Molecular dynamics simulation of the transport of small molecules across a polymer membrane

The transport of small molecules through a polymer membrane is modeled using the computer simulation technique of molecular dynamics (MD). The transport coefficient is derived from a combination of the excess free energy and the diffusion constant. Both properties are derived from MD simulations, applied to helium and methane in polydimethylsiloxane (PDMS). The diffusional process appears to have the character of a jump diffusion for methane and less so for helium. Jumps are allowed by fluctuations of the size and shape of holes. Experimental diffusion constants are well reproduced. The excess free energies, determined by a particle insertion method, are lower by 5-7 kJ/mol than experimental values. It is shown that, as a result of a higher solubility, methane has a higher permeability constant than helium, despite its lower diffusion constant

The Role of Interferon Regulatory Factor-1 and Interferon Regulatory Factor-2 in IFN-γ Growth Inhibition of Human Breast Carcinoma Cell Lines

Interferon (IFN) regulatory factor-1 (IRF-1) and IRF-2 play opposing roles in the regulation of many IFN-γ-inducible genes. To investigate the signal transduction pathway in response to IFN-γ in light of differences in growth effects, we selected four human breast carcinoma cell lines based on a spectrum of growth inhibition by IFN-γ. MDA468 growth was markedly inhibited by IFN-γ, and it showed substantial induction of IRF-1 mRNA but little IRF-2 induction. SKBR3 showed little growth inhibition and little induction of IRF-1 mRNA but significant induction of IRF-2 mRNA. HS578T and MDA436 growth inhibition and IRF-1/IRF-2 induction were intermediate. All four cell lines showed intact receptor at the cell surface and Stat1 translocation to the nucleus by immunostaining. By EMSA, there were marked differences in the induced ratio of IRF-1 and IRF-2 binding activity between the cell lines that correlated with growth inhibition. Finally, antisense oligonucleotides specific for IRF-1 attenuated IFN-γ growth inhibition in MDA436 and MDA468, confirming the direct role of IRF-1 in IFN-γ growth inhibition. Induction of IRF-1 causes growth inhibition in human breast cancer cell lines, and induction of IRF-2 can oppose this. The relative induction of IRF-1 to IRF-2 is a critical control point in IFN-γ response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63111/1/10799900360708623.pd

Critical point network for drainage between rough surfaces

In this paper, we present a network method for computing two-phase flows between two rough surfaces with significant contact areas. Low-capillary number drainage is investigated here since one-phase flows have been previously investigated in other contributions. An invasion percolation algorithm is presented for modeling slow displacement of a wetting fluid by a non wetting one between two rough surfaces. Short-correlated Gaussian process is used to model random rough surfaces.The algorithm is based on a network description of the fracture aperture field. The network is constructed from the identification of critical points (saddles and maxima) of the aperture field. The invasion potential is determined from examining drainage process in a flat mini-channel. A direct comparison between numerical prediction and experimental visualizations on an identical geometry has been performed for one realization of an artificial fracture with a moderate fractional contact area of about 0.3. A good agreement is found between predictions and observations

Enkephalon - technological platform to support the diagnosis of alzheimer’s disease through the analysis of resonance images using data mining techniques

Dementia can be considered as a decrease in the cognitive function of the person. The main diseases that appear are Alzheimer and vascular dementia. Today, 47 million people live with dementia around the world. The estimated total cost of dementia worldwide is US $ 818 billion, and it will become a trilliondollar disease by 2019 The vast majority of people with dementia not received a diagnosis, so they are unable to access care and treatment. In Colombia, two out of every five people presented a mental disorder at some point in their lives and 90% of these have not accessed a health service. Here it´s proposed a technological platform so early detection of Alzheimer. This tool complements and validates the diagnosis made by the health professional, based on the application of Machine Learning techniques for the analysis of a dataset, constructed from magnetic resonance imaging, neuropsychological test and the result of a radiological test. A comparative analysis of quality metrics was made, evaluating the performance of different classifier methods: Random subspace, Decorate, BFTree, LMT, Ordinal class classifier, ADTree and Random forest. This allowed us to identify the technique with the highest prediction rate, that was implemented in ENKEPHALON platform

Mark correlations: relating physical properties to spatial distributions

Mark correlations provide a systematic approach to look at objects both distributed in space and bearing intrinsic information, for instance on physical properties. The interplay of the objects' properties (marks) with the spatial clustering is of vivid interest for many applications; are, e.g., galaxies with high luminosities more strongly clustered than dim ones? Do neighbored pores in a sandstone have similar sizes? How does the shape of impact craters on a planet depend on the geological surface properties? In this article, we give an introduction into the appropriate mathematical framework to deal with such questions, i.e. the theory of marked point processes. After having clarified the notion of segregation effects, we define universal test quantities applicable to realizations of a marked point processes. We show their power using concrete data sets in analyzing the luminosity-dependence of the galaxy clustering, the alignment of dark matter halos in gravitational $N$-body simulations, the morphology- and diameter-dependence of the Martian crater distribution and the size correlations of pores in sandstone. In order to understand our data in more detail, we discuss the Boolean depletion model, the random field model and the Cox random field model. The first model describes depletion effects in the distribution of Martian craters and pores in sandstone, whereas the last one accounts at least qualitatively for the observed luminosity-dependence of the galaxy clustering.Comment: 35 pages, 12 figures. to be published in Lecture Notes of Physics, second Wuppertal conference "Spatial statistics and statistical physics

Approximate Ginzburg-Landau solution for the regular flux-line lattice. Circular cell method

A variational model is proposed to describe the magnetic properties of type-II superconductors in the entire field range between $H_{c1}$ and $H_{c2}$ for any values of the Ginzburg-Landau parameter $\kappa>1/\sqrt{2}$. The hexagonal unit cell of the triangular flux-line lattice is replaced by a circle of the same area, and the periodic solutions to the Ginzburg-Landau equations within this cell are approximated by rotationally symmetric solutions. The Ginzburg-Landau equations are solved by a trial function for the order parameter. The calculated spatial distributions of the order parameter and the magnetic field are compared with the corresponding distributions obtained by numerical solution of the Ginzburg-Landau equations. The comparison reveals good agreement with an accuracy of a few percent for all $\kappa$ values exceeding $\kappa \approx 1$. The model can be extended to anisotropic superconductors when the vortices are directed along one of the principal axes. The reversible magnetization curve is calculated and an analytical formula for the magnetization is proposed. At low fields, the theory reduces to the London approach at $\kappa \gg 1$, provided that the exact value of $H_{c1}$ is used. At high fields, our model reproduces the main features of the well-known Abrikosov theory. The magnetic field dependences of the reversible magnetization found numerically and by our variational method practically coincide. The model also refines the limits of some approximations which have been widely used. The calculated magnetization curves are in a good agreement with experimental data on high-T$_c$ superconductors.Comment: 8 pages, RevTex, 6 figures, submitted to Phys. Rev.

A Mendelian Trait for Olfactory Sensitivity Affects Odor Experience and Food Selection

SummaryHumans vary in acuity to many odors [1–4], with variation within olfactory receptor (OR) genes contributing to these differences [5–9]. How such variation also affects odor experience and food selection remains uncertain [10], given that such effects occur for taste [11–15]. Here we investigate β-ionone, which shows extreme sensitivity differences [4, 16, 17]. β-ionone is a key aroma in foods and beverages [18–21] and is added to products in order to give a pleasant floral note [22, 23]. Genome-wide and in vitro assays demonstrate rs6591536 as the causal variant for β-ionone odor sensitivity. rs6591536 encodes a N183D substitution in the second extracellular loop of OR5A1 and explains >96% of the observed phenotypic variation, resembling a monogenic Mendelian trait. Individuals carrying genotypes for β-ionone sensitivity can more easily differentiate between food and beverage stimuli with and without added β-ionone. Sensitive individuals typically describe β-ionone in foods and beverages as “fragrant” and “floral,” whereas less-sensitive individuals describe these stimuli differently. rs6591536 genotype also influences emotional associations and explains differences in food and product choices. These studies demonstrate that an OR variant that influences olfactory sensitivity can affect how people experience and respond to foods, beverages, and other products

Hydrogen Sulfide Protects HUVECs against Hydrogen Peroxide Induced Mitochondrial Dysfunction and Oxidative Stress

10.1371/journal.pone.0053147PLoS ONE82

Inhibition of StearoylCoA Desaturase Activity Blocks Cell Cycle Progression and Induces Programmed Cell Death in Lung Cancer Cells

Lung cancer is the most frequent form of cancer. The survival rate for patients with metastatic lung cancer is ∼5%, hence alternative therapeutic strategies to treat this disease are critically needed. Recent studies suggest that lipid biosynthetic pathways, particularly fatty acid synthesis and desaturation, are promising molecular targets for cancer therapy. We have previously reported that inhibition of stearoylCoA desaturase-1 (SCD1), the enzyme that produces monounsaturated fatty acids (MUFA), impairs lung cancer cell proliferation, survival and invasiveness, and dramatically reduces tumor formation in mice. In this report, we show that inhibition of SCD activity in human lung cancer cells with the small molecule SCD inhibitor CVT-11127 reduced lipid synthesis and impaired proliferation by blocking the progression of cell cycle through the G1/S boundary and by triggering programmed cell death. These alterations resulting from SCD blockade were fully reversed by either oleic (18:1n-9), palmitoleic acid (16:1n-7) or cis-vaccenic acid (18:1n-7) demonstrating that cis-MUFA are key molecules for cancer cell proliferation. Additionally, co-treatment of cells with CVT-11127 and CP-640186, a specific acetylCoA carboxylase (ACC) inhibitor, did not potentiate the growth inhibitory effect of these compounds, suggesting that inhibition of ACC or SCD1 affects a similar target critical for cell proliferation, likely MUFA, the common fatty acid product in the pathway. This hypothesis was further reinforced by the observation that exogenous oleic acid reverses the anti-growth effect of SCD and ACC inhibitors. Finally, exogenous oleic acid restored the globally decreased levels of cell lipids in cells undergoing a blockade of SCD activity, indicating that active lipid synthesis is required for the fatty acid-mediated restoration of proliferation in SCD1-inhibited cells. Altogether, these observations suggest that SCD1 controls cell cycle progression and apoptosis and, consequently, the overall rate of proliferation in cancer cells through MUFA-mediated activation of lipid synthesis