Similar Stability Properties Research Articles

On the stochastic engine of contagious diseases in exponentially growing populations

The purpose of this paper is to analyze the mechanism for the interplay of deterministic and stochastic models for contagious diseases. Deterministic models for contagious diseases are prone to predict global stability. Small natural birth and death rates in comparison to disease parameters like the contact rate and the removal rate ensures that the globally stable endemic equilibrium corresponds to a tiny average proportion of infected individuals. Asymptotic equilibrium levels corresponding to low numbers of individuals invalidate the deterministic results.Diffusion effects force probability mass functions of the stochastic model to possess similar stability properties as the deterministic model. Particular simulations of the stochastic model predict, however, oscillatory patterns. Small and isolated populations show longer periods, more violent oscillations, and larger probabilities of extinction.We prove that evolution maximizes the infectiousness of the disease as measured by the ability to increase the proportion of infected individuals. This holds provided the stochastic oscillations are moderate enough to keep the proportion of susceptible individuals near a deterministic equilibrium.We close our paper with a discussion of the herd-immunity concept and stress its close relation to vaccination-programs.

Data-driven discovery of 2D materials by deep generative models

Efficient algorithms to generate candidate crystal structures with good stability properties can play a key role in data-driven materials discovery. Here, we show that a crystal diffusion variational autoencoder (CDVAE) is capable of generating two-dimensional (2D) materials of high chemical and structural diversity and formation energies mirroring the training structures. Specifically, we train the CDVAE on 2615 2D materials with energy above the convex hull ΔHhull < 0.3 eV/atom, and generate 5003 materials that we relax using density functional theory (DFT). We also generate 14192 new crystals by systematic element substitution of the training structures. We find that the generative model and lattice decoration approach are complementary and yield materials with similar stability properties but very different crystal structures and chemical compositions. In total we find 11630 predicted new 2D materials, where 8599 of these have ΔHhull < 0.3 eV/atom as the seed structures, while 2004 are within 50 meV of the convex hull and could potentially be synthesised. The relaxed atomic structures of all the materials are available in the open Computational 2D Materials Database (C2DB). Our work establishes the CDVAE as an efficient and reliable crystal generation machine, and significantly expands the space of 2D materials.

A Multiple-Reference Complex-Based Controller for Power Converters

A multiple-reference complex-based controller is proposed for three-phase power converters feeding nonlinear and unbalanced loads. The control scheme incorporates a stable multiple-complex coefficient filter with bandwidths that are set arbitrarily and independently for every harmonic under consideration. The multiple-reference complex-based control scheme is applied to an uninterruptible power supply system with a voltage source converter. Each harmonic is controlled using a standard complex proportional-resonant controller that is designed for stability and robustness using the Nyquist criterion. Similar stability and robustness properties follow for the overall system due to the frequency-domain properties of the filter and of the controllers. The proposed methodology is validated in simulation and experimental tests.

Crosslinking porcine aortic valve by radical polymerization for the preparation of BHVs with improved cytocompatibility, mild immune response, and reduced calcification.

Over one million artificial heart valve transplantations are performed each year due to valvular stenosis or regurgitation. Among them, bioprosthetic heart valves (BHVs) are increasingly being used because of the absence of the need for lifelong anticoagulation. Almost all of the commercial BHVs are treated with Glutaraldehyde (GLUT). As GLUT-treated BHVs are prone to calcification and structural degradation, their durability is greatly reduced with a service life of only 12-15 years. The physiological structure and mechanical properties of the porcine aortic valve (PAV) are closer to that of a human heart valve, so in this study, PAV is used as the model to explore the comprehensive properties of the prepared BHVs by radical polymerization crosslinking method. We found that PAV treated by radical polymerization crosslinking method showed similar ECM stability and biaxial mechanical properties with GLUT-treated PAV. However, radical polymerization crosslinked PAV exhibited better cytocompatibility and endothelialization potential in vitro cell experiment as better anticalcification potential and reduced immune response than GLUT-treated PAV through subcutaneous animal experiments in rats. To conclude, a novel crosslinking method of non-glutaraldehyde fixation of xenogeneic tissues for the preparation of BHVs is expected.

High Order Cut Discontinuous Galerkin Methods for Hyperbolic Conservation Laws in One Space Dimension

In this paper, we develop a family of high order cut discontinuous Galerkin (DG) methods for hyperbolic conservation laws in one space dimension. Ghost penalty stabilization is used to stabilize the scheme for small cut elements. Analysis shows that our proposed methods have similar stability and accuracy properties as the standard DG methods on a regular mesh. We also prove that the cut DG method with piecewise constants in space is total variation diminishing. We use the strong stability preserving Runge--Kutta method for time discretization and the time step is independent on the size of cut element. Numerical examples demonstrate the cut DG methods are high order accurate for smooth problems and perform well for discontinuous problems.

Rectangular lattice Boltzmann method using multiple relaxation time collision operator in two and three dimensions

We present a lattice Boltzmann (lb) method using a rectangular, non-isotropic lattice based on d2q9 and d3q27 velocity sets in two and three dimensions. A second order multi-scale expansion ensures that the scheme correctly reproduces hydrodynamic behaviour. A novel set of basis vectors is introduced in order to allow independent adjustment of eigenvalues corresponding to second order moments as required in order to ensure correct hydrodynamic behaviour using the non-isotropic lattice. Errors are reduced compared to other rectangular grid implementations. Linear perturbation analysis indicates that our scheme has similar stability properties to the isotropic lb method. We investigate the error behaviour of our scheme by performing Taylor-Green vortex flow simulations and comparing our results to simulations using a square grid and also to analytical results. We demonstrate that our scheme is well suited to direct numerical simulation of wall bounded turbulent flows and compare to well known benchmark results.

Synthesis and Comparison of Chitosan and Methocel Based Flexible Gels for Potential Use As Organic Electrolytes in Batteries

Reversibility, power output, and energy storage capability are considered to be the primary requirements when fabricating a rechargeable battery. These attributes are majorly based on the composition along with the interactions (redox reactions) occurring between them. An electrolyte is majorly responsible for the redox-reactions to occur at interfaces, and thus its preparation is a vital step in constructing a battery. Liquid electrolytes were mostly used during the advent of batteries, but due to hindrances like toxicity, corrosive nature, safety and leakage issues, and dendrite formation leading to battery failure; polymeric electrolytes (PEO, PVS, PEG, etc.) were found to be the best alternative. This was due to their similar ionic conductivity (σi), electrochemical stability and transport properties to their liquid counterparts but with better dynamic properties suitable for varied applications. Although relatively high values of σi were already reported by various groups for various polymer systems, they are made with synthetic polymers along with acids and other hazardous components. This leaves the possibility of leaching into the environment due to the corrosion of the casing unless safely disposed. Also, most of their preparation processes are complex, time and energy intensive. Our study focuses on the possibility of the use of the naturally available class of polymers called polysaccharides to form free-standing, flexible films that act as gel electrolytes. Chitosan and Methocel are chosen among various polysaccharides for testing due to the ease of preparation from the shells of crabs, shrimps and prawns and cellulose respectively. Also, they are naturally abundant, renewable, biodegradable, cost-effective, eco-friendly, environmentally benign and have a high degree of functionality which is not available in most synthetic polymers. During initial testing, the ionic conductivity values obtained for pristine chitosan and methocel were approximately 10-6S/cm, which is at least two orders of magnitude higher than the conventionally used synthetic polymers (PEO, PVP, etc.). This inherent advantage of these biopolymers encouraged us to explore the possibility of their use as an electrolyte layer in batteries. It was noted that a semi-stable gel is formed when these biopolymers were vigorously mixed with minute amounts of acetic acid and dissolved in deionized water and allowed to sit for a while. It was also noted from the literature that chitosan films have an enormous surface area per unit volume (high aspect ratio), which makes us anticipate higher efficiencies. The possibility of forming a semi-stable gel eliminates the need to base the electrolyte primarily on synthetic materials such as PEO, which are non-biodegradable and also possess a crystallization tendency which results in lowering of ionic conductivity and flexibility of the films. In our effort to make stable yet flexible organic films, various amounts of PVA (x=0.2, 0.4, 0.6, 0.8, 1) were added individually to Chitosan (CPx, CP=Chitosan: PVA) and methocel (MPx, MP=Methocel: PVA), vortex mixed, cast into films, dried and then tested against SS blocking electrodes. Unlike most other polymer preparation processes that are complex and energy intensive, we prepare organic electrolytes in much simpler stages and dry at temperatures close to room temperature. Ionic conductivity studies were performed on the various films obtained by AC impedance spectra analysis. The best average ionic conductivity values recorded were 6.804mS/cm and 0.0442mS/cm for CP0.2 and MP1 respectively. These samples CP0.2 and MP1 were then chosen and used for future experimentations due to enhanced conductivity and flexibility properties in comparison to pristine chitosan and methocel respectively. To further enhance the ionic conductivities, varying amounts of KOH (y=0.1, 0.2, 0.3, 0.4, 0.5) were added individually to CP0.2 (CPKy, CPK= CP0.2: KOH) and MP1 (MPKy, MPK= MP1: KOH) respectively, and cast into films and tested in a similar process as earlier. An average highest ionic conductivity of 105mS/cm and 7mS/cm was obtained for CPK0.3 (Chitosan: PVA: KOH= 1:0.2:0.3) sample among the CP0.2 samples, and for MPK0.4 (Methocel: PVA: KOH= 1:1:0.4) sample among the MP1 samples respectively. When comparing the results obtained, though the stability and flexibility of chitosan and methocel films were relatively similar their ionic conductivity values were extremely different. Chitosan films with PVA and KOH had much higher ionic conductivity than methocel films and we attribute this to the inherent high aspect ratio nature of chitosan. The best average conductivity value of 105mS/cm obtained for CPK0.3 is comparable to the values of other existing synthetic polymer electrolytes. For future experimentation, we plan to test the CPK0.3 electrolyte in a full cell against suitable cathode and anode and characterize it.

L2-stability analysis of IMEX-(σ,μ)DG schemes for linear advection-diffusion equations

A fully discrete L2-stability analysis is carried out for linear advection-diffusion problems in one space dimension, discretized in space by discontinuous Galerkin methods based on the (σ,μ)-family of diffusion schemes and implicit-explicit Runge-Kutta schemes in time. Advection terms are discretized explicitly while diffusion terms are solved implicitly. Conditions on the parameters σ and μ are derived which guarantee L2-stability for time steps Δt=O(d/a2), where a and d denote the advection and diffusion coefficient, respectively, i.e. the allowable time step size does not decrease under grid refinement. These conditions are fulfilled in particular by the BR2 scheme as well as the recent (14,94)-recovery scheme. However, the BR1 scheme and the Baumann-Oden method do not possess a similar stability property which is also confirmed by numerical experiments.

Physical–chemical investigation of the oxidation reaction of biodiesel during storage in contact with carbon steel and 1020 steel in the presence of natural rosemary extract

Biodiesel is a renewable fuel derived from oilseeds or animal fats. Biofuel has low oxidative stability due to the high content of esters of unsaturated fatty acids, which are easily oxidized when exposed to air, light, heat and metals. Antioxidants are added to biodiesel to retard the oxidative process, which can capture free radicals making them thermodynamically more stable. This study aims to analyze the oxidative stability of biodiesel in the presence of metallic alloys of carbon steel and 1020 steel with the presence of rosemary extract. The rosemary extract had a phenol content of of 25,579 mgEAG/gdry mass, acting as antioxidant. In the presence of the natural rosemary extract, the biodiesel samples with metallic alloys but without rosemary extract presented similar oxidative stability and physicochemical properties, but when the rosemary extract is present, the carbon steel alloy presented a considerable compatibility, reaching higher induction periods. The thermodynamic parameters of the biodiesel sample with carbon steel and natural rosemary extract showed a significant improvement with the addition of antioxidant.

Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model.

Characterization of a pandemic 2009 H1N1 influenza virus isolated from a fatal case patient (F-IAV), showed the presence of three different mutations; potential determinants of its high pathogenicity that were located in the polymerase subunits (PB2 A221T and PA D529N) and the hemagglutinin (HA S110L). Recombinant viruses containing individually or in combination the polymerase mutations in the backbone of A/California/04/09 (CAL) showed that PA D529N was clearly involved in the increased pathogenicity of the F-IAV virus. Here, we have evaluated the contribution of HA S110L to F-IAV pathogenicity, through introduction of this point mutation in CAL recombinant virus (HA mut). The HA S110L protein has similar pH stability, comparable mobility, and entry properties both in human and mouse cultured cells that wild type HA. The change HA S110L leads to a non-significant trend to reduce the replication capacity of influenza virus in tissue culture, and HA mut is better neutralized than CAL virus by monoclonal and polyclonal antibodies against HA from CAL strain. In addition, recombinant viruses containing HA S110L alone or in combination with polymerase mutations considerably increased the LD50 in infected mice. Characterization of the lungs of HA mut infected animals showed reduced lung damage and inflammation compared with CAL infected mice. Accordingly, lower virus replication, decreased presence in bronchioli and parenchyma and lower leukocytes and epithelial infected cells were found in the lungs of HA mut-infected animals. Our results indicate that, mutation HA S110L constitutes a determinant of attenuation and suggest that its interaction with components of the respiratory tract mucus and lectins, that play an important role on influenza virus outcome, may constitute a physical barrier impeding the infection of the target cells, thus compromising the infection outcome.

Modulating electronic and magnetic properties of zigzag MoSe2 nanoribbons with different edge structures

In this paper, we performed the first-principles calculations to investigate the effect of different edge structures on stability, electronic and magnetic properties of zigzag MoSe2 nanoribbons and their corresponding variation by saturating the ribbon edges with H. We have taken twelve patterns of edge structure into consideration due to the chemical nonequivalence of Mo and Se atoms. We found that H-NR-u and H-NR-s have the highest stability by analysing binding energies. Specially, all of the zigzag MoSe2 nanoribbons exhibit obvious metallicity, whether they are hydrogenated or not. What's more, the pristine and hydrogenated zigzag nanoribbons have stable ferrimagnetism with a wide range of total magnetic moment 0.27–3.59 μB. The Mo-terminated nanoribbon has the largest magnetic moment and hydrogenation can significantly reduce the magnetic moment of nanoribbons. We also reveal zigzag MoSe2 nanoribbons with same terminal have very similar stability, electronic and magnetic properties, which have nothing to do with the symmetry of the system. Above all, these unique properties of zigzag MoSe2 nanoribbons have the great potential for electronic, spintronic and magnetoresistive nano-devices in the future.

Rapidly Reprocessable Cross-Linked Polyhydroxyurethanes Based on Disulfide Exchange.

Polymer networks that are cross-linked by dynamic covalent bonds often sacrifice the robust mechanical properties of traditional thermosets in exchange for rapid and efficient reprocessability. Polyurethanes are attractive materials for reprocessable cross-linked polymers because of their excellent mechanical properties, widespread use, and ease of synthesis, but their syntheses typically rely on harmful isocyanate precursors. Polyhydroxyurethanes (PHUs), derived from amines and cyclic carbonates, are promising alternatives to traditional polyurethanes. PHU networks are reprocessable via transcarbamoylation reactions even in the absence of external catalysts, but this process occurs over hours at temperatures above 150 °C. We have dramatically shortened the reprocessing times of PHU networks by incorporating dynamic disulfide bonds. Using cystamine as a comonomer gives materials with similar thermal stability and mechanical properties to other rigid cross-linked PHUs. Despite their excellent mechanical properties, these materials show rapid stress relaxation and have characteristic relaxation times as low as 30 s at 150 °C. This property enables reprocessing with quantitative recovery of cross-link density as measured by DMTA after only 30 min of elevated-temperature compression molding. Disulfide incorporation is a promising approach to obtain reprocessable, cross-linked PHU resins that are not derived from isocyanates.

Robust Sampled-Data Bilateral Teleoperation: Single-Rate and Multirate Stabilization

This paper investigates robust sampled-data control design strategies for nonlinear bilateral teleoperators exposed to communication constraints, using discrete-time approximate models of the master and slave robots and assuming both single-rate and multirate sampling. The single-rate design guarantees input-to-state stability of the (unknown) exact discrete-time model in a semiglobal practical sense, in spite of norm-bounded channel uncertainties. Then imposing different sampling rates on positions/velocities or torque inputs in each side of the system, a multirate scheme is proposed and shown to maintain similar stability properties under a well-known Nyquist frequency assumption on control torques. Simulation results verify the advantages of our direct sampled-data design. The example also shows that the multirate controller successfully stabilizes the teleoperation system even when the single-rate bilateral setup is ineffective in the presence of different sampling rates.

A Third Order Hierarchical Basis WENO Interpolation for Sparse Grids with Application to Conservation Laws with Uncertain Data

In this paper, we introduce a third order hierarchical basis WENO interpolation, which possesses similar accuracy and stability properties as usual WENO interpolations. The main motivation for the hierarchical approach is the direct applicability on sparse grids. This is for instance of large practical interest in the numerical solution of conservation laws with uncertain data, where discontinuities in the physical domain often carry over to the (potentially high-dimensional) stochastic domain. For this, we apply the introduced hierarchical basis WENO interpolation within a non-intrusive collocation method and present first results on 2- and 3-dimensional sparse grids.

Available energy and ground states of collisionless plasmas

The energy budget of a collisionless plasma subject to electrostatic fluctuations is considered, and the excess of thermal energy over the minimum accessible to it under various constraints that limit the possible forms of plasma motion is calculated. This excess measures how much thermal energy is ‘available’ for conversion into plasma instabilities, and therefore constitutes a nonlinear measure of plasma stability. A distribution function with zero available energy defines a ‘ground state’ in the sense that its energy cannot decrease by any linear or nonlinear plasma motion. In a Vlasov plasma with small density and temperature fluctuations, the available energy is proportional to the mean square of these quantities, and exceeds the corresponding energy in ideal or resistive magnetohydrodynamics. If the first or second adiabatic invariant is conserved, ground states generally have inhomogeneous density and temperature. Magnetically confined plasmas are usually not in any ground state, but certain types of stellarator plasmas are so with respect to fluctuations that conserve both these adiabatic invariants, making the plasma linearly and nonlinearly stable to such fluctuations. Similar stability properties can also be enjoyed by plasmas confined by a dipole magnetic field.

Synthesis of Mo-doped CeO2 by the Combustion Method for Carbon-Air Fuel Cells Applications: Study of Composition, Crystalline Structure and Mechanical Properties

The electrochemical oxidation of carbonaceous fuels in solid oxide fuel cells (SOFCs) appears as a promising alternative for energy generation, considering the high chemical to electrical energy conversion efficiencies of these systems [1]. However, carbonaceous fuels usually contain a significant amount of sulfur, which can poison SOFCs anode materials such as nickel-yttria stabilized zirconia (Ni-YSZ) composites [2,3], which in addition suffers from carbon deposition [2,4]. For this reason, it is necessary to develop alternative materials to be used in carbon-air fuel cells (CAFCs) applications. In this respect, ceria (CeO2) appears as a material of interest for fabrication of CAFCs anodes due to its catalytic activity in the oxidation of carbonaceous fuels and its good tolerance to sulfur poisoning [5]. However, ceria-based materials present low electronic conductivity for SOFCs applications, thus it needs to be improved by doping ceria with other metal oxides, such as molybdenum trioxide (MoO3) which shows similar catalytic and stability properties than ceria [6-9]. Recently, ball milling followed by solid-state reaction processes has been reported in the literature as a method for the synthesis of Mo-doped ceria (CMO) nanoparticles (Ce0.9Mo0.1O2+δ) for SOFCs applications [10]. However, this method is associated with contamination of the products and low synthesis rates. Therefore, this research project proposes the combustion method as an alternative to produce these CMO nanoparticles. As-prepared powders and calcined powders (700 °C / 2 hours in air) were characterized by XRD, TEM, UV-visible spectrophotometry, EDS, XPS and TGA. Figure 1a shows the XRD pattern of as-prepared and calcined powders. These results together with TEM analysis (Figures 1b and 1c) show that CMO nanoparticles crystallize in the fluorite-type structure, similarly to its CeO2 parent, and have an average size of 14 nm. It was not detected MoO3 signals or any secondary phase in these XRD patterns. To determine the effect of molybdenum as a dopant, the lattice parameter was calculated using Rietveld refinement and compared with that for pure ceria. The results obtained (see Table 1) show that the lattice parameter of the CMO nanoparticles synthesized present a different lattice parameter from pure ceria, which evidences the presence of a dopant in the matrix of ceria. UV-visible spectrophotometry analysis (Figure 2a) confirm this result by showing a shift of the absorbance spectra towards higher wavelength values which can be related to a change in the electronic structure of ceria. The presence of molybdenum in the CMO nanoparticles was evidenced as well by EDS and XPS analysis (Figure 2b and Figure 2c), the last of which showed a Mo 3d double peak which indicates the presence of Mo6+. Finally, the thermal stability of the synthesized material was confirmed by TGA under a nitrogen atmosphere at 950 °C (Figure 3). Currently, dense pellets made from CMO nanoparticles are being produced by pressing and calcination for mechanical strength (elasticity modulus, micro-hardness and fracture toughness) and electrical-ionic conductivity (electrochemical impedance spectroscopy) tests. The density of the pellets obtained was 6.954 g cm-3, which is similar to the value reported in [10]. Acknowledgments. The authors thank the Chilean Government for a CONICYT studentship for IDA. References. [1] S. Giddey et al. (2012) Prog. Energy Combust. Sci., 38(3) 360-399.[2] T.M. Gür et al. (2010) J. Power Sources, 195(4) 1085-1090. [3] S.P. Jiang and S.H. Chan (2004) J. Mater. Sci., 39(14) 4405-4439. [4] I.F. Elbaba and P.T. Williams (2014) Energy Fuels, 28(3) 2104-2113.[5] G.K. Reddy et al. (2011) J. Catal., 282(2) 258-269. [6] H. Tu et al. (2008) J. Fuel Cell Sci. Technol., 5(3) 31203. [7] H. Lv et al. (2007) Solid State Ion., 177(39-40) 3467-3472. [8] O. Marin-Flores et al. (2010) Appl. Catal. B – Environ., 98(3-4) 186-192.[9] J.A. Rodriguez and J. Hrbek (1999) Acc. Chem. Res., 32(9) 719-728. [10] Q. Li and V. Thangadurai (2009) Fuel Cells, 9(5) 684-698. Figure 1

Production of biodiesel from Vernicia montana Lour. oil using a co-solvent method and the subsequent evaluation of its stability during storage

AbstractThe costs associated with the production of biodiesel fuel (BDF) are directly affected by the nature of the feedstock material and the methods used during the production process. In Southeast Asia, many non-edible oils are used to produce BDFs, as exemplified by the recent use of the non-edible oil derived fromVernicia montanaLour. in Laos and Vietnam for the production of BDF. In this work, we developed an improved procedure for the production of BDF fromVernicia montanaoil consisting of 80.3%±0.5% α-eleostearic acid moiety (C18:3) using a co-solvent method. Furthermore, the stability of the BDF was evaluated based on its iodine value and unsaturated ester content. The optimized production conditions were determined to be as follows: methanol/oil molar ratio of 6:1, 1% (wt/wt) KOH, 20% (wt/wt) acetone as a co-solvent, and a reaction temperature of 40°C. Under these conditions, we achieved a BDF conversion efficiency of 99%±0.3% within 30 min of initiating the transesterification process. Notably, the BDF produced fromVernicia montanaoil showed good stability to air at temperatures ≤30°C for 1 month, showing similar stability properties to the BDF produced from rapeseed oil.

The synergic control of multi-finger force production: stability of explicit and implicit task components.

Manipulating objects with the hands requires the accurate production of resultant forces including shear forces; effective control of these shear forces also requires the production of internal forces normal to the surface of the object(s) being manipulated. In the present study, we investigated multi-finger synergies stabilizing shear and normal components of force, as well as drifts in both components of force, during isometric pressing tasks requiring a specific magnitude of shear force production. We hypothesized that shear and normal forces would evolve similarly in time and also show similar stability properties as assessed by the decomposition of inter-trial variance within the uncontrolled manifold hypothesis. Healthy subjects were required to accurately produce total shear and total normal forces with four fingers of the hand during a steady-state force task (with and without visual feedback) and a self-paced force pulse task. The two force components showed similar time profiles during both shear force pulse production and unintentional drift induced by turning the visual feedback off. Only the explicitly instructed components of force, however, were stabilized with multi-finger synergies. No force-stabilizing synergies and no anticipatory synergy adjustments were seen for the normal force in shear force production trials. These unexpected qualitative differences in the control of the two force components-which are produced by some of the same muscles and show high degree of temporal coupling-are interpreted within the theory of control with referent coordinates for salient variables. These observations suggest the existence of two classes of neural variables: one that translates into shifts of referent coordinates and defines changes in magnitude of salient variables, and the other controlling gains in back-coupling loops that define stability of the salient variables. Only the former are shared between the explicit and implicit task components.

Recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in the methylotrophic yeast Pichia pastoris.

Mucopolysaccharidosis IV A (MPS IV A, Morquio A disease) is a lysosomal storage disease (LSD) produced by mutations on N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Recently an enzyme replacement therapy (ERT) for this disease was approved using a recombinant enzyme produced in CHO cells. Previously, we reported the production of an active GALNS enzyme in Escherichia coli that showed similar stability properties to that of a recombinant mammalian enzyme though it was not taken-up by culture cells. In this study, we showed the production of the human recombinant GALNS in the methylotrophic yeast Pichia pastoris GS115 (prGALNS). We observed that removal of native signal peptide and co-expression with human formylglycine-generating enzyme (SUMF1) allowed an improvement of 4.5-fold in the specific GALNS activity. prGALNS enzyme showed a high stability at 4 °C, while the activity was markedly reduced at 37 and 45 °C. It was noteworthy that prGALNS was taken-up by HEK293 cells and human skin fibroblasts in a dose-dependent manner through a process potentially mediated by an endocytic pathway, without any additional protein or host modification. The results show the potential of P. pastoris in the production of a human recombinant GALNS for the development of an ERT for Morquio A.

Erythrocyte glutathione transferase: a general probe for chemical contaminations in mammals.

Glutathione transferases (GSTs) are enzymes devoted to the protection of cells against many different toxins. In erythrocytes, the isoenzyme (e-GST) mainly present is GSTP1-1, which is overexpressed in humans in case of increased blood toxicity, as it occurs in nephrophatic patients or in healthy subjects living in polluted areas. The present study explores the possibility that e-GST may be used as an innovative and highly sensitive biomarker of blood toxicity also for other mammals. All distinct e-GSTs from humans, Bos taurus (cow), Sus scrofa (pig), Capra hircus (goat), Equus caballus (horse), Equus asinus (donkey) and Ovis aries (sheep), show very similar amino acid sequences, identical kinetics and stability properties. Reference values for e-GST in all these mammals reared in controlled farms span from 3.5±0.2 U/gHb in the pig to 17.0±0.9 U/gHb in goat; such activity levels can easily be determined with high precision using only a few microliters of whole blood and a simple spectrophotometric assay. Possibly disturbing factors have been examined to avoid artifact determinations. This study provides the basis for future screening studies to verify if animals have been exposed to toxicologic insults. Preliminary data on cows reared in polluted areas show increased expression of e-GST, which parallels the results found for humans.