2,127 research outputs found
From modular to centralized organization of synchronization in functional areas of the cat cerebral cortex
Recent studies have pointed out the importance of transient synchronization
between widely distributed neural assemblies to understand conscious
perception. These neural assemblies form intricate networks of neurons and
synapses whose detailed map for mammals is still unknown and far from our
experimental capabilities. Only in a few cases, for example the C. elegans, we
know the complete mapping of the neuronal tissue or its mesoscopic level of
description provided by cortical areas. Here we study the process of transient
and global synchronization using a simple model of phase-coupled oscillators
assigned to cortical areas in the cerebral cat cortex. Our results highlight
the impact of the topological connectivity in the developing of
synchronization, revealing a transition in the synchronization organization
that goes from a modular decentralized coherence to a centralized synchronized
regime controlled by a few cortical areas forming a Rich-Club connectivity
pattern.Comment: 24 pages, 8 figures. Final version published in PLoS On
Protocol for studying cough frequency in people with pulmonary tuberculosis.
INTRODUCTION: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed
Vortex deformation and breaking in superconductors: A microscopic description
Vortex breaking has been traditionally studied for nonuniform critical
current densities, although it may also appear due to nonuniform pinning force
distributions. In this article we study the case of a
high-pinning/low-pinning/high-pinning layered structure. We have developed an
elastic model for describing the deformation of a vortex in these systems in
the presence of a uniform transport current density for any arbitrary
orientation of the transport current and the magnetic field. If is above a
certain critical value, , the vortex breaks and a finite effective
resistance appears. Our model can be applied to some experimental
configurations where vortex breaking naturally exists. This is the case for
YBaCuO (YBCO) low angle grain boundaries and films on vicinal
substrates, where the breaking is experienced by Abrikosov-Josephson vortices
(AJV) and Josephson string vortices (SV), respectively. With our model, we have
experimentally extracted some intrinsic parameters of the AJV and SV, such as
the line tension and compared it to existing predictions based on
the vortex structure.Comment: 11 figures in 13 files; minor changes after printing proof
Controlled release from zein matrices: Interplay of drug hydrophobicity and pH
Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent
Multiple dynamical time-scales in networks with hierarchically nested modular organization
Many natural and engineered complex networks have intricate mesoscopic
organization, e.g., the clustering of the constituent nodes into several
communities or modules. Often, such modularity is manifested at several
different hierarchical levels, where the clusters defined at one level appear
as elementary entities at the next higher level. Using a simple model of a
hierarchical modular network, we show that such a topological structure gives
rise to characteristic time-scale separation between dynamics occurring at
different levels of the hierarchy. This generalizes our earlier result for
simple modular networks, where fast intra-modular and slow inter-modular
processes were clearly distinguished. Investigating the process of
synchronization of oscillators in a hierarchical modular network, we show the
existence of as many distinct time-scales as there are hierarchical levels in
the system. This suggests a possible functional role of such mesoscopic
organization principle in natural systems, viz., in the dynamical separation of
events occurring at different spatial scales.Comment: 10 pages, 4 figure
Building development and roads: implications for the distribution of stone curlews across the Brecks
Background: Substantial new housing and infrastructure development planned within England has the potential to conflict with the nature conservation interests of protected sites. The Breckland area of eastern England (the Brecks) is designated as a Special Protection Area for a number of bird species, including the stone curlew (for which it holds more than 60% of the UK total population). We explore the effect of buildings and roads on the spatial distribution of stone curlew nests across the Brecks in order to inform strategic development plans to avoid adverse effects on such European protected sites. Methodology: Using data across all years (and subsets of years) over the period 1988 – 2006 but restricted to habitat areas of arable land with suitable soils, we assessed nest density in relation to the distances to nearest settlements and to major roads. Measures of the local density of nearby buildings, roads and traffic levels were assessed using normal kernel distance-weighting functions. Quasi-Poisson generalised linear mixed models allowing for spatial auto-correlation were fitted. Results: Significantly lower densities of stone curlew nests were found at distances up to 1500m from settlements, and distances up to 1000m or more from major (trunk) roads. The best fitting models involved optimally distance-weighted variables for the extent of nearby buildings and the trunk road traffic levels. Significance : The results and predictions from this study of past data suggests there is cause for concern that future housing development and associated road infrastructure within the Breckland area could have negative impacts on the nesting stone curlew population. Given the strict legal protection afforded to the SPA the planning and conservation bodies have subsequently agreed precautionary restrictions on building development within the distances identified and used the modelling predictions to agree mitigation measures for proposed trunk road developments
An effective all-atom potential for proteins
We describe and test an implicit solvent all-atom potential for simulations
of protein folding and aggregation. The potential is developed through studies
of structural and thermodynamic properties of 17 peptides with diverse
secondary structure. Results obtained using the final form of the potential are
presented for all these peptides. The same model, with unchanged parameters, is
furthermore applied to a heterodimeric coiled-coil system, a mixed alpha/beta
protein and a three-helix-bundle protein, with very good results. The
computational efficiency of the potential makes it possible to investigate the
free-energy landscape of these 49--67-residue systems with high statistical
accuracy, using only modest computational resources by today's standards
Beyond Volume: The Impact of Complex Healthcare Data on the Machine Learning Pipeline
From medical charts to national census, healthcare has traditionally operated
under a paper-based paradigm. However, the past decade has marked a long and
arduous transformation bringing healthcare into the digital age. Ranging from
electronic health records, to digitized imaging and laboratory reports, to
public health datasets, today, healthcare now generates an incredible amount of
digital information. Such a wealth of data presents an exciting opportunity for
integrated machine learning solutions to address problems across multiple
facets of healthcare practice and administration. Unfortunately, the ability to
derive accurate and informative insights requires more than the ability to
execute machine learning models. Rather, a deeper understanding of the data on
which the models are run is imperative for their success. While a significant
effort has been undertaken to develop models able to process the volume of data
obtained during the analysis of millions of digitalized patient records, it is
important to remember that volume represents only one aspect of the data. In
fact, drawing on data from an increasingly diverse set of sources, healthcare
data presents an incredibly complex set of attributes that must be accounted
for throughout the machine learning pipeline. This chapter focuses on
highlighting such challenges, and is broken down into three distinct
components, each representing a phase of the pipeline. We begin with attributes
of the data accounted for during preprocessing, then move to considerations
during model building, and end with challenges to the interpretation of model
output. For each component, we present a discussion around data as it relates
to the healthcare domain and offer insight into the challenges each may impose
on the efficiency of machine learning techniques.Comment: Healthcare Informatics, Machine Learning, Knowledge Discovery: 20
Pages, 1 Figur
Prediction of peptide and protein propensity for amyloid formation
Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation
Investigation on the competing effects of clay dispersion and matrix plasticisation for polypropylene/clay nanocomposites. Part I: morphology and mechanical properties
The key compatibiliser role of maleated polypropylene (MAPP) to improve the clay dispersability has been explicitly addressed in the fabrication process and material characterisation of polypropylene (PP)/clay nanocomposites. However, its matrix plasticiser role, which has been rarely mentioned, could adversely influence the excellent mechanical properties of such nanocomposites, resulting from the homogeneous clay dispersion. PP/clay nanocomposites in the presence of MAPP were prepared by twin screw extrusion and subsequently injection moulded with three typical material formulations in fixed parametric settings: (1) weight ratio (WR) of clay and MAPP, WR = 1:2; (2) MAPP content of 6 wt% and (3) clay content of 5 wt%. The morphological structures and mechanical properties of PP/clay nanocomposites were examined by using X-ray diffraction (XRD) analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and universal mechanical testing. The further improvement of mechanical properties was evidently hindered with very inconsiderable alteration of morphological structures in terms of the clay dispersion level. This observation could be ascribed to the change of MAPP role from a compatibiliser to a plasticiser because of its excessive amount used above a certain saturation level, which was found in the range of 3–6 wt% in MAPP contents for the enhancements of tensile and flexural properties of PP/clay nanocomposites
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