Experimental and numerical cross-validation of flow in real porous media. Part 1: Experimental framework

International audienceIn this study, we present the design of a purpose-built test cell, capable of closely mimicking boundary conditions which can be routinely imposed in fluid flow simulators. The test cell permits conducting systematic studies on the influence of unresolved pore-scale wall-roughness and pore space morphology on the hydraulic conductivity: it is therefore an ideal instrument for the generation of validation datasets for the next generation numerical flow models

Shimura varieties in the Torelli locus via Galois coverings of elliptic curves

We study Shimura subvarieties of $\mathsf{A}_g$ obtained from families of Galois coverings $f: C \rightarrow C'$ where $C'$ is a smooth complex projective curve of genus $g' \geq 1$ and $g= g(C)$. We give the complete list of all such families that satisfy a simple sufficient condition that ensures that the closure of the image of the family via the Torelli map yields a Shimura subvariety of $\mathsf{A}_g$ for $g' =1,2$ and for all $g \geq 2,4$ and for $g' > 2$ and $g \leq 9$. In a previous work of the first and second author together with A. Ghigi [FGP] similar computations were done in the case $g'=0$. Here we find 6 families of Galois coverings, all with $g' = 1$ and $g=2,3,4$ and we show that these are the only families with $g'=1$ satisfying this sufficient condition. We show that among these examples two families yield new Shimura subvarieties of $\mathsf{A}_g$, while the other examples arise from certain Shimura subvarieties of $\mathsf{A}_g$ already obtained as families of Galois coverings of $\mathbb{P}^1$ in [FGP]. Finally we prove that if a family satisfies this sufficient condition with $g'\geq 1$, then $g \leq 6g'+1$.Comment: 18 pages, to appear in Geometriae Dedicat

Agricultural use of copper and its link to Alzheimer’s disease

Copper is an essential nutrient for plants, animals, and humans because it is an indispensable component of several essential proteins and either lack or excess are harmful to human health. Recent studies revealed that the breakdown of the regulation of copper homeostasis could be associated with Alzheimer’s disease (AD), the most common form of dementia. Copper accumulation occurs in human aging and is thought to increase the risk of AD for individuals with a susceptibility to copper exposure. This review reports that one of the leading causes of copper accumulation in the environment and the human food chain is its use in agriculture as a plant protection product against numerous diseases, especially in organic production. In the past two decades, some countries and the EU have invested in research to reduce the reliance on copper. However, no single alternative able to replace copper has been identified. We suggest that agroecological approaches are urgently needed to design crop protection strategies based on the complementary actions of the wide variety of crop protection tools for disease control

Possible relevance of pigeons as an indicator species for monitoring air pollution.

Wild city pigeons were caught at four different locations in the Netherlands to represent areas of high (Amsterdam-high), moderate (Amsterdam-medium), and low (Maastricht and Assen) traffic density. It is assumed that local ambient air pollution decreases as a function of traffic density. In these pigeons levels of polycyclic aromatic hydrocarbon (PAH)-DNA adducts, oxidative DNA damage, and heavy metal residues were determined in kidney, lung, liver, and blood (no adduct analysis in blood). The contribution of leaded gasoline to total body lead content was estimated by measuring concentrations of Pb and its isotopes in blood. We also analyzed samples of ambient air particulate matter for PAH and heavy metal concentrations at the four different locations. Interregional differences in heavy metals in ambient air particulate matter were reflected relatively well by pigeon body loads. The higher lead and cadmium concentrations in blood, kidney, liver, and lung were found in the Amsterdam high traffic density area, followed by Amsterdam medium, Assen, and Maastricht. A high Pb concentration in blood coincided with relatively low 206Pb/207Pb values, indicating a high contribution of leaded gasoline to total blood Pb concentrations in pigeons from the Amsterdam high traffic density area. Significantly enhanced blood zinc values were found in pigeons from both locations in Amsterdam compared to pigeons from the other two areas. However, no differences in Zn tissue levels between the four different groups were found. Oxidative DNA damage, determined as the ratio of 7-Hydro-8-oxo-2'-deoxyguanosine/ deoxyguanosine, in pigeon liver was highest in Amsterdam-high, followed by Assen (low traffic density). Pb content, but not the Cd content, was positively associated with oxidative DNA damage in liver tissue. In lung tissue, a negative correlation was found between oxidative DNA damage and Zn content. These results indicate that the carcinogenic potential of Pb might be ascribed to oxygen radical formation, whereas Zn plays a protective role against oxidative DNA damage. Places with high and medium traffic density could be clearly discriminated on the basis of PAH levels in the ambient air. The PAH content in particulate air samples was not, however, reflected in total PAH-related DNA adduct levels because no differences could be observed in tissue adduct levels in pigeons from the four different locations. Our results indicate that wild city pigeons can be used as biological indicators of exposure to heavy metal pollution in outdoor air

First-Order Melting and Dynamics of Flux Lines in a Model for YBa2_2Cu3_3O7−δ_{7-\delta}

We have studied the statics and dynamics of flux lines in a model for YBCO, using both Monte Carlo simulations and Langevin dynamics. For a clean system, both approaches yield the same melting curve, which is found to be weakly first order with a heat of fusion of about $0.02 k_BT_m$ per vortex pancake at a field of $50 {\rm kG}.$ The time averaged magnetic field distribution experienced by a fixed spin is found to undergo a qualitative change at freezing, in agreement with NMR and $\mu {\rm SR}$ experiments. Melting in the clean system is accompanied by a proliferation of free disclinations which show a clear B-dependent 3D-2D crossover from long disclination lines parallel to the c-axis at low fields, to 2D ``pancake'' disclinations at higher fields. Strong point pins produce a logarithmical $\ln t$ relaxation which results from slow annealing out of disclinations in disordered samples.Comment: 31 pages, latex, revtex, 12 figures available upon request, No major changes to the original text, but some errors in the axes scale for Figures 6 and 7 were corrected(new figures available upon request), to be published in Physical Review B, July 199

INPP4B overexpression and c-KIT downregulation in human achalasia.

BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P 64 10-3 . Nine genes with a P 64 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was significantly reduced in achalasia patients vs controls. CONCLUSIONS & INFERENCES: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia

Microbubble-Assisted Ultrasound for Drug Delivery to the Retina in an Ex Vivo Eye Model

Drug delivery to the retina is one of the major challenges in ophthalmology due to the biological barriers that protect it from harmful substances in the body. Despite the advancement in ocular therapeutics, there are many unmet needs for the treatment of retinal diseases. Ultrasound combined with microbubbles (USMB) was proposed as a minimally invasive method for improving delivery of drugs in the retina from the blood circulation. This study aimed to investigate the applicability of USMB for the delivery of model drugs (molecular weight varying from 600 Da to 20 kDa) in the retina of ex vivo porcine eyes. A clinical ultrasound system, in combination with microbubbles approved for clinical ultrasound imaging, was used for the treatment. Intracellular accumulation of model drugs was observed in the cells lining blood vessels in the retina and choroid of eyes treated with USMB but not in eyes that received ultrasound only. Specifically, 25.6 ± 2.9% of cells had intracellular uptake at mechanical index (MI) 0.2 and 34.5 ± 6.0% at MI 0.4. Histological examination of retinal and choroid tissues revealed that at these USMB conditions, no irreversible alterations were induced at the USMB conditions used. These results indicate that USMB can be used as a minimally invasive targeted means to induce intracellular accumulation of drugs for the treatment of retinal diseases