A Random Matrix Approach to VARMA Processes

We apply random matrix theory to derive spectral density of large sample covariance matrices generated by multivariate VMA(q), VAR(q) and VARMA(q1,q2) processes. In particular, we consider a limit where the number of random variables N and the number of consecutive time measurements T are large but the ratio N/T is fixed. In this regime the underlying random matrices are asymptotically equivalent to Free Random Variables (FRV). We apply the FRV calculus to calculate the eigenvalue density of the sample covariance for several VARMA-type processes. We explicitly solve the VARMA(1,1) case and demonstrate a perfect agreement between the analytical result and the spectra obtained by Monte Carlo simulations. The proposed method is purely algebraic and can be easily generalized to q1>1 and q2>1.Comment: 16 pages, 6 figures, submitted to New Journal of Physic

Excessive ENaC-mediated sodium influx drives NLRP3 inflammasome-dependent autoinflammation in cystic fibrosis

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and results in defective CFTR-mediated chloride transport, dysregulation of epithelial sodium channels (ENaC) and exaggerated innate immune responses. We tested the hypothesis that upregulation of ENaC drives autoinflammation in this complex monogenic disease.We show that monocytes from patients with CF exhibit a systemic proinflammatory cytokine signature, with associated anti-inflammatory M2-type macrophage deficiency. Cells harboring CF mutations are hyperresponsive to NLRP3 stimulation, as evidenced by increased IL-18, IL-1β, ASC-specks levels in serum and caspase-1 activity in monocytes, and by increased IL-18 production and caspase-1 activity in human bronchial epithelial cells (HBECs). In both cell types there is an associated shift to glycolytic metabolism with succinate release, in response to increased energy requirements. Inhibition of amiloride-sensitive sodium channels partially reverses the NLRP3-dependent inflammation and metabolic shift in these cells. Overexpression of β-ENaC, in the absence of CFTR dysfunction, increases NLRP3-dependent inflammation, indicating a CFTR-independent ENaC axis in CF pathophysiology. Sodium channel modulation provides an important therapeutic strategy to combat lung inflammation in CF.</jats:p

Bridging the gap between atmospheric concentrations and local ecosystem measurements

This paper demonstrates that atmospheric inversions of CO₂ are a reliable tool for estimating regional fluxes. We compare results of an inversion over 18 days and a 300 x 300 km 2 domain in southwest France against independent measurements of fluxes from aircraft and towers. The inversion used concentration measurements from 2 towers while the independent data included 27 aircraft transects and 5 flux towers. The inversion reduces the mismatch between prior and independent fluxes, improving both spatial and temporal structures. The present mesoscale atmospheric inversion improves by 30% the CO₂ fluxes over distances of few hundreds of km around the atmospheric measurement locations. Citation: Lauvaux, T., et al. (2009), Bridging the gap between atmospheric concentrations and local ecosystem measurements, Geophys. Res. Lett., 36, L19809, doi: 10.1029/2009GL039574

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Metabolic Reprograming of Cystic Fibrosis Macrophages via the IRE1α Arm of the Unfolded Protein Response Results in Exacerbated Inflammation

Cystic Fibrosis (CF) is a recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR mutations cause dysregulation of channel function with intracellular accumulation of misfolded proteins and endoplasmic reticulum (ER) stress, with activation of the IRE1α-XBP1 pathway that regulates a subset of unfolded protein response (UPR) genes. This pathway regulates a group of genes that control proinflammatory and metabolic responses in different immune cells; however, the metabolic state of immune cells and the role of this pathway in CF remain elusive. Our results indicate that only innate immune cells from CF patients present increased levels of ER stress, mainly affecting neutrophils, monocytes, and macrophages. An overactive IRE1α-XBP1 pathway reprograms CF M1 macrophages toward an increased metabolic state, with increased glycolytic rates and mitochondrial function, associated with exaggerated production of TNF and IL-6. This hyper-metabolic state, seen in CF macrophages, is reversed by inhibiting the RNase domain of IRE1α, thereby decreasing the increased glycolic rates, mitochondrial function and inflammation. Altogether, our results indicate that innate immune cells from CF patients are primarily affected by ER stress. Moreover, the IRE1α-XBP1 pathway of the UPR is responsible for the hyper-metabolic state seen in CF macrophages, which is associated with the exaggerated inflammatory response. Modulating ER stress, metabolism and inflammation, by targeting IRE1α, may improve the metabolic fitness of macrophages, and other immune cells in CF and other immune-related disorders

Empirical Survival Jensen-Shannon Divergence as a Goodness-of-Fit Measure for Maximum Likelihood Estimation and Curve Fitting

The coefficient of determination, known as R2, is commonly used as a goodness-of-fit criterion for fitting linear models. R2 is somewhat controversial when fitting nonlinear models, although it may be generalised on a case-by-case basis to deal with specific models such as the logistic model. Assume we are fitting a parametric distribution to a data set using, say, the maximum likelihood estimation method. A general approach to measure the goodness-of-fit of the fitted parameters, which is advocated herein, is to use a non- parametric measure for comparison between the empirical distribution, comprising the raw data, and the fitted model. In particular, for this purpose we put forward the Survi- val Jensen-Shannon divergence (SJS) and its empirical counterpart (ESJS) as a metric which is bounded, and is a natural generalisation of the Jensen-Shannon divergence. We demonstrate, via a straightforward procedure making use of the ESJS, that it can be used as part of maximum likelihood estimation or curve fitting as a measure of goodness-of-fit, including the construction of a confidence interval for the fitted parametric distribution. Furthermore, we show the validity of the proposed method with simulated data, and three empirical data sets

Strong, Light, Multifunctional Fibers of Carbon Nanotubes with Ultrahigh Conductivity

Broader applications of carbon nanotubes to real-world problems have largely gone unfulfilled because of difficult material synthesis and laborious processing. We report high-performance multifunctional carbon nanotube (CNT) fibers that combine the specific strength, stiffness, and thermal conductivity of carbon fibers with the specific electrical conductivity of metals. These fibers consist of bulk-grown CNTs and are produced by high-throughput wet spinning, the same process used to produce high-performance industrial fibers. These scalable CNT fibers are positioned for high-value applications, such as aerospace electronics and field emission, and can evolve into engineered materials with broad long-term impact, from consumer electronics to long-range power transmission

Epistatic Roles for Pseudomonas aeruginosa MutS and DinB (DNA Pol IV) in Coping with Reactive Oxygen Species-Induced DNA Damage

Pseudomonas aeruginosa is especially adept at colonizing the airways of individuals afflicted with the autosomal recessive disease cystic fibrosis (CF). CF patients suffer from chronic airway inflammation, which contributes to lung deterioration. Once established in the airways, P. aeruginosa continuously adapts to the changing environment, in part through acquisition of beneficial mutations via a process termed pathoadaptation. MutS and DinB are proposed to play opposing roles in P. aeruginosa pathoadaptation: MutS acts in replication-coupled mismatch repair, which acts to limit spontaneous mutations; in contrast, DinB (DNA polymerase IV) catalyzes error-prone bypass of DNA lesions, contributing to mutations. As part of an ongoing effort to understand mechanisms underlying P. aeruginosa pathoadaptation, we characterized hydrogen peroxide (H2O2)-induced phenotypes of isogenic P. aeruginosa strains bearing different combinations of mutS and dinB alleles. Our results demonstrate an unexpected epistatic relationship between mutS and dinB with respect to H2O2-induced cell killing involving error-prone repair and/or tolerance of oxidized DNA lesions. In striking contrast to these error-prone roles, both MutS and DinB played largely accurate roles in coping with DNA lesions induced by ultraviolet light, mitomycin C, or 4-nitroquinilone 1-oxide. Models discussing roles for MutS and DinB functionality in DNA damage-induced mutagenesis, particularly during CF airway colonization and subsequent P. aeruginosa pathoadaptation are discussed

Influence of very low doses of mediators on fungal laccase activity - nonlinearity beyond imagination

Laccase, an enzyme responsible for aerobic transformations of natural phenolics, in industrial applications requires the presence of low-molecular substances known as mediators, which accelerate oxidation processes. However, the use of mediators is limited by their toxicity and the high costs of exploitation. The activation of extracellular laccase in growing fungal culture with highly diluted mediators, ABTS and HBT is described. Two high laccase-producing fungal strains, Trametes versicolor and Cerrena unicolor, were used in this study as a source of enzyme. Selected dilutions of the mediators significantly increased the activity of extracellular laccase during 14 days of cultivation what was distinctly visible in PAGE technique and in colorimetric tests. The same mediator dilutions increased demethylation properties of laccase, which was demonstrated during incubation of enzyme with veratric acid. It was established that the activation effect was assigned to specific dilutions of mediators. Our dose-response dilution process smoothly passes into the range of action of homeopathic dilutions and is of interest for homeopaths

Exploring the contribution of alternative food networks to food security. A comparative analysis

[EN] Food (in)security has become a challenge not only for developing economies but also for High Income Countries. In parallel, food scholars have actively investigated the contribution of alternative food networks (AFNs) to the development of more sustainable and just food systems, paying attention to drivers, initiatives and policies supporting the development of alternatives to the dominant industrialised food system and its detrimental environmental and socio-economic impacts. However, few studies have directly addressed the contribution of AFNs to food security in the Global North. This paper aims to establish new linkages between food security debates and critical AFNs literature. For that purpose, we conduct a place-based approach to food security in a comparative analysis of initiatives of three different European contexts: Cardiff city-region (UK), the Flemish Region (Belgium) and the peri-urban area of the city of Valencia (Spain). The results unfold: i) how AFNs weave a more localised socio-economic fabric that creates new relationships between food security outcomes and specific territories, ii) hybridization processes within alternative but also conventional systems and iii) the role of advocacy and collective action at different levels. The analysis allows identification of key elements on which food security debates hinge and provides new insights to ground conceptual discussions on territorial and place-based food security approaches.This research is part of the project "Assessment of the impact of global drivers of change on Europe's food security" (TRANSMANGO), granted by the EU under 7th Framework Programme; theme KBBE.2013.2.5-01; Grant agreement no: 613532. Dr. Ana Moragues-Faus also acknowledges the funding of the European Commission and the Welsh Government that currently supports her Ser Cymru fellowship. 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