Nanobodies raised against monomeric α-synuclein distinguish between fibrils at different maturation stages.

Nanobodies are single-domain fragments of camelid antibodies that are emerging as versatile tools in biotechnology. We describe here the interactions of a specific nanobody, NbSyn87, with the monomeric and fibrillar forms of α-synuclein (αSyn), a 140-residue protein whose aggregation is associated with Parkinson's disease. We have characterized these interactions using a range of biophysical techniques, including nuclear magnetic resonance and circular dichroism spectroscopy, isothermal titration calorimetry and quartz crystal microbalance measurements. In addition, we have compared the results with those that we have reported previously for a different nanobody, NbSyn2, also raised against monomeric αSyn. This comparison indicates that NbSyn87 and NbSyn2 bind with nanomolar affinity to distinctive epitopes within the C-terminal domain of soluble αSyn, comprising approximately amino acids 118-131 and 137-140, respectively. The calorimetric and quartz crystal microbalance data indicate that the epitopes of both nanobodies are still accessible when αSyn converts into its fibrillar structure. The apparent affinities and other thermodynamic parameters defining the binding between the nanobody and the fibrils, however, vary significantly with the length of time that the process of fibril formation has been allowed to progress and with the conditions under which formation occurs, indicating that the environment of the C-terminal domain of αSyn changes as fibril assembly takes place. These results demonstrate that nanobodies are able to target forms of potentially pathogenic aggregates that differ from each other in relatively minor details of their structure, such as those associated with fibril maturation.

Development of accurate, robust liquid equations of state for multi-phase CFD simulations with a modified AUSM+-up scheme

Eight equations of state (EOS) have been evaluated for the simulation of compressible liquid water properties, based on empirical correlations, the principle of corresponding states and thermodynamic relations. The IAPWS-IF97 EOS for water was employed as the reference case. These EOSs were coupled to a modified AUSM+-up convective flux solver to determine flow profiles for three test cases of differing flow conditions. The impact of the non-viscous interaction term discretisation scheme, interfacial pressure method and selection of low-Mach number diffusion were also compared. It was shown that a consistent discretisation scheme using the AUSM+-up solver for both the convective flux and the non-viscous interfacial term demonstrated both robustness and accuracy whilst facilitating a computationally cheaper solution than discretisation of the interfacial term independently by a central scheme. The simple empirical correlations gave excellent results in comparison to the reference IAPWS-IF97 EOS and were recommended for developmental work involving water as a cheaper and more accurate EOS than the more commonly used stiffened-gas model. The correlations based on the principles of corresponding-states and the modified Peng-Robinson cubic EOS also demonstrated a high degree of accuracy, which is promising for future work with generic fluids. Further work will encompass extension of the solver to multiple dimensions and to account for other source terms such as surface tension, along with the incorporation of phase changes. © 2013.

Local equilibrium of the Gibbs interface in two-phase systems

We analyze the local equilibrium assumption for interfaces from the perspective of gauge transformations, which are the small displacements of Gibbs' dividing surface. The gauge invariance of thermodynamic properties turns out to be equivalent to conditions for jumps of bulk densities across the interface. This insight strengthens the foundations of the local equilibrium assumption for interfaces and can be used to characterize nonequilibrium interfaces in a compact and consistent way, with a clear focus on gauge-invariant properties. Using the principle of gauge invariance, we show that the validity of Clapeyron equations can be extended to nonequilibrium interfaces, and an additional jump condition for the momentum density is recognized to be of the Clapeyron type. © 2012 Europhysics Letters Association.

Nanobodies raised against monomeric α-synuclein distinguish between fibrils at different maturation stages

Nanobodies are single-domain fragments of camelid antibodies that are emerging as versatile tools in biotechnology. We describe here the interactions of a specific nanobody, NbSyn87, with the monomeric and fibrillar forms of α-synuclein (αSyn), a 140-residue protein whose aggregation is associated with Parkinson's disease. We have characterized these interactions using a range of biophysical techniques, including nuclear magnetic resonance and circular dichroism spectroscopy, isothermal titration calorimetry and quartz crystal microbalance measurements. In addition, we have compared the results with those that we have reported previously for a different nanobody, NbSyn2, also raised against monomeric αSyn. This comparison indicates that NbSyn87 and NbSyn2 bind with nanomolar affinity to distinctive epitopes within the C-terminal domain of soluble αSyn, comprising approximately amino acids 118-131 and 137-140, respectively. The calorimetric and quartz crystal microbalance data indicate that the epitopes of both nanobodies are still accessible when αSyn converts into its fibrillar structure. The apparent affinities and other thermodynamic parameters defining the binding between the nanobody and the fibrils, however, vary significantly with the length of time that the process of fibril formation has been allowed to progress and with the conditions under which formation occurs, indicating that the environment of the C-terminal domain of αSyn changes as fibril assembly takes place. These results demonstrate that nanobodies are able to target forms of potentially pathogenic aggregates that differ from each other in relatively minor details of their structure, such as those associated with fibril maturation. © 2013 Elsevier Ltd.

Phase separation induced by Au catalysts in ternary InGaAs nanowires.

We report a novel phase separation phenomenon observed in the growth of ternary In(x)Ga(1-x)As nanowires by metalorganic chemical vapor deposition. A spontaneous formation of core-shell nanowires is investigated by cross-sectional transmission electron microscopy, revealing the compositional complexity within the ternary nanowires. It has been found that for In(x)Ga(1-x)As nanowires high precursor flow rates generate ternary In(x)Ga(1-x)As cores with In-rich shells, while low precursor flow rates produce binary GaAs cores with ternary In(x)Ga(1-x)As shells. First-principle calculations combined with thermodynamic considerations suggest that this phenomenon is due to competitive alloying of different group-III elements with Au catalysts, and variations in elemental concentrations of group-III materials in the catalyst under different precursor flow rates. This study shows that precursor flow rates are critical factors for manipulating Au catalysts to produce nanowires of desired composition.

Unsteady numerical study of wet steam flow in a low pressure steam turbine

In steam power plants condensation already starts in the flow path of the low pressure part of the steam turbine, which leads to a complex three-dimensional two-phase flow. Wetness losses are caused due to thermodynamic and mechanical relaxation processes during condensation and droplet transport. The present investigation focuses on the unsteady effects due to rotor-stator interaction on the droplet formation process. Results of unsteady three dimensional flow simulations of a two-stage steam turbine are presented, whereby this is the first time that non-equilibrium condensation is considered in such simulations. The numerical approach is based on RANS equations, which are extended by a wet steam specific nucleation and droplet growth model. Despite the use of a high performance cluster the unsteady simulation has a considerably high simulation time of approximately 60 days by use of 48 CPUs. © Springer-Verlag Berlin Heidelberg 2012.

Non-equilibirum condensation effects on the flow field and the performance of a low pressure steam turbine

The influence of non-equilibrium condensation on the flow field and performance of a three stage low pressure model steam turbine is examined using modern three dimensional CFD techniques. An equilibrium steam model and a non-equilibrium steam model, which accounts for both subcooling and condensation effects, are used, and have been verified by comparison with test data in an earlier publication [1]. The differences in the calculated flow field and turbine performance with these models show that the latent heat released during condensation influences both the thermodynamic and the aerodynamic performance of the turbine, leading to a change in inlet flow angles of about 5°. The calculated three dimensional flowfield is used to investigate the magnitude and distribution of the additional thermo-dynamic wetness loss arising from steam condensation under non-equilibrium flow conditions. Three simple methods are described to calculate this, and all show that this amounts to around 6.5% of the total losses at the design condition. At other load conditions the wetness losses change in magnitude and axial distribution in the turbine. © 2010 by ASME.

Cellular contractility and substrate elasticity: A numerical investigation of the actin cytoskeleton and cell adhesion

Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation. © 2013 Springer-Verlag Berlin Heidelberg.

A framework for the analysis of thermal losses in reciprocating compressors and expanders

This article presents a framework that describes formally the underlying unsteady and conjugate heat transfer processes that are undergone in thermodynamic systems, along with results from its application to the characterization of thermodynamic losses due to irreversible heat transfer during reciprocating compression and expansion processes in a gas spring. Specifically, a heat transfer model is proposed that solves the one-dimensional unsteady heat conduction equation in the solid simultaneously with the first law in the gas phase, with an imposed heat transfer coefficient taken from suitable experiments in gas springs. Even at low volumetric compression ratios (of 2.5), notable effects of unsteady heat transfer to the solid walls are revealed, with thermally induced thermodynamic cycle (work) losses of up to 14% (relative to the work input/output in equivalent adiabatic and reversible compression/expansion processes) at intermediate Péclet numbers (i.e., normalized frequencies) when unfavorable solid and gas materials are selected, and closer to 10-12% for more common material choices. The contribution of the solid toward these values, through the conjugate variations attributed to the thickness of the cylinder wall, is about 8% and 2% points, respectively, showing a maximum at intermediate thicknesses. At higher compression ratios (of 6) a 19% worst-case loss is reported for common materials. These results suggest strongly that in designing high-efficiency reciprocating machines the full conjugate and unsteady problem must be considered and that the role of the solid in determining performance cannot, in general, be neglected. © 2014 Richard Mathie, Christos N. Markides, and Alexander J. White. Published with License by Taylor & Francis.

Wetness loss prediction for a low pressure steam turbine using computational fluid dynamics

Two-phase computational fluid dynamics modelling is used to investigate the magnitude of different contributions to the wet steam losses in a three-stage model low pressure steam turbine. The thermodynamic losses (due to irreversible heat transfer across a finite temperature difference) and the kinematic relaxation losses (due to the frictional drag of the drops) are evaluated directly from the computational fluid dynamics simulation using a concept based on entropy production rates. The braking losses (due to the impact of large drops on the rotor) are investigated by a separate numerical prediction. The simulations show that in the present case, the dominant effect is the thermodynamic loss that accounts for over 90% of the wetness losses and that both the thermodynamic and the kinematic relaxation losses depend on the droplet diameter. The numerical results are brought into context with the well-known Baumann correlation, and a comparison with available measurement data in the literature is given. The ability of the numerical approach to predict the main wetness losses is confirmed, which permits the use of computational fluid dynamics for further studies on wetness loss correlations. © IMechE 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Microcalorimetric studies on the thermogenesis of energy release of mitochondria isolated from rice

After isolation from rice mitochondria still have activity and can live for a long time by using its stored nutrients. The thermogenesis curves of energy release of the mitochondria isolated from variant strains of rice have been determined by using an LKB2277 bioactivity monitor. The differences in shape of the curves and the thermodynamic and kinetic characteristics of the thermogenesis of the mitochondria have been compared. The thermodynamic and kinetic parameters of energy release of the mitochondria in the thermogenesis increasing stage have been calculated, and the experimental thermokinetic equations of the thermogenesis have been established. (C) 2001 Elsevier Science B.V. All rights reserved.

Studies on the energy release of rice mitochondria under different conditions by means of microcalorimetry

The thermodynamic and kinetic behaviors of energy release of mitochondria isolated from rice (Oryza sative L.) were studied by using a LKB 2277 Bioactivity Monitor under different conditions. The thermogenesis curves of energy release of the rice mitochondria (which had been kept at 0-3 degreesC for 15 h and 40 day before the determination) were determined respectively at 25 and 30 degreesC, and the difference in shape of the thermogenesis curves and thermodynamic and kinetic characteristics were compared. The thermodynamic and kinetic parameters of energy release of the mitochondria in the thermogenesis increasing stage have been calculated, and the experimental thermokinetic equations of the thermogenesis have been established. The results indicated that the lower the temperature, the slower the energy release of the rice mitochondria. Both the thermogenesis and the energy release late of the rice mitochondria increased after the mitochondria was kept at lower temperature for 40 days. One can use the methods to characterize the ability of the rice mitochondria to release energy under different conditions. (C) 2001 Published by Elsevier Science B.V.

First-principles study of UC2 and U2C3

The electronic structure and mechanical properties Of UC2 and U2C3 have been systematically investigated using first-principles calculations by the projector-augmented-wave (PAW) method. Furthermore, in order to describe precisely the strong on-site Coulomb repulsion among the localized U 5f electrons, we adopt the generalized gradient approximation +U formalisms for the exchange-correlation term. We show that our calculated structural parameters and electronic properties for UC2 and U2C3 are in good agreement with the experimental data by choosing an appropriate Hubbard U = 3 eV. As for the chemical bonding nature, the contour plot of charge density and total density of states suggest that UC2 and U2C3 are metallic mainly contributed by the 5f electrons, mixed with significant covalent component resulted from the strong C-C bonds. The present results also illustrate that the metal-carbon (U-C) bonding and the carbon-carbon covalent bonding in U2C3 are somewhat weaker than those in UC2, leading to the weaker thermodynamic stability at high temperature as observed by experiments.

Quantum phase transitions in the S=1/2 distorted diamond chain

By means of the second derivative of the ground-state and first-excited energy, the quantum phase transitions (QPTs) for the distorted diamond chain (DDC) with ferromagnetic and antiferromagnetic frustrated interactions and the trimerized case are investigated, respectively. Our results show the plentiful quantum phases owing to the spin interaction competitions in the model. Meanwhile, by using the transfer-matrix renormalization-group technique, we study the two-site thermal entanglement of the DDC model in the thermodynamic limit for a further understanding of the QPTs.

Electromagnetic-field-induced cohesive force enhancement in a metallic nanowire

We theoretically study the conducting electronic contribution to the cohesive force in a metallic nanowire irradiated under a transversely polarized external electromagnetic field at low temperatures and in the ballistic regime. In the framework of the free-electron model, we have obtained a time-dependent two-level electronic wavefunction by means of a unitary transformation. Using a thermodynamic statistical approach with this wavefunction, we have calculated the cohesive force in the nanowire. We show that the cohesive force can be divided into two components, one of which is independent of the electromagnetic field (static component), which is consistent with the existing results in the literature. The magnitude of the other component is proportional to the electromagnetic field strength. This extra component of the cohesive force is originally from the coherent coupling between the two lateral energy levels of the wire and the electromagnetic field.