A conservative implicit finite difference algorithm for the unsteady transonic full potential equation

An implicit finite difference procedure is developed to solve the unsteady full potential equation in conservation law form. Computational efficiency is maintained by use of approximate factorization techniques. The numerical algorithm is first order in time and second order in space. A circulation model and difference equations are developed for lifting airfoils in unsteady flow; however, thin airfoil body boundary conditions have been used with stretching functions to simplify the development of the numerical algorithm

The structure of trailing vortices generated by model rotor blades

Hot-wire anemometry to analyze the structure and geometry of rotary wing trailing vortices is studied. Tests cover a range of aspect ratios and blade twist. For all configurations, measured vortex strength correlates well with maximum blade-bound circulation. Measurements of wake geometry are in agreement with classical data for high-aspect ratios. The detailed vortex structure is similar to that found for fixed wings and consists of four well defined regions--a viscous core, a turbulent mixing region, a merging region, and an inviscid outer region. A single set of empirical formulas for the entire set of test data is described

Cysteine Residues Contribute to the Dimerization and Enzymatic Activity of Human Nuclear dUTP Nucleotidohydrolase (nDut).

dUTPase is an enzyme found in all organisms that have thymine as a constituent of DNA. Through evolution, humans have two major isoforms of dUTPase: a mitochondrial (mDut) and a nuclear (nDut) isoform. The nuclear isoform of dUTPase is a 164-amino-acids-long protein containing three cysteine residues. nDut\u27s starting methionine is post-translationally cleaved, leaving four unique amino acids on its amino-terminus including one cysteine residue (C3). These are not present in the mitochondrial isoform (mDut). Using mass spectrometry analyses of recombinant dUTPase constructs, we have discovered an intermolecular disulfide bridge between cysteine-3 of each nDut monomer. We have found that these two residues stabilize a dimer configuration that is unique to the nDut isoform. We have also uncovered an intramolecular disulfide linkage between cysteine residues C78 and C134, stabilizing the monomeric state of the protein. Of note, both disulfide linkages are essential for nDut\u27s enzymatic activity and dimeric formation can be augmented by the addition of the oxidizing agent, hydrogen peroxide to cells. Analyses of endogenous cellular dUTPase proteins confirm these differences between the two isoforms. We observed that mDut appears to be a mixture of monomer, dimer, and trimer conformations, as well as higher-order subunit interactions. In contrast, nDut appeared to exist only in monomeric and dimeric forms. Cysteine-based redox switches have recently emerged as a distinct class of post-translational modification. In light of this and our results, we propose that nDut possesses a redox switch whereby cysteine interactions regulate nDut\u27s dUTP-hydrolyzing activity

Platform optimization and cost analysis in a floating offshore wind farm

Floating offshore wind represents a new frontier of renewable energies. The absence of a fixed structure allows exploiting wind potential in deep seas, like the Atlantic Ocean and Mediterranean Sea, characterized by high availability and wind potential. However, a floating offshore wind system, which includes an offshore turbine, floating platform, moorings, anchors, and electrical system, requires very high capital investments: One of the most relevant cost items is the floating substructure. This work focuses on the choice of a floating platform that minimizes the global weight, in order to reduce the material cost, but ensuring buoyancy and static stability. Subsequently, the optimized platform is used to define a wind farm located near the island of Pantelleria, Italy in order to meet the island’s electricity needs. A sensitivity analysis to estimate the Levelized Cost Of Energy is presented, analyzing the parameters that influence it most, like Capacity Factor, Weighted Average Capital Cost (WACC) and number of wind turbines

Can Early Life Exposure to Permethrin lead to intergenerational effects?

Pesticides are largely used in agriculture against pests and consequently are present in fruits and vegetables. The wide presence of pesticide residues in breast milk underline the risk for the population, focalizing the long-term consequence of early life pyrethroid exposure. The significant presence of pyrethroid metabolites in the urine of population over the world confirms that their presence in food is a global problem. It has been demonstrated that there is a correlation between the environmental exposure to pesticides and the development of neurodegenerative diseases. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce neurodegeneration (i.e. Parkinson’s –like disease) and it can cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. The aim of this study was to evaluate if the rat offspring (F1 generation) exposed to a low dose of PERM from postnatal day 6 to 21, presents alterations in Nurr1 gene expression as previously observed in early life permethrin treated male rats. Moreover, global DNA methylation was analyzed in untreated early life exposed mothers and offspring (F1 generation). Methods Through Nurr1gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Results 33% of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Conclutions Intergenerational PERM-induced damage on progenies has been identified for the first time. On the light of these results, pesticide residues in the food could represent a risk factor for the health of children especially in early life when the brain is still in the developing phase. Further studies are needed to elucidate the molecular mechanisms associated with the damage

Antiproliferative and pro-apoptotic effects of the phytochemical Indicaxanthin on human intestinal (Caco-2) and hepatic (Ha 22T) cancer cell lines

In the present study antiproliferative effects of Indicaxanthin (Ind), a highly bioavailable pigment from the fruits of Opuntia ficus-indica (1), were investigated on a number of human cancer cell lines including hepatocarcinoma cells (HepG2, Ha22T, HUH 7), breast cancer cells (MCF7), cervix epithelial carcinoma (HeLa), and colorectal carcinoma cells (Caco-2). Cytotoxicity of Ind, in a concentration range between 25 to 100 \uf06dM, was evaluated by Trypan blue exclusion method and MTT assay. Ind caused a clear dose- and time-dependent decrease in the proliferation of Caco-2 and Ha 22T cells with an IC(50) of about 50 \uf06dM, with minor effect on the other cell lines. Flow cytometric analysis after Annexin V-FITC and propidium iodure double staining, at 24, 48 and 72 h of treatment with 100 \uf06dM Ind, showed a pro-apoptotic effect of the pigment at 48 and 72 h. Effect of Ind on DNA methylation investigated on DNA from Ha22T cells line and Caco2 cells line at 48 h of treatment with 10 \uf06dM Ind, using MESAP-PCR (Methylation-Sensitive Arbitrarily-Primed Polymerase Chain Reaction) (3) showed that Ind induces a slight global demethylation. While antiproliferative effects of indicaxanthin add further value to the nutritional characteristics of the fruits of O. ficus-indica (2), our results also are consistent with the emerging role of dietary phytochemicals on the epigenetic regulation of gene expression

Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme

Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach,we studied the polymorphisms andmethylation of sites contained in the 5′ flanking region of themetabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associatedwith the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentially influenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed a greater expression inhibition (ranging from 20% to 30%) compared with others carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an increase of expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 alleles play a more important role in the expression of the enzyme, compared with other (epi)genetic factors, since they are binding sites for trans-acting proteins

(2-Aminobenzothiazole)-Methyl-1,1-bisphosphonic acids: Targeting matrix metalloproteinase 13 inhibition to the bone

Matrix Metalloproteinases (MMPs) are a family of secreted and membrane-bound enzymes, of which 24 isoforms are known in humans. These enzymes degrade the proteins of the extracellular matrix and play a role of utmost importance in the physiological remodeling of all tissues. However, certain MMPs, such as MMP-2, -9, and -13, can be overexpressed in pathological states, including cancer and metastasis. Consequently, the development of MMP inhibitors (MMPIs) has been explored for a long time as a strategy to prevent and hinder metastatic growth, but the important side effects linked to promiscuous inhibition of MMPs prevented the clinical use of MMPIs. Therefore, several strategies were proposed to improve the therapeutic profile of this pharmaceutical class, including improved selectivity toward specific MMP isoforms and targeting of specific organs and tissues. Combining both approaches, we conducted the synthesis and preliminary biological evaluation of a series of (2-aminobenzothiazole)-methyl-1,1-bisphosphonic acids active as selective inhibitors of MMP-13 via in vitro and in silico studies, which could prove useful for the treatment of bone metastases thanks to the bone-targeting capabilities granted by the bisphosphonic acid group