Repair of Electronics for Long Duration Spaceflight

To reduce mission risk, long duration spaceflight and exploration activities will require greater degrees of self-sufficiency with regards to repair capability than have ever been employed before in space exploration. The current repair paradigm of replacing Orbital Replacement Units (ORUs) of malfunctioning avionics and electronic hardware will be impractical, since carrying all of the spares that could possibly be needed for a long duration mission would require upmass and volume at unprecedented and unacceptable levels. A strategy of component-level repair for electronics, however, could significantly reduce the mass and volume necessary for spares and enhance mission safety via a generic contingency capability. This approach is already used to varying degrees by the U.S. Navy, where vessels at sea experience some similar constraints such as the need for self sufficiency for moderately long time periods, and restrictions on volume of repair spares and infrastructure. The concept of conducting component-level repairs of electronics in spacecraft requires the development of design guidelines for future avionics (to enable repair), development of diagnostic techniques to allow an astronaut to pinpoint the faulty component aboard a vastly complex vehicle, and development of tools and methodologies for dealing with the physical processes of replacing the component. This physical process includes tasks such as conformal coating removal and replacement, component removal, replacement, and alignment--all in the difficulty of a reduced gravity environment. Further, the gravitational effects on the soldering process must be characterized and accounted for to ensure reliability of the newly repaired components. The Component-Level Electronics-Assembly Repair (CLEAR) project under the NASA Supportability program was established to develop and demonstrate the practicality of this repair approach. CLEAR involves collaborative efforts between NASA s Glenn Research Center, Langley Research Center, Johnson Space Center, the National Center for Space Exploration Research, and the U.S. Navy. The project goals are 1) develop and demonstrate a manually-operated electronics repair capability to be conducted in a spacecraft environment; and 2) develop guidelines for designs of electronics that facilitates component-level repair for future space exploration efforts. This multi-faceted program utilizes a cross-disciplinary approach to examine pre- and post-repair diagnostics, conformal coating removal and replacement, component soldering, and electronics design for supportability. These areas are investigated by a combination of trade studies, ground based testing, reduced gravity aircraft testing, and actual spaceflight testing on the International Space Station (ISS) in multiple experiments. This paper details the efforts of this program, with emphasis on early trade study results, ground-based efforts, and two upcoming ISS experiments

In situ X-ray imaging of hot cracking and porosity during LPBF of Al-2139 with TiB2 additions and varied process parameters

Laser powder bed fusion (LPBF) additive manufacturing of 2XXX series Al alloys could be used for low volume specialist aerospace components, however, such alloys exhibit hot cracking susceptibility that can lead to component failure. In this study, we show two approaches to suppress the formation of hot cracks by controlling solidification behaviour using: (1) TiB2 additions; and (2) optimisation of LPBF process parameters. Using high-speed synchrotron X-ray radiography, we monitored LPBF of Al-2139 in situ, with and without TiB2 under a range of process conditions. In situ X-ray radiography results captured the crack growth over 1.0 ms at a rate of ca. 110 mm s−1, as well as pore evolution, wetting behaviour and build height. High-resolution synchrotron X-ray computed tomography (sCT) was used to measure the volume fraction of defects, e.g. hydrogen pores and microcracks, in the as-built LPBF samples. Our results show adding TiB2 in Al-2139 reduces the volume of cracks by up to 79 % under a volume energy density of 1000 to 5000 J mm−3, as well as reducing the average length, breadth, and surface area of cracks

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Interdisciplinary research: putting the methods under the microscope

BACKGROUND: While the desirability of interdisciplinary inquiry has been widely acknowledged, indeed has become 'the mantra of science policy', the methods of interdisciplinary collaboration are opaque to outsiders and generally remain undescribed. DISCUSSION: Many have analysed interdisciplinarity, especially in relation to the creation of new disciplines and institutions. These analyses are briefly outlined. Still, there currently persists a silence about the methods of interdisciplinary collaboration itself, and the core of this paper proposes a template for such methods. SUMMARY: Breaking this silence – by making the methods of interdisciplinary projects transparent – could further invigorate interdisciplinary research

The genetic interplay between body mass index, breast size and breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: Evidence linking breast size to breast cancer risk has been inconsistent, and its interpretation is often hampered by confounding factors such as body mass index (BMI). Here, we used linkage disequilibrium score regression and two-sample Mendelian randomization (MR) to examine the genetic associations between BMI, breast size and breast cancer risk. METHODS: Summary-level genotype data from 23andMe, Inc (breast size, n = 33 790), the Breast Cancer Association Consortium (breast cancer risk, n = 228 951) and the Genetic Investigation of ANthropometric Traits (BMI, n = 183 507) were used for our analyses. In assessing causal relationships, four complementary MR techniques [inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger regression] were used to test the robustness of the results. RESULTS: The genetic correlation (rg) estimated between BMI and breast size was high (rg = 0.50, P = 3.89x10-43). All MR methods provided consistent evidence that higher genetically predicted BMI was associated with larger breast size [odds ratio (ORIVW): 2.06 (1.80-2.35), P = 1.38x10-26] and lower overall breast cancer risk [ORIVW: 0.81 (0.74-0.89), P = 9.44x10-6]. No evidence of a relationship between genetically predicted breast size and breast cancer risk was found except when using the weighted median and weighted mode methods, and only with oestrogen receptor (ER)-negative risk. There was no evidence of reverse causality in any of the analyses conducted (P > 0.050). CONCLUSION: Our findings indicate a potential positive causal association between BMI and breast size and a potential negative causal association between BMI and breast cancer risk. We found no clear evidence for a direct relationship between breast size and breast cancer risk