Hair cell maturation is differentially regulated along the tonotopic axis of the mammalian cochlea

Sound amplification within the mammalian cochlea depends upon specialized hair cells, the outer hair cells (OHCs), which possess both sensory and motile capabilities. In various altricial rodents, OHCs become functionally competent from around postnatal day 7 (P7), before the primary sensory inner hair cells (IHCs), which become competent at about the onset of hearing (P12). The mechanisms responsible for the maturation of OHCs and their synaptic specialization remain poorly understood. We report that spontaneous Ca2+ activity in the immature cochlea, which is generated by CaV1.3 Ca2+ channels, differentially regulates the maturation of hair cells along the cochlea. Under near‐physiological recording conditions we found that, similar to IHCs, immature OHCs elicited spontaneous Ca2+ action potentials (APs), but only during the first few postnatal days. Genetic ablation of these APs in vivo, using CaV1.3−/− mice, prevented the normal developmental acquisition of mature‐like basolateral membrane currents in low‐frequency (apical) hair cells, such as IK,n (carried by KCNQ4 channels), ISK2 and IACh (α9α10nAChRs) in OHCs and IK,n and IK,f (BK channels) in IHCs. Electromotility and prestin expression in OHCs were normal in CaV1.3−/− mice. The maturation of high‐frequency (basal) hair cells was also affected in CaV1.3−/− mice, but to a much lesser extent than apical cells. However, a characteristic feature in CaV1.3−/− mice was the reduced hair cell size irrespective of their cochlear location. We conclude that the development of low‐ and high‐frequency hair cells is differentially regulated during development, with apical cells being more strongly dependent on experience‐independent Ca2+ APs

Functional Brain Imaging with Multi-Objective Multi-Modal Evolutionary Optimization

Functional brain imaging is a source of spatio-temporal data mining problems. A new framework hybridizing multi-objective and multi-modal optimization is proposed to formalize these data mining problems, and addressed through Evolutionary Computation (EC). The merits of EC for spatio-temporal data mining are demonstrated as the approach facilitates the modelling of the experts' requirements, and flexibly accommodates their changing goals

Using landscape topology to compare continuous metaheuristics: a framework and case study on EDAs and ridge structure

In this paper we extend a previously proposed randomized landscape generator in combination with a comparative experimental methodology to study the behavior of continuous metaheuristic optimization algorithms. In particular, we generate twodimensional landscapes with parameterized, linear ridge structure, and perform pairwise comparisons of algorithms to gain insight into what kind of problems are easy and difficult for one algorithm instance relative to another.We apply thismethodology to investigate the specific issue of explicit dependency modeling in simple continuous estimation of distribution algorithms. Experimental results reveal specific examples of landscapes (with certain identifiable features) where dependency modeling is useful, harmful, or has little impact on mean algorithm performance. Heat maps are used to compare algorithm performance over a large number of landscape instances and algorithm trials. Finally, we perform ameta-search in the landscape parameter space to find landscapes which maximize the performance between algorithms. The results are related to some previous intuition about the behavior of these algorithms, but at the same time lead to new insights into the relationship between dependency modeling in EDAs and the structure of the problem landscape. The landscape generator and overall methodology are quite general and extendable and can be used to examine specific features of other algorithms

Orchestration of renewable generation in low energy buildings and districts using energy storage and load shifting

There is increasing penetration of renewable generation in buildings and districts. There are challenges in making the effective use of this generation. The objective of the ORIGIN project (Orchestration of Renewable Integrated Generation In Neighborhoods) is to shape loads so that the fraction of energy consumed that is from local renewable generation is maximized, and energy imported from outside sources is minimized. This paper presents the overall approach taken in the ORIGIN project and explores building physics aspects of solar thermal storage system orchestration. The case study districts are briefly introduced and characteristics of their generation, buildings, districts and shiftable loads described. The orchestration approach taken in ORIGIN is then presented. At the core of the ORIGIN system is the orchestration algorithm which generates informational and control outputs to shape future loads to best meet the objectives. The model based approach used to quantify thermal and electrical load shifting opportunities for pre-charging, coasting or avoiding loads, while meeting thermal comfort and other demands, is described using a solar thermal storage system as an example. The future steps for the ORIGIN project; retrofit of the ORIGIN system into existing districts and potential for other future applications is briefly discussed

Modelling of Multi-Agent Systems: Experiences with Membrane Computing and Future Challenges

Formal modelling of Multi-Agent Systems (MAS) is a challenging task due to high complexity, interaction, parallelism and continuous change of roles and organisation between agents. In this paper we record our research experience on formal modelling of MAS. We review our research throughout the last decade, by describing the problems we have encountered and the decisions we have made towards resolving them and providing solutions. Much of this work involved membrane computing and classes of P Systems, such as Tissue and Population P Systems, targeted to the modelling of MAS whose dynamic structure is a prominent characteristic. More particularly, social insects (such as colonies of ants, bees, etc.), biology inspired swarms and systems with emergent behaviour are indicative examples for which we developed formal MAS models. Here, we aim to review our work and disseminate our findings to fellow researchers who might face similar challenges and, furthermore, to discuss important issues for advancing research on the application of membrane computing in MAS modelling.Comment: In Proceedings AMCA-POP 2010, arXiv:1008.314

ParadisEO-MOEO: A Software Framework for Evolutionary Multi-Objective Optimization

This chapter presents ParadisEO-MOEO, a white-box object-oriented software framework dedicated to the flexible design of metaheuristics for multi-objective optimization. This paradigm-free software proposes a unified view for major evolutionary multi-objective metaheuristics. It embeds some features and techniques for multi-objective resolution and aims to provide a set of classes allowing to ease and speed up the development of computationally efficient programs. It is based on a clear conceptual distinction between the solution methods and the problems they are intended to solve. This separation confers a maximum design and code reuse. This general-purpose framework provides a broad range of fitness assignment strategies, the most common diversity preservation mechanisms, some elitistrelated features as well as statistical tools. Furthermore, a number of state-of-the-art search methods, including NSGA-II, SPEA2 and IBEA, have been implemented in a user-friendly way, based on the fine-grained ParadisEO-MOEO components

Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations

A comparison of strain rates and seismicity for Fennoscandia: depth dependency of deformation from glacial isostatic adjustment

We investigate the influence of the glacial isostatic adjustment (GIA) on the deformation at the surface and at seismogenic depths in Fennoscandia. The surface strain rate field, derived from geodetic data, is controlled by GIA which causes NW-SE extension of up to 4 x 10(-)(9) yr(-1) in most of mainland Fennoscandia, surrounded by regions of radial shortening towards the centre of uplift. The seismic deformation field, derived from a new compilation of focal mechanisms, shows consistent NW-SE compression on the Norwegian continental margin and a tendency towards tension in mainland Fennoscandia. The seismic moment rate is at least two orders of magnitude smaller than the geodetic moment rate. We propose that the low level of seismicity and the tendency towards tensional focal mechanisms in mainland Fennoscandia may be explained by the destructive interference of the regional stress from ridge push with the flexural stress due to GIA

Herpesvirus-Associated Acute Urticaria: An Age Matched Case-Control Study

Background Acute and recurrent acute urticaria are often associated with multiple factors including infections and recent data suggest a role for herpesviruses. Objective To test the null hypothesis, that is, there is no association of herpesvirus infections with urticaria. Methods Thirty-seven patients between one month and 15 years of age were age matched to 37 controls who were healthy or had mild acute respiratory infections but without urticaria. Patients and controls were followed for 1 to 6 years. Diagnostic studies included DNA detection by real-time PCR for herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6). Tests for other infections included adenovirus, parvovirus B 19, respiratory syncytial virus, influenza A, Group A streptococci, rotavirus, and parasites. Results Specific infections were diagnosed in 26 of 37 cases and among 9 of 37 control children (P=0.0002). Single or concomitant herpesvirus infections occurred in 24 cases and in 4 controls (65% vs 11 %, p=0.0003). Cases had 10 HHV-6 infections, 8 CMV infections, 5 EBV infections, and 4 HSV-1 infections. Conclusion Herpesvirus infections are associated with acute or recurrent acute urticaria