Cerebrovascular muscle atrophy is a feature of Alzheimer's disease

We examined vascular amyloid-beta deposition and other abnormalities in the posterior cerebral artery of consecutive cases of Alzheimer's disease (AD) compared to controls. Smooth muscle atrophy was a consistent feature in the cases of AD examined (p<0.01) and was surprisingly independent of adjacent amyloid-beta deposition. These findings suggest that vascular abnormalities are a consistent feature in AD and may be an important contributor to the pathogenesis and complications of AD.     

Mechanistic simulation of radiation damage to DNA and its repair: on the track towards systems radiation biology modelling

The biophysical simulation code PARTRAC enables, by combining track structure calculations with DNA models on diverse genomic scales, prediction of DNA damage yields and patterns for various radiation qualities. To extend its applicability to later endpoints such as mutagenesis or cell killing, a continuative model for repair of radiation-induced double-strand break (DSB) via non-homologous end-joining has complemented the PARTRAC code by about 12 orders of magnitude on a temporal scale. The repair model describes step-by-step by the Monte Carlo method the attachment and dissociation of involved repair enzymes and diffusion motion of DNA ends. The complexity of initial DNA lesion patterns influences the repair kinetics and outcome via additional cleaning steps required for dirty DNA ends. Model parameters have been taken from measured attachment kinetics of repair enzymes and adaptation to DSB rejoining kinetics after gamma irradiation. Application of the DNA repair model to damage patterns following nitrogen ion irradiation and comparison with experimental results reveal the need for further model refinements. Nevertheless, already the present model represents a promising step towards systems modelling of cellular response to radiation.     

Track structure calculations on hypothetical subcellular targets for the release of cell-killing signals in bystander experiments with medium transfer

Track structure studies using PARTRAC have been performed with the aim to investigate the possibility of revealing information on initiating targets and mechanisms of bystander effects mediated by signals released into the culture medium. Dependences on radiation dose have been assessed for alternative signal emission scenarios, defined by required energy deposits in a number of subcellular targets, mimicking e.g. mitochondria as hypothetical targets for the release of signals. The simulation results agree with target theory, and elucidate the characteristic dose for signal emission as a function of target topology, size and activation energy. The observed dose dependence of bystander cell kill in medium transfer experiments is not as steep as predicted by the considered simple signal emission scenarios with a single or even multiple hits to the hypothetical targets. This has been resolved by accounting for variations in cellular characteristics among the irradiated cells.     

Modelling of intercellular induction of apoptosis in oncogenic transformed cells and radiation effects on the phenomenon

The removal of transformed cells via induction of apoptosis through intercellular signalling by surrounding cells is supposed to represent an important control mechanism limiting carcinogenesis. Low doses of radiation influence the efficiency of this anti-carcinogenesis process, indicating possible beneficial effects of low doses of radiation mediated by intercellular communication ('non-targeted effects'). To quantitatively understand the signalling system involved and the effects of radiation and to assess the role of this phenomenon in radiation-induced carcinogenesis, multi-scale modelling studies have been started. The proposed kinetic model takes into account (i) triggering of the effector function in cells in the vicinity of transformed cells, (ii) intercellular signalling between effector and transformed cells and (iii) execution of apoptosis in attacked cells. The systems model without radiation perturbance is reviewed. First results accounting for radiation-induced modulations of the signalling schemes are presented.     

Using stable and radioactive isotopes to trace atmospherically deposited Pb in montane forest soils

Atmospheric deposition of lead (Pb) throughout the 1900s resulted in elevated amounts of this toxic metal even in remote forest soils of the northeastern United States. Soils can act as a net sink for metals and thus minimize groundwater and surface water contamination. Recent studies utilizing forest floor temporal data and models of total Pb in precipitation, surface soils, and streams have estimated the time scale of Pb release from soils. However, due to the limited availability and spatial variability of forest floor survey data, other methods for quantifying anthropogenic Pb movement are needed. This study uses the isotopic composition (206Pb/207Pb) of soil Pb and measurements of 210Pb and 226Ra to directly trace the transit of atmospherically deposited Pb in the soil profile. We also report on the recovery of an enriched 207Pb dose applied in 1984 to the surface of a soil plot in the coniferous forest at Camels Hump in Vermont. The isotopic composition of soil Pb in low elevation deciduous forests suggests that approximately 65% of the original atmospheric Pb load has migrated from the forest floor to the upper 10 cm of the mineral soil. Higher elevation sites with coniferous vegetation have thicker forest floors, which have prevented significant amounts of Pb from entering the mineral soil. After 17 years, the soil organic horizon in the coniferous zone prevented any penetration of the applied Pb into the mineral soil. Using 210Pb budgets in different soil compartments, we determine forest floor response times for atmospherically delivered Pb to be approximately 60 years in the low elevation deciduous forest zone and 150 years for the high elevation spruce-fir forest zone at Camels Hump. According to its distribution in the soil profile, we conclude that a dispersed release of anthropogenic Pb to groundwater and surface water is possible this century. Our results also offer independent confirmation of Pb deposition models previously generated for the region.     

Dynamic Friction Model of Lubricated Surfaces for Precise Motion Control

A model is developed to describe dynamic friction effects in lubricated surfaces. The model covers the hydrodynamic, mixed and boundary lubrication regions. The dynamic friction model can predict the friction force for time-varying velocity, and is useful in precise motion control. The model presented is for a short journal bearing, but can be extended to other geometries of sliding surfaces, such as point and line contacts or rolling element bearings. The friction is related to a time variable fluid film thickness, resulting from journal vibrations relative to the sleeve. The proposed model agrees qualitatively with experimental results for lubricated line contact. Both show similar hysteresis-type friction curves under oscillating velocity.     

Alterations in Tau Protein Level and Phosphorylation State in the Brain of the Autistic-Like Rats Induced by Prenatal Exposure to Valproic Acid

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction and communication besides repetitive, stereotyped behaviours. A characteristic feature of ASD is altered dendritic spine density and morphology associated with synaptic plasticity disturbances. Since microtubules (MTs) regulate dendritic spine morphology and play an important role in spine development and plasticity the aim of the present study was to investigate the alterations in the content of neuronal α/β-tubulin and Tau protein level as well as phosphorylation state in the valproic acid (VPA)-induced rat model of autism. Our results indicated that maternal exposure to VPA induces: (1) decrease the level of α/β-tubulin along with Tau accumulation in the hippocampus and cerebral cortex; (2) excessive Tau phosphorylation and activation of Tau-kinases: CDK5, ERK1/2, and p70S6K in the cerebral cortex; (3) up-regulation of mTOR kinase-dependent signalling in the hippocampus and cerebral cortex of adolescent rat offspring. Moreover, immunohistochemical staining showed histopathological changes in neurons (chromatolysis) in both analysed brain structures of rats prenatally exposed to VPA. The observed changes in Tau protein together with an excessive decrease in α/β-tubulin level may suggest destabilization and thus dysfunction of the MT cytoskeleton network, which in consequence may lead to the disturbance in synaptic plasticity and the development of autistic-like behaviours.     

Buckling of composite circular plates under radial compression

Summary Axisymmetric nonlinear buckling equations are introduced for thin elastic circular plates composed of isotropic or orthotropic layers, uniformly compressed in the radial direction.The linear eigenvalue problem is solved in closed form for heterogeneous isotropic circular plates with clamped or simply supported circumference. Invariant buckling parameters are obtained which enable optimization. Several numerical examples are shown.

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Beulen von Kreisplatten aus Verbundwerkstoff unter radialem Druck

Zusammenfassung Für dünne, elastische, in radialer Richtung gedrückte Kreisplatten aus isotropen oder orthotropen Schichten werden drehsymmetrische nichtlineare Beulgleichungen hergeleitet.Das lineare Eigenwertproblem wird für am Rand eingespannte oder frei aufliegende heterogene isotrope Kreisplatten in geschlossener Form gelöst. Invariante Beulparameter, die eine Optimierung ermöglichen, werden erhalten und einige numerische Beispiele angegeben.

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Nomenclature a radius of plate - A _ij elastic area - A _ij ^* extensional rigidity - B _ij elastic statical moment - B _ij ^* , C _ij ^* extensional-flexural coupled rigidities - D _ij elastic moment of inertia - D _ij ^* modified flexural rigidity - flexural rigidity defined in equation (3.32.3) - E Young's modulus - h plate thickness - h ₀ distance to reference plane defined in equation (3.11) - J _i Bessel function of first kind and orderi - L _ij functional operator - m coefficient defined in equation (3.15) - M _r, M radial and circumferential couples, respectively - n constant defined in equation (3.21) - N _r, N radial and circumferential forces, respectively - N ₀ radial compression - p, q coefficients defined in equations (3.32) - Q transverse shear resultant - r radial coordinate - t invariant parameter defined in equation (3.44) - u, w radial and transverse displacements, respectively - x variable defined in equation (3.43) - Y ₁ Bessel function of second kind and first order - z vertical coordinate - change of slope in radial direction - _r0, ₀ radial and circumferential strain components, respectively atz=0 - circumferential coordinate - _r, curvatures in radial and circumferential directions, respectively - v Poisson's ratio - , slope angle before and after deformation, respectively - stress resultant function With 1 FigureThis study was supported by the Israel Academy of Sciences and Humanities and the Technion-Israel Institute of Technology. The numerical examples were carried out at the Technion's Computation Center by I. Smolash.Dedicated to the memory of Mr.Israel Stavsky, father of senior author.Visiting Professor, Washington University, St. Louis, Missouri., 1969/70.     

Simplified small signal gain calculations in free electron lasers

A method proposed recently is used for the evaluation of the small signal gain in various free electron laser configurations. The theory is applied to (a) the wigglerfree free electron laser with a uniform axial guide magnetic field and arbitrary direction of propagation of the amplified radiation and (b) the free electron laser with the axially modulated guide field (lowbitron). It is demonstrated that the new approach simplifies the gain calculation significantly in comparison with the traditional method.