| 1. |
- Abou, Diane S., et al.
(author)
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Improved 223Ra Therapy with Combination Epithelial Sodium Channel Blockade
- 2021
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 62:12, s. 1751-1758
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Journal article (peer-reviewed)abstract
- [223Ra]RaCl2 is the first approved a-particle-emitting therapy and is indicated for treatment of bonemetastatic castration-resistant prostate cancer. Approximately half the dose is absorbed into the gastrointestinal tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here,we investigated the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects. Methods: Using primary human duodenal organoids (enteroids) asin vitromodelsof the functionalgastrointestinal epithelium, we found that amiloride (epithelial sodium ion channel blocker) and NS-1619 (K+ channel activator) presented significant effects in 223Ramembranal transport.Radioactivedrugdistributionwas evaluated for lead combinations in vivo and in osteosarcoma and prostate cancermodels.Results:Amiloride shifted 223Ra uptake in vivo fromthe gut and nearly doubled the uptake at sites of bone remodeling. Bone tumor growth inhibition with the combination as measured by bioluminescent imaging and radiographywas significantly greater than that with single agents alone, and the combination resulted in noweight loss.Conclusion: This combination of approved agentsmay readily be implemented as a clinical approach to improve the outcomes of bonemetastatic cancer patients with the benefit of ameliorated tolerability. COPYRIGHT
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| 2. |
- Crossfield, Ian J. M., et al.
(author)
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197 CANDIDATES AND 104 VALIDATED PLANETS IN K2's FIRST FIVE FIELDS
- 2016
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 226:1
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Journal article (peer-reviewed)abstract
- We present 197 planet candidates discovered using data from the first year of the NASA K2 mission (Campaigns 0-4), along with the results of an intensive program of photometric analyses, stellar spectroscopy, high-resolution imaging, and statistical validation. We distill these candidates into sets of 104 validated planets (57 in multi-planet systems), 30 false positives, and 63 remaining candidates. Our validated systems span a range of properties, with median values of R-P = 2.3 R-circle plus, P = 8.6 days, T-eff = 5300 K, and Kp = 12.7 mag. Stellar spectroscopy provides precise stellar and planetary parameters for most of these systems. We show that K2 has increased by 30% the number of small planets known to orbit moderately bright stars (1-4 R-circle plus, Kp = 9-13. mag). Of particular interest are 76 planets smaller than 2 R-circle plus, 15 orbiting stars brighter than Kp = 11.5. mag, 5 receiving Earth-like irradiation levels, and several multi-planet systems-including 4 planets orbiting the M dwarf K2-72 near mean-motion resonances. By quantifying the likelihood that each candidate is a planet we demonstrate that our candidate sample has an overall false positive rate of 15%-30%, with rates substantially lower for small candidates (<2 R-circle plus) and larger for candidates with radii >8 R-circle plus and/or with P < 3 days. Extrapolation of the current planetary yield suggests that K2 will discover between 500 and 1000 planets in its planned four-year mission, assuming sufficient follow-up resources are available. Efficient observing and analysis, together with an organized and coherent follow-up strategy, are essential for maximizing the efficacy of planet-validation efforts for K2, TESS, and future large-scale surveys.
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| 3. |
- Jencson, Jacob E., et al.
(author)
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Discovery of an Intermediate-luminosity Red Transient in M51 and Its Likely Dust-obscured, Infrared-variable Progenitor
- 2019
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 880:2
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Journal article (peer-reviewed)abstract
- We present the discovery of an optical transient (OT) in Messier. 51, designated M51 OT2019-1 (also ZTF 19aadyppr, AT 2019abn, ATLAS19bz1), by the Zwicky Transient Facility (ZTF). The OT rose over 15. days to an observed luminosity of M-r = -13 (nu L-nu = 9 x 10(6) L-circle dot), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of approximate to 400 km s(-1), Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called SN impostors and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a 4.5 mu m luminosity of M-[4.5] approximate to -12.2 mag and a [3.6]-[4.5] color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [ 4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of E(B - V) approximate to 0.7 mag and higher intrinsic luminosity of M-r approximate to -14.9 mag (nu L-nu = 5.3 x 10(7) L-circle dot) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51. OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.
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| 4. |
- Khalil, Ibrahim, et al.
(author)
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Burden of Diarrhea in the Eastern Mediterranean Region, 1990-2013 : Findings from the Global Burden of Disease Study 2013
- 2016
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In: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 95:6, s. 1319-1329
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Journal article (peer-reviewed)abstract
- Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.
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| 5. |
- Roy, Sushmita, et al.
(author)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Journal article (peer-reviewed)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 6. |
- Schweinsberg, Martin, et al.
(author)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Journal article (peer-reviewed)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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