Optimal Timer Based Selection Schemes

Timer-based mechanisms are often used to help a given (sink) node select the best helper node among many available nodes. Specifically, a node transmits a packet when its timer expires, and the timer value is a monotone non-increasing function of its local suitability metric. The best node is selected successfully if no other node's timer expires within a 'vulnerability' window after its timer expiry, and so long as the sink can hear the available nodes. In this paper, we show that the optimal metric-to-timer mapping that (i) maximizes the probability of success or (ii) minimizes the average selection time subject to a minimum constraint on the probability of success, maps the metric into a set of discrete timer values. We specify, in closed-form, the optimal scheme as a function of the maximum selection duration, the vulnerability window, and the number of nodes. An asymptotic characterization of the optimal scheme turns out to be elegant and insightful. For any probability distribution function of the metric, the optimal scheme is scalable, distributed, and performs much better than the popular inverse metric timer mapping. It even compares favorably with splitting-based selection, when the latter's feedback overhead is accounted for.Comment: 21 pages, 6 figures, 1 table, submitted to IEEE Transactions on Communications, uses stackrel.st

Large deviations of the maximal eigenvalue of random matrices

We present detailed computations of the 'at least finite' terms (three dominant orders) of the free energy in a one-cut matrix model with a hard edge a, in beta-ensembles, with any polynomial potential. beta is a positive number, so not restricted to the standard values beta = 1 (hermitian matrices), beta = 1/2 (symmetric matrices), beta = 2 (quaternionic self-dual matrices). This model allows to study the statistic of the maximum eigenvalue of random matrices. We compute the large deviation function to the left of the expected maximum. We specialize our results to the gaussian beta-ensembles and check them numerically. Our method is based on general results and procedures already developed in the literature to solve the Pastur equations (also called "loop equations"). It allows to compute the left tail of the analog of Tracy-Widom laws for any beta, including the constant term.Comment: 62 pages, 4 figures, pdflatex ; v2 bibliography corrected ; v3 typos corrected and preprint added ; v4 few more numbers adde

Evaluation of Ablation Patterns Using a Biophysical Model of Atrial Fibrillation

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Surgical/Radiofrequency (RF) ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. The present study evaluated 13 different ablation patterns by means of a biophysical model of the human atria. In this model, ablation lines were abruptly applied transmurally during simulated sustained AF, and success rate, time to AF termination and average beat-to-beat interval were documented. The gold standard Cox's Maze III procedure was taken as reference. The effectiveness of twelve less invasive patterns was compared to it. In some of these incomplete lines (entailing a gap) were simulated. Finally, the computer simulations were compared to clinical data. The results show that the model reproduces observations made in vivo: (1) the Maze III is the most efficient ablation procedure; (2) less invasive patterns should include lines in both right and left atrium; (3) incomplete ablation lines between the pulmonary veins and the mitral valve annulus lead to uncommon flutter; (4) computer simulations of incomplete lines are consistent with clinical results of non-transumural RF ablation. Biophysical modeling may therefore be considered as a useful tool for understanding the mechanisms underlying AF therapie

EphA2-receptor deficiency exacerbates myocardial infarction and reduces survival in hyperglycemic mice

Background We have previously shown that EphrinA1/EphA expression profile changes in response to myocardial infarction (MI), exogenous EphrinA1-Fc administration following MI positively influences wound healing, and that deletion of the EphA2 Receptor (EphA2-R) exacerbates injury and remodeling. To determine whether or not ephrinA1-Fc would be of therapeutic value in the hyperglycemic infarcted heart, it is critical to evaluate how ephrinA1/EphA signaling changes in the hyperglycemic myocardium in response to MI. Methods Streptozotocin (STZ)-induced hyperglycemia in wild type (WT) and EphA2-receptor mutant (EphA2-R-M) mice was initiated by an intraperitoneal injection of STZ (150 mg/kg) 10 days before surgery. MI was induced by permanent ligation of the left anterior descending coronary artery and analyses were performed at 4 days post-MI. ANOVAs with Student-Newman Keuls multiple comparison post-hoc analysis illustrated which groups were significantly different, with significance of at least p < 0.05. Results Both WT and EphA2-R-M mice responded adversely to STZ, but only hyperglycemic EphA2-R-M mice had lower ejection fraction (EF) and fractional shortening (FS). At 4 days post-MI, we observed greater post-MI mortality in EphA2-R-M mice compared with WT and this was greater still in the EphA2-R-M hyperglycemic mice. Although infarct size was greater in hyperglycemic WT mice vs normoglycemic mice, there was no difference between hyperglycemic EphA2-R-M mice and normoglycemic EphA2-R-M mice. The hypertrophic response that normally occurs in viable myocardium remote to the infarct was noticeably absent in epicardial cardiomyocytes and cardiac dysfunction worsened in hyperglycemic EphA2-R-M hearts post-MI. The characteristic interstitial fibrotic response in the compensating myocardium remote to the infarct also did not occur in hyperglycemic EphA2-R-M mouse hearts to the same extent as that observed in the hyperglycemic WT mouse hearts. Differences in neutrophil and pan-leukocyte infiltration and serum cytokines implicate EphA2-R in modulation of injury and the differences in ephrinA1 and EphA6-R expression in governing this are discussed. Conclusions We conclude that EphA2-mutant mice are more prone to hyperglycemia-induced increased injury, decreased survival, and worsened LV remodeling due to impaired wound healing

Agile Project Management Styles and Control Ambidexterity in Agile Information Systems Development Projects: An Exploratory Case Study

Agile information systems development (ISD) projects face the dilemma of control versus autonomy. Although autonomy benefits agile ISD, many projects in practice nevertheless feature project managers who exert control for more formal structure and guidance. To address this autonomy-control dilemma, prior research on traditional ISD highlights the need for control ambidexterity, which is the simultaneous execution of contrasting control activities. However, little is known about achieving control ambidexterity in agile ISD projects, and, in particular, how agile project managers dynamically adapt controls to changing contextual requirements. Our in-depth case study in the IT department of a multinational container shipping company that runs several Scrum ISD projects identifies four agile project management styles (Landscaper, Buddy, Detective, and Commander) and associated balanced practices for control ambidexterity. We also show how agile project managers blend or shift their styles in response to conflicts, revealing different levels of adherence to agile development principles. We contribute to the ISD control literature by reflecting on different forms of contextual and temporal control ambidexterity and theorizing how the interplay between control conflicts and underlying factors leads to varied ambidexterity forms. Furthermore, our insights suggest signaling theory should complement agency and stewardship theories to better understand agile ISD control

Comparative Live-Cell Imaging Analyses of SPA-2, BUD-6 and BNI-1 in Neurospora crassa Reveal Novel Features of the Filamentous Fungal Polarisome

A key multiprotein complex involved in regulating the actin cytoskeleton and secretory machinery required for polarized growth in fungi, is the polarisome. Recognized core constituents in budding yeast are the proteins Spa2, Pea2, Aip3/Bud6, and the key effector Bni1. Multicellular fungi display a more complex polarized morphogenesis than yeasts, suggesting that the filamentous fungal polarisome might fulfill additional functions. In this study, we compared the subcellular organization and dynamics of the putative polarisome components BUD-6 and BNI-1 with those of the bona fide polarisome marker SPA-2 at various developmental stages of Neurospora crassa. All three proteins exhibited a yeast-like polarisome configuration during polarized germ tube growth, cell fusion, septal pore plugging and tip repolarization. However, the localization patterns of all three proteins showed spatiotemporally distinct characteristics during the establishment of new polar axes, septum formation and cytokinesis, and maintained hyphal tip growth. Most notably, in vegetative hyphal tips BUD-6 accumulated as a subapical cloud excluded from the Spitzenkörper (Spk), whereas BNI-1 and SPA-2 partially colocalized with the Spk and the tip apex. Novel roles during septal plugging and cytokinesis, connected to the reinitiation of tip growth upon physical injury and conidial maturation, were identified for BUD-6 and BNI-1, respectively. Phenotypic analyses of gene deletion mutants revealed additional functions for BUD-6 and BNI-1 in cell fusion regulation, and the maintenance of Spk integrity. Considered together, our findings reveal novel polarisome-independent functions of BUD-6 and BNI-1 in Neurospora, but also suggest that all three proteins cooperate at plugged septal pores, and their complex arrangement within the apical dome of mature hypha might represent a novel aspect of filamentous fungal polarisome architecture

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors

Use of a biophysical model of atrial fibrillation in the interpretation of the outcome of surgical ablation procedures

OBJECTIVE: To determine the adequacy of 'in silico' biophysical models of atrial fibrillation (AF) in the design of different ablation line patterns. BACKGROUND: Permanent AF is a severe medical problem for which (surgical) ablation is a possible treatment. The ideal ablation pattern remains to be defined. METHODS: Forty-six consecutive adult patients with symptomatic permanent drug refractory AF underwent mitral surgery combined with non-transmural, (n=20) and transmural (n=26) radiofrequency Minimaze. The fraction of 'in vivo' conversions to sinus rhythm (SR) in both groups was compared with the performance of the fraction of 'in silico' conversions observed in a biophysical model of permanent AF. The simulations allowed us to study the effectiveness of incomplete and complete ablation patterns. A simulated, complete, transmural Maze III ablation pattern was applied to 118 different episodes of simulated AF set-up in the model and its effectiveness was compared with the clinical results reported by Cox. RESULTS: The fraction of conversions to SR was 92% 'in vivo' and 88% 'in silico' (p=ns) for transmural/complete ablations, 60% respectively 65% for non-transmural/incomplete Minimaze (p=ns) and 98% respectively 100% for Maze III ablations (p=ns). The fraction of conversions to SR 'in silico' correlated with the rates 'in vivo' (r2=0.973). CONCLUSIONS: The fraction of conversions to SR observed in the model closely corresponded to the conversion rate to SR post-surgery. This suggests that the model provides an additional, non-invasive tool for optimizing ablation line patterns for treating permanent AF

A biophysical model of atrial fibrillation to define the appropriate ablation pattern in modified maze

OBJECTIVE: The surgical Maze III procedure remains the gold standard in treating atrial fibrillation (AF); however due to clinical difficulties and higher risks, less invasive ablation alternatives are clinically investigated. The present study aims to define more efficient ablation patterns of the modified maze procedure using a biophysical model of human atria with chronic AF. METHODS: A three-dimensional model of human atria was developed using both MRI-imaging and a one-layer cellular model reproducing experimentally observed atrial cellular properties. Sustained AF could be induced by a burst-pacing protocol. Ablation lines were implemented in rendering the cardiac cells non-conductive, mimicking transmural lines. Lines were progressively implemented respectively around pulmonary veins (PV), left atrial appendage (LAA), left atrial isthmus (LAI), cavo-tricuspid isthmus (CTI), and intercaval lines (SIVC) in the computer model, defining the following patterns: P1=PV, P2=P1+LAA, P3=P2+LAI, P4=P3+CTI, P5=P3+SIVC, P6=P5+CTI. Forty simulations were done for each pattern and proportion of sinus rhythm (SR) conversion and time-to-AF termination (TAFT) were assessed. RESULTS: The most efficient patterns are P5, P6, and Maze III with 100% success. The main difference is expressed in decreasing mean TAFT with a correlation coefficient R=-0.8. There is an inflexion point for 100% success rate at a 7.5s TAFT, meaning that no additional line is mandatory beyond pattern P5. CONCLUSIONS: Our biophysical model suggests that Maze III could be simplified in his right atrial pattern to a single line joining both vena cavae. This has to be confirmed in clinical settings