Bearing Down on the Lone Wolf

Out of all of literature’s enduring themes, the dichotomy between the individual and society proves continually relevant no matter what the era. It makes sense-- it is only natural that as humans confined to seeing the world through our own differing person-by-person lenses, we constantly find ourselves attempting to understand how our neighbor’s perception contrasts with our own. The collective sum of these variations is the whole of society, shifting its form based on the fluctuations of its countless individual elements. Nineteenth century American literature saw a proliferation of writers addressing this issue more overtly than ever before, thus bringing individualism to the thematic forefront of a generation of writer’s works. As contemporaries, Nathaniel Hawthorne and Herman Melville engaged previously celebrated notions of individualism in varyingly nuanced ways, both ultimately leaning towards the belief that incongruence with society will unavoidably lead to the degradation of the individual

The shrinking instability of toroidal liquid droplets in the Stokes flow regime

We analyze the stability and dynamics of toroidal liquid droplets. In addition to the Rayleigh instabilities akin to those of a cylindrical droplet there is a shrinking instability that is unique to the topology of the torus and dominates in the limit that the aspect ratio is near one (fat tori). We first find an analytic expression for the pressure distribution inside the droplet. We then determine the velocity field in the bulk fluid, in the Stokes flow regime, by solving the biharmonic equation for the stream function. The flow pattern in the external fluid is analyzed qualitatively by exploiting symmetries. This elucidates the detailed nature of the shrinking mode and the swelling of the cross-section following from incompressibility. Finally the shrinking rate of fat toroidal droplets is derived by energy conservation.Comment: 6 pages, 7 figure

Discovery and Observations of ASASSN-13db, an EX Lupi-Type Accretion Event on a Low-Mass T Tauri Star

We discuss ASASSN-13db, an EX Lupi-type ("EXor") accretion event on the young stellar object (YSO) SDSS J051011.01$-$032826.2 (hereafter SDSSJ0510) discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN). Using archival photometric data of SDSSJ0510 we construct a pre-outburst spectral energy distribution (SED) and find that it is consistent with a low-mass class II YSO near the Orion star forming region ($d \sim 420$ pc). We present follow-up photometric and spectroscopic observations of the source after the $\Delta V \sim-$5.4 magnitude outburst that began in September 2013 and ended in early 2014. These data indicate an increase in temperature and luminosity consistent with an accretion rate of $\sim10^{-7}$ $\rm{M}_\odot$ yr$^{-1}$, three or more orders of magnitude greater than in quiescence. Spectroscopic observations show a forest of narrow emission lines dominated by neutral metallic lines from Fe I and some low-ionization lines. The properties of ASASSN-13db are similar to those of the EXor prototype EX Lupi during its strongest observed outburst in late 2008.Comment: 14 pages, 4 figures, 1 table. Updated May 2014 to reflect changes in the final version published in ApJL. Photometric data presented in this submission are included as ancillary files. For a brief video explaining this paper, see http://youtu.be/yRCCrNJnvt

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

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

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

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics

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

Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts. Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context