Update of the NEXT Ion Thruster Service Life Assessment with Post-Test Correlation to the Long Duration Test

The service life assessment for NASA's Evolutionary Xenon Thruster is updated to incorporate the results from the successful and voluntarily early completion of the 51,184 hour long duration test which demonstrated 918 kg of total xenon throughput. The results of the numerous post-test investigations including destructive interrogations have been assessed against all of the critical known and suspected failure mechanisms to update the life and throughput expectations for each major component. Analysis results of two of the most acute failure mechanisms, namely pit-and-groove erosion and aperture enlargement of the accelerator grid, are not updated in this work but will be published at a future time after analysis completion

3D Simulations of Ion Thruster Accelerator Grid Erosion Accounting for Charge Exchange Ion Space Charge

Accelerator (accel) grid sputtering by ions formed through charge-exchange (CEX) reactions between beam ions and residual neutral gas is a critical life-limiting mechanism for gridded ion thrusters. The three-dimensional ion optics code CEX3D is designed to simulate this grid erosion for a single beamlet, with a particular emphasis on non-axisymmetric features such as the "pits and grooves" erosion commonly observed on the accel grid downstream face in two-grid thrusters. The treatment of CEX ions in the code was recently upgraded with a new particle-in-cell (PIC) module to account for the influence of these ions' space charge on the electrostatic potential downstream of the grids. In order to achieve reasonable computation times while resolving the Debye length near the grids and avoiding gross violations of the Courant-Friedrichs-Lewy (CFL) condition, macroparticle velocities in the PIC calculation are limited through a rescaling procedure that preserves ion trajectories and space charge density. The code accounts for beam divergence, finite momentum transfer in CEX collisions, and radial losses of CEX ions from the beam; these effects are important for determining the CEX ion flux to the accel grid because the calculated potential downstream of the grids can become very flat. The upgraded code has been used to simulate operation of NASA's Evolutionary Xenon Thruster (NEXT) during the 51 kHr Long Duration Test - a selection of results is presented and compared with experimental data

Wear Testing and Analysis of Ion Engine Discharge Cathode Keeper

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77116/1/AIAA-4441-635.pd

Measurement of 30-Centimeter Ion Thruster Discharge Cathode Erosion

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76209/1/AIAA-22982-649.pd

Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes. We found that ∼59% of these transcribed sequences contain at least one RLFS. We created R-loopDB (http://rloop.bii.a-star.edu.sg/), the database that collects all RLFS identified within over half of the human genes and links to the UCSC Genome Browser for information integration and visualisation across a variety of bioinformatics sources. We found that many oncogenes and tumour suppressors (e.g. Tp53, BRCA1, BRCA2, Kras and Ptprd) and neurodegenerative diseases related genes (e.g. ATM, Park2, Ptprd and GLDC) could be prone to significant R-loop formation. Our findings suggest that R-loops provide a novel level of RNA–DNA interactome complexity, playing key roles in gene expression controls, mutagenesis, recombination process, chromosomal rearrangement, alternative splicing, DNA-editing and epigenetic modifications. RLFSs could be used as a novel source of prospective therapeutic targets

Aggregatibacter actinomycetemcomitans Omp29 Is Associated with Bacterial Entry to Gingival Epithelial Cells by F-Actin Rearrangement

The onset and progressive pathogenesis of periodontal disease is thought to be initiated by the entry of Aggregatibacter actinomycetemcomitans (Aa) into periodontal tissue, especially gingival epithelium. Nonetheless, the mechanism underlying such bacterial entry remains to be clarified. Therefore, this study aimed to investigate the possible role of Aa outer membrane protein 29 kD (Omp29), a homologue of E. coli OmpA, in promoting bacterial entry into gingival epithelial cells. To accomplish this, Omp29 expression vector was incorporated in an OmpA-deficient mutant of E. coli. Omp29+/OmpA− E. coli demonstrated 22-fold higher entry into human gingival epithelial line cells (OBA9) than Omp29−/OmpA− E. coli. While the entry of Aa and Omp29+/OmpA− E. coli into OBA9 cells were inhibited by anti-Omp29 antibody, their adherence to OBA9 cells was not inhibited. Stimulation of OBA9 cells with purified Omp29 increased the phosphorylation of focal adhesion kinase (FAK), a pivotal cell-signaling molecule that can up-regulate actin rearrangement. Furthermore, Omp29 increased the formation of F-actin in OBA9 cells. The internalization of Omp29-coated beads and the entry of Aa into OBA9 were partially inhibited by treatment with PI3-kinase inhibitor (Wortmannin) and Rho GTPases inhibitor (EDIN), both known to convey FAK-signaling to actin-rearrangement. These results suggest that Omp29 is associated with the entry of Aa into gingival epithelial cells by up-regulating F-actin rearrangement via the FAK signaling pathway

The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins

The Ku-binding motif (KBM) is a short peptide module first identified in APLF that we now show is also present in Werner syndrome protein (WRN) and in Modulator of retrovirus infection homologue (MRI). We also identify a related but functionally distinct motif in XLF, WRN, MRI and PAXX, which we denote the XLF-like motif. We show that WRN possesses two KBMs; one at the N terminus next to the exonuclease domain and one at the C terminus next to an XLF-like motif. We reveal that the WRN C-terminal KBM and XLF-like motif function cooperatively to bind Ku complexes and that the N-terminal KBM mediates Ku-dependent stimulation of WRN exonuclease activity. We also show that WRN accelerates DSB repair by a mechanism requiring both KBMs, demonstrating the importance of WRN interaction with Ku. These data define a conserved family of KBMs that function as molecular tethers to recruit and/or stimulate enzymes during NHEJ

Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

Background: Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline’s functions are not well defined. Methods: Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results: Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/ macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/ Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion: Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. Citation: Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, et al. (2011) Minocycline Inhibition of Monocyte Activation Correlate

Mre11 modulates the fidelity of fusion between short telomeres in human cells

The loss of telomere function can result in the fusion of telomeres with other telomeric loci, or non-telomeric double-stranded DNA breaks. Sequence analysis of fusion events between short dysfunctional telomeres in human cells has revealed that fusion is characterized by a distinct molecular signature consisting of extensive deletions and micro-homology at the fusion points. This signature is consistent with alternative error-prone end-joining processes. We have examined the role that Mre11 may play in the fusion of short telomeres in human cells; to do this, we have analysed telomere fusion events in cells derived from ataxia-telangiectasia-like disorder (ATLD) patients that exhibit hypomorphic mutations in MRE11. The telomere dynamics of ATLD fibroblasts were indistinguishable from wild-type fibroblasts and they were proficient in the fusion of short telomeres. However, we observed a high frequency of insertion of DNA sequences at the fusion points that created localized sequence duplications. These data indicate that Mre11 plays a role in the fusion of short dysfunctional telomeres in human cells and are consistent with the hypothesis that as part of the MRN complex it serves to stabilize the joining complex, thereby controlling the fidelity of the fusion reaction

Overview of the Development of the Solar Electric Propulsion Technology Demonstration Mission 12.5-kW Hall Thruster

NASA is developing mission concepts for a solar electric propulsion technology demonstration mission. A number of mission concepts are being evaluated including ambitious missions to near Earth objects. The demonstration of a high-power solar electric propulsion capability is one of the objectives of the candidate missions under consideration. In support of NASA's exploration goals, a number of projects are developing extensible technologies to support NASA's near and long term mission needs. Specifically, the Space Technology Mission Directorate Solar Electric Propulsion Technology Demonstration Mission project is funding the development of a 12.5-kilowatt magnetically shielded Hall thruster system to support future NASA missions. This paper presents the design attributes of the thruster that was collaboratively developed by the NASA Glenn Research Center and the Jet Propulsion Laboratory. The paper provides an overview of the magnetic, plasma, thermal, and structural modeling activities that were carried out in support of the thruster design. The paper also summarizes the results of the functional tests that have been carried out to date. The planned thruster performance, plasma diagnostics (internal and in the plume), thermal, wear, and mechanical tests are outlined