An efficient, spectral numerical method is presented for solving problems in a spherical shell geometry that employs spherical harmonics in the angular dimensions and Chebyshev polynomials in the ...radial direction. We exploit the three‐term recurrence relation for Chebyshev polynomials that renders all matrices sparse in spectral space. This approach is significantly more efficient than the collocation approach and is generalizable to both the Galerkin and tau methodologies for enforcing boundary conditions. The sparsity of the matrices reduces the computational complexity of the linear solution of implicit‐explicit time stepping schemes to O(N) operations, compared to
O(N2) operations for a collocation method. The method is illustrated by considering several example problems of important dynamical processes in the Earth's liquid outer core. Results are presented from both fully nonlinear, time‐dependent numerical simulations and eigenvalue problems arising from the investigation of the onset of convection and the inertial wave spectrum. We compare the explicit and implicit temporal discretization of the Coriolis force; the latter becomes computationally feasible given the sparsity of the differential operators. We find that implicit treatment of the Coriolis force allows for significantly larger time step sizes compared to explicit algorithms; for hydrodynamic and dynamo problems at an Ekman number of
E=10−5, time step sizes can be increased by a factor of 3 to 16 times that of the explicit algorithm, depending on the order of the time stepping scheme. The implementation with explicit Coriolis force scales well to at least 2048 cores, while the implicit implementation scales to 512 cores.
Key Points:
Fully spectral discretization of the Boussinesq equations using Chebyshev polynomials and spherical harmonics that leads to sparse matrices
The implicit temporal discretization of the Coriolis force permits up to 16 times larger time step at moderate Ekman number
Parallelization of the nonlinear simulations using a 2‐D data distribution coupled with a parallel sparse linear solver
Chronic renal allograft injury is often reflected by interstitial fibrosis (IF) and tubular atrophy (TA) without evidence of specific etiology. In most instances, IF/TA remains an irreversible ...disorder, representing a major cause of long‐term allograft loss. As members of the protease family metzincins and functionally related genes are involved in fibrotic and sclerotic processes of the extracellular matrix (ECM), we hypothesized their deregulation in IF/TA. Gene expression and protein level analyses using allograft biopsies with and without Banff'05 classified IF/TA illustrated their deregulation. Expression profiles of these genes differentiated IF/TA from Banff'05 classified Normal biopsies in three independent microarray studies and demonstrated histological progression of IF/TA I to III. Significant upregulation of matrix metalloprotease‐7 (MMP‐7) and thrombospondin‐2 (THBS‐2) in IF/TA biopsies and sera was revealed in two independent patient sets. Furthermore, elevated THBS‐2, osteopontin (SPP1) and β‐catenin may play regulatory roles on MMP. Our findings further suggest that deregulated ECM remodeling and possibly epithelial to mesenchymal transition (EMT) are implicated in IF/TA of kidney transplants, and that metzincins and related genes play an important role in these processes. Profiling of these genes may be used to complement IF/TA diagnosis and to disclose IF/TA progression in kidney transplant recipients.
Microarray based gene expression profiling reveals deregulation of metzincins, especially overexpression of MMP‐7, in IF/TA and identifies a set of metzincins and related genes that allows classification of biopsies from three independent studies into IF/TA and normal/unremarkable histology.
Submarine canyons are known as one of the seafloor morphological features where living cold-water coral (CWC) communities develop in the Mediterranean Sea. We investigated the CWC community of the ...two westernmost submarine canyons of the Gulf of Lions canyon system: the Cap de Creus Canyon (CCC) and Lacaze-Duthiers Canyon (LDC). Coral associations have been studied through video material recorded by means of a manned submersible and a remotely operated vehicle. Video transects have been conducted and analyzed in order to obtain information on (1) coral bathymetric distribution and density patterns, (2) size structure of coral populations, and (3) coral colony position with respect to the substrate. Madrepora oculata was the most abundant CWC in both canyons, while Lophelia pertusa and Dendrophyllia cornigera mostly occurred as isolated colonies or in small patches. An important exception was detected in a vertical cliff in LDC where a large L. pertusa framework was documented. This is the first record of such an extended L. pertusa framework in the Mediterranean Sea. In both canyons coral populations were dominated by medium and large colonies, but the frequent presence of small-sized colonies also indicate active recruitment. The predominant coral orientation (90° and 135°) is probably driven by the current regime as well as by the sediment load transported by the current flows. In general, no clear differences were observed in the abundance and in the size structure of the CWC populations between CCC and LDC, despite large differences in particulate matter between canyons.
We present numerical solutions of the flow in precessing spheres and spherical shells with small (r(i)/r(o)=0.1) inner cores and either stress-free or no-slip inner boundary conditions. For each of ...these three cases we consider the sequence of bifurcations as the Reynolds number Re=r(o)(2)Ω/ν is increased up to ~1280, focusing particular attention on bifurcations that break the antipodal symmetry U(-r)=-U(r). All three cases have steady and time-periodic symmetric solutions at smaller Re, and quasiperiodic asymmetric solutions at larger Re, but the details of the transitions differ, and include also periodic asymmetric and quasiperiodic symmetric solutions in some of the cases.
Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T‐cell–mediated AR are tubulointerstitial and vascular inflammation associated with excessive ...extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t‐ and i‐scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, ‐9, TIMP1, ‐2, thrombospondin2 (THBS2) and fibrillin1. RT‐PCR using microdissected glomeruli/tubuli confirmed MMP7, ‐9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, ‐9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/‐9 represent potential molecular AR markers.
Microarray data using four studies of renal allograft biopsies qualified the extracellular matrix remodeling proteases metzincins and related genes as molecular classifiers of acute rejection, revealed uniform enrichment of 13 genes, further analyzed on protein and mRNA level, and correlated to Banff histological lesion scores
Summary
There are few data about the long‐term histological outcome of HIV‐/HCV‐coinfected patients after therapy with interferon and ribavirin. We performed an observational study of 216 patients ...who received therapy against HCV and who had at least three successive transient elastographies (TE) during the follow‐up. The primary endpoint was confirmed fibrosis regression, defined as a reduction of at least 1 point in Metavir fibrosis score, confirmed and without worsening in successive TE. At baseline, 23% had fibrosis stage 4 or cirrhosis. Overall, 82 (38%) achieved sustained virological response (SVR), without differences in baseline fibrosis or time of follow‐up. Confirmed fibrosis regression was observed in 55% of patients, higher for SVR (71% vs 44%; P < 0.01), and the likelihood of achieving fibrosis regression at 3, 5 and 7 years was 0.17, 0.51 and 0.67, respectively, for SVR patients, in comparison with 0.02, 0.23 and 0.41 for no SVR patients (P < 0.01, log‐rank test at any time point). Progressive regression, defined as continuous improvement in successive TE, was observed in 62% of patients with advanced liver fibrosis or cirrhosis who achieved SVR. In a Cox regression model, only SVR (HR, 4.01; 95% CI, 2.33–7.57; P < 0.01) and a younger age (HR, 1.14; 95% CI, 1.05–1.25; P < 0.01; per year) were associated with fibrosis regression. This study confirms that the rate of liver fibrosis regression increases during the follow‐up after SVR to interferon therapy in HIV‐/HCV‐coinfected patients.
Nowadays, the possible public health risk associated with the presence of quinolone residues and other antibiotics in milk is well-known, but there is a lack of information about the effect milk ...processing temperatures have on the presence of antimicrobial residues. The aim of this work was to determine the effect of different temperatures and heating times on the concentration of quinolones in milk by employing liquid chromatographic equipment analysis with fluorescence detection. In order to determine the thermo-stability of these compounds, the first-order kinetic model was applied, and the activation energies, half-lives, and percentages of degradation of each compound were calculated. Results showed that quinolones are very resistant to different heat treatments with maximum losses of concentration of 12.71% for ciprofloxacin and 12.01% for norfloxacin at 120 °C and 20 min. The high stability of quinolones represents a significant risk to human health because the residues of these antibiotics can remain in milk after heat treatment and, therefore, can reach the dairy industry and consumers.
Convection in planetary cores can generate fluid flow and magnetic fields, and a number of sophisticated codes exist to simulate the dynamic behaviour of such systems. We report on the first ...community activity to compare numerical results of computer codes designed to calculate fluid flow within a whole sphere. The flows are incompressible and rapidly rotating and the forcing of the flow is either due to thermal convection or due to moving boundaries. All problems defined have solutions that allow easy comparison, since they are either steady, slowly drifting or perfectly periodic. The first two benchmarks are defined based on uniform internal heating within the sphere under the Boussinesq approximation with boundary conditions that are uniform in temperature and stress-free for the flow. Benchmark 1 is purely hydrodynamic, and has a drifting solution. Benchmark 2 is a magnetohydrodynamic benchmark that can generate oscillatory, purely periodic, flows and magnetic fields. In contrast, Benchmark 3 is a hydrodynamic rotating bubble benchmark using no slip boundary conditions that has a stationary solution. Results from a variety of types of code are reported, including codes that are fully spectral (based on spherical harmonic expansions in angular coordinates and polynomial expansions in radius), mixed spectral and finite difference, finite volume, finite element and also a mixed Fourier-finite element code. There is good agreement between codes. It is found that in Benchmarks 1 and 2, the approximation of a whole sphere problem by a domain that is a spherical shell (a sphere possessing an inner core) does not represent an adequate approximation to the system, since the results differ from whole sphere results.
Impaired wound healing in the elderly represents a major clinical problem. Delineating the cellular and molecular mechanisms by which aging impairs wound healing may lead to the development of ...improved treatment strategies for elderly patients with non-healing wounds. Neovascularization is an essential step in wound healing, and bone marrow-derived angiogenic cells (BMDACs) play an important role in vascularization. Using a mouse full-thickness burn wound model, we demonstrate that perfusion and vascularization of burn wounds were impaired by aging and were associated with dramatically reduced mobilization of BMDACs bearing the cell surface molecules CXCR4 and Sca1. Expression of stromal-derived factor 1 (SDF-1), the cytokine ligand for CXCR4, was significantly decreased in peripheral blood and burn wounds of old mice. Expression of hypoxia-inducible factor (HIF)-1α was detected in burn wounds from young (2-month-old), but not old (2-year-old), mice. When BMDACs from young donor mice were injected intravenously, homing to burn wound tissue was impaired in old recipient mice, whereas the age of the BMDAC donor mice had no effect on homing. Our results indicate that aging impairs burn wound vascularization by impairing the mobilization of BMDACs and their homing to burn wound tissue as a result of impaired HIF-1 induction and SDF-1 signaling.
The problem of optimally designing the topology of plane trusses has, in most cases, been dealt with as a size problem in which members are eliminated when their size tends to zero. This article ...presents a novel growth method for the optimal design in a sequential manner of size, geometry, and topology of plane trusses without the need of a ground structure. The method has been applied to single load case problems with stress and size constraints. It works sequentially by adding new joints and members optimally, requiring five basic steps: (1) domain specification, (2) topology and size optimization, (3) geometry optimization, (4) optimality verification, and (5) topology growth. To demonstrate the proposed growth method, three examples were carried out: Michell cantilever, Messerschmidt–Bölkow–Blohm beam, and Michell cantilever with fixed circular boundary. The results obtained with the proposed growth method agree perfectly with the analytical solutions. A Windows XP program, which demonstrates the method, can be downloaded from http://www.upct.es/~deyc/software/tto/.