Elucidating the role of DEPTOR in Alzheimer's disease

This article has been made available through the Brunel Open Access Publishing Fund.The mammalian or mechanistic target of rapamycin (mTOR) is a Ser/Thr protein kinase that, in response to nutrient stimulation, regulates cellular growth, proliferation, survival, protein synthesis and gene transcription. It has also been implicated in Alzheimer's disease (AD) with neuronal cells and hippocampal slices of AD transgenic mice experiencing dysregulated mTOR and synaptic plasticity in response to treatment with the toxic amyloid β (Aβ1-42) peptide, which has been implicated in AD. DEP domain-containing mTOR-interacting protein (DEPTOR) is a protein which can bind to mTOR and cause its inhibition, and functions as a regulatory protein of mTOR to control its activity. The inhibition of mTOR has been shown to have a neuroprotective effect; in an animal model, it was shown to protect against Aβ-induced neurotoxicity. In the present study, to investigate to role of DEPTOR in a model of AD, we neuronally differentiated the SH-SY5Y cell line and examined the effects of treatment with an Aβ42 peptide, thus mimicking plaque formation. This resulted in a significant increase in mTOR and a significant decrease in DEPTOR expression compared to the unstimulated controls. Moreover, to the best of our knowledge, we demonstrate for the first time a reduction in the protein level of DEPTOR in the precentral gyrus, postcentral gyrus and occipital lobe of a brain with AD compared to a normal control, as well as a significant reduction in DEPTOR expression in samples from late-onset AD (LOAD) compared to early-onset familial AD (EOFAD). The reduction in DEPTOR expression in cases of AD compared to healthy controls can lead to an augmentation of mTOR signalling, leading to Aβ accumulation, which in turn leads to a further reduction in DEPTOR expression. This results in the accumulation of amyloid plaque, shifting the balance from neuroprotection to neurodegeneration

Affordable Development and Optimization of CERMET Fuels for NTP Ground Testing

CERMET fuel materials for Nuclear Thermal Propulsion (NTP) are currently being developed at NASA's Marshall Space Flight Center. The work is part of NASA's Advanced Space Exploration Systems Nuclear Cryogenic Propulsion Stage (NCPS) Project. The goal of the FY12-14 project is to address critical NTP technology challenges and programmatic issues to establish confidence in the affordability and viability of an NTP system. A key enabling technology for an NCPS system is the fabrication of a stable high temperature nuclear fuel form. Although much of the technology was demonstrated during previous programs, there are currently no qualified fuel materials or processes. The work at MSFC is focused on developing critical materials and process technologies for manufacturing robust, full-scale CERMET fuels. Prototypical samples are being fabricated and tested in flowing hot hydrogen to understand processing and performance relationships. As part of this initial demonstration task, a final full scale element test will be performed to validate robust designs. The next phase of the project will focus on continued development and optimization of the fuel materials to enable future ground testing. The purpose of this paper is to provide a detailed overview of the CERMET fuel materials development plan. The overall CERMET fuel development path is shown in Figure 2. The activities begin prior to ATP for a ground reactor or engine system test and include materials and process optimization, hot hydrogen screening, material property testing, and irradiation testing. The goal of the development is to increase the maturity of the fuel form and reduce risk. One of the main accomplishmens of the current AES FY12-14 project was to develop dedicated laboratories at MSFC for the fabrication and testing of full length fuel elements. This capability will enable affordable, near term development and optimization of the CERMET fuels for future ground testing. Figure 2 provides a timeline of the development and optimization tasks for the AES FY15-17 follow on program

Advances in the Development of a WCl6 CVD System for Coating UO2 Powders with Tungsten

W-UO2 CERMET fuels are under development to enable Nuclear Thermal Propulsion (NTP) for deep space exploration. Research efforts with an emphasis on fuel fabrication, testing, and identification of potential risks is underway. One primary risk is fuel loss due to CTE mismatch between W and UO2 and the grain boundary structure of W particles resulting in higher thermal stresses. Mechanical failure can result in significant reduction of the UO2 by hot hydrogen. Fuel loss can be mitigated if the UO2 particles are coated with a layer of high density tungsten before the consolidation process. This paper discusses the work to date, results, and advances of a fluidized bed chemical vapor deposition (CVD) system that utilizes the H2-WCl6 reduction process. Keywords: Space, Nuclear, Thermal, Propulsion, Fuel, CERMET, CVD, Tungsten, Uraniu

Development Status of a CVD System to Deposit Tungsten onto UO2 Powder via the WCI6 Process

Nuclear Thermal Propulsion (NTP) is under development for deep space exploration. NTP's high specific impulse (> 850 second) enables a large range of destinations, shorter trip durations, and improved reliability. W-60vol%UO2 CERMET fuel development efforts emphasize fabrication, performance testing and process optimization to meet service life requirements. Fuel elements must be able to survive operation in excess of 2850 K, exposure to flowing hydrogen (H2), vibration, acoustic, and radiation conditions. CTE mismatch between W and UO2 result in high thermal stresses and lead to mechanical failure as a result UO2 reduction by hot hydrogen (H2) [1]. Improved powder metallurgy fabrication process control and mitigated fuel loss can be attained by coating UO2 starting powders within a layer of high density tungsten [2]. This paper discusses the advances of a fluidized bed chemical vapor deposition (CVD) system that utilizes the H2-WCl6 reduction process

Compact Fuel Element Environment Test

Deep space missions with large payloads require high specific impulse (I(sub sp)) and relatively high thrust to achieve mission goals in reasonable time frames. Conventional, storable propellants produce average I(sub sp). Nuclear thermal rockets (NTRs) capable of high I(sub sp) thrust have been proposed. NTR employs heat produced by fission reaction to heat and therefore accelerate hydrogen, which is then forced through a rocket nozzle providing thrust. Fuel element temperatures are very high (up to 3,000 K) and hydrogen is highly reactive with most materials at high temperatures. Data covering the effects of high-temperature hydrogen exposure on fuel elements are limited. The primary concern is the mechanical failure of fuel elements that employ high melting point metals, ceramics, or a combination (cermet) as a structural matrix into which the nuclear fuel is distributed. It is not necessary to include fissile material in test samples intended to explore high-temperature hydrogen exposure of the structural support matrices. A small-scale test bed designed to heat fuel element samples via noncontact radio frequency heating and expose samples to hydrogen for typical mission durations has been developed to assist in optimal material and manufacturing process selection without employing fissile material. This Technical Memorandum details the test bed design and results of testing conducted to date

Spin properties of dense near-surface ensembles of nitrogen-vacancy centres in diamond

We present a study of the spin properties of dense layers of near-surface nitrogen-vacancy (NV) centres in diamond created by nitrogen ion implantation. The optically detected magnetic resonance contrast and linewidth, spin coherence time, and spin relaxation time, are measured as a function of implantation energy, dose, annealing temperature and surface treatment. To track the presence of damage and surface-related spin defects, we perform in situ electron spin resonance spectroscopy through both double electron-electron resonance and cross-relaxation spectroscopy on the NV centres. We find that, for the energy ($4-30$~keV) and dose ($5\times10^{11}-10^{13}$~ions/cm$^2$) ranges considered, the NV spin properties are mainly governed by the dose via residual implantation-induced paramagnetic defects, but that the resulting magnetic sensitivity is essentially independent of both dose and energy. We then show that the magnetic sensitivity is significantly improved by high-temperature annealing at $\geq1100^\circ$C. Moreover, the spin properties are not significantly affected by oxygen annealing, apart from the spin relaxation time, which is dramatically decreased. Finally, the average NV depth is determined by nuclear magnetic resonance measurements, giving $\approx10$-17~nm at 4-6 keV implantation energy. This study sheds light on the optimal conditions to create dense layers of near-surface NV centres for high-sensitivity sensing and imaging applications.Comment: 12 pages, 7 figure

Design Evolution of Hot Isostatic Press Cans for NTP Cermet Fuel Element Fabrication

No abstract availabl

Development of a Fluidized Bed CVD System for Coating UO2 Particles with Tungsten

No abstract availabl

Yeast Pro- and Paraprobiotics Have the Capability to Bind Pathogenic Bacteria Associated With Animal Disease

Live yeast probiotics and yeast cell wall components (paraprobiotics) may serve as an alternative to the use of antibiotics in prevention and treatment of infections caused by pathogenic bacteria. Probiotics and paraprobiotics can bind directly to pathogens, which limits binding of the pathogens to the intestinal cells and also facilitates removal from the host. However, knowledge of bacterial binding, specificity, and/or capability is limited with regard to probiotics or paraprobiotics. The goal of this study was to characterize the qualitative and quantitative nature of two Saccharomyces cerevisiae probiotics and three S. cerevisiae paraprobiotics to adhere to thirteen different pathogenic bacteria using scanning electron miscroscopy and filtration assays. On average, the yeast probiotics (LYA and LYB) exhibited overall greater (P \u3c 0.05) adhesion to the pathogenic bacteria tested (41% and 34%) in comparison to paraprobiotics (23%, 21%, and 22%), though variations were observed between pathogens tested. The ability of Salmonella and Listeriato utilize components of the yeast as a nutrient source was also tested. Bacteria were cultured in media with limited carbon and supplemented with cell free extracts of the probiotics and paraprobiotics. Salmonella exhibited growth, indicating these pathogens could utilize the yeast lysates as a carbon source. Listeria monocytogenes had limited growth in only one of the lysates tested. Together, these data indicate that the interaction between probiotics and paraprobiotics occurs in a strain dependent mechanism. Administration of probiotics and paraprobiotics as therapeutics therefore needs to be specific against the bacterial pathogen target

Nuclear Cryogenic Propulsion Stage

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP