Impact of neurite alignment on organelle motion

Intracellular transport is pivotal for cell growth and survival. Malfunctions in this process have been associated with devastating neurodegenerative diseases, highlighting the need for a deeper understanding of the mechanisms involved. Here, we use an experimental methodology that leads neurites of differentiated PC12 cells into either one of two configurations: a one-dimensional configuration, where the neurites align along lines, or a two-dimensional configuration, where the neurites adopt a random orientation and shape on a flat substrate. We subsequently monitored the motion of functional organelles, the lysosomes, inside the neurites. Implementing a time-resolved analysis of the mean-squared displacement, we quantitatively characterized distinct motion modes of the lysosomes. Our results indicate that neurite alignment gives rise to faster diffusive and super-diffusive lysosomal motion than the situation in which the neurites are randomly oriented. After inducing lysosome swelling through an osmotic challenge by sucrose, we confirmed the predicted slowdown in diffusive mobility. Surprisingly, we found that the swelling-induced mobility change affected each of the (sub-/super-)diffusive motion modes differently and depended on the alignment configuration of the neurites. Our findings imply that intracellular transport is significantly and robustly dependent on cell morphology, which might in part be controlled by the extracellular matrix.     

Donorsubstituierte 2,4-Diazacyclopentadienone und indigoide 1,3,5,7-Tetraazafulvalene

Donor Substituted 2,4-Diazacyclopentadienones and Indigoid 1,3,5,7-Tetraazafulvalenes Hydrolysis of tris(diethylamino)imidazolylium chloride gives rise to 2,5-bis-diethyl-amino-4H-imidazolin-4-one; thiolysis leads, depending on conditions, to 2,5-bis-diethylamino-4H-imidazolin-4-thione or potassium 2,6-bis-diethylamino-1,3,5,7-tetraazafulvalene-4,8-dithiolate. The latter can be protonated to form green 2,6-bis(dimethylamino)-3,4,7,8-tetrahydro-1,3,5,7-tetraaza-fulvalen-4,8-dithione, a new indigoid compound, and alkylated to give blue 2,6-bis-diethylamino-4,8-bis-alkylthio-1,3,5,7-tetraazafulvalenes. Treatment of 2,5-bis-diethylamino-4H-imidazolin-4-thione with copper furnishes 2,6,4,8-tetrakis-diethylamino-1,3,5,7-tetraazafulvalene. – Oxidation of 2,6-bis-dimethylamino-3,4,7,8-tetrahydro-1,3,5,7-tetraazafulvalen-4,8-dithione gives rise to (2,2′-bis-diethylamino-4,4′-bi(4H-imidazol)-5,5′-dithione, corresponding to dehydroindigo, and reduction leads to a colorless compound, corresponding to leucoindigo.     

Effect of Ions and Sequence Variants on the Antagonist Binding Properties of the Histamine H1 Receptor

The histamine H₁ receptor (H₁R) is a G protein-coupled receptor (GPCR) and represents a main target in the treatment of allergic reactions as well as inflammatory reactions and depressions. Although the overall effect of antagonists on H₁ function has been extensively investigated, rather little is known about the potential modulatory effect of ions or sequence variants on antagonist binding. We investigated the dynamics of a phosphate ion present in the crystal structure and of a sodium ion, for which we determined the position in the allosteric pocket by metadynamics simulations. Both types of ions exhibit significant dynamics within their binding site; however, some key contacts remain stable over the simulation time, which might be exploited to develop more potent drugs targeting these sites. The dynamics of the ions is almost unaffected by the presence or absence of doxepin, as also reflected in their small effect (less than 1 kcal·mol⁻¹) on doxepin binding affinity. We also examined the effect of four H₁R sequence variants observed in the human population on doxepin binding. These variants cause a reduction in doxepin affinity of up to 2.5 kcal·mol⁻¹, indicating that personalized medical treatments that take into account individual mutation patterns could increase precision in the dosage of GPCR-targeting drugs.     

Trends in prices to commercial energy consumers in the competitive Texas electricity market

To date, the price of electricity to commercial or business energy consumers has generally increased at greater rates in the areas of Texas where retail competition has been introduced than in areas that do not enjoy competition. Trends in commercial competitive prices have largely mirrored trends in residential prices. Market restructuring has tended to increase the sensitivity of retail electricity prices to changes in the price of natural gas, the marginal fuel used for generation in Texas. Consequently, the rapid increases in the commodity price of natural gas following restructuring led to increases in competitive electric rates which exceeded the increases in areas not exposed to restructuring, where the fuel component of electric rates tend to reflect a weighted average of the utilities’ fuel costs. There is some evidence that pricing behavior by competitive retailers changed when the retailers affiliated with the incumbent utilities were permitted some pricing flexibility, resulting in a reduction in prices.     

Prudent constraint-handling technique for multiobjective propeller optimisation

The paper presents an alternative constraint-handling technique that converts a nonlinear constrained programming problem into an unconstrained multi-objective optimisation problem. The technique is derived from the behavioural memory constraint-handling method, which was originally implemented for single-objective optimisation with genetic algorithms. We compare our presented technique with two other popular constraint-handling concepts and demonstrate its superiority over them when applied to a propeller optimisation problem. We conclude that the multi-objective behavioural memory constraint-handling technique conjugated with the non-dominated sorting genetic algorithm (NSGA-II) is a prudent method to apply to problems with an infeasible initial design and where constraints have a natural order of satisfaction, which, if not conformed to, would lead to unrealistic designs that impair the search by GA.     

Energy absorption during compression and impact of dry elastic-plastic spherical granules

The discrete modelling and understanding of the particle dynamics in fluidized bed apparatuses, mixers, mills and others are based on the knowledge about the physical properties of particles and their mechanical behaviour during slow, fast and repeated stressing. In this paper model parameters (modulus of elasticity, stiffness, yield pressure, restitution coefficient and strength) of spherical granules (γ-Al₂O₃, zeolites 4A and 13X, sodium benzoate) with different mechanical behaviour have been measured by single particle compression and impact tests. Starting with the elastic compression behaviour of granules as described by Hertz theory, a new contact model was developed to describe the force-displacement behaviour of elastic-plastic granules. The aim of this work is to understand the energy absorption during compression (slow stressing velocity of 0.02 mm/s) and impact (the impact velocity of 0.5–4.5 m/s) of granules. For all examined granules the estimated energy absorption during the impact is found to be far lower than that during compression. Moreover, the measured restitution coefficient is independent of the impact velocity in the examined range and independent of the load intensity by compression (i.e. maximum compressive load). In the case of repeated loading with a constant load amplitude, the granules show cyclic hardening with increasing restitution coefficient up to a certain saturation in the plastic deformation. A model was proposed to describe the increase of the contact stiffness with the number of cycles. When the load amplitude is subsequently increased, further plastic deformation takes place and the restitution coefficient strongly decreases.     

Numerical Study of Turbulent Flow and Heat Transfer of Nanofluids in Pipes

In this work, Nusselt number and friction factor are calculated numerically for turbulent pipe flow (Reynolds number between 6000 and 12000) with constant heat flux boundary condition using nanofluids. The nanofluid is modeled with the single-phase approach and the simulation results are compared with correlations from experimental data. Ethylene glycol and water, 60:40 EG/W mass ratio, as base fluid and SiO₂ nanoparticles are used as nanofluid with particle volume concentrations ranging from 0% to 10%. Nusselt number predictions for the nanofluid are in agreement with experimental results and a conventional single-phase correlation. The mean deviation is in the range of ?5%. Friction factor values show a mean deviation of 0.5% to a conventional single-phase correlation, however, they differ considerably from the nanofluid experimental data. The results indicate that the nanofluid requires more pumping power than the base fluid for high particle concentrations and Reynolds numbers on the basis of equal heat transfer rate.     

The influence of a corrosive wood-cutting environment on the mechanical properties of hardmetal tools

The influence of a corrosive wood-cutting environment on the strength of hardmetals and on their behaviour under static loading conditions has been investigated. Two commercial hardmetals were tested, which differed in hard phase composition. The results show exposure to this environment to have a highly detrimental influence on the strength of both hardmetals investigated, due to localised corrosive attack which results in the formation of stress raisers. The relative loss in strength as a function of corrosion time is the same for both hardmetals. However, the performance of the two grades differ significantly when a static load is applied in this corrosive environment: the strength of the WC-Co grade remains unaffected by the applied load, while the grade containing a mixed carbide phase exhibits stress corrosion cracking which results in a further reduction in strength.