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

Investigating the thermo-mechanical behavior of a ceramic matrix composite wing leading edge by sub-modeling based numerical analyses

The thermo-structural design of the wing leading edge of hypersonic vehicles is a very challenging task as high gradients in thermal field, and hence high thermal stresses, are expected. Indeed, when employing passive hot structures based thermal protection systems, very high temperatures (e.g., 1400 °C) are expected on the external surface of the wing leading edge, while the internal structural components are required to not exceed a few hundred degrees Celsius (e.g., 400 °C) at the interface with the internal cold structure. Hence, ceramic matrix composites (CMC) are usually adopted for the manufacturing of the external surface of the wing leading edge since they are characterized by good mechanical properties at very high temperatures (up to 1900 °C) together with an excellent thermal shock resistance. Furthermore, the orthotropic behavior of these materials together with the possibility to tailor their lamination sequence to minimize the heat transferred to internal components, make them very attractive for hot structure based thermal protection systems applications. However, the numerical predictions of the thermo-mechanical behavior of such materials, taking into account the influence of each ply (whose thickness generally ranges between 0.2 and 0.3 mm), can be very expensive from a computational point of view. To overcome this limitation, usually, sub-models are adopted, able to focus on specific and critical areas of the structure where very detailed thermo-mechanical analyses can be performed without significantly affecting the computational efficiency of the global model. In the present work, sub-modeling numerical approaches have been adopted for the analysis of the thermo-mechanical behavior of a ceramic matrix composite wing leading edge of a hypersonic vehicle. The main aim is to investigate the feasibility, in terms of computational efficiency and accuracy of results, in using sub-models for dimensioning complex ceramic matrix components. Hence, a comprehensive study on the size of sub-models and on the choice of their boundaries has been carried out in order to assess the advantages and the limitations in approximating the thermo-mechanical behavior of the investigated global ceramic matrix composite component

AN INNOVATIVE NUMERICAL APPROACH FOR TRAIN PASS-BY NOISE FORECASTING

This paper deals with an engineering method for the prediction of vehicle pass-by noise based on a FEM/ BEM exterior acoustic calculation in the frequency domain. The researchers simulate, in a virtual environment, the experimental outdoor pass-by noise measurement. The simulated pass-by noise campaign is synthesized from multiple acoustic transfer functions between a line of virtual microphones located 7.5m on the side of the vehicle and each noise source. A numerical FEM/BEM train bogie acoustic model has been created within the MSC ACTRAN commercial softwares. Wheel-rail rolling noise, engine and powertrain noise acoustic source have been implemented and posi-tioned inside the FEM and BEM model to demonstrate the validity of the proposed methods. The contribu-tion from noise sources, expressed both in terms of sound pressure level and overall value, to the pass-by noise were evaluated up to 5 kHz. The virtual pass-by-noise assessment has been then validated by experi-mental measurement of the complete four coach’s train with respect to different speed regimes

Biotechnological Transformation of Hydrocortisone into 16α-Hydroxyprednisolone by Coupling Arthrobacter simplex and Streptomyces roseochromogenes

16α-Hydroxyprednisolone, an anti-inflammatory drug, could be potentially obtained from hydrocortisone bioconversion by combining a 1,2-dehydrogenation reaction performed by Arthrobacter simplexATCC31652 with a 16α-hydroxylation reaction by Streptomyces roseochromogenes ATCC13400. In this study we tested, for the first time, potential approaches to couple the two reactions using similar pH and temperature conditions for hydrocortisone bioconversion by the two strains. The A. simplex capability to 1,2-dehydrogenate the 16α-hydroxyhydrocortisone, the product of S. roseochromogenes transformation of hydrocortisone, and vice versa the capability of S. roseochromogenes to 16α-hydroxylate the prednisolone were assessed. Bioconversions were studied in shake flasks and strain morphology changes were observed by SEM. Whole cell experiments were set up to perform the two reactions in a sequential mode in alternate order or contemporarily at diverse temperature conditions. A. simplex catalyzed either the dehydrogenation of hydrocortisone into prednisolone efficiently or of 16α-hydroxyhydrocortisone into 16α-hydroxyprednisolone in 24 h (up to 93.9%). Surprisingly S. roseochromogenes partially converted prednisolone back to hydrocortisone. A 68.8% maximum of 16α-hydroxyprednisolone was obtained in 120-h bioconversion by coupling whole cells of the two strains at pH 6.0 and 26 °C. High bioconversion of hydrocortisone into 16α-hydroxyprednisolone was obtained for the first time by coupling A. simplex and S. roseochromogenes

Deficits in mitochondrial spare respiratory capacity contribute to the neuropsychological changes of alzheimer’s disease

Alzheimer’s disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate with neuropsychological changes. Fibroblasts were taken from 10 AD patients and 10 controls. Metabolic assessment included measuring total cellular ATP, extracellular lactate, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolytic function. All participants were assessed with neuropsychological testing and brain structural MRI. AD patients had significantly lower scores in delayed and immediate recall, semantic memory, phonemic fluency and Mini Mental State Examination (MMSE). AD patients also had significantly smaller left hippocampal, left parietal, right parietal and anterior medial prefrontal cortical grey matter volumes. Fibroblast MMP, mitochondrial spare respiratory capacity (MSRC), glycolytic reserve, and extracellular lactate were found to be lower in AD patients. MSRC/MMP correlated significantly with semantic memory, immediate and delayed episodic recall. Correlations between MSRC and delayed episodic recall remained significant after controlling for age, education and brain reserve. Grey matter volumes did not correlate with MRSC/MMP. AD fibroblast metabolic assessment may represent an emergent disease biomarker of AD

Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines

Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. In the present study, we investigate the anticancer effects of Agave leaf extract in OS cells suggesting that Agave inhibits cell viability, colony formation, and cell migration, and can induce apoptosis in OS cell lines. Moreover, Agave sensitizes OS cells to cisplatin (CDDP) and radiation, to overcome chemo- and radio-resistance. We demonstrate that Agave extract induces a marked decrease of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression upon treatment. We propose an initial mechanism of action in which Agave induces YAP/TAZ protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription, effectively deregulating the Nuclear Factor kappa B (NF-\u3baB) p65:p50 heterodimers responsible for transcriptional induction of YAP and TAZ

SRSF1-dependent nuclear export of C9ORF72 repeat-transcripts: targeting toxic gain-of-functions induced by protein sequestration as a selective therapeutic strategy for neuroprotection

Microsatellite repeat expansions cause several incurable and lethal neurodegenerative disorders including ataxias, myotonic dystrophy, Huntington's disease and C9ORF72-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Abnormal repeat transcripts generated from the expanded loci are substrates of repeat-associated non-AUG (RAN) translation, an unconventional form of translation leading to the production of polymeric repeat proteins with cytotoxic and aggregating properties. The mechanisms involved in the pathogenesis of microsatellite repeat expansion disorders remain a hotly debated topic. They are shared between toxic loss/gain of functions due to intranuclear RNA foci that sequesters RNA-binding proteins and RAN translation of repeat proteins in the cytoplasm. We recently elucidated the molecular mechanism driving the nuclear export of C9ORF72 repeat transcripts and showed for the first time that this pathway can be manipulated to confer neuroprotection. Strikingly, we discovered that intron-retaining C9ORF72 repeat transcripts hijack the physiological NXF1-dependent export pathway by selective RNA-repeat sequestration of SRSF1. Antagonizing SRSF1 and the nuclear export of C9ORF72 repeat transcripts promoted in turn the survival of patient-derived motor neurons and suppressed neurodegeneration-associated motor deficits in Drosophila (Hautbergue et al. Nature Communications 2017; 8:16063). In this invited Research Highlight review, we aim to place this work in the context of our previous studies on the nuclear export of mRNAs, provide a summary of the published research and highlight the significance of these findings as a novel therapeutic strategy for neuroprotection in C9ORF72-ALS/FTD. In addition, we emphasize that protein sequestration, often thought as of inducing loss-of-function mechanisms, can also trigger unwanted protein interactions and toxic gain-of-functions

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

Mitochondrial dysfunction in Alzheimer’s disease : a biomarker of the future?

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is characterised pathologically by the accumulation of amyloid beta and tau protein aggregates. Currently, there are no approved disease modifying therapies for clearance of either of these proteins from the brain of people with AD. As well as abnormalities in protein aggregation, other pathological changes are seen in this condition. The function of mitochondria in both the nervous system and rest of the body is altered early in this disease, and both amyloid and tau have detrimental effects on mitochondrial function. In this review article, we describe how the function and structure of mitochondria change in AD. This review summarises current imaging techniques that use surrogate markers of mitochondrial function in both research and clinical practice, but also how mitochondrial functions such as ATP production, calcium homeostasis, mitophagy and reactive oxygen species production are affected in AD mitochondria. The evidence reviewed suggests that the measurement of mitochondrial function may be developed into a future biomarker for early AD. Further work with larger cohorts of patients is needed before mitochondrial functional biomarkers are ready for clinical use