NURBS-Enhanced Finite Element Method (NEFEM)

The development of NURBS-Enhanced Finite Element Method (NEFEM) is revisited. This technique allows a seamless integration of the CAD boundary representation of the domain and the finite element method (FEM). The importance of the geometrical model in finite element simulations is addressed and the benefits and potential of NEFEM are discussed and compared with respect to other curved finite element techniques.     

Molecular basis of agonicity and antagonicity in the androgen receptor studied by molecular dynamics simulations

Treatment of prostate cancer patients with antiandrogens is initially successful, though the therapy often becomes refractory over the time. This mechanism is not fully understood, but the presence of androgen receptor (AR) mutant forms which are activated by antiandrogens and other endogenous ligands, and overexpression of the receptor have been suggested. In an attempt to explain the molecular basis for agonicity and antagonicity in the androgen receptor, and the changes on biological activity of subtle modifications at the ligand and receptor (mutations) level, molecular dynamics simulations were performed on the androgen receptor wild type (WT), and T877A and W741 mutant forms, complexed with several non-steroidal androgens. The stabilizing role of residues from helices 3, 5, 11 and 12 was observed in non-steroidal androgens R-3, S-1, and R-bicalutamide and hydroxyflutamide in resistant mutations. In the AR WT antiandrogen R-bicalutamide complex, destabilization of M895 by both W741 and the sulfonyl linkage of the ligand may be responsible for reported antagonism. Changes in the ligand or mutations alleviating this effect were observed to stabilize the receptor in the active conformation, thus developing resistance to R-bicalutamide. The results presented provide a plausible explanation for the molecular basis of agonicity and antagonicity in the androgen receptor, and complement previous studies using static crystal structures, incorporating for the first time protein dynamics into the analysis. Thus, our results provide a valuable framework for the structure-based design of improved antiandrogens.     

Programmable logic construction kits for hyper-real-time neuronal modeling

Programmable logic designs are presented that achieve exact integration of leaky integrate-and-fire soma and dynamical synapse neuronal models and incorporate spike-time dependent plasticity and axonal delays. Highly accurate numerical performance has been achieved by modifying simpler forward-Euler-based circuitry requiring minimal circuit allocation, which, as we show, behaves equivalently to exact integration. These designs have been implemented and simulated at the behavioral and physical device levels, demonstrating close agreement with both numerical and analytical results. By exploiting finely grained parallelism and single clock cycle numerical iteration, these designs achieve simulation speeds at least five orders of magnitude faster than the nervous system, termed here hyper-real-time operation, when deployed on commercially available field-programmable gate array (FPGA) devices. Taken together, our designs form a programmable logic construction kit of commonly used neuronal model elements that supports the building of large and complex architectures of spiking neuron networks for real-time neuromorphic implementation, neurophysiological interfacing, or efficient parameter space investigations.     

Output feedback trajectory stabilization of the uncertainty DC servomechanism system

This work proposes a solution for the output feedback trajectory-tracking problem in the case of an uncertain DC servomechanism system. The system consists of a pendulum actuated by a DC motor and subject to a time-varying bounded disturbance. The control law consists of a Proportional Derivative controller and an uncertain estimator that allows compensating the effects of the unknown bounded perturbation. Because the motor velocity state is not available from measurements, a second-order sliding-mode observer permits the estimation of this variable in finite time. This last feature allows applying the Separation Principle. The convergence analysis is carried out by means of the Lyapunov method. Results obtained from numerical simulations and experiments in a laboratory prototype show the performance of the closed loop system.     

Teaching Macroeconomics with GAMS

Our general goal in this paper is to show how to implement in GAMS standard deterministic nonlinear macro models, and stochastic linear macro models with rational expectations. We will also present basic concepts on solution methods and policy analysis for these kinds of models. As a practical illustration, we will use some well known teaching and experimental models in the macroeconomic literature.     

Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: what can vertical Pt-C replication tell us about the organization of the pronase-digested PHF core?

Untreated paired helical filaments (PHFs) and pronase-digested PHF-core filaments were stereoscopically imaged with a freeze-drying vertical platinum-carbon replication preparation method for TEM. The untreated PHF have an average wide region (W) = 22.8 +/- 2.4 nm, a narrow region (T) = 10.6 +/- 1.7 nm, and a helical turn period (L) = 78.6 +/- 13.4. The surfaces of the untreated PHF's fuzzy coat appears disorganized. The widths of the pronase-treated PHF-core filaments were significantly reduced (W(d) = 14.8 +/- 1.2 nm, T(d) = 5.7 +/- 1.0 nm, and L(d) = 75.4 +/- 17 nm). The surfaces of the untreated PHF contained approximately 1.1 nm strands, the same size as tau monomer ( approximately 1.0 nm). The pronase-digested PHF cores mostly contained approximately 1.6 +/- 0.3 nm strands although strand diameters ranged from 0.6-2.5 nm. The strands sometimes appear to be wrapped around the filament axis; less often, they appear to be roughly parallel to the PHF axis, and otherwise appear to be randomly oriented. Images of pronase-digested PHF core images are discussed in relation to the core's biochemical composition, its proposed beta structure, and structural subunit models. Images of the untreated and the pronase-digested PHF support a helical ribbon morphology.     

Mice Lacking Gpr179 with Complete Congenital Stationary Night Blindness Are a Good Model for Myopia

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179^−/− mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179^+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions.     

Influence of arsenate adsorption to ferrihydrite, goethite, and boehmite on the kinetics of arsenate reduction by Shewanella putrefaciens strain CN-32

The kinetics of As(V) reduction by Shewanella putrefaciens strain CN-32 was investigated in suspensions of 0.2, 2, or 20 g L(-1) ferrihydrite, goethite, or boehmite at low As (10 μM) and lactate (25 μM) concentrations. Experimental data were compared with model predictions based on independently determined sorption isotherms and rates of As(V) desorption, As(III) adsorption, and microbial reduction of dissolved As(V), respectively. The low lactate concentration was chosen to prevent significant Fe(III) reduction, but still allowing complete As(V) reduction. Reduction of dissolved As(V) followed first-order kinetics with a 3 h half-life of As(V). Addition of mineral sorbents resulted in pronounced decreases in reduction rates (32-1540 h As(V) half-life). The magnitude of this effect increased with increasing sorbent concentration and sorption capacity (goethite < boehmite < ferrihydrite). The model consistently underestimated the concentrations of dissolved As(V) and the rates of microbial As(V) reduction after addition of S. putrefaciens (～5 × 10(9) cells mL(-1)), suggesting that attachment of S. putrefaciens cells to oxide mineral surfaces promoted As(V) desorption and thereby facilitated As(V) reduction. The interplay between As(V) sorption to mineral surfaces and bacterially induced desorption may thus be critical in controlling the kinetics of As reduction and release in reducing soils and sediments.     

Stability Analysis of a Human Arm Interacting with a Force Augmenting Device

This paper presents a stability analysis of the interaction between a human and a linear moving Force Augmenting Device (FAD). The analysis employs a mathematical model of the human arm, the FAD and their interaction. As a depart from past works, this article presents a stability analysis considering time-delays in the human model. A key ingredient in the analysis is the use of the Rekasius substitution for replacing the time-delay terms. It is proved that the human machine interaction is stable when the human model has no delays. When delays are considered in the human model, the analysis provides an upper bound for the time-delays preserving a stable interaction. Numerical simulations allow to assess the human-FAD interaction. An experiment is performed with a laboratory prototype, where a human operator lifts a load. It is observed that the human machine interaction is stable and the human operator is able to move the load to a desired position by experiencing very little effort.     

In vitro intestinal absorption of amino acid mixtures extracted from codfish (Gadus morhua L.) salting wastewater

This study reports on the intestinal permeability of salt‐containing mixtures of amino acids extracted from codfish salting wastewater. Permeability was evaluated in vitro using the Caco‐2 cell line model; cell integrity during exposure to mixtures of amino acids was estimated by measuring the transepithelial electrical resistance (TEER). The effect of salt (NaCl) on the permeability and on the intestinal cell's integrity was also examined. Permeation rate (i.e. transport) was ≥95% for all amino acids except for creatine, for which it was 6%. Values for apparent permeability coefficients, P_app > 10^?5 cm s^?1, for mixture with isotonic concentration of NaCl suggest that amino acids are very likely to be absorbed in humans. Mixture with a hypertonic level of NaCl exerts a cytotoxic effect in intestinal cells resulting in a loss of epithelium integrity. Results show that isotonic mixture of amino acids extracted from codfish salting wastewater could be used in food, feed, cosmetic and pharmaceutical formulations. These applications could contribute to the fish industry sustainability.