: NZ) and EBZ myocytes were incorporated into one-dimensional models of propagation to gain mechanistic insight into how ion channel remodeling affects APD and refractoriness, vulnerability to conduction block and conduction safety post-infarction. Simulations of EBZ APD restitution show that remodeled INa and ICaL promote increased effective refractory period: ERP) and prolonged APD at short diastolic interval: DI). Heterogeneous tissue simulations show that increased post-repolarization refractoriness and altered restitution lead to a large rate dependent vulnerable window for conduction block. In simulations of conduction post-infarction, EBZ IK1 remodeling partially offsets the reduction in conduction safety due to altered INa, while Ito1 and ICaL have a negligible effect on conduction. Further simulations show that injection of skeletal muscle sodium channel SkM1-INa, a recently proposed anti-arrhythmic therapy, has several desirable effects including normalization of EBZ ERP and APD restitution, elimination of vulnerability to conduction block and normalization of conduction in uncoupled tissue

Does Augmented Reality Augment the Experience? A Qualitative Analysis of Enjoyment for Sports Spectators

This study examined users' attitudes and opinions of using augmented reality technology in comparison to other non-augmented reality technologies. Broadly, there were differences between users when using different devices. These differences help shed light onto the process of implementation of such new technologies in various sports settings, from arenas and stadiums to at-home viewership. From the results of this study, it is likely that this technology may not lead to better fan experience, but instead might leave them feeling frustrated and potentially isolated. Particularly given the expense of technology like Google Glass, this study suggests such technology should be implemented selectively and carefully. Additionally, the effects of using Google Glass in stadiums and arenas may not simply be on the users, but also on those seated around them, who may be bothered by the deliberate actions of those wearing such augmented reality devices. Notably, this may shift as the devices become more prevalent

Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions

The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signaling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. Although previous studies have focused on ligand-dependent AR signaling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal

Analysis of methods

Information is one of an organization's most important assets. For this reason the development and maintenance of an integrated information system environment is one of the most important functions within a large organization. The Integrated Information Systems Evolution Environment (IISEE) project has as one of its primary goals a computerized solution to the difficulties involved in the development of integrated information systems. To develop such an environment a thorough understanding of the enterprise's information needs and requirements is of paramount importance. This document is the current release of the research performed by the Integrated Development Support Environment (IDSE) Research Team in support of the IISEE project. Research indicates that an integral part of any information system environment would be multiple modeling methods to support the management of the organization's information. Automated tool support for these methods is necessary to facilitate their use in an integrated environment. An integrated environment makes it necessary to maintain an integrated database which contains the different kinds of models developed under the various methodologies. In addition, to speed the process of development of models, a procedure or technique is needed to allow automatic translation from one methodology's representation to another while maintaining the integrity of both. The purpose for the analysis of the modeling methods included in this document is to examine these methods with the goal being to include them in an integrated development support environment. To accomplish this and to develop a method for allowing intra-methodology and inter-methodology model element reuse, a thorough understanding of multiple modeling methodologies is necessary. Currently the IDSE Research Team is investigating the family of Integrated Computer Aided Manufacturing (ICAM) DEFinition (IDEF) languages IDEF(0), IDEF(1), and IDEF(1x), as well as ENALIM, Entity Relationship, Data Flow Diagrams, and Structure Charts, for inclusion in an integrated development support environment

Developing an Inclusive K-12 Outreach Model

This paper outlines the longitudinal development of a K-12 outreachmodel, to promote Computer Science in Ireland. Over a three-yearperiod, it has been piloted to just under 9700 K-12 students fromalmost every county in Ireland. The model consists of a two-hourcamp that introduces students to a range of Computer Sciencetopics: addressing computing perceptions, introduction to codingand exploration of computational thinking. The model incorporateson-site school delivery and is available at no cost to any interestedschool across Ireland. The pilot study so far collected over 3400surveys (pre- and post-outreach delivery).Schools from all over Ireland self-selected to participate, includ-ing male only, female only and mixed schools. The no-cost natureof the model meant schools deemed disadvantaged , to privatefee-paying schools participated. Initial findings are very positive,including the balance of male and female participants, where in the2017-18 academic year it was 56:44 and in 2019-20 (to date), it is35:65 respectively. Once the model is validated and tweaked (basedon survey data), the model will be published (open access) for otherinstitutions to implement the model locally. In addition, the authorsintend to link schools (that the team have worked with over thethree years) with local institutions, thus developing a sustainableecosystem for the program to continue. This paper describes themodel structure and outlines early finding

Validity and Wearability of Consumer-based Fitness Trackers in Free-living Children

International Journal of Exercise Science 12(5): 471-482, 2019. Over the past decade wearable fitness trackers (WFTs) have grown in popularity with more recent versions able to capture the pulse rate noninvasively on the wrist of the wearer. Most of evidence on the validity of WFTs have explored adults in clinical settings. Thus, the purpose of this study is to 1) evaluate the validity of a wrist-placed WFT in determining heart rate, and 2) examine the wear compliance of a wrist-placed WFT, in children in free-living settings. In study 1, 19 children (5-12yrs) wore a Fitbit Charge HR© and a Polar chest strap heart rate (HR) monitor for 2 hours while performing sedentary-to-vigorous activities at a holiday camp in December 2016. In study 2, 20 children with mild developmental disabilities (8-13yrs) were asked to wear a Fitbit Alta HR© during summer 2017. In study 1, mean absolute percent difference between the WFT HR and criterion was 6.9%. Overall, \u3e75% of WFT HRs were within 5-10% of the criterion. Bland Altman plots indicated a moderate-to-high level of agreement between the WFT and criterion (mean difference 4.1%; Limits of Agreement 26.8, -18.5%). In study 2, participants had the device in their possession for 43 days (SD±14, range 14 – 56 days) and wore it on 67% of those days (range: 20 – 96%) for at least 10 hours/day. Preliminary evidence suggests that WFTs can provide comparable HR estimates to a criterion field-based measure and children can wear WFTs for extended monitoring periods in free-living settings

A Long Spell of Uncertainity

We find ourselves in a period of sustained economic uncertainty. Today, like 6 months ago, the U.S. economy is on the brink of a recession. Weakness in lending activity, coupled with weakness in the housing sector and related manufacturing industries has stymied economic growth since late 2007. At times, recession seems imminent. But, the official measures, such as quarterly gross domestic product, do not clearly signal that the economy is contracting. Further, prices are rising rapidly for food and energy. That is the uncertainty. Will 2008 be remembered as a recession year, or as a period of disappointing but slow growth? And, will 2008 be known as the year when inflation reignited in America. In some sense, the answer does not matter. The United States and its citizens already are experiencing some of the consequences of recession, and of higher inflation. Job counts are declining and unemployment is rising. Many face the prospect of losing their homes. Prices including food and energy are rising 2% faster than in most recent years. But, of course, the answer matters quite a lot. If the U.S. economy falls into recession, or if a recession has already begun, job losses will accelerate and unemployment will rise sharply. The real estate and financial markets may spiral down faster. There is also a risk that prices increases will accelerate if inflation in food and energy spreads into wage inflation impacting a broad spectrum of sectors. Our view is that the economy will avoid both a significant recession and rapid inflation. Strong exports will encourage growth, and consumers and the financial sector will slowly work their way through their current difficulties. Inflation largely will be contained to the food and energy sectors. But, the scenario is far from rosy. We expect weak economic growth through 2008 and early 2009, and elevated inflation rates through 2010. In particular, we expected annual growth in real GDP of 1.1% in 2008, 1.7% in 2009. GDP growth rates only returns to trend growth of 2.8% in 2010. Inflation will hit 4.0% in 2008, and will be well above 2% in subsequent years, at 2.6% in 2009, and 2.7% in 2010. A significant slowdown will be avoided because the weak dollar will encourage strong exports, and because consumer spending will expand modestly despite a weak employment situation and high energy prices. Consumer confidence has declined rapidly but consumer spending should stay steady thanks to lower interest rates, and in the very short-term, federal government rebate checks. Current high energy prices also are expected to stabilize, and therefore, will not cause even further strain on consumer spending for other goods and services. This relatively positive scenario naturally assumes that the U.S. economy will avoid other major dislocations. The economy may fall into a significant recession if there are other major disruptions in the financial system that limit access to capital. Inflation may spike further if oil prices rise or additional weather causes further increases in food prices

A Long Spell of Uncertainty

We find ourselves in a period of sustained economic uncertainty. Today, like 6 months ago, the U.S. economy is on the brink of a recession. Weakness in lending activity, coupled with weakness in the housing sector and related manufacturing industries has stymied economic growth since late 2007. At times, recession seems imminent. But, the official measures, such as quarterly gross domestic product, do not clearly signal that the economy is contracting. Further, prices are rising rapidly for food and energy. That is the uncertainty. Will 2008 be remembered as a recession year, or as a period of disappointing but slow growth? And, will 2008 be known as the year when inflation reignited in America. I