Surface coupling effects on the capacitance of thin insulating films

A general form for the surface roughness effects on the capacitance of a capacitor is proposed. We state that a capacitor with two uncoupled rough surfaces could be treated as two capacitors in series which have been divided from the mother capacitor by a slit. This is in contrast to the case where the two rough surfaces are coupled. When the rough surfaces are coupled, the type of coupling decides the modification of the capacitance in comparison to the uncoupled case. It is shown that if the coupling between the two surfaces of the capacitor is positive (negative), the capacitance is less (higher) than the case of two uncoupled rough plates. Also, we state that when the correlation length and the roughness exponent are small, the coupling effect is not negligible

Design of metallic nanoparticles gratings for filtering properties in the visible spectrum

Plasmonic resonances in metallic nanoparticles are exploited to create efficient optical filtering functions. A Finite Element Method is used to model metallic nanoparticles gratings. The accuracy of this method is shown by comparing numerical results with measurements on a two-dimensional grating of gold nanocylinders with elliptic cross section. Then a parametric analysis is performed in order to design efficient filters with polarization dependent properties together with high transparency over the visible range. The behavior of nanoparticle gratings is also modelled using the Maxwell-Garnett homogenization theory and analyzed by comparison with the diffraction by a single nanoparticle. The proposed structures are intended to be included in optical systems which could find innovative applications.Comment: submitted to Applied Optic

A modal model for diffraction gratings

A description of an algorithm for a rather general modal grating calculation is presented. Arbitrary profiles, depth, and permittivity are allowed. Gratings built up from sub-gratings are allowed, as are coatings on the sidewalls of lines, and arbitrary complex structure. Conical angles and good conductors are supported

Use of Biliary Organoids in Cholestasis Research.

Cholangiocytes play a crucial role in the pathophysiology of cholestasis. However, research on human cholangiocytes has been restricted by challenges in long-term propagation and large-scale expansion of primary biliary epithelium. The advent of organoid technology has overcome this limitation allowing long-term culture of a variety of epithelia from multiple organs. Here, we describe two methods for growing human cholangiocytes in organoid format. The first applies to the generation of intrahepatic bile ducts using human induced pluripotent stem cells using a protocol of differentiation that recapitulates physiological bile duct development. The second method allows the propagation of primary biliary epithelium from the extrahepatic ducts or gallbladder. Both protocols result in large numbers of cholangiocyte organoids expressing biliary markers and maintaining key cholangiocyte functions

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

<p>Abstract</p> <p>Background</p> <p>Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies.</p> <p>Methods</p> <p>Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients.</p> <p>Results</p> <p>We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). <it>CYP3A4*1B</it>, <it>CYP3A5*3 </it>and <it>CYP3A5*6 </it>alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. <it>CYP3A5*1/CYP3A5*1 </it>and <it>CYP3A5*1/CYP3A5*3 </it>genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin.</p> <p>Conclusion</p> <p>A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.</p

Friction phenomena and their impact on the shear behaviour of granular material

In the discrete element simulation of granular materials, the modelling of contacts is crucial for the prediction of the macroscopic material behaviour. From the tribological point of view, friction at contacts needs to be modelled carefully, as it depends on several factors, e.g. contact normal load or temperature to name only two. In discrete element method (DEM) simulations the usage of Coulomb’s law of friction is state of the art in modelling particle–particle contacts. Usually in Coulomb’s law, for all contacts only one constant coefficient of friction is used, which needs to reflect all tribological effects. Thus, whenever one of the influence factors of friction varies over a wide range, it can be expected that the usage of only one constant coefficient of friction in Coulomb’s law is an oversimplification of reality. For certain materials, e.g. steel, it is known that a dependency of the coefficient of friction on the contact normal load exists. A more tribological tangential contact law is implemented in DEM, where the interparticle friction coefficient depends on the averaged normal stress in the contact. Simulations of direct shear tests are conducted, using steel spheres of different size distributions. The strong influence of interparticle friction on the bulk friction is shown via a variation of the constant interparticle friction coefficient. Simulations with constant and stress-dependent interparticle friction are compared. For the stress-dependent interparticle friction, a normal stress dependency of the bulk friction is seen. In the literature, measurements of different granular materials and small normal loads also show a stress dependency of the bulk friction coefficient. With increasing applied normal stress, the bulk friction coefficient reduces both in the experiments and in the simulations

Activity-Dependent Shedding of the NMDA Receptor Glycine Binding Site by Matrix Metalloproteinase 3: A PUTATIVE Mechanism of Postsynaptic Plasticity

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS

Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype

Antiracist Feminism and the Politics of Solidarity in Neoliberal Times

The chapter analyses the establishment and expansion of antiracist feminism in the last decade throughout the Nordic region, with new groups, media sites, and public events organised, especially in the large cities. Keskinen examines antiracist feminist and queer of colour activism in which the main or sole actors belong to groups racialised as non-white or ‘others’ in Nordic societies. A fundamental argument developed in the chapter is the central role and potential of these emerging social movements in the reconfiguring of political agendas and tackling pressing societal issues, due to its capacity to overlap and connect the borders of antiracist, feminist, and (to some extent) class-based politics. The chapter further argues for the usefulness of theorising the neoliberal turn of racial capitalism as the societal condition in which feminist activism takes place.Peer reviewe