An adaptive wavelet-based collocation method for solving multiscale problems in continuum mechanics

Computational multiscale methods are highly sophisticated numerical approaches to predict the constitutive response of heterogeneous materials from their underlying microstructures. However, the quality of the prediction intrinsically relies on an accurate representation of the microscale morphology and its individual constituents, which makes these formulations computationally demanding. Against this background, the applicability of an adaptive wavelet-based collocation approach is studied in this contribution. It is shown that the Hill–Mandel energy equivalence condition can naturally be accounted for in the wavelet basis, (discrete) wavelet-based scale-bridging relations are derived, and a wavelet-based mapping algorithm for internal variables is proposed. The characteristic properties of the formulation are then discussed by an in-depth analysis of elementary one-dimensional problems in multiscale mechanics. In particular, the microscale fields and their macroscopic analogues are studied for microstructures that feature material interfaces and material interphases. Analytical solutions are provided to assess the accuracy of the simulation results

The role of starch as transient energy buffer in synchronized microalgal growth in Acutodesmus obliquus

publishedVersionPaid Open Acces

Resolution of Biphasic Binding of the Opioid Antagonist Naltrexone in Brain Membranes

In synaptosomal membranes from rat brain cortex, in the presence of 150 m M NaC1, the opioid antagonist [ 3 H] naltrexone bound to two populations of receptor sites with affinities of 0.27 and 4.3 n M , respectively. Guanosine-5′-(3-thiotriphosphate) had little modulating effect and did not alter the biphasic nature of ligand binding. On the other hand, receptor-selective opioids differentially inhibited the two binding components of [ 3 H] naltrexone. As shown by nonlinear least-squares analysis, the Μ opioids Tyr-D-Ala-Gly-(Me)Phe-Gly-ol or sufentanil abolished high-affinity [ 3 H] naltrexone binding, whereas the Δ-selective ligands [D- Pen 2 , D-Pen 5 ] enkephalin, ICI 174, 864, and oxymorphindole inhibited and eventually eliminated the low-affinity component in a concentration-dependent manner. These results indicate that, in contrast to the guanine nucleotide-sensitive biphasic binding of opioid-alkaloid agonists, the heterogeneity of naltrexone binding in brain membranes reflects ligand interaction with different opioid-receptor types.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66340/1/j.1471-4159.1991.tb08288.x.pd

Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study

Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices. Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) >= 3+ 4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments. Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (> 1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa. Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.Peer reviewe

Evaluation of diurnal responses of Tetradesmus obliquus under nitrogen limitation

Tetradesmus obliquus is an oleaginous microalga with high potential for triacylglycerol production. We characterized the biochemical composition and the transcriptional landscape of T. obliquus wild-type and the starchless mutant (slm1), adapted to 16:8 h light dark (LD) cycles under nitrogen limitation. In comparison to the nitrogen replete conditions, the diurnal RNA samples from both strains also displayed a cyclic pattern, but with much less variation which could be related to a reduced transcription activity in at least the usually highly active processes. During nitrogen limitation, the wild-type continued to use starch as the preferred storage compound to store energy and carbon. Starch was accumulated to an average content of 0.25 g·gDW−1, which is higher than the maximum observed under nitrogen replete conditions. Small oscillations were observed, indicating that starch was being used as a diurnal energy storage compound, but to a lesser extent than under nitrogen replete conditions. For the slm1 mutant, TAG content was higher than for the wild-type (average steady state value was 0.26 g·gDW−1 for slm1 compared to 0.06 g·gDW−1 for the wild-type). Despite the higher TAG content in the slm1, the conversion efficiency of photons into biomass components for the slm1 was only half of the one obtained for the wild-type. This is related to the observed decrease in biomass productivity (from 1.29 gDW·L−1·day−1 for the wild-type to 0.52 gDW·L−1·day−1 for the slm1). While the transcriptome of slm1 displayed clear signs of energy generation by degrading TAG and amino-acids during the dark period, no significant variation of these metabolites could be measured. When looking through the diurnal cycle, the photosynthetic efficiency was lower for the slm1 mutant compared to the wild-type especially during the second half of the light period, where starch accumulation occurred in the wild-type.publishedVersionPaid Open Acces

Generalized Interpolation Material Point Approach to High Melting Explosive with Cavities Under Shock

Criterion for contacting is critically important for the Generalized Interpolation Material Point(GIMP) method. We present an improved criterion by adding a switching function. With the method dynamical response of high melting explosive(HMX) with cavities under shock is investigated. The physical model used in the present work is an elastic-to-plastic and thermal-dynamical model with Mie-Gr\"uneissen equation of state. We mainly concern the influence of various parameters, including the impacting velocity $v$, cavity size $R$, etc, to the dynamical and thermodynamical behaviors of the material. For the colliding of two bodies with a cavity in each, a secondary impacting is observed. Correspondingly, the separation distance $D$ of the two bodies has a maximum value $D_{\max}$ in between the initial and second impacts. When the initial impacting velocity $v$ is not large enough, the cavity collapses in a nearly symmetric fashion, the maximum separation distance $D_{\max}$ increases with $v$. When the initial shock wave is strong enough to collapse the cavity asymmetrically along the shock direction, the variation of $D_{\max}$ with $v$ does not show monotonic behavior. Our numerical results show clear indication that the existence of cavities in explosive helps the creation of ``hot spots''.Comment: Figs.2,4,7,11 in JPG format; Accepted for publication in J. Phys. D: Applied Physic

Rotterdam mobile phone appincluding MRI data for the prediction of prostate cancer. A multicenter external validation

The Rotterdam Prostate Cancer Risk calculator (RPCRC, available as mobile phone app) has been extensively validated in the past years. Recently, a new version including MRI data has been released. The aim of our study was to analyze the performance of the MRI RPCRC app in a multicenter cohort of patients undergoing prostate biopsies

A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5

Systemic lupus erythematosus (SLE) is the prototype autoimmune disease where genes regulated by type I interferon (IFN) are over-expressed and contribute to the disease pathogenesis. Because signal transducer and activator of transcription 4 (STAT4) plays a key role in the type I IFN receptor signaling, we performed a candidate gene study of a comprehensive set of single nucleotide polymorphism (SNPs) in STAT4 in Swedish patients with SLE. We found that 10 out of 53 analyzed SNPs in STAT4 were associated with SLE, with the strongest signal of association (P = 7.1 × 10−8) for two perfectly linked SNPs rs10181656 and rs7582694. The risk alleles of these 10 SNPs form a common risk haplotype for SLE (P = 1.7 × 10−5). According to conditional logistic regression analysis the SNP rs10181656 or rs7582694 accounts for all of the observed association signal. By quantitative analysis of the allelic expression of STAT4 we found that the risk allele of STAT4 was over-expressed in primary human cells of mesenchymal origin, but not in B-cells, and that the risk allele of STAT4 was over-expressed (P = 8.4 × 10−5) in cells carrying the risk haplotype for SLE compared with cells with a non-risk haplotype. The risk allele of the SNP rs7582694 in STAT4 correlated to production of anti-dsDNA (double-stranded DNA) antibodies and displayed a multiplicatively increased, 1.82-fold risk of SLE with two independent risk alleles of the IRF5 (interferon regulatory factor 5) gene

Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease