The Cytotoxic Effect of α-Synuclein Aggregates

Parkinson's disease is a neurodegenerative disorder involving a functional protein, α-synuclein, whose primary function is related to vesicle trafficking. However, α-synuclein is prone to form aggregates, and these inclusions, known as Lewy bodies, are the hallmark of Parkinson's disease. α-synuclein can alter its conformation and acquire aggregating capacity, forming aggregates containing β-sheets. This protein's pathogenic importance is based on its ability to form oligomers that impair synaptic transmission and neuronal function by increasing membrane permeability and altering homeostasis, generating a deleterious effect over cells. First, we establish that oligomers interfere with the mechanical properties of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane, as demonstrated by nanoindentation curves. In contrast, nanoindentation revealed that the α-synuclein monomer's presence leads to a much more resistant lipid bilayer. Moreover, the oligomers’ interaction with cell membranes can promote lactate dehydrogenase (LDH) release, suggesting the activation of cytotoxic events.     

Data‐Driven Optimal Transport

The problem of optimal transport between two distributions ρ(x) and μ(y) is extended to situations where the distributions are only known through a finite number of samples {x_i} and {y_j}. A weak formulation is proposed, based on the dual of the Kantorovich formulation, with two main modifications: replacing the expected values in the objective function by their empirical means over the {x_i} and {y_j}, and restricting the dual variables u(x) and v(y) to a suitable set of test functions adapted to the local availability of sample points. A procedure is proposed and tested for the numerical solution of this problem, based on a fluidlike flow in phase space, where the sample points play the role of active Lagrangian markers. © 2016 Wiley Periodicals, Inc.     

Voltammetric Determination of Pb(II) and Cd(II) Ions in Well Water Using a Sputtered Bismuth Screen‐Printed Electrode

A method using commercially available sputtered bismuth screen‐printed electrodes (Bi_spSPE), as substitute to mercury electrodes, for the determination of trace Pb(II) and Cd(II) ions in drinking well water samples collected in a contaminated area in The Republic of El Salvador by means of differential pulse anodic stripping voltammetry (DPASV) has been proposed. The comparable detection and quantification limits obtained for both Bi_spSPE and hanging mercury drop electrode (HMDE), together with the similar results with a high reproducibility obtained in these water samples analyses recommend the applicability of Bi_spSPE for the determination of low level of metal concentrations in natural samples.     

Cyclopalladation and Reactivity of Amino Esters through C?H Bond Activation: Experimental,Kinetic, and Density Functional Theory Mechanistic Studies

The orthopalladation, through C? H bond activation, of a large number of amino esters and amino phosphonates derived from phenylglycine, and having different substituents at the aryl ring and the C‐α atom, as well as on the N‐amine atom, has been studied. The experimental observations indicated an improvement in the yields of the orthopalladated compounds when the N‐amine and/or the C‐α atom are substituted, when compared with the unsubstituted methyl phenylglycinate derivatives. In contrast, substitutions at the aryl ring do not promote significant changes in the orthometalation results. Furthermore, the use of hydrochloride salts of the amino esters has also been shown to have a remarkably favorable effect on the process. All these observations have been fully quantified at different temperatures and pressures by a detailed kinetic study in solution in different solvents and in the presence and absence of added Brønsted acids and chloride anions. The data collected indicate relevant changes in the process depending on these conditions, as expected from the general background known for cyclopalladation reactions. An electronic mechanism of the orthopalladation has been proposed based on DFT calculations at the B3LYP level, and a very good agreement between the trends kinetically measured and the theoretically calculated activation barriers has been obtained. The reactivity of the new orthopalladated amino phosphonate derivatives has been tested and it was found that their halogenation, alkoxylation and carbonylation resulted in formation of the corresponding functionalized ortho‐haloaminophosphonates, ortho‐alkoxyaminophosphonates and oxoisoindolinylphosphonates.     

Homogeneous diffusion in ℝ with power-like nonlinear diffusivity

We study the nonnegative solutions of the initial-value problem u_t=(u^r|u_x|^p-1u_x)_x,u(x, 0)L ¹(), where p>0, r+p>0. The local velocity of propagation of the solutions is identified as V = -v_x| v_x|^p-1 where v =cu (with r +p - 1)/p and c (r +p/(r +p- 1)) is the nonlinear potential. Our main result is the a priori estimate (v_x|v_x|^p-1)_x-

Complex dynamics in double-diffusive convection

The dynamics of a small Prandtl number binary mixture in a laterally heated cavity is studied numerically. By combining temporal integration, steady state solving and linear stability analysis of the full PDE equations, we have been able to locate and characterize a codimension-three degenerate Takens–Bogdanov point whose unfolding describes the dynamics of the system for a certain range of Rayleigh numbers and separation ratios near S=-1. PACS 44.25.+f, 47.20.Bp, 05.45.-a     

Numerical study of sliding wear caused by a loaded pin on a rotating disc

A computational approach is proposed to predict the sliding wear caused by a loaded spherical pin contacting a rotating disc, a condition typical of the so-called pin-on-disc test widely used in tribological studies. The proposed framework relies on the understanding that, when the pin contacts and slides on the disc, a predominantly plane strain region exists at the centre of the disc wear track. The wear rate in this plane strain region can therefore be determined from a two dimensional idealisation of the contact problem, reducing the need for computationally expensive three dimensional contact analyses. Periodic unit cell techniques are used in conjunction with a ratchetting-based failure criterion to predict the wear rate in the central plane strain region. The overall three dimensional wear rate of the disc is then determined by scaling the plane strain wear rate with a conversion factor related to the predicted shape of the wear track. The approach is used to predict pin-on-disc test data from an Al-Si coating using a tungsten carbide pin. The predicted results are found to be consistent with measured data.     

Simultaneous determination of a selected group of cytostatic drugs in water using high-performance liquid chromatography-triple-quadrupole mass spectrometry

In recent years, an increasing concern has risen about the presence of pharmaceuticals in the aquatic environment. Despite their toxicity, increasing consumption and release into the municipal sewage, only a few studies have been focused on cytostatic drugs, mainly due to the lack of methods for their simultaneous analysis. In this work, a method, based on solid-phase extraction prior to high-performance liquid chromatography-triple quadrupole mass spectrometry determination, was optimized and validated for the simultaneous determination of some (14) of the most widely used cytostatic drugs in river water, influent and effluent wastewater. Process efficiency was in the range between 41 and 99% in real samples, except for cytarabine (24%), docetaxel (17%) and methotrexate (30%), due to suppression effects; precision values were <11%, except for gemcitabine (up to 19%); and detection limits were in the range between 0.1 and 38 ng/L. Cytarabine, doxorubicin, etoposide, gemcitabine, iphosphamide and vinorelbine were found at concentration levels up to 14 ng/L in influent and effluent wastewater, showing an insignificant decrease during sewage treatment; cytarabine and gemcitabine were found in effluent wastewater and were also detected in river water associated with effluent discharges.