NASA Magnetospheric MultiScale Mission TableSat 1C

The NASA Magnetospheric MultiScale (MMS) mission (to be launched in 2014) consists of four spin-stabilized spacecraft flying in precise formation. The MMS spacecraft, which have wire booms up to 60 m long, are analyzed using the UNH MMS TableSat IC, a limited 3-DOF rotation (full spin, limited nutation) table top prototype of the MMS spacecraft. A PID controller is implemented on TableSat IC to observe the effects of spin rate and nutation control on the experimental satellite bus and scaled booms. Nutation and spin are implemented independently and the behavior of the test bed with and without SDP booms is examined. The SDP booms are shown to increase the response time of the controlled platform

A Spherical Magnetic Dipole Actuator for Spacecraft Attitude Control

Spacecraft generally require multiple attitude control devices to achieve full attitude actuation because of the limited control authority a single, traditional device can provide. This work presents a new momentum-exchange device that has the potential to replace traditional attitude control systems with a single actuator, in turn providing mass, volume, and power savings. The proposed actuator consists of a spherical dipole magnet enclosed in an array of coils that are fixed to the spacecraft body. Excitation of the coils as prescribed by the control law accelerates the dipole magnet in such a manner as to produce a desired reaction torque for orienting the spacecraft. The coils also control the magnet's position inside the spacecraft body via a separate control law, which is necessary because of the non-contact nature of the device. Analytical force and torque models are developed and are used in an attitude regulation maneuver. Simulations conducted so far indicate that full attitude control is possible from a single device despite the axisymmetric field of the magnetic dipole rotor, which was anticipated to cause control issues. Finally, the single actuator system is compared to a cluster of three reaction wheels, illustrating how this device can provide mass, volume, and power savings

A MAGNETICALLY SUSPENDED, SPHERICAL PERMANENT MAGNETIC DIPOLE ACTUATOR

The attitude control system (ACS) of a spacecraft contains a minimum of three reaction wheels to rotate the spacecraft in 3 degrees of freedom (DoF), but typically contains additional reaction wheels for both redundancy and improved pointing accuracy. Each wheel rotates the spacecraft about its axis by imparting an equal-and-opposite torque when the spacecraft accelerates the wheel. Since space, weight, and power (SWaP) are a premium on a spacecraft, reaction spheres, which impart an equal-and-opposite torque about an arbitrary axis when the spacecraft accelerates the sphere about that axis, have been proposed to reduce the ACS down to a single device. While NASA first proposed reaction spheres over a half century ago, limitations with previous designs have kept the technology from commercialization. These designs can be generalized into two categories: asynchronous, induction-type actuators and synchronous actuators similar to DC and hysteresis motors. The induction-type designs are difficult to model and suffer from eddy current losses in the rotor while the synchronous designs often have rotors constructed from multiple magnets which presents fabrication, strength, and balance issues. To incorporate the best of both worlds, the mechanical simplicity of an induction motor with the efficiency and simple model of a brushless DC motor, a spherical permanent magnetic dipole rotor actuated by a stator of surrounding soils has been considered. This paper presents the modeling, design, and vertical suspension of a prototype permanent magnetic dipole reaction sphere depicted in Figure 1

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

Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity, using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two prostate cancer patients including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were observed in matched tissue. Moreover, we identified 10 early-trunk and 56 metastatic-trunk mutations in the non-CTC tumor samples and found 90% and 73% of these, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic

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

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Le FORUM, Vol. 39 No. 2

https://digitalcommons.library.umaine.edu/francoamericain_forum/1045/thumbnail.jp

Complement C3d Conjugation to Anthrax Protective Antigen Promotes a Rapid, Sustained, and Protective Antibody Response

B. anthracis is the causative agent of anthrax. Pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (PA) to gain entry into the host cell. The current anthrax vaccine (AVA, Biothrax™) consists of aluminum-adsorbed cell-free filtrates of unencapsulated B. anthracis, wherein PA is thought to be the principle target of neutralization. In this study, we evaluated the efficacy of the natural adjuvant, C3d, versus alum in eliciting an anti-PA humoral response and found that C3d conjugation to PA and emulsion in incomplete Freund's adjuvant (IFA) imparted superior protection from anthrax challenge relative to PA in IFA or PA adsorbed to alum. Relative to alum-PA, immunization of mice with C3d-PA/IFA augmented both the onset and sustained production of PA-specific antibodies, including neutralizing antibodies to the receptor-binding portion (domain 4) of PA. C3d-PA/IFA was efficacious when administered either i.p. or s.c., and in adolescent mice lacking a fully mature B cell compartment. Induction of PA-specific antibodies by C3d-PA/IFA correlated with increased efficiency of germinal center formation and plasma cell generation. Importantly, C3d-PA immunization effectively protected mice from intranasal challenge with B. anthracis spores, and was approximately 10-fold more effective than alum-PA immunization or PA/IFA based on dose challenge. These data suggest that incorporation of C3d as an adjuvant may overcome shortcomings of the currently licensed aluminum-based vaccine, and may confer protection in the early days following acute anthrax exposure