Detecting event-related recurrences by symbolic analysis: Applications to human language processing

Quasistationarity is ubiquitous in complex dynamical systems. In brain dynamics there is ample evidence that event-related potentials reflect such quasistationary states. In order to detect them from time series, several segmentation techniques have been proposed. In this study we elaborate a recent approach for detecting quasistationary states as recurrence domains by means of recurrence analysis and subsequent symbolisation methods. As a result, recurrence domains are obtained as partition cells that can be further aligned and unified for different realisations. We address two pertinent problems of contemporary recurrence analysis and present possible solutions for them.Comment: 24 pages, 6 figures. Draft version to appear in Proc Royal Soc

Examining the geographies of human trafficking: Methodological challenges in mapping trafficking's complexities and connectivities

There is relatively little empirical research into the geographies of human trafficking, despite its inherent spatiality and the clear benefits of geographical perspectives. An emerging but vibrant body of qualitative work explores different aspects of trafficking's spatiality and spatio-temporality in depth and nuance, but equivalent quantitative analyses are notably lacking. What exists is largely limited to crude maps and broad-brushed assessments of patterns and trends. Yet, rigorous quantitative work is also vital in advancing understanding, informing responses and increasing accountability. In this paper, we present a novel, empirically-substantiated examination of methodological challenges in mapping trafficking. We draw on analysis of data extracted from the case files of 450 formally identified labour trafficking victims (accessed via the UK's National Crime Agency). We identify and illustrate five characteristics of the data creating particular challenges for geospatial analysis: data integrity (regarding completeness, accuracy and consistency); geographical uncertainty (regarding spatial accuracy and specificity); managing multiple geographies (trafficking is a complex process with various stages, each potentially involving numerous locations); diversity and disaggregation (important geographical variations can be masked in aggregated analysis); and unclear journeys (analysing trafficking routes proved particularly complicated). We also consider possible solutions and explore implications for future research, policy and practice

The proteostasis boundary in misfolding diseases of membrane traffic

AbstractProtein function is regulated by the proteostasis network (PN) [Balch, W.E., Morimoto, R.I., Dillin, A. and Kelly, J.W. (2008) Adapting proteostasis for disease intervention. Science 319, 916–919], an integrated biological system that generates and protects the protein fold. The composition of the PN is regulated by signaling pathways including the unfolded protein response (UPR), the heat-shock response (HSR), the ubiquitin proteasome system (UPS) and epigenetic programs. Mismanagement of protein folding and function during membrane trafficking through the exocytic and endocytic pathways of eukaryotic cells by the PN is responsible for a wide range of diseases that include, among others, lysosomal storage diseases, myelination diseases, cystic fibrosis, systemic amyloidoses such as light chain myeloma, and neurodegenerative diseases including Alzheimer’s. Toxicity from misfolding can be cell autonomous (affect the producing cell) or cell non-autonomous (affect a non-producing cell) or both, and have either a loss-of-function or gain-of-toxic function phenotype. Herein, we review the role of the PN and its regulatory transcriptional circuitry likely to be operational in managing the protein fold and function during membrane trafficking. We emphasize the enabling principle of a ‘proteostasis boundary (PB)’ [Powers, E.T., Morimoto, R.T., Dillin, A., Kelly, J.W., and Balch, W.E. (2009) Biochemical and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78, 959–991]. The PB is defined by the combined effects of the kinetics and thermodynamics of folding and the kinetics of misfolding, which are linked to the variable and adjustable PN capacity found different cell types. Differences in the PN account for the versatility of protein folding and function in health, and the cellular and tissue response to mutation and environmental challenges in disease. We discuss how manipulation of the folding energetics or the PB through metabolites and pharmacological intervention provides multiple routes for restoration of biological function in trafficking disease

Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.

To understand the impact of epigenetics on human misfolding disease, we apply Gaussian-process regression (GPR) based machine learning (ML) (GPR-ML) through variation spatial profiling (VSP). VSP generates population-based matrices describing the spatial covariance (SCV) relationships that link genetic diversity to fitness of the individual in response to histone deacetylases inhibitors (HDACi). Niemann-Pick C1 (NPC1) is a Mendelian disorder caused by >300 variants in the NPC1 gene that disrupt cholesterol homeostasis leading to the rapid onset and progression of neurodegenerative disease. We determine the sequence-to-function-to-structure relationships of the NPC1 polypeptide fold required for membrane trafficking and generation of a tunnel that mediates cholesterol flux in late endosomal/lysosomal (LE/Ly) compartments. HDACi treatment reveals unanticipated epigenomic plasticity in SCV relationships that restore NPC1 functionality. GPR-ML based matrices capture the epigenetic processes impacting information flow through central dogma, providing a framework for quantifying the effect of the environment on the healthspan of the individual

Toward a Framework for Public Accountability in Education Reform

Public accountability through information disclosure is a pillar of modern education reform efforts. Despite the ubiquity of this approach, we argue that public accountability in education is undertheorized and often predictably unlikely to achieve its intended policy goals. Drawing on examples from an equity-oriented court case in California and the literatures on democratic engagement and parent use of school performance data, we propose a framework for thinking about the design of public accountability systems in education. The framework could provide guidance for policymakers considering new efforts at improving schools through the production and dissemination of educational data

AXISYMMETRIC, THROTTLEABLE NON-GIMBALLED ROCKET ENGINE

A rocket engine assembly is provided for a vertically launched rocket vehicle. A rocket engine housing of the assembly includes two or more combustion chambers each including an outlet end defining a sonic throat area. A propellant supply for the combustion chambers includes a throttling injector, associated with each of the combustion chambers and located opposite to sonic throat area, which injects the propellant into the associated combustion chamber. A modulator, which may form part of the injector, and which is controlled by a controller, modulates the flow rate of the propellant to the combustion chambers so that the chambers provide a vectorable net thrust. An expansion nozzle or body located downstream of the throat area provides expansion of the combustion gases produced by the combustion chambers so as to increase the net thrust

The roles of specialist provision for children with specific speech and language difficulties in England and Wales: a model for inclusion?

Children with specific speech and language difficulties pose a challenge to the education and health systems. In addition to their language difficulties they are also at risk of literacy and social, emotional and behavioural difficulties. The main support for children with more severe difficulties has been enhanced provision in mainstream schools (language units or integrated resources) and special schools. The move to an inclusive education system challenges this tradition. The present paper reports the results of interviews with heads of language units/integrated resources and headteachers of special schools (n=57) as part of a larger study within England and Wales. Their views are considered with reference to criteria for entry to specialist provision, the development of collaborative practice between teachers, teaching assistants and speech and language therapists, and the implications for inclusive education

Numerical simulation scheme of one-and two-dimensional neural fields involving space-dependent delays

International audienceNeural Fields describe the spatio-temporal dynamics of neural populations involving spatial axonal connections between neurons. These neuronal connections are delayed due to the finite axonal transmission speeds along the fibers inducing a distance-dependent delay between two spatial locations. The numerical simulation in 1-dimensional neural fields is numerically demanding but may be performed in a reasonable run time by implementing standard numerical techniques. However 2-dimensional neural fields demand a more sophisticated numerical technique to simulate solutions in a reasonable time. The work presented shows a recently developed numerical iteration scheme that allows to speed up standard implementations by a factor 10-20. Applications to some pattern forming systems illustrate the power of the technique