Integral transform solution of random coupled parabolic partial differential models

[EN] Random coupled parabolic partial differential models are solved numerically using random cosine Fourier transform together with non-Gaussian random numerical integration that captures the highly oscillatory behaviour of the involved integrands. Sufficient condition of spectral type imposed on the random matrices of the system is given so that the approximated stochastic process solution and its statistical moments are numerically convergent. Numerical experiments illustrate the results.Spanish Ministerio de Economia, Industria y Competitividad (MINECO); Agencia Estatal de Investigacion (AEI); Fondo Europeo de Desarrollo Regional (FEDER UE), Grant/Award Number: MTM2017-89664-PCasabán Bartual, MC.; Company Rossi, R.; Egorova, VN.; Jódar Sánchez, LA. (2020). Integral transform solution of random coupled parabolic partial differential models. Mathematical Methods in the Applied Sciences. 43(14):8223-8236. https://doi.org/10.1002/mma.6492S822382364314Bäck, J., Nobile, F., Tamellini, L., & Tempone, R. (2010). Stochastic Spectral Galerkin and Collocation Methods for PDEs with Random Coefficients: A Numerical Comparison. Spectral and High Order Methods for Partial Differential Equations, 43-62. doi:10.1007/978-3-642-15337-2_3Bachmayr, M., Cohen, A., & Migliorati, G. (2016). Sparse polynomial approximation of parametric elliptic PDEs. Part I: affine coefficients. ESAIM: Mathematical Modelling and Numerical Analysis, 51(1), 321-339. doi:10.1051/m2an/2016045Ernst, O. G., Sprungk, B., & Tamellini, L. (2018). Convergence of Sparse Collocation for Functions of Countably Many Gaussian Random Variables (with Application to Elliptic PDEs). SIAM Journal on Numerical Analysis, 56(2), 877-905. doi:10.1137/17m1123079Sheng, D., & Axelsson, K. (1995). Uncoupling of coupled flows in soil—a finite element method. International Journal for Numerical and Analytical Methods in Geomechanics, 19(8), 537-553. doi:10.1002/nag.1610190804Mitchell, J. K. (1991). Conduction phenomena: from theory to geotechnical practice. Géotechnique, 41(3), 299-340. doi:10.1680/geot.1991.41.3.299Das, P. K. (1991). Optical Signal Processing. doi:10.1007/978-3-642-74962-9Ashkenazy, Y. (2017). Energy transfer of surface wind-induced currents to the deep ocean via resonance with the Coriolis force. Journal of Marine Systems, 167, 93-104. doi:10.1016/j.jmarsys.2016.11.019Hodgkin, A. L., & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. The Journal of Physiology, 117(4), 500-544. doi:10.1113/jphysiol.1952.sp004764Galiano, G. (2012). On a cross-diffusion population model deduced from mutation and splitting of a single species. Computers & Mathematics with Applications, 64(6), 1927-1936. doi:10.1016/j.camwa.2012.03.045Casabán, M. C., Company, R., & Jódar, L. (2019). Numerical solutions of random mean square Fisher‐KPP models with advection. Mathematical Methods in the Applied Sciences, 43(14), 8015-8031. doi:10.1002/mma.5942Casabán, M. C., Company, R., & Jódar, L. (2019). Numerical Integral Transform Methods for Random Hyperbolic Models with a Finite Degree of Randomness. Mathematics, 7(9), 853. doi:10.3390/math7090853Shampine, L. F. (2008). Vectorized adaptive quadrature in MATLAB. Journal of Computational and Applied Mathematics, 211(2), 131-140. doi:10.1016/j.cam.2006.11.021Iserles, A. (2004). On the numerical quadrature of highly-oscillating integrals I: Fourier transforms. IMA Journal of Numerical Analysis, 24(3), 365-391. doi:10.1093/imanum/24.3.365Ma, J., & Liu, H. (2018). On the Convolution Quadrature Rule for Integral Transforms with Oscillatory Bessel Kernels. Symmetry, 10(7), 239. doi:10.3390/sym10070239Jódar, L., & Goberna, D. (1996). Exact and analytic numerical solution of coupled diffusion problems in a semi-infinite medium. Computers & Mathematics with Applications, 31(9), 17-24. doi:10.1016/0898-1221(96)00038-7Jódar, L., & Goberna, D. (1998). A matrix D’Alembert formula for coupled wave initial value problems. Computers & Mathematics with Applications, 35(9), 1-15. doi:10.1016/s0898-1221(98)00052-2Ostrowski, A. M. (1959). A QUANTITATIVE FORMULATION OF SYLVESTER’S LAW OF INERTIA. Proceedings of the National Academy of Sciences, 45(5), 740-744. doi:10.1073/pnas.45.5.740Ashkenazy, Y., Gildor, H., & Bel, G. (2015). The effect of stochastic wind on the infinite depth Ekman layer model. EPL (Europhysics Letters), 111(3), 39001. doi:10.1209/0295-5075/111/3900

High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes

Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case–control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC–MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment

Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study

Cortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel �10,000 solar masses of material at velocities exceeding 1,000 km/s. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of the thermonuclear runaway, prolonged optically thick winds, or binary interaction with the nova envelope. Classical novae are now routinely detected in GeV gamma-rays, suggesting that relativistic particles are accelerated by strong shocks in nova ejecta. Here we present high-resolution imaging of the gamma-ray-emitting nova V959 Mon at radio wavelengths, showing that its ejecta were shaped by binary motion: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are gamma-ray emitters

Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner

OBJECTIVE: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of IBD. This clinical association is linked pathologically to the recruitment of mucosal T cells to the liver, via vascular adhesion protein (VAP)-1-dependent enzyme activity. Our aim was to examine the expression, function and enzymatic activation of the ectoenzyme VAP-1 in patients with PSC.DESIGN: We examined VAP-1 expression in patients with PSC, correlated levels with clinical characteristics and determined the functional consequences of enzyme activation by specific enzyme substrates on hepatic endothelium.RESULTS: The intrahepatic enzyme activity of VAP-1 was elevated in PSC versus immune-mediated disease controls and non-diseased liver (p<0.001). The adhesion of gut-tropic α4β7+lymphocytes to hepatic endothelial cells in vitro under flow was attenuated by 50% following administration of the VAP-1 inhibitor semicarbazide (p<0.01). Of a number of natural VAP-1 substrates tested, cysteamine-which can be secreted by inflamed colonic epithelium and gut bacteria-was the most efficient (yielded the highest enzymatic rate) and efficacious in its ability to induce expression of functional mucosal addressin cell adhesion molecule-1 on hepatic endothelium. In a prospectively evaluated patient cohort with PSC, elevated serum soluble (s)VAP-1 levels predicted poorer transplant-free survival for patients, independently (HR: 3.85, p=0.003) and additively (HR: 2.02, p=0.012) of the presence of liver cirrhosis.CONCLUSIONS: VAP-1 expression is increased in PSC, facilitates adhesion of gut-tropic lymphocytes to liver endothelium in a substrate-dependent manner, and elevated levels of its circulating form predict clinical outcome in patients.</p

Testing foundations of quantum mechanics with photons

The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

Setback distances as a conservation tool in wildlife-human interactions : testing their efficacy for birds affected by vehicles on open-coast sandy beaches

In some wilderness areas, wildlife encounter vehicles disrupt their behaviour and habitat use. Changing driver behaviour has been proposed where bans on vehicle use are politically unpalatable, but the efficacy of vehicle setbacks and reduced speeds remains largely untested. We characterised bird-vehicle encounters in terms of driver behaviour and the disturbance caused to birds, and tested whether spatial buffers or lower speeds reduced bird escape responses on open beaches. Focal observations showed that: i) most drivers did not create sizeable buffers between their vehicles and birds; ii) bird disturbance was frequent; and iii) predictors of probability of flushing (escape) were setback distance and vehicle type (buses flushed birds at higher rates than cars). Experiments demonstrated that substantial reductions in bird escape responses required buffers to be wide (&gt; 25 m) and vehicle speeds to be slow (&lt; 30 km h-1). Setback distances can reduce impacts on wildlife, provided that they are carefully designed and derived from empirical evidence. No speed or distance combination we tested, however, eliminated bird responses. Thus, while buffers reduce response rates, they are likely to be much less effective than vehicle-free zones (i.e. beach closures), and rely on changes to current driver behaviou

Setback distances as a conservation tool in wildlife-human interactions : testing their efficacy for birds affected by vehicles on open-coast sandy beaches

In some wilderness areas, wildlife encounter vehicles disrupt their behaviour and habitat use. Changing driver behaviour has been proposed where bans on vehicle use are politically unpalatable, but the efficacy of vehicle setbacks and reduced speeds remains largely untested. We characterised bird-vehicle encounters in terms of driver behaviour and the disturbance caused to birds, and tested whether spatial buffers or lower speeds reduced bird escape responses on open beaches. Focal observations showed that: i) most drivers did not create sizeable buffers between their vehicles and birds; ii) bird disturbance was frequent; and iii) predictors of probability of flushing (escape) were setback distance and vehicle type (buses flushed birds at higher rates than cars). Experiments demonstrated that substantial reductions in bird escape responses required buffers to be wide (&gt; 25 m) and vehicle speeds to be slow (&lt; 30 km h-1). Setback distances can reduce impacts on wildlife, provided that they are carefully designed and derived from empirical evidence. No speed or distance combination we tested, however, eliminated bird responses. Thus, while buffers reduce response rates, they are likely to be much less effective than vehicle-free zones (i.e. beach closures), and rely on changes to current driver behaviou

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family