Shuttle flight experiment preliminary proposal: Demonstration of welding applications in space

In June 1991 work was initiated at MSFC on an end-effector for 'Robotic Assembly of Welded Truss Structures in Space'. The case for welded joint assembly on orbit was discussed in the 1991 SFFP Final Report 'D'. Data drawn from Aerobrake studies (supported by the ISAAC program) allowed the more detailed investigations that accompany a design with relatively concrete goals. This principle guides current efforts to develop scenarios that further demonstrate the utility of welding for space construction and/or repair

Space Station racks weight and CG measurement using the rack insertion end-effector

The objective was to design a method to measure weight and center of gravity (C.G.) location for Space Station Modules by adding sensors to the existing Rack Insertion End Effector (RIEE). Accomplishments included alternative sensor placement schemes organized into categories. Vendors were queried for suitable sensor equipment recommendations. Inverse mathematical models for each category determine expected maximum sensor loads. Sensors are selected using these computations, yielding cost and accuracy data. Accuracy data for individual sensors are inserted into forward mathematical models to estimate the accuracy of an overall sensor scheme. Cost of the schemes can be estimated. Ease of implementation and operation are discussed

Advanced Payload Transfer Measurement System (APT-MS) Mechanical Features

During the last two feet or so of transfer, for a large or heavy payload to its restraining fixture, the consequences of unplanned contact (or impact) between payload and support structure can range from merely annoying to something approaching disaster. Current transfer methods employ technicians with meter sticks stationed at the various hold-down locations to estimate the distances to contact. This information is communicated orally to the crane operator. It is understandable that this work proceeds carefully and therefore slowly. The objectives of this study are (1) to explore mechanical sources of measurement error; and (2) to develop an improved prototype design that is compact, inexpensive, and addresses the measurement error issues. APT is a relatively inexpensive electro-mechanical device that reduces both time and manpower required to make shuttle payload transfers. APT measurement system would provide a GUI for the 'move-conductor' (crane operator) so he could see the displacements of all hold-down interfaces as they move together and thus have a more accurate, comprehensive and 'real-time' picture of the engagement activity. An error model attempts to include all estimatable sources of mechanical error and design features were introduced to reduce or eliminate major sources of error

End-effector-joint conjugates for robotic assembly of large truss structures in space: A second generation

Attachment of strut to node can be accomplished with a variety of mechanisms. All require extensive standoff elements (called scars) added to the nodes. These increase packaging volume for the nodes by as much as 300 percent. First generation designs also tend to be either heavy or expensive due to complex parts. Screws thread mechanisms are discussed simplest and most easily manufactured of alternatives. Torque and rotational motion must be transmitted across the strut to end-effector interface accomplishing the joining process and establishing a specific preload. Four drive mechanisms are considered: worm, helical, bevel, and differential gears

Rocket Propellant Ducts (Cryogenic Fuel Lines): First Cut Approximations and Design Guidance

The design team has to set parameters before analysis can take place. Analysis is customarily a thorough and time consuming process which can take weeks or even months. Only when analysis is complete can the designer obtain feedback. If margins are negative, the process must be repeated to a greater or lesser degree until satisfactory results are achieved. Reduction of the number of iterations thru this loop would beneficially conserve time and resources. The task was to develop relatively simple, easy to use, guidelines and analytic tools that allow the designer to evaluate what effect various alternatives may have on performance as the design progresses. "Easy to use" is taken to mean closed form approximations and the use of graphic methods. "Simple" implies that 2-d and quasi 3-d approximations be exploited to whatever degree is useful before more resource intensive methods are applied. The objective is to avoid the grosser violation of performance margins at the outset. Initial efforts are focused on thermal expansion/contraction and rigid body kinematics as they relate to propellant duct displacements in the gimbal plane loop (GPL). The purpose of the loop is to place two flexible joints on the same two orthogonal intersecting axes as those of the rocket motor gimbals. This supposes the ducting will flex predictably with independent rotations corresponding to those of the motor gimbal actions. It can be shown that if GPL joint axes do not coincide with motor gimbal axes, displacement incompatibilities result in less predictable movement of the ducts

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Progress report no. 2

Statement of responsibility on title-page reads: Editors: I.A. Forbes, M.J. Driscoll, N.C. Rasmussen, D.D. Lanning and I. Kaplan; Contributors: S.T. Brewer, G.J. Brown, P.DeLaquil, III, M.J. Driscoll, I.A. Forbes, C.W. Forsberg, E.P. Gyftopoulos, P.L. Hendrick, C.S. Kang, I. Kaplan, J.L. Klucar, D.D. Lanning, T.C. Leung, E.A. Mason, N.R. Ortiz, N.A. Passman, N.C. Rasmussen, I.C. Rickard, V.C. Rogers, G.E. Sullivan, A.T. Supple, and C. P. TzanosIncludes bibliographical referencesProgress report; June 30, 1971U.S. Atomic Energy Commission contract AT(11-1)306

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin