State-of-the-art review on adjustable pallet racks testing for seismic design

This paper presents a state-of-the-art review on seismic tests of adjustable pallet rack systems: on particular components of racks, subassemblies, full racks and stored goods. The tested particular components are the most critical connections: beams-to-uprights, braces-to-uprights, and floor-to-uprights; subassemblies also include beam-to-upright connections, among other components. Tests on full racks can be static (pushover), pseudo-dynamic, or dynamic (pullout and shaking table). Finally, tests on stored goods are sliding (aimed to identify the friction coefficient with the supporting members) and tilting (to check their confinement). The examination of the discussed experiments provides relevant conclusions and allows identifying research needs.Peer ReviewedPostprint (published version

Investigation on the down-aisle ductility of multiple bay pallet racks by means of pushover analyses

This paper presents numerical pushover analyses on multiple bay pallet racks, aiming to quantify variations in global ductility when using different beam-to-upright connections. The connections differ in the layout of the beam-to-endplate welding, being one of them a technological novelty. They are modeled with envelopes of monotonic and cyclic moment-rotation curves obtained from component tests and presented in previous research. Moreover, the influence of the level height is studied throughout two different rack configurations. A single-column model for multiple bay racks, made with 3D beams and shells, is presented and compared with simpler 2D models to quantify the influence of 3D effects and upright perforations. Results exhibit that the novel connection improves the capacity to absorb energy, but an inappropriate rack configuration can lead to a soft-story mechanism, thus not taking full advantage of its ductility.Peer ReviewedPostprint (published version

The CD200R1 Microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson's disease

Background It is suggested that neuroinflammation, in which activated microglial cells play a relevant role, contributes to the development of Parkinson's disease (PD). Consequently, the modulation of microglial activation is a potential therapeutic target to be taken into account to act against the dopaminergic neurodegeneration occurring in this neurological disorder. Several soluble and membrane-associated inhibitory mechanisms contribute to maintaining microglial cells in a quiescent/surveillant phenotype in physiological conditions. However, the presence of activated microglial cells in the brain in PD patients suggests that these mechanisms have been somehow overloaded. We focused our interest on one of the membrane-associated mechanisms, the CD200-CD200R1 ligand-receptor pair. Methods The acute MPTP experimental mouse model of PD was used to study the temporal pattern of mRNA expression of CD200 and CD200R1 in the context of MPTP-induced dopaminergic neurodegeneration and neuroinflammation. Dopaminergic damage was assessed by tyrosine hydroxylase (TH) immunoreactivity, and neuroinflammation was evaluated by the mRNA expression of inflammatory markers and IBA1 and GFAP immunohistochemistry. The effect of the modulation of the CD200-CD200R1 system on MPTP-induced damage was determined by using a CD200R1 agonist or CD200 KO mice. Results MPTP administration resulted in a progressive decrease in TH-positive fibres in the striatum and TH-positive neurons in the substantia nigra pars compacta, which were accompanied by transient astrogliosis, microgliosis and expression of pro- and anti-inflammatory markers. CD200 mRNA levels rapidly decreased in the ventral midbrain after MPTP treatment, while a transient decrease of CD200R1 mRNA expression was repeatedly observed in this brain area at earlier and later phases. By contrast, a transient increase in CD200R1 expression was observed in striatum. The administration of a CD200R1 agonist resulted in the inhibition of MPTP-induced dopaminergic neurodegeneration, while microglial cells showed signs of earlier activation in CD200-deficient mice. Conclusions Collectively, these findings provide evidence for a correlation between CD200-CD200R1 alterations, glial activation and neuronal loss. CD200R1 stimulation reduces MPTP-induced loss of dopaminergic neurons, and CD200 deficiency results in earlier microglial activation, suggesting that the potentiation of CD200R1 signalling is a possible approach to controlling neuroinflammation and neuronal death in PD

DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease

In the brain, programmed cell death (PCD) serves to adjust the numbers of the different types of neurons during development, and its pathological reactivation in the adult leads to neurodegeneration. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) is a pleiotropic kinase involved in neural proliferation and cell death, and its role during brain growth is evolutionarily conserved. Human DYRK1A lies in the Down syndrome critical region on chromosome 21, and heterozygous mutations in the gene cause microcephaly and neurological dysfunction. The mouse model for DYRK1A haploinsufficiency (the Dyrk1a +/− mouse) presents neuronal deficits in specific regions of the adult brain, including the substantia nigra (SN), although the mechanisms underlying these pathogenic effects remain unclear. Here we study the effect of DYRK1A copy number variation on dopaminergic cell homeostasis. We show that mesencephalic DA (mDA) neurons are generated in the embryo at normal rates in the Dyrk1a haploinsufficient model and in a model (the mBACtg Dyrk1a mouse) that carries three copies of Dyrk1a. We also show that the number of mDA cells diminishes in postnatal Dyrk1a +/− mice and increases in mBACtg Dyrk1a mice due to an abnormal activity of the mitochondrial caspase9 (Casp9)-dependent apoptotic pathway during the main wave of PCD that affects these neurons. In addition, we show that the cell death induced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), a toxin that activates Casp9-dependent apoptosis in mDA neurons, is attenuated in adult mBACtg Dyrk1a mice, leading to an increased survival of SN DA neurons 21 days after MPTP intoxication. Finally, we present data indicating that Dyrk1a phosphorylation of Casp9 at the Thr125 residue is the mechanism by which this kinase hinders both physiological and pathological PCD in mDA neurons. These data provide new insight into the mechanisms that control cell death in brain DA neurons and they show that deregulation of developmental apoptosis may contribute to the phenotype of patients with imbalanced DYRK1A gene dosage

Selective suppression of α-Synuclein in monoaminergic neurons of mice by intranasal delivery of targeted small interfering RNA or antisense oligonucleotides: Potential therapy for Parkinson's disease

Póster presentado en: ACNP (American College of Neuropsychopharmacology) 52nd Annual Conference, celebrada del 8 al 12 de diciembre de 2013 en Hollywood, Florida (Estados Unidos)Abstract publicado en: Neuropsychopharmacology 38:S419-S420 (2013). ISSN: 0893-133X. eISSN: 1740-634X. DOI:10.1038/npp.2013.280α-Synuclein (α-Syn) appears to play a crucial role in the pathogenesis of several neurodegenerative disorders including Parkinson's disease (PD). The brains of Parkinson patients typically contain insoluble intracellular protein inclusions called Lewy bodies. Increased neuronal α-Syn levels represent a major component of Lewy bodies and therefore, the suppression of α-Syn expression provides a valid therapeutic target for PD. The goal of this study was to assess the ability of various small interfering RNA (siRNA) and antisense oligonucleotide (ASO) sequences directed against α-Syn to downregulate endogenous or overexpressed α-Syn mRNA levels in BE-M17 neuroblastoma cells. Moreover, we evaluated the feasibility of reducing α-Syn expression selectively in PD-vulnerable brain areas including substantia nigra pars compacta (SNc), ventral tegmental area (VTA), locus coeruleus (LC) and dorsal raphe nucleus (DR) of mice after the internalization of conjugated siRNA/ASO molecules into monoamine neurons following intranasal administration. Conclusions: These results set the stage for the testing of these molecules as potential disease-modifying agents in neurotoxin-based and genetic models of PD linked to pathogenic increases in α-Syn. In this study we have characterized conjugated siRNA and ASO molecules that actively reduce endogenous α-Syn expression in vivo using the intranasal route to deliver directly siRNA/ASO into the brainPeer Reviewe

Planta de producció d'àcid oxàlic dihidrat

L'objectiu principal del present projecte és el disseny complet d'una planta en continu per a la producció de 32.000 tones a l'any d'àcid oxàlic dihidrat en forma sòlida. El procés consta de tres etapes principals: la preparació de les matèries primeres (àcid nítric, etilenglicol, àcid sulfúric i aigua), l'etapa de reacció i l'etapa de purificació i separació del producte

What makes an animal? The molecular quest for the origin of the Animal Kingdom

What makes an animal? To find the answer we need to integrate data from disciplines such as phylogenetics, palaeontology, ecology, development, anatomy and physiology, as well as molecular biology and genomics. Knowledge of which groups branched before and after the origin of animals is essential. Recent advances in molecular phylogenetics, together with the discovery of new eukaryotic lineages, have drawn a new picture of the ancestry of animals. The nature of the early diverging animal lineages and the timing of the transition are in a state of flux. Various factors have been linked to this striking transition to multicellularity, including changes in environmental conditions and the ecological interactions between unicellular eukaryotes. The current wealth of genomic data has also shed new light on this question. The analysis of the genome of various close relatives of animals has revealed the importance that recycling of ancient genes into metazoan biological functions played into animal origins. A recent study reconstructing the genome of the last common ancestor of extant animals has unveiled an unprecedented emergence of new genes, highlighting the role of genomic novelty in the origin of metazoans