Shedding a new light on Huntington's disease: how blood can both propagate and ameliorate disease pathology

Huntington's disease (HD) is a monogenic neurodegenerative disorder resulting from a mutation in the huntingtin gene. This leads to the expression of the mutant huntingtin protein (mHTT) which provokes pathological changes in both the central nervous system (CNS) and periphery. Accumulating evidence suggests that mHTT can spread between cells of the CNS but here, we explored the possibility that mHTT could also propagate and cause pathology via the bloodstream. For this, we used a parabiosis approach to join the circulatory systems of wild-type (WT) and zQ175 mice. After surgery, we observed mHTT in the plasma and circulating blood cells of WT mice and post-mortem analyses revealed the presence of mHTT aggregates in several organs including the liver, kidney, muscle and brain. The presence of mHTT in the brain was accompanied by vascular abnormalities, such as a reduction of Collagen IV signal intensity and altered vessel diameter in the striatum, and changes in expression of Glutamic acid decarboxylase 65/67 (GAD65-67) in the cortex. Conversely, we measured reduced pathology in zQ175 mice by decreased mitochondrial impairments in peripheral organs, restored vessel diameter in the cortex and improved expression of Dopamine- and cAMP-regulated phosphoprotein 32 (DARPP32) in striatal neurons. Collectively, these results demonstrate that circulating mHTT can disseminate disease, but importantly, that healthy blood can dilute pathology. These findings have significant implications for the development of therapies in HD

Aluminium sheet metal scrap recycling through friction consolidation

In the last decades, several direct-recycling techniques have been developed and investigated in order to avoid material remelting, typical of the conventional aluminum alloys recycling processes. Moreover, the remelting step for aluminum recycling is affected by permanent material losses. Solid-state recycling processes have proven to be a suitable strategy to face such issues. Friction Consolidation is an innovative solid state-recycling technology developed for metal chips. During the process, a rotating die is plunged into a hollow chamber containing the material to be processed. The work of friction forces decaying into heat soften the material and, together with the stirring action of the die, enable solid bonding phenomena producing a consolidated metal disc. This technology has been successively applied to metal chips; in this paper, the feasibility of the process to recycle sheet metal scrap is investigated. The quality of the obtained billets is evaluated through morphological observation and hardness measurements

A linear programming model for optimal subassembly level determination in shipbuilding industry

Shipbuilding industry is an industrial sector characterized by a customized make-to-order production process. The shipbuilding process can be roughly divided into four steps: design, assembly planning, manufacturing and final assembly. In this paper assembly planning is investigated: it consists in subdividing the ship structure into blocks and grand-blocks, thus involving a two levels subassembly generation. Any mechanical assembly process can be decomposed into a set of tasks, each task involving joining two or more components or subassemblies together. The sequence of assembly tasks has a major influence on completion time and resource utilization and it drastically impacts costs and efficiency through the whole production process. To determine the optimal assembly policy and subassembly level a Linear Programming model is proposed. The model allows the determination of the optimal block grouping policy, in order to minimize the total assembly time or to achieve workload balancing

Job shop scheduling by a parallel approach

The paper deals with a parallel approach to job shop scheduling by a branch and bound methodology using the lower bound proposed by Ashour and Hiremath. The optimal solution is achieved by an iterative-reductive strategy. At each iteration the algorithm investigates the conflict intervals and it selects a subset of the possible solutions. The makespan value, achieved by the parallel processes, gives the upper limit for the admissible lower bound of the intermediate solutions. Furthermore the best makespan reached by each iteration is reused as a filter to reduce the complexity of the next iteration. The computation is speeded up by a parallel implementation, giving the possibility of distributing code and data into a network of processors. In particular a transputer network and a hypercube system have been employed to carry out the experiments. The concurrent running of more searches manages to reach more makespan values in a shorter time, thus determining a better filtering of the branches to be explored. This facility, in spite of the redundancy due to the parallel approach, produces a total number of opened nodes less than Ashour's serial algorithm

Crack identification in a beam by measure of the response to white noise

The aim of this paper is to inspect the vibrational response of a beam with an edge non-propagating crack by means of stochastic analysis, in order to detect the presence and the location of structural damage. The non- linear behavior of the beam due to the opening and closing of the crack is fully exploited. The non-linearity measure is based on the response evaluation of the beam subjected to a white noise process. Both numerical and experimental investigations regarding a cantilever beam with a crack are reported in the paper

Numerical and experimental verification of a technique for locating a fatigue crack on beams vibrating under Gaussian excition

The stationary vibrations of a beam excited by Gaussian noise are strongly affected by the presence of a fatigue crack. Indeed, as soon as the crack arises the system response becomes non-linear due to crack breathing and a non-Gaussian behaviour is encountered. The paper presents both numerical and experimental investigations in order to assess the capability of the non-Gaussianity measures to detect crack presence and position. Monte Carlo method is applied to evaluate in time domain the higher order statistics of a cantilever beam modelled by finite elements. The skewness coefficient of the rotational degrees of freedom appears the most suitable quantity for identification purpose being very sensitive to the non-linear behaviour of the cracked beam