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

War and dissociation : the case of futurist aesthetics

Thanks to their deliberate engagement in state propaganda Italian Futurists deserved a prominent spot in the history of military aesthetics in the 20th century. However, under what looked like an unequivocal expression of support for war, lied a deep philosophical disagreement concerning its existential and epistemological value. The bone of contention concerned the effects of warfare on perception and, consequently, the means of its depiction. The author analyses this intellectual disagreement within the group and focuses, in particular, on its philosophical implications

[Memorias sobre el estado de la Agricultura]

Contiene: Memoria sobre el estado de la Agricultura en la provincia de Jaén y mejoras que pueden introducirse en ella / Mariano Serra y Navarro ; escrita de órden del Real Consejo de Agricultura, Industria y Comercio. -- Jaén : Imp. de la Diputación Provincial, 1876. -- 132 p. -- Indice. -- Informe sobre el estado actual de la Agricultura en la provincia de Castellón/ por Enrique Martin S. Bonisana. -- [S.l.] : Imp. del Diario de Castellón, 1878. -- 96, [2] p., [1] h. pleg. -- Memoria sobre el estado actual de la Agricultura en la provincia de Salamanca / por Cecilio González Domingo ; escrita de órden del presidente del Consejo superior del ramo... -- Salamanca : [s.n.], 1876 (Estab. tip. del Hospicio). -- 61, [1] p. -- Memoria sobre el estado de la agricultura é industrias derivadas en la provincia de Logroño / por Antonio Tadeo Delgado y Masnata ; escrita de órden del Consejo Superior de Agricultura, Industria y Comercio é impresa por acuerdo... -- Logroño : Imp. de Federico Sanz, Compañía, 1876. -- 82 p., 3 h. pleg. -- Informe sobre el estado de la Agricultura en la provincia de las Baleares / por Francisco Satorras. -- Palma : Imp. de Pedro José Gelabert, 1878. -- 62 p. -- Memoria sobre el estado de la agricultura en la provincia de Madrid y mejoras convenientes para su desarrollo / por Eduardo Abela y Sáinz de Andino ; precedida del informe redactado por Carlos A. de Castro y Franganillo ; fué aprobada esta memoria... -- Madrid : [s.n.], 1876 (Imp., Estereotipia y Galvanoplastia de Aribau y Cª). -- XXVI, 182 p. -- Contestación acordada por la Comisión Provincial en sesión del día 20 de diciembre de 1887 al interrogatorio del 15 de septiembre del mismo año, formado por la Comisión nombrada para el estudio de la crisis agrícola y pecuaria. -- Zaragoza : Imp. del Hospicio Provincial, 1888. -- 52 p.Enc. cartonéEnc. varias obras formando un vol. facticioNota ms a tinta sueltaSello en guarda : Encuadernador Cayetano Fernández, ZaragozaTít. tomado del lom

[Memorias sobre el estado de la Agricultura]

Obra facticia que contiene: Memoria sobre el estado de la Agricultura en la provincia de Jaén y mejoras que pueden introducirse en ella / Mariano Serra y Navarro ; escrita de órden del Real Consejo de Agricultura, Industria y Comercio. -- Jaén : Imp. de la Diputación Provincial, 1876. -- 132 p. -- Indice. -- Informe sobre el estado actual de la Agricultura en la provincia de Castellón/ por Enrique Martin S. Bonisana. -- [S.l.] : Imp. del Diario de Castellón, 1878. -- 96, [2] p., [1] h. pleg. -- Memoria sobre el estado actual de la Agricultura en la provincia de Salamanca / por Cecilio González Domingo ; escrita de órden del presidente del Consejo superior del ramo... -- Salamanca : [s.n.], 1876 (Estab. tip. del Hospicio). -- 61, [1] p. -- Memoria sobre el estado de la agricultura é industrias derivadas en la provincia de Logroño / por Antonio Tadeo Delgado y Masnata ; escrita de órden del Consejo Superior de Agricultura, Industria y Comercio é impresa por acuerdo... -- Logroño : Imp. de Federico Sanz, Compañía, 1876. -- 82 p., 3 h. pleg. -- Informe sobre el estado de la Agricultura en la provincia de las Baleares / por Francisco Satorras. -- Palma : Imp. de Pedro José Gelabert, 1878. -- 62 p. -- Memoria sobre el estado de la agricultura en la provincia de Madrid y mejoras convenientes para su desarrollo / por Eduardo Abela y Sáinz de Andino ; precedida del informe redactado por Carlos A. de Castro y Franganillo ; fué aprobada esta memoria... -- Madrid : [s.n.], 1876 (Imp., Estereotipia y Galvanoplastia de Aribau y Cª). -- XXVI, 182 p. -- Contestación acordada por la Comisión Provincial en sesión del día 20 de diciembre de 1887 al interrogatorio del 15 de septiembre del mismo año, formado por la Comisión nombrada para el estudio de la crisis agrícola y pecuaria. -- Zaragoza : Imp. del Hospicio Provincial, 1888. -- 52 p

A variant design of Tuned Mass Damper Inerter for reducing displacements of base isolated structures

In this study an innovative passive control strategy, referred to as New Tuned Mass Damper Inerter (New TMDI), coupled with a base isolation system (BI), is presented with the aim of reducing displacements in base isolated structures subject to seismic actions. The proposed New TMDI employs the synergetic benefits of a recently developed non-traditional Tuned Mass Damper (known as New TMD) and an inerter device to achieve higher control performances in isolated structures. Specifically, the New TMD is a secondary mass system connected to the BI system by a spring and to the ground by a dashpot. In addition, in the New TMDI configuration, the inerter device is placed in parallel with the damper. The New TMDI optimal parameters are determined by performing a simplified approach which provides simple closed-form formulae as a quick tool to design the examined device. The reliability of the proposed approach is assessed by a comparison with a more accurate and computationally complex numerical optimization procedure. Further, the performance of a base-isolated multi-degree-of-freedom structure equipped with a New TMDI is investigated taking into account different recorded ground motions as base excitation. Results from time history analyses assess the mitigation effect due to the optimal New TMDI on the response of base-isolated structures, also in comparison with those of a conventional Tuned Mass Damper Inerter (TMDI). On this base, the proposed New TMDI might be considered as preventive conservation strategy for applications also in historic buildings, where general constraints require limited space for the base displacements

Effect of position and force tool control in friction stir welding of dissimilar aluminum-steel lap joints for automotive applications

Widespread use of aluminum alloys for the fabrication of car body parts is conditional to the use of appropriate welding methods, especially if dissimilar welding must be performed with automotive steel grades. Friction stir welding (FSW) is considered to be a reasonable solution to obtain sound aluminum-steel joints. In this context, this work studies the effects of tool position and force control in dissimilar friction stir welding of AA6061 aluminum alloy on DC05 low carbon steel in lap joint configuration, also assessing proper welding parameter settings. Naked eye and scanning electron microscopy (SEM) have been used to detect macroscopic and microscopic defects in joints, as well as to determine the type of intermixture between aluminum and steel. The joint strength of sound joints has been assessed by shear tension test. Results point out that tool force control allows for obtaining joints with better quality and strength in a wider range of process parameters. A process window has been determined for tool force conditions to have joints with adequate strength for automotive purposes