Competence, specification and commitment in otic placode induction

The inner ear is induced from cranial ectoderm adjacent to the hindbrain. Despite almost a century of study, the molecular mechanisms of inner ear induction remain obscure. We have identified four genes expressed very early in the anlage of the inner ear, the otic placode. Pax-2, Sox-3, BMP-7 and Notch are all expressed in placodal ectoderm from the 4-5 somite stage (ss) onwards, well before the otic placode becomes morphologically visible at the 12-14ss. We have used these four molecular markers to show that cranial ectoderm becomes specified to form the otic placode at the 4-6ss, and that this ectoderm is committed to a placodal fate by the 10ss. We also demonstrate that much of the embryonic ectoderm is competent to generate an otic placode if taken at a sufficiently early age. We have mapped the location of otic placode-inducing activity along the rostrocaudal axis of the embryo, and have determined that this activity persists at least until the 10ss. Use of the four molecular otic placode markers suggests that induction of the otic placode in birds occurs earlier than previously thought, and proceeds in a series of steps that are independently regulated

Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear

An early and crucial event in vertebrate inner ear development is the acquisition of axial identities that in turn dictate the positions of all subsequent inner ear components. Here, we focus on the role of the hindbrain in establishment of inner ear axes and show that axial specification occurs well after otic placode formation in chicken. Anteroposterior (AP) rotation of the hindbrain prior to specification of this axis does not affect the normal AP orientation and morphogenesis of the inner ear. By contrast, reversing the dorsoventral (DV) axis of the hindbrain results in changing the DV axial identity of the inner ear. Expression patterns of several ventrally expressed otic genes such as NeuroD, Lunatic fringe (Lfng) and Six1 are shifted dorsally, whereas the expression pattern of a normally dorsal-specific gene, Gbx2, is abolished. Removing the source of Sonic Hedgehog (SHH) by ablating the floor plate and/or notochord, or inhibiting SHH function using an antibody that blocks SHH bioactivity results in loss of ventral inner ear structures. Our results indicate that SHH, together with other signals from the hindbrain, are important for patterning the ventral axis of the inner ear. Taken together, our studies suggest that tissue(s) other than the hindbrain confer AP axial information whereas signals from the hindbrain are necessary and sufficient for the DV axial patterning of the inner ear

The horizon problem for prevalent surfaces

We investigate the box dimensions of the horizon of a fractal surface defined by a function $f \in C[0,1]^2$. In particular we show that a prevalent surface satisfies the `horizon property', namely that the box dimension of the horizon is one less than that of the surface. Since a prevalent surface has box dimension 3, this does not give us any information about the horizon of surfaces of dimension strictly less than 3. To examine this situation we introduce spaces of functions with surfaces of upper box dimension at most \alpha, for \alpha $\in$ [2,3). In this setting the behaviour of the horizon is more subtle. We construct a prevalent subset of these spaces where the lower box dimension of the horizon lies between the dimension of the surface minus one and 2. We show that in the sense of prevalence these bounds are as tight as possible if the spaces are defined purely in terms of dimension. However, if we work in Lipschitz spaces, the horizon property does indeed hold for prevalent functions. Along the way, we obtain a range of properties of box dimensions of sums of functions

Trends in concussions at Ontario schools prior to and subsequent to the introduction of a concussion policy - an analysis of the Canadian hospitals injury reporting and prevention program from 2009 to 2016

Background: Concussion is a preventable injury that can have long-term health consequences for children and youth. In Ontario, the Policy/Program Memorandum # 158 (PPM) was introduced by the Ministry of Education of Ontario in March 2014. The PPM’s main purpose is to require each school board in the province to create and implement a concussion policy. The purpose of this paper is to examine trends in school-based concussions prior to and subsequent to the introduction of the PPM. Methods: This report examined emergency department (ED) visits in 5 Ontario hospitals that are part of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), and compared trends over time in diagnosed concussions, and suspected concussions identified as “other head injury” in children and youth aged 4–18. Results: From 2009 to 2016 study years, there were 21,094 suspected concussions, including 8934 diagnosed concussions in youth aged 4–18. The average number of diagnosed concussions in the 5 years before the PPM was 89 concussions/month, compared to approximately 117 concussions per month after; a 30% increase in the monthly rate of concussions presenting to the ED. The total number of concussion or head injury-related ED visits remained relatively unchanged but the proportion of diagnosed concussions rose from 31% in 2009 to 53% in 2016. The proportion of diagnosed concussions in females also increased from 38% in 2013 to 46% in 2016. The percent of all diagnosed concussions occurring at schools increased throughout the study reaching almost 50% in 2016 with most injuries taking place at the playground (24%), gymnasium (22%) or sports field (20%). Conclusions: The introduction of the PPM may have contributed to a general increase in concussion awareness and an improvement in concussion identification at the school level in children and youth aged 4–18. Keywords: Concussion, Policy, Emergency department, YouthYork University Librarie

The Mass, Orbit, and Tidal Evolution of the Quaoar-Weywot System

Here we present new adaptive optics observations of the Quaoar-Weywot system. With these new observations we determine an improved system orbit. Due to a 0.39 day alias that exists in available observations, four possible orbital solutions are available with periods of $\sim11.6$, $\sim12.0$, $\sim12.4$, and $\sim12.8$ days. From the possible orbital solutions, system masses of $1.3-1.5\pm0.1\times10^{21}$ kg are found. These observations provide an updated density for Quaoar of 2.7-5.0{g cm^{-3}}. In all cases, Weywot's orbit is eccentric, with possible values $\sim0.13-0.16$. We present a reanalysis of the tidal orbital evolution of the Quoaor-Weywot system. We have found that Weywot has probably evolved to a state of synchronous rotation, and have likely preserved their initial inclinations over the age of the Solar system. We find that for plausible values of the effective tidal dissipation factor tides produce a very slow evolution of Weywot's eccentricity and semi-major axis. Accordingly, it appears that Weywot's eccentricity likely did not tidally evolve to its current value from an initially circular orbit. Rather, it seems that some other mechanism has raised its eccentricity post-formation, or Weywot formed with a non-negligible eccentricity.Comment: Accepted to Icarus, Nov. 8 201

Robust filtering for gene expression time series data with variance constraints

This is the post print version of the article. The official published version can be obtained from the link below - Copyright 2007 Taylor & Francis Ltd.In this paper, an uncertain discrete-time stochastic system is employed to represent a model for gene regulatory networks from time series data. A robust variance-constrained filtering problem is investigated for a gene expression model with stochastic disturbances and norm-bounded parameter uncertainties, where the stochastic perturbation is in the form of a scalar Gaussian white noise with constant variance and the parameter uncertainties enter both the system matrix and the output matrix. The purpose of the addressed robust filtering problem is to design a linear filter such that, for the admissible bounded uncertainties, the filtering error system is Schur stable and the individual error variance is less than a prespecified upper bound. By using the linear matrix inequality (LMI) technique, sufficient conditions are first derived for ensuring the desired filtering performance for the gene expression model. Then the filter gain is characterized in terms of the solution to a set of LMIs, which can easily be solved by using available software packages. A simulation example is exploited for a gene expression model in order to demonstrate the effectiveness of the proposed design procedures.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC) of the UK under Grants GR/S27658/01 and EP/C524586/1, the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK under Grants BB/C506264/1 and 100/EGM17735, the Nuffield Foundation of the UK under Grant NAL/00630/G, and the Alexander von Humboldt Foundation of Germany

Filtering for nonlinear genetic regulatory networks with stochastic disturbances

In this paper, the filtering problem is investigated for nonlinear genetic regulatory networks with stochastic disturbances and time delays, where the nonlinear function describing the feedback regulation is assumed to satisfy the sector condition, the stochastic perturbation is in the form of a scalar Brownian motion, and the time delays exist in both the translation process and the feedback regulation process. The purpose of the addressed filtering problem is to estimate the true concentrations of the mRNA and protein. Specifically, we are interested in designing a linear filter such that, in the presence of time delays, stochastic disturbances as well as sector nonlinearities, the filtering dynamics of state estimation for the stochastic genetic regulatory network is exponentially mean square stable with a prescribed decay rate lower bound beta. By using the linear matrix inequality (LMI) technique, sufficient conditions are first derived for ensuring the desired filtering performance for the gene regulatory model, and the filter gain is then characterized in terms of the solution to an LMI, which can be easily solved by using standard software packages. A simulation example is exploited in order to illustrate the effectiveness of the proposed design procedures

Can graph-cutting improve microarray gene expression reconstructions?

Microarrays produce high-resolution image data that are, unfortunately, permeated with a great deal of “noise” that must be removed for precision purposes. This paper presents a technique for such a removal process. On completion of this non-trivial task, a new surface (devoid of gene spots) is subtracted from the original to render more precise gene expressions. The graph-cutting technique as implemented has the benefits that only the most appropriate pixels are replaced and these replacements are replicates rather than estimates. This means the influence of outliers and other artifacts are handled more appropriately (than in previous methods) as well as the variability of the final gene expressions being considerably reduced. Experiments are carried out to test the technique against commercial and previously researched reconstruction methods. Final results show that the graph-cutting inspired identification mechanism has a positive significant impact on reconstruction accuracy

Copasetic analysis: Automated analysis of biological gene expression images

Copyright [2004] IEEE. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In the past decade computational biology has come to the forefront of the public's perception with advancements in domain knowledge and a variety of analysis techniques. With the recent completion of projects like the human genome sequence, and the development of microarray chips it has become possible to simultaneously analyse expression levels for thousands of genes. Typically, a slide surface of less than 24 cm2, receptors for 30,000 genes can be printed, but currently the analysis process is a time consuming semi-autonomous step requiring human guidance. The paper proposes a framework, which facilitates automated processing of these images. This is supported by real world examples, which demonstrate the technique's capabilities along with results, which show a marked improvement over existing implementations