Stable habitable zones of single Jovian planet systems

With continued improvement in telescope sensitivity and observational techniques, the search for rocky planets in stellar habitable zones is entering an exciting era. With so many exoplanetary systems available for follow-up observations to find potentially habitable planets, one needs to prioritise the ever-growing list of candidates. We aim to determine which of the known planetary systems are dynamically capable of hosting rocky planets in their habitable zones, with the goal of helping to focus future planet search programs. We perform an extensive suite of numerical simulations to identify regions in the habitable zones of single Jovian planet systems where Earth mass planets could maintain stable orbits, specifically focusing on the systems in the Catalog of Earth-like Exoplanet Survey Targets (CELESTA). We find that small, Earth-mass planets can maintain stable orbits in cases where the habitable zone is largely, or partially, unperturbed by a nearby Jovian, and that mutual gravitational interactions and resonant mechanisms are capable of producing stable orbits even in habitable zones that are significantly or completely disrupted by a Jovian. Our results yield a list of 13 single Jovian planet systems in CELESTA that are not only capable of supporting an Earth-mass planet on stable orbits in their habitable zone, but for which we are also able to constrain the orbits of the Earth-mass planet such that the induced radial velocity signals would be detectable with next generation instruments.Comment: 15 pages, 12 figures, Accepted for publication by MNRA

Tiny grains shining bright in the gaps of Herbig Ae transitional discs

This work presents a study of two Herbig Ae transitional discs, Oph IRS 48 and HD 169142; which both have reported rings in their dust density distributions. We use Keck-II/NIRC2 adaptive optics imaging observations in the L′ filter (3.8 μm) to probe the regions of these discs inwards of ∼20au from the star. We introduce our method for investigating these transitional discs, which takes a forward modelling approach: making a model of the disc (using the Monte Carlo radiative transfer code RADMC3D), convolving it with point spread functions of calibrator stars, and comparing the convolved models with the observational data. The disc surface density parameters are explored with a Monte Carlo Markov Chain technique. Our analysis recovers emission from both of the discs interior to the well-known optically thick walls, modelled as a ring of emission at ∼15au in Oph IRS 48, and ∼7au for HD 169142, and identifies asymmetries in both discs. Given the brightness of the near-symmetric rings compared to the reported companion candidates, we suggest that the reported companion candidates can be interpreted as slightly asymmetric disc emission or illumination.EKB would like to thank the Australian Government for their support through the Australian Government Research Training Program Stipend Scholarship and the Research School of Astronomy and Astrophysics at the Australian National University for the Masters of Astronomy and Astrophysics (Advanced) Scholarship. MJI gratefully acknowledges funding provided by the Australian Research Council’s Future Fellowship (FT130100235). CF gratefully acknowledges funding provided by the Australian Research Council’s Discovery Projects (grants DP150104329 and DP170100603) and Future Fellowship Scheme (grant FT180100495), as well as the Australia-Germany Joint Research Cooperation Scheme (UA-DAAD

Protein Catalyzed Capture Agents with Tailored Performance for In Vitro and In Vivo Applications

We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T_(1/2)) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 100°C, and  > 81% binding activity for PA after heating at 90°C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives

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

Protein Catalyzed Capture Agents with Tailored Performance for In Vitro and In Vivo Applications

We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T_(1/2)) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 100°C, and  > 81% binding activity for PA after heating at 90°C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives