Indigenous research sovereignties: Sparking the deeper conversations we need

This article is part of the Environment and Planning F: Philosophy, Theory, Models, Methods and Practice special issue on ‘Indigenous Research Sovereignty’, edited by Jay T. Johnson, Joseph P. Brewer II., Melissa K. Nelson, Mark H. Palmer, and Renee Pualani Louis.This article seeks to spark a conversation and further debate through the 15 papers and 3 commentaries comprising this special issue entitled “Indigenous Research Sovereignty.” By inviting the authors to publish in this special edition and address Indigenous Research Sovereignty from a variety of viewpoints, we have brought together a collection that inspires, transforms, and expands on the ways in which Indigenous and non-Indigenous researchers are engaging with Indigenous communities to address the research agendas of communities across the globe. Through our work together over the past 8 years, the editorial team have identified eight themes within this broad concept of Indigenous Research Sovereignty. This article provides an introduction to those eight themes in the broadest strokes, while the papers and commentaries explore and refine them with significant depth. We seek to spark a conversation, we do not intend to provide answers to any of the dilemma facing Indigenous communities as they engage, or choose not to engage, in research. Our primary goal is to express an all-encompassing concern for the protection of Indigenous Communities’ inherent rights and knowledges.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The guest editors acknowledge financial support for the FIRST Network by the United States National Science Foundation through grant number 1417767

Planet Hunters X: Searching for Nearby Neighbors of 75 Planet and Eclipsing Binary Candidates from the K2 Kepler Extended Mission

We present high-resolution observations of a sample of 75 K2 targets from Campaigns 1-3 using speckle interferometry on the Southern Astrophysical Research (SOAR) telescope and adaptive optics (AO) imaging at the Keck II telescope. The median SOAR $I$-band and Keck $K_s$-band detection limits at 1" were $\Delta m_{I}=4.4$~mag and $\Delta m_{K_s}=6.1$~mag, respectively. This sample includes 37 stars likely to host planets, 32 targets likely to be eclipsing binaries (EBs), and 6 other targets previously labeled as likely planetary false positives. We find nine likely physically bound companion stars within 3" of three candidate transiting exoplanet host stars and six likely EBs. Six of the nine detected companions are new discoveries; one of the six, EPIC 206061524, is associated with a planet candidate. Among the EB candidates, companions were only found near the shortest period ones ($P<3$ days), which is in line with previous results showing high multiplicity near short-period binary stars. This high-resolution data, including both the detected companions and the limits on potential unseen companions, will be useful in future planet vetting and stellar multiplicity rate studies for planets and binaries.Comment: Accepted in A

The Cosmology Large Angular Scale Surveyor

The Cosmology Large Angular Scale Surveyor (CLASS) is a four telescope array designed to characterize relic primordial gravitational waves from inflation and the optical depth to reionization through a measurement of the polarized cosmic microwave background (CMB) on the largest angular scales. The frequencies of the four CLASS telescopes, one at 38 GHz, two at 93 GHz, and one dichroic system at 145/217 GHz, are chosen to avoid spectral regions of high atmospheric emission and span the minimum of the polarized Galactic foregrounds: synchrotron emission at lower frequencies and dust emission at higher frequencies. Low-noise transition edge sensor detectors and a rapid front-end polarization modulator provide a unique combination of high sensitivity, stability, and control of systematics. The CLASS site, at 5200 m in the Chilean Atacama desert, allows for daily mapping of up to 70\% of the sky and enables the characterization of CMB polarization at the largest angular scales. Using this combination of a broad frequency range, large sky coverage, control over systematics, and high sensitivity, CLASS will observe the reionization and recombination peaks of the CMB E- and B-mode power spectra. CLASS will make a cosmic variance limited measurement of the optical depth to reionization and will measure or place upper limits on the tensor-to-scalar ratio, $r$, down to a level of 0.01 (95\% C.L.)

The History of Flow Chemistry at Eli Lilly and Company

Flow chemistry was initially used for speed to early phase material delivery in the development laboratories, scaling up chemical transformations that we would not or could not scale up batch for safety reasons. Some early examples included a Newman Kwart Rearrangement, Claisen rearrangement, hydroformylation, and thermal imidazole cyclization. Next, flow chemistry was used to enable safe scale up of hazardous chemistries to manufacturing plants. Examples included high pressure hydrogenation, aerobic oxidation, and Grignard formation reactions. More recently, flow chemistry was used in Small Volume Continuous (SVC) processes, where highly potent oncolytic molecules were produced by fully continuous processes at about 10 kg/day including reaction, extraction, distillation, and crystallization, using disposable equipment contained in fume hoods

Lactic Acid Induces Aberrant Amyloid Precursor Protein Processing by Promoting Its Interaction with Endoplasmic Reticulum Chaperone Proteins

Lactic acid, a natural by-product of glycolysis, is produced at excess levels in response to impaired mitochondrial function, high-energy demand, and low oxygen availability. The enzyme involved in the production of β-amyloid peptide (Aβ) of Alzheimer's disease, BACE1, functions optimally at lower pH, which led us to investigate a potential role of lactic acid in the processing of amyloid precursor protein (APP).Lactic acid increased levels of Aβ40 and 42, as measured by ELISA, in culture medium of human neuroblastoma cells (SH-SY5Y), whereas it decreased APP metabolites, such as sAPPα. In cell lysates, APP levels were increased and APP was found to interact with ER-chaperones in a perinuclear region, as determined by co-immunoprecipitation and fluorescence microscopy studies. Lactic acid had only a very modest effect on cellular pH, did increase the levels of ER chaperones Grp78 and Grp94 and led to APP aggregate formation reminiscent of aggresomes.These findings suggest that sustained elevations in lactic acid levels could be a risk factor in amyloidogenesis related to Alzheimer's disease through enhanced APP interaction with ER chaperone proteins and aberrant APP processing leading to increased generation of amyloid peptides and APP aggregates

The Cosmology Large Angular Scale Surveyor

The Cosmology Large Angular Scale Surveyor (CLASS) is a four telescope array designed to characterize relic primordial gravitational waves from inflation and the optical depth to reionization through a measurement of the polarized cosmic microwave background (CMB) on the largest angular scales. The frequencies of the four CLASS telescopes, one at 38 GHz, two at 93 GHz, and one dichroic system at 145217 GHz, are chosen to avoid spectral regions of high atmospheric emission and span the minimum of the polarized Galactic foregrounds: synchrotron emission at lower frequencies and dust emission at higher frequencies. Low-noise transition edge sensor detectors and a rapid front-end polarization modulator provide a unique combination of high sensitivity, stability, and control of systematics. The CLASS site, at 5200 m in the Chilean Atacama desert, allows for daily mapping of up to 70% of the sky and enables the characterization of CMB polarization at the largest angular scales. Using this combination of a broad frequency range, large sky coverage, control over systematics, and high sensitivity, CLASS will observe the reionization and recombination peaks of the CMB E- and B-mode power spectra. CLASS will make a cosmic variance limited measurement of the optical depth to reionization and will measure or place upper limits on the tensor-to-scalar ratio, r, down to a level of 0.01 (95% C.L.)

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

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

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