A Multiple Model Based Approach for Deep Space Power System Fault Diagnosis

Improving protection and health management capabilities onboard the electrical power system (EPS) for spacecraft is essential for ensuring safe and reliable conditions for deep space human exploration. Electrical protection and control technologies on the National Aeronautics and Space Administration's (NASA's) current human space platform relies heavily on ground support to monitor and diagnose power systems and failures. As communication bandwidth diminishes for deep space applications, a transformation in system monitoring and control becomes necessary to maintain high reliability of electric power service. This paper presents a novel approach for on-line power system security monitoring for autonomous deep space spacecraft

Radio-Frequency Tank Eigenmode Sensor for Propellant Quantity Gauging

Although there are several methods for determining liquid level in a tank, there are no proven methods to quickly gauge the amount of propellant in a tank while it is in low gravity or under low-settling thrust conditions where propellant sloshing is an issue. Having the ability to quickly and accurately gauge propellant tanks in low-gravity is an enabling technology that would allow a spacecraft crew or mission control to always know the amount of propellant onboard, thus increasing the chances for a successful mission. The Radio Frequency Mass Gauge (RFMG) technique measures the electromagnetic eigenmodes, or natural resonant frequencies, of a tank containing a dielectric fluid. The essential hardware components consist of an RF network analyzer that measures the reflected power from an antenna probe mounted internal to the tank. At a resonant frequency, there is a drop in the reflected power, and these inverted peaks in the reflected power spectrum are identified as the tank eigenmode frequencies using a peak-detection software algorithm. This information is passed to a pattern-matching algorithm, which compares the measured eigenmode frequencies with a database of simulated eigenmode frequencies at various fill levels. A best match between the simulated and measured frequency values occurs at some fill level, which is then reported as the gauged fill level. The database of simulated eigenmode frequencies is created by using RF simulation software to calculate the tank eigenmodes at various fill levels. The input to the simulations consists of a fairly high-fidelity tank model with proper dimensions and including internal tank hardware, the dielectric properties of the fluid, and a defined liquid/vapor interface. Because of small discrepancies between the model and actual hardware, the measured empty tank spectra and simulations are used to create a set of correction factors for each mode (typically in the range of 0.999 1.001), which effectively accounts for the small discrepancies. These correction factors are multiplied to the modes at all fill levels. By comparing several measured modes with the simulations, it is possible to accurately gauge the amount of propellant in the tank. An advantage of the RFMG approach of applying computer simulations and a pattern-matching algorithm is that the Although there are several methods for determining liquid level in a tank, there are no proven methods to quickly gauge the amount of propellant in a tank while it is in low gravity or under low-settling thrust conditions where propellant sloshing is an issue. Having the ability to quickly and accurately gauge propellant tanks in low-gravity is an enabling technology that would allow a spacecraft crew or mission control to always know the amount of propellant onboard, thus increasing the chances for a successful mission. The Radio Frequency Mass Gauge (RFMG) technique measures the electromagnetic eigenmodes, or natural resonant frequencies, of a tank containing a dielectric fluid. The essential hardware components consist of an RF network analyzer that measures the reflected power from an antenna probe mounted internal to the tank. At a resonant frequency, there is a drop in the reflected power, and these inverted peaks in the reflected power spectrum are identified as the tank eigenmode frequencies using a peak-detection software algorithm. This information is passed to a pattern-matching algorithm, which compares the measured eigenmode frequencies with a database of simulated eigenmode frequencies at various fill levels. A best match between the simulated and measured frequency values occurs at some fill level, which is then reported as the gauged fill level. The database of simulated eigenmode frequencies is created by using RF simulation software to calculate the tank eigenmodes at various fill levels. The input to the simulations consists of a fairly high-fidelity tank model with proper dimensions and including internal tank harare, the dielectric properties of the fluid, and a defined liquid/vapor interface. Because of small discrepancies between the model and actual hardware, the measured empty tank spectra and simulations are used to create a set of correction factors for each mode (typically in the range of 0.999 1.001), which effectively accounts for the small discrepancies. These correction factors are multiplied to the modes at all fill levels. By comparing several measured modes with the simulations, it is possible to accurately gauge the amount of propellant in the tank. An advantage of the RFMG approach of applying computer simulations and a pattern-matching algorithm is that th

An Autonomous Power Controller for the NASA Human Deep Space Gateway

Autonomous control of a spacecraft is an enabling technology that must be developed for deep space human exploration. NASA's current long term human space platform, the International Space Station which is in Low Earth Orbit, is in almost continuous communication with ground based mission control. This allows near real-time control of all the vehicle core systems, including power, to be controlled by the ground. As the focus shifts from Low Earth Orbit, communication time-lag and bandwidth limitations beyond geosynchronous orbit does not permit this type of ground based operation. This paper presents the ongoing work at NASA to develop an architecture for autonomous power control system and a vehicle manager which monitors, coordinates, and delegates all the onboard subsystems to enable autonomous control of the complete spacecraft

Nuclear phospholipase C β1 signaling, epigenetics and treatments in MDS.

Myelodysplastic syndromes (MDS), clonal hematopoietic stem-cell disorders mainly affecting older adult patients, show ineffective hematopoiesis in one or more of the lineages of the bone marrow. Most MDS are characterized by anemia, and a number of cases progresses to acute myeloid leukemia (AML). Indeed, the molecular mechanisms underlying the MDS evolution to AML are still unclear, even though the nuclear signaling elicited by PI-PLCβ1 has been demonstrated to play an important role in the control of the balance between cell cycle progression and apoptosis in MDS cells. Here we review both the role of epigenetic therapy on PI-PLCβ1 promoter and the changes in PI-PLCβ1 expression in MDS patients treated for anemia.Myelodysplastic syndromes (MDS), clonal hematopoietic stem-cell disorders mainly affecting older adult patients, show ineffective hematopoiesis in one or more of the lineages of the bone marrow. Most MDS are characterized by anemia, and a number of cases progresses to acute myeloid leukemia (AML). Indeed, the molecular mechanisms underlying the MDS evolution to AML are still unclear, even though the nuclear signaling elicited by PI-PLCβ1 has been demonstrated to play an important role in the control of the balance between cell cycle progression and apoptosis in MDS cells. Here we review both the role of epigenetic therapy on PI-PLCβ1 promoter and the changes in PI-PLCβ1 expression in MDS patients treated for anemia. © 2012 Elsevier Ltd

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

Evaluating the Effectiveness of Online Educational Modules and Interactive Workshops in Alleviating Symptoms of Mild to Moderate Depression: A Pilot Trial

Introduction: Depression is a common health concern in primary care with barriers to treatment well documented in the literature. Innovative online psychoeducational approaches to address barriers to care have been well received and can be cost effective. This pilot trial evaluated the effectiveness of an online psychoeducation curriculum intended to alleviate symptoms of depression while utilizing minimal staff resources. Methods: A small (n=29) randomized control pilot study was conducted. Online psychoeducational content was delivered in 5 to 10-minute videos over 8weeks. Participants engaged in moderated discussions on workshop topics. The Patient Health Care Questionnaire (PHQ-9) was used to measure pre/ post scores. Two Likert scale questions were used to determine subjective changes in understanding of depression and coping skills. Results: Paired T-test analysis showed an average PHQ-9 improvement of 4.37 (P=.01) in the intervention arm and 1.81 (P=.172) in the control group. No significant difference in delta PHQ-9 score was found between groups via difference in difference analysis (P=.185). Effect size was 0.59. No improvement in Likert scores for question 1 or 2 were detected by paired T test in either group. Conclusion: This pilot trial of interactive online psychoeducational content shows initial promise as there was a significant improvement in PHQ-9 scores within the intervention arm. The comparison of delta scores between intervention and control arms was not statistically significant although this is likely due to the underpowered nature of the pilot trial. This data trend justifies the need for a larger validation trial of this intervention

PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration.

Proliferating cancer cells oxidize glucose through the glycolytic pathway. Since this metabolism is less profitable in terms of ATP production, cancer cells consume large quantity of glucose, and those that experience insufficient blood supply become glucose-addicted. We have analyzed the response to glucose depletion in WRO and FTC133 follicular thyroid cancer cells, which differ in the expression of two key regulators of the glucose metabolism. WRO cells, which express wild type p53 and PTEN, showed a higher rate of cell proliferation and were much less sensitive to glucose-depletion than FTC133 cells, which are PTEN null and express mutant p53. Glucose depletion slowed-down the autophagy flux in FTC133 cells, not in WRO cells. In a wound-healing assay, WRO cells were shown to migrate faster than FTC133 cells. Glucose depletion slowed down the cell migration rate, and these effects were more evident in FTC133 cells. Genetic silencing of either wild-type PTEN or p53 in WRO cells resulted in increased uptake of glucose, whereas the ectopic expression of PTEN in FTC133 cells resulted in diminished glucose uptake. In conclusion, compared to WRO, FTC133 cells were higher glucose up-taker and consumer. These data do not support the general contention that cancer cells lacking PTEN or expressing the mutant p53R273H are more aggressive and prone to better face glucose depletion. We propose that concurrent PTEN deficiency and mutant p53 leads to a glucose-addiction state that renders the cancer cell more sensitive to glucose restriction. The present observation substantiates the view that glucose-restriction may be an adjuvant strategy to combat these tumours

Effects of chloroquine and hydroxychloroquine on the sensitivity of pancreatic cancer cells to targeted therapies

Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is a cancer which is difficult to effectively treat as it is often detected late in the disease process. Almost all PDACs (over 90%) have activating mutations in the GTPase gene KRAS. These mutations result in constitutive KRas activation and the mobilization of downstream pathways such as the Raf/MEK/ERK pathway. Small molecule inhibitors of key components of the KRas/Raf/MEK/ERK pathways as well as monoclonal antibodies (MoAbs) specific for upstream growth factor receptors such insulin like growth factor-1 receptor (IGF1-R) and epidermal growth factor receptors (EGFRs) have been developed and have been evaluated in clinical trials. An additional key regulatory gene frequently mutated (∼75%) in PDAC is the TP53 tumor suppressor gene which controls the transcription of multiple genes involved in cell cycle progression, apoptosis, metabolism, cancer progression and other growth regulatory processes. Small molecule mutant TP53 reactivators have been developed which alter the structure of mutant TP53 protein and restore some of its antiproliferative activities. Some mutant TP53 reactivators have been examined in clinical trials with patients with mutant TP53 genes. Inhibitors to the TP53 negative regulator Mouse Double Minute 2 (MDM2) have been developed and analyzed in clinical trials. Chloroquine and hydroxychloroquine are established anti-malarial and anti-inflammatory drugs that also prevent the induction of autophagy which can have effects on cancer survival. Chloroquine and hydroxychloroquine have also been examined in various clinical trials. Recent studies are suggesting effective treatment of PDAC patients may require chemotherapy as well as targeting multiple pathways and biochemical processes

Advances in MDS/AML and inositide signalling

Aberrant signaling pathways regulating proliferation and differentiation of hematopoietic stem cells (HSCs) can contribute to disease pathogenesis and neoplastic growth. Phosphoinositides (PIs) are inositol phospholipids that are implicated in the regulation of critical signaling pathways: aberrant regulation of Phospholipase C (PLC) beta1, PLCgamma1 and the PI3K/Akt/mTOR pathway play essential roles in the pathogenesis of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)