185 research outputs found
Therapeutic options for mucinous ovarian carcinoma
OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents. METHODS: We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117-166). RESULTS: Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184). CONCLUSIONS: Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition
Genomic Diversity and Introgression in O. sativa Reveal the Impact of Domestication and Breeding on the Rice Genome
The domestication of Asian rice (Oryza sativa) was a complex process punctuated by episodes of introgressive hybridization among and between subpopulations. Deep genetic divergence between the two main varietal groups (Indica and Japonica) suggests domestication from at least two distinct wild populations. However, genetic uniformity surrounding key domestication genes across divergent subpopulations suggests cultural exchange of genetic material among ancient farmers.In this study, we utilize a novel 1,536 SNP panel genotyped across 395 diverse accessions of O. sativa to study genome-wide patterns of polymorphism, to characterize population structure, and to infer the introgression history of domesticated Asian rice. Our population structure analyses support the existence of five major subpopulations (indica, aus, tropical japonica, temperate japonica and GroupV) consistent with previous analyses. Our introgression analysis shows that most accessions exhibit some degree of admixture, with many individuals within a population sharing the same introgressed segment due to artificial selection. Admixture mapping and association analysis of amylose content and grain length illustrate the potential for dissecting the genetic basis of complex traits in domesticated plant populations.Genes in these regions control a myriad of traits including plant stature, blast resistance, and amylose content. These analyses highlight the power of population genomics in agricultural systems to identify functionally important regions of the genome and to decipher the role of human-directed breeding in refashioning the genomes of a domesticated species
Characteristics of the diffuse astrophysical electron and tau neutrino flux with six years of IceCube high energy cascade data
We report on the first measurement of the astrophysical neutrino flux using
particle showers (cascades) in IceCube data from 2010 -- 2015. Assuming
standard oscillations, the astrophysical neutrinos in this dedicated cascade
sample are dominated () by electron and tau flavors. The flux,
observed in the sensitive energy range from to
, is consistent with a single power-law model as expected
from Fermi-type acceleration of high energy particles at astrophysical sources.
We find the flux spectral index to be and a flux
normalization for each neutrino flavor of
at , in agreement with IceCube's complementary muon
neutrino results and with all-neutrino flavor fit results. In the measured
energy range we reject spectral indices at
significance level. Due to high neutrino energy resolution and low atmospheric
neutrino backgrounds, this analysis provides the most detailed characterization
of the neutrino flux at energies below compared to
previous IceCube results. Results from fits assuming more complex neutrino flux
models suggest a flux softening at high energies and a flux hardening at low
energies (p-value ). The sizable and smooth flux measured below remains a puzzle. In order to not violate the isotropic
diffuse gamma-ray background as measured by the Fermi-LAT, it suggests the
existence of astrophysical neutrino sources characterized by dense environments
which are opaque to gamma-rays.Comment: 4 figures, 4 tables, includes supplementary materia
IceCube Search for Neutrinos Coincident with Compact Binary Mergers from LIGO-Virgo's First Gravitational-Wave Transient Catalog
Using the IceCube Neutrino Observatory, we search for high-energy neutrino
emission coincident with compact binary mergers observed by the LIGO and Virgo
gravitational wave (GW) detectors during their first and second observing runs.
We present results from two searches targeting emission coincident with the sky
localization of each gravitational wave event within a 1000 second time window
centered around the reported merger time. One search uses a model-independent
unbinned maximum likelihood analysis, which uses neutrino data from IceCube to
search for point-like neutrino sources consistent with the sky localization of
GW events. The other uses the Low-Latency Algorithm for Multi-messenger
Astrophysics, which incorporates astrophysical priors through a Bayesian
framework and includes LIGO-Virgo detector characteristics to determine the
association between the GW source and the neutrinos. No significant neutrino
coincidence is seen by either search during the first two observing runs of the
LIGO-Virgo detectors. We set upper limits on the time-integrated neutrino
emission within the 1000 second window for each of the 11 GW events. These
limits range from 0.02-0.7 . We also set limits on the
total isotropic equivalent energy, , emitted in high-energy
neutrinos by each GW event. These limits range from 1.7 10 -
1.8 10 erg. We conclude with an outlook for LIGO-Virgo
observing run O3, during which both analyses are running in real time
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