Thermal–Mechanical FEM Analyses of a Liquid Rocket Engines Thrust Chamber

The Italian Ministry of University and Research (MIUR) funded the HYPROB Program to develop regeneratively cooled liquid rocket engines. In this type of engine, liquid propellant oxygen–methane is used, allowing us to reach very good performances in terms of high vacuum specific impulse and high thrust-to-weight ratio. The present study focused on the HYPROB final ground demonstrator, which will be able to produce a 30 kN thrust in flight conditions. In order to achieve such a thrust level, very high chamber pressures (up to 50 bar) and consequently high thermal fluxes and gradients are expected inside the thrust chamber. Very complex and high-fidelity numerical FEM models were adopted here to accurately simulate the thermal–mechanical behavior of the thrust chamber cooling channels, accounting for plasticity, creep, and low-cycle fatigue (LCF) phenomena. The aim of the current work was to investigate the main failure phenomena that could occur during the thrust chamber’s service life. Results demonstrated that LCF is the main cause of failure. The corresponding number of loading cycles to failure were calculated accordingly

Plastic strain arrangement in copper single crystals in sliding

Deformation of tribologically loaded contact zone is one of the wear mechanisms in spite of the fact that no mass loss may occur during this process. Generation of optimal crystallographic orientations of the grains in a polycrystalline materials (texturing) may cause hardening and reducing the deformation wear. To reveal the orientation dependence of an individual gain and simplify the task we use copper single crystals with the orientations of the compression axis along [11 1] and [110]. The plastic deformation was investigated by means of optical, scanning electron microscopy and EBSD techniques. It was established that at least four different zones were generated in the course of sliding test, such as non-deformed base metal, plastic deformation layer sliding, crystalline lattice reorientation layer and subsurface grain structure layer. The maximum plastic strain penetration depth was observed on [110]-single crystals. The minimum stability of [11 1]-crystals with respect to rotation deformation mode as well as activation of shear in the sliding contact plane provide for rotation deformation localization below the worn surface. The high-rate accumulation of misorientations and less strain penetration depth was observed on [11 1]-crystals as compared to those of [110]-oriented ones

A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5′cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T is a nucleocytoplasmic shuttling protein, which mediates the import of eIF4E into the nucleus. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described processing bodies (P-bodies), which are believed to be sites of mRNA decay. In this paper, we demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies. Moreover, 4E-T controls mRNA half-life, because its depletion from cells using short interfering RNA increases mRNA stability. The 4E-T binding partner, eIF4E, also is localized in P-bodies. 4E-T interaction with eIF4E represses translation, which is believed to be a prerequisite for targeting of mRNAs to P-bodies. Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay

The cyclin-like protein Spy1/RINGO promotes mammary transformation and is elevated in human breast cancer

Abstract Background Spy1 is a novel \u27cyclin-like\u27 activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis. Methods Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation. Results We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. Importantly, we show for the first time that enhanced levels of Spy1 protein are found in a large number of human breast cancers and that knockdown of Spy1 impairs breast cancer cell proliferation. Conclusions Collectively, this work supports that Spy1 is a unique activator of Cdk1 in breast cancer cells and may represent a valuable drug target and/or a prognostic marker for subsets of breast cancers

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Investigation of Superconducting Molybdenum Silicide Nanostrips and Microstrips for Single Photon Detectors

Superconducting nanostrip single photon detectors have emerged as the highest performing single-photon detectors; however, the possibility to use superconducting microstrip as single photon detectors is very appealing both to use them as larger areas detectors and for an easier technology in the manufacturing. The aim of this work is to test the photoresponse in liquid helium dewar of 9 nm thick MoSi covered with a very thin (2 nm) layer of Al, in two different configurations: nanomeanders and microstrips. We demonstrate that MoSi/Al microstrips can work as photodetectors also at T = 4.2 K. We also compare the dark count rate of the microstrip and the nanowire, confirming the lower noise for the microstrips also at 4.2 K

Transcriptomic indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis

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Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis

Gene expression profiling has been used previously with spinal cord homogenates and laser capture microdissected motor neurons to determine the mechanisms involved in neurodegeneration in amyotrophic lateral sclerosis. However, while cellular and animal model work has focused on superoxide dismutase 1-related amyotrophic lateral sclerosis, the transcriptional profile of human mutant superoxide dismutase 1 motor neurons has remained undiscovered. The aim of this study was to apply gene expression profiling to laser captured motor neurons from human superoxide dismutase 1-related amyotrophic lateral sclerosis and neurologically normal control cases, in order to determine those pathways dysregulated in human superoxide dismutase 1-related neurodegeneration and to establish potential pathways suitable for therapeutic intervention. Identified targets were then validated in cultured cell models using lentiviral vectors to manipulate the expression of key genes. Microarray analysis identified 1170 differentially expressed genes in spinal cord motor neurons from superoxide dismutase 1-related amyotrophic lateral sclerosis, compared with controls. These genes encoded for proteins in multiple functional categories, including those involved in cell survival and cell death. Further analysis determined that multiple genes involved in the phosphatidylinositol-3 kinase signalling cascade were differentially expressed in motor neurons that survived the disease process. Functional experiments in cultured cells and primary motor neurons demonstrate that manipulating this pathway by reducing the expression of a single upstream target, the negative phosphatidylinositol-3 kinase regulator phosphatase and tensin homology, promotes a marked pro-survival effect. Therefore, these data indicate that proteins in the phosphatidylinositol-3 kinase pathway could represent a target for therapeutic manipulation in motor neuron degeneration