Techniques for Solution- Assisted Optical Contacting

A document discusses a solution-assisted contacting technique for optical contacting. An optic of surface flatness Lambda/20 was successfully contacted with one of moderate surface quality, or Lambda/4. Optics used were both ultra-low expansion (ULE) glass (Lambda/4 and Lambda/20) and fused silica (Lambda/20). A stainless steel template of the intended interferometer layout was designed and constructed with three contact points per optic. The contact points were all on a common side of the template. The entire contacting jig was tilted at about 30 . Thus, when the isopropanol was applied, each optic slid due to gravity, resting on the contact points. All of the contacting was performed in a relatively dusty laboratory. A number of successful contacts were achieved where up to two or three visible pieces of dust could be seen. These were clearly visible due to refraction patterns between the optic and bench. On a number of optics, the final step of dropping isopropyl between the surfaces was repeated until a successful contact was achieved. The new procedures realized in this work represent a simplification for optical contacting in the laboratory. They will both save time and money spent during the contacting process, and research and development phases. The techniques outlined are suitable for laboratory experiments, research, and initial development stages

CSO Bolocam 1.1 mm continuum mapping of the Braid Nebula star formation region in Cygnus OB7

We present a 1.1 mm map of the Braid Nebula star formation region in Cygnus OB7 taken using Bolocam on the Caltech Submillimeter Observatory. Within the 1 deg2 covered by the map, we have detected 55 cold dust clumps all of which are new detections. A number of these clumps are coincident with IRAS point sources although the majority are not. Some of the previously studied optical/near-IR sources are detected at 1.1 mm. We estimate total dust/gas masses for the 55 clumps together with peak visual extinctions. We conclude that over the whole region, approximately 20% of the clumps are associated with IRAS sources suggesting that these are protostellar objects. The remaining 80% are classed as starless clumps. In addition, both FU Orionis (FUor) like objects in the field, the Braid Star and HH 381 IRS, are associated with strong millimeter emission. This implies that FUor eruptions can occur at very early stages of pre-main-sequence life. Finally, we determine that the cumulative clump mass function for the region is very similar to that found in both the Perseus and Ï? Ophiuchus star-forming regions. © 2011. The American Astronomical Society. All rights reserved

Technology Development Roadmap: A Technology Development Roadmap for a Future Gravitational Wave Mission

Humankind will detect the first gravitational wave (GW) signals from the Universe in the current decade using ground-based detectors. But the richest trove of astrophysical information lies at lower frequencies in the spectrum only accessible from space. Signals are expected from merging massive black holes throughout cosmic history, from compact stellar remnants orbiting central galactic engines from thousands of close contact binary systems in the Milky Way, and possibly from exotic sources, some not yet imagined. These signals carry essential information not available from electromagnetic observations, and which can be extracted with extraordinary accuracy. For 20 years, NASA, the European Space Agency (ESA), and an international research community have put considerable effort into developing concepts and technologies for a GW mission. Both the 2000 and 2010 decadal surveys endorsed the science and mission concept of the Laser Interferometer Space Antenna (LISA). A partnership of the two agencies defined and analyzed the concept for a decade. The agencies partnered on LISA Pathfinder (LPF), and ESA-led technology demonstration mission, now preparing for a 2015 launch. Extensive technology development has been carried out on the ground. Currently, the evolved Laser Interferometer Space Antenna (eLISA) concept, a LISA-like concept with only two measurement arms, is competing for ESA's L2 opportunity. NASA's Astrophysics Division seeks to be a junior partner if eLISA is selected. If eLISA is not selected, then a LISA-like mission will be a strong contender in the 2020 decadal survey. This Technology Development Roadmap (TDR) builds on the LISA concept development, the LPF technology development, and the U.S. and European ground-based technology development. The eLISA architecture and the architecture of the Mid-sized Space-based Gravitational-wave Observatory (SGO Mid)-a competitive design with three measurement arms from the recent design study for a NASA-led mission after 2020-both use the same technologies. Further, NASA participation in an ESA-led mission would likely augment the eLISA architecture with a third arm to become the SGO Mid architecture. For these reasons, this TDR for a future GW mission applies to both designs and both programmatic paths forward. It is adaptable to the different timelines and roles for an ESA-led or a NASA-led mission, and it is adaptable to available resources. Based on a mature understanding of the interaction between technology and risk, the authors of this TDR have chosen a set of objectives that are more expansive than is usual. The objectives for this roadmap are: (1) reduce technical and development risks and costs; (2) understand and, where possible, relieve system requirements and consequences; (3) increase technical insight into critical technologies; and (4) validate the design at the subsystem level. The emphasis on these objectives, particularly the latter two, is driven by outstanding programmatic decisions, namely whether a future GW mission is ESA-led or NASA-led, and availability of resources. The relative emphasis is best understood in the context of prioritization

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

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

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Tracking Subtle Stereotypes of Children with Trisomy 21: From Facial-Feature-Based to Implicit Stereotyping

Background: Stigmatization is one of the greatest obstacles to the successful integration of people with Trisomy 21 (T21 or Down syndrome), the most frequent genetic disorder associated with intellectual disability. Research on attitudes and stereotypes toward these people still focuses on explicit measures subjected to social-desirability biases, and neglects how variability in facial stigmata influences attitudes and stereotyping. Methodology/Principal Findings: The participants were 165 adults including 55 young adult students, 55 non-student adults, and 55 professional caregivers working with intellectually disabled persons. They were faced with implicit association tests (IAT), a well-known technique whereby response latency is used to capture the relative strength with which some groups of people—here photographed faces of typically developing children and children with T21—are automatically (without conscious awareness) associated with positive versus negative attributes in memory. Each participant also rated the same photographed faces (consciously accessible evaluations). We provide the first evidence that the positive bias typically found in explicit judgments of children with T21 is smaller for those whose facial features are highly characteristic of this disorder, compared to their counterparts with less distinctive features and to typically developing children. We also show that this bias can coexist with negative evaluations at the implicit level (with large effect sizes), even among professional caregivers

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies