Real-time extraction of the Madden-Julian oscillation using empirical mode decomposition and statistical forecasting with a VARMA model

A simple guide to the new technique of empirical mode decomposition (EMD) in a meteorological-climate forecasting context is presented. A single application of EMD to a time series essentially acts as a local high-pass filter. Hence, successive applications can be used to produce a bandpass filter that is highly efficient at extracting a broadband signal such as the Madden-Julian Oscillation (MJO). The basic EMD method is adapted to minimize end effects, such that it is suitable for use in real time. The EMD process is then used to efficiently extract the MJO signal from gridded time series of outgoing longwave radiation (OLR) data. A range of statistical models from the general class of vector autoregressive moving average (VARMA) models was then tested for their suitability in forecasting the MJO signal, as isolated by the EMD. A VARMA (5, 1) model was selected and its parameters determined by a maximum likelihood method using 17 yr of OLR data from 1980 to 1996. Forecasts were then made on the remaining independent data from 1998 to 2004. These were made in real time, as only data up to the date the forecast was made were used. The median skill of forecasts was accurate (defined as an anomaly correlation above 0.6) at lead times up to 25 days

Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs—artificial TG-rich CMR-like particles (A-CRLPs)—containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARβ/δ culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction

Modulation of endoglin expression in islets of langerhans by VEGF reveals a novel regulator of islet endothelial cell function

BACKGROUND: Endoglin/CD105 is an auxiliary receptor for transforming growth factor-β with established roles in vascular remodelling. It has recently been shown that heterozygous endoglin deficiency in mice decreases insulin secretion in an animal model of obesity, highlighting a potential role for endoglin in the regulation of islet function. We have previously identified two different populations of endoglin expressing cells in human and mouse islets which are: (i) endothelial cells (ECs) and (ii) islet mesenchymal stromal cells. The contribution of islet EC endoglin expression to islet development and sensitivity to VEGF is unknown and is the focus of this study. RESULTS: In vitro culture of mouse islets with VEGF164 for 48 h increased endoglin mRNA levels above untreated controls but VEGF did not modulate VEGFR2, CD31 or CD34 mRNA expression or islet viability. Removal of EC-endoglin expression in vivo reduced islet EC area but had no apparent effect on islet size or architecture. CONCLUSION: EC-specific endoglin expression in islets is sensitive to VEGF and plays partial roles in driving islet vascular development, however such regulation appears to be distinct to mechanisms required to modulate islet viability and size

Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury

Chronic kidney disease (CKD) is a common medical condition of ageing cats. In most cases the underlying aetiology is unknown, but the most frequently reported pathological diagnosis is renal tubulointerstitial fibrosis. Renal fibrosis, characterised by extensive accumulation of extra-cellular matrix within the interstitium, is thought to be the final common pathway for all kidney diseases and is the pathological lesion best correlated with function in both humans and cats. As a convergent pathway, renal fibrosis provides an ideal target for the treatment of CKD and knowledge of the underlying fibrotic process is essential for the future development of novel therapies. There are many mediators and mechanisms of renal fibrosis reported in the literature, of which only a few have been investigated in the cat. This article reviews the process of renal fibrosis and discusses the most commonly cited mediators and mechanisms of progressive renal injury, with particular focus on the potential significance to feline CKD

High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F-2 alpha concentrations relative to a control high-oleic acid meal: a randomized controlled trial

Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high–oleic acid meals; the secondary objective was to characterize the effects of linoleic acid–enriched high-fat meals relative to the control meal. Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high–oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high–linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35–70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Results: Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0–3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse–reflection index was not significantly different. Plasma 8-isoprostane F(2α) analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. Conclusions: These data show differential postprandial 8-isoprostane F(2α) responses to high-fat meals containing EPA + DHA–rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid–derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific

Infrastructure for Rapid Development of Java GUI Programs

The Java Application Shell (JAS) is a software framework that accelerates the development of Java graphical-user-interface (GUI) application programs by enabling the reuse of common, proven GUI elements, as distinguished from writing custom code for GUI elements. JAS is a software infrastructure upon which Java interactive application programs and graphical user interfaces (GUIs) for those programs can be built as sets of plug-ins. JAS provides an application- programming interface that is extensible by application-specific plugins that describe and encapsulate both specifications of a GUI and application-specific functionality tied to the specified GUI elements. The desired GUI elements are specified in Extensible Markup Language (XML) descriptions instead of in compiled code. JAS reads and interprets these descriptions, then creates and configures a corresponding GUI from a standard set of generic, reusable GUI elements. These elements are then attached (again, according to the XML descriptions) to application-specific compiled code and scripts. An application program constructed by use of JAS as its core can be extended by writing new plug-ins and replacing existing plug-ins. Thus, JAS solves many problems that Java programmers generally solve anew for each project, thereby reducing development and testing time

Real-time localised forecasting of the Madden-Julian Oscillation using neural network models

Existing statistical forecast models of the Madden-Julian Oscillation (MJO) are generally of very low order and predict the evolution of a small number (typically two) of principal components (PCs). While such models are skilful up to 25 days lead time, by design they only predict the very largest-scale features of the MJO. Here we present a higher-order MJO statistical forecast model that is able to predict MJO variability on smaller, more localised scales, that will be of more direct benefit to national weather agencies and regional government planning. The model is based on daily outgoing long-wave radiation (OLR) data that are intraseasonally filtered using a recently developed technique of empirical mode decomposition that can be used in real time. A standard truncated PC analysis is then used to isolate the maximum amount of variance in a finite number of modes. The evolution of these modes is then forecast using a neural network model, which does not suffer from the parametrisation problems of other statistical forecast techniques when applied to a higher number of modes. Compared to a standard 2-PC model, the higher-order PC model showed improved skill over the whole MJO domain, with substantial improvements over the western Pacific, Arabian Sea, Bay of Bengal, South China Sea and Phillipine Sea

Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

© 2019 Published by Elsevier Inc.Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, inthe medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associatedwith the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. Thisstudy used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely usedin vitromodels of AMC and bone formation. Significant differences were identified between osteoblasts andcalcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespreaddeposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcifi-cation that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCsdisplayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis,whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels ofalkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity incalcifying VSMCs was∼100-fold lower than that of bone-forming osteoblasts and cultures treated withβ-gly-cerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calci-fication. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-relatedgenes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-foldlower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCsin vitrodisplay somelimited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effectof calcification on their viability.Peer reviewedFinal Published versio