Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy ...(DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPSc as the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPSc formation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPSc is more susceptible to degradation when compared to PrPSc from other lymphotrophic strains. We hypothesize that the relative rates of PrPSc formation and clearance can influence prion tropism.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lyme disease is a tick-borne disease caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex. The disease is characterized by a varied course; therefore, the basis for ...diagnosis is laboratory methods. Currently, a two-tiered serological test is recommended, using an ELISA as a screening test and a Western blot as a confirmatory test. This approach was introduced due to the relatively high number of false-positive results obtained when using an ELISA alone. However, even this approach has not entirely solved the problem of false-positive results caused by cross-reactive antibodies. Many highly immunogenic B. burgdorferi s.l. proteins are recognized nonspecifically by antibodies directed against other pathogens. This also applies to antigens, such as OspC, BmpA, VlsE, and FlaB, i.e., those commonly used in serodiagnostic assays. Cross-reactions can be caused by both bacterial (relapsing fever Borrelia, Treponema pallidum) and viral (Epstein–Baar virus, Cytomegalovirus) infections. Additionally, a rheumatoid factor has also been shown to nonspecifically recognize B. burgdorferi s.l. proteins, resulting in false-positive results. Therefore, it is necessary to carefully interpret the results of serodiagnostic tests so as to avoid overdiagnosis of Lyme disease, which causes unnecessary implementations of strong antibiotic therapies and delays in the correct diagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Highly accurate simulation of plasma transport is needed to drive the successful design and operation of magnetically confined fusion reactors. Unfortunately, the extreme anisotropy present in ...magnetized plasmas results in thin boundary layers that are expensive to resolve. This work investigates how various mesh refinement strategies might reduce that expense to allow for more efficient simulation by comparing standard variable refinement approaches that use a field quantity to an adaptive approach that uses an error estimator. It is first verified that higher order discretization only realizes the proper rate of convergence once the mesh resolves the thin boundary layer, therefore motivating the focusing of refinement on the boundary layer. For three two-dimensional test cases that contain characteristic features of tokamak magnetic fields, an exponential refinement strategy based on the magnetic flux function, which is the standard refinement approach in the field, is compared to an adaptive strategy utilizing the established Zienwiekicz and Zhu error estimator. The adaptive mesh refinement strategy consistently achieves the same accuracy using orders of magnitude less degrees of freedom than either exponential or uniform refinement. This result makes the adaptive refinement strategy more efficient than the exponential refinement strategy while also being more generalizable to problems with complex magnetic geometries. Scaling laws are derived that quantify the improvement in cost of the adaptive refinement strategy over other refinement approaches in 2D and 3D.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The study describes the origin, glory and fall of several important business families (Fries, Henikstein, Friesenhof and others), who gained noble status in Vienna at the end of the 18th century and ...retained considerable social prestige and wealth in the early 19th century. However, their minimal political influence as new noblemen did not correspond to their enormous economic and great cultural importance. The strong founding generation was usually followed by stagnation and often gradual decline with members of later generations not having the necessary persistence and qualities.
This development is shown in most detail in the case of the Friesenhof family, with Johann Michael (1739–1812) founding a tradition as the first baron. His son Adolph (1798–1853) still significantly applied himself in the field of business, but his younger brother Gustav (1807–1889) already settled at Brodzany in territory now belonging to Slovakia, where he devoted his attention to business on the local level rather than on that of the whole state. With a loyal attitude to the court and the monarch, strong links with Russia, the Slovak national emancipation movement and Germany, he became a representative of a unique type within the new aristocracy with very strong European connections. His children developed these tendencies further. All this made the Friesenhofs a very interesting and entirely atypical noble family, which only confirmed the variety of this social group.
Superlattice (SL) thin films composed of refractory ceramics unite extremely high hardness and enhanced fracture toughness; a material combination which is often mutually exclusive. While the ...hardness enhancement is well described by existing models based on dislocation mobility, the underlying mechanisms behind the increase in fracture toughness are yet to be unraveled. Here, we provide a model based on linear elasticity theory to predict the fracture toughness in (semi-)epitaxial nanolayers. As representative of cubic transition metal nitrides, a TiN/CrN superlattice structure on MgO (100) is studied. The density of misfit dislocations is estimated by minimizing the overall strain energy, each time a new layer is added on the nanolayered stack. The partly relaxed coherency stresses are then used to calculate the apparent fracture toughness (Kapp) by applying the weight function method. The results show that Kapp increases steeply with increasing bilayer period for very thin SLs, before the values decline more gently along with the formation of misfit dislocations. The characteristic Kapp vs. bilayer-period-dependence nicely matches experimental trends. Importantly, all critical stress intensity values of the SLs clearly exceed the intrinsic fracture toughness of the layer materials, evincing the importance of coherency stresses for increasing the crack growth resistance.
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•An algorithm based on elasticity theory is proposed to estimate the dislocation densities in ceramic superlattice thin films.•The bilayer period significantly influences the misfit dislocation densities and the associated coherency stresses.•Predictions of the apparent fracture toughness of TiN/CrN superlattices match experimental trends.•The model reveals the potential of a superlattice structure to increase the crack growth resistance of a thin film.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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