A Bayesian approach to high fidelity interferometric calibration II: demonstration with simulated data

In a companion paper, we presented BayesCal, a mathematical formalism for mitigating sky-model incompleteness in interferometric calibration. In this paper, we demonstrate the use of BayesCal to calibrate the degenerate gain parameters of full-Stokes simulated observations with a HERA-like hexagonal close-packed redundant array, for three assumed levels of completeness of the a priori known component of the calibration sky model. We compare the BayesCal calibration solutions to those recovered by calibrating the degenerate gain parameters with only the a priori known component of the calibration sky model both with and without imposing physically motivated priors on the gain amplitude solutions and for two choices of baseline length range over which to calibrate. We find that BayesCal provides calibration solutions with up to four orders of magnitude lower power in spurious gain amplitude fluctuations than the calibration solutions derived for the same data set with the alternate approaches, and between $\sim10^7$ and $\sim10^{10}$ times smaller than in the mean degenerate gain amplitude on the full range of spectral scales accessible in the data. Additionally, we find that in the scenarios modelled only BayesCal has sufficiently high fidelity calibration solutions for unbiased recovery of the 21 cm power spectrum on large spectral scales ($k_\parallel \lesssim 0.15~h\mathrm{Mpc}^{-1}$). In all other cases, in the completeness regimes studied, those scales are contaminated

Graph complexity analysis identifies an ETV5 tumor-specific network in human and murine low-grade glioma

Conventional differential expression analyses have been successfully employed to identify genes whose levels change across experimental conditions. One limitation of this approach is the inability to discover central regulators that control gene expression networks. In addition, while methods for identifying central nodes in a network are widely implemented, the bioinformatics validation process and the theoretical error estimates that reflect the uncertainty in each step of the analysis are rarely considered. Using the betweenness centrality measure, we identified Etv5 as a potential tissue-level regulator in murine neurofibromatosis type 1 (Nf1) low-grade brain tumors (optic gliomas). As such, the expression of Etv5 and Etv5 target genes were increased in multiple independently-generated mouse optic glioma models relative to non-neoplastic (normal healthy) optic nerves, as well as in the cognate human tumors (pilocytic astrocytoma) relative to normal human brain. Importantly, differential Etv5 and Etv5 network expression was not directly the result of Nf1 gene dysfunction in specific cell types, but rather reflects a property of the tumor as an aggregate tissue. Moreover, this differential Etv5 expression was independently validated at the RNA and protein levels. Taken together, the combined use of network analysis, differential RNA expression findings, and experimental validation highlights the potential of the computational network approach to provide new insights into tumor biology

Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature

The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue. To explore this neoplastic ground state, we leveraged several preclinical mouse models of neurofibromatosis type 1 (NF1) optic glioma, a low-grade astrocytoma whose formation and maintenance requires productive interactions between non-neoplastic and neoplastic cells, and employed whole tumor RNA-sequencing and mathematical deconvolution strategies to characterize this low-grade glioma ecosystem as an aggregate of cellular and acellular elements. Using this approach, we demonstrate that optic gliomas generated by altering the germlin

Reproductive history differs by molecular subtypes of breast cancer among women aged ≤50 years in Scotland in 2009-16:A cross-sectional study

BACKGROUND: The aetiology of breast cancers diagnosed ≤ 50 years of age remains unclear. We aimed to compare reproductive risk factors between molecular subtypes of breast cancer, thereby suggesting possible aetiologic clues, using routinely collected cancer registry and maternity data in Scotland. METHODS: We conducted a cross-sectional study of 4108 women aged ≤ 50 years with primary breast cancer diagnosed between 2009 and 2016 linked to maternity data. Molecular subtypes of breast cancer were defined using immunohistochemistry (IHC) tumour markers, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and tumour grade. Age-adjusted polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of number of births, age at first birth and time since last birth with IHC-defined breast cancer subtypes. Luminal A-like was the reference compared to luminal B-like (HER2−), luminal B-like (HER2+), HER2-overexpressed and triple-negative breast cancer (TNBC). RESULTS: Mean (SD) for number of births, age at first birth and time since last birth was 1.4 (1.2) births, 27.2 (6.1) years and 11.0 (6.8) years, respectively. Luminal A-like was the most common subtype (40%), while HER2-overexpressed and TNBC represented 5% and 15% of cases, respectively. Larger numbers of births were recorded among women with HER2-overexpressed and TNBC compared with luminal A-like tumours (> 3 vs 0 births, OR 1.87, 95%CI 1.18–2.96; OR 1.44, 95%CI 1.07–1.94, respectively). Women with their most recent birth > 10 years compared to < 2 years were less likely to have TNBC tumours compared to luminal A-like (OR 0.63, 95%CI 0.41–0.97). We found limited evidence for differences by subtype with age at first birth. CONCLUSION: Number of births and time since last birth differed by molecular subtypes of breast cancer among women aged ≤ 50 years. Analyses using linked routine electronic medical records by molecularly defined tumour pathology data can be used to investigate the aetiology and prognosis of cancer

A Bayesian Calibration Framework for EDGES

We develop a Bayesian model that jointly constrains receiver calibration, foregrounds and cosmic 21cm signal for the EDGES global 21\,cm experiment. This model simultaneously describes calibration data taken in the lab along with sky-data taken with the EDGES low-band antenna. We apply our model to the same data (both sky and calibration) used to report evidence for the first star formation in 2018. We find that receiver calibration does not contribute a significant uncertainty to the inferred cosmic signal (<1%), though our joint model is able to more robustly estimate the cosmic signal for foreground models that are otherwise too inflexible to describe the sky data. We identify the presence of a significant systematic in the calibration data, which is largely avoided in our analysis, but must be examined more closely in future work. Our likelihood provides a foundation for future analyses in which other instrumental systematics, such as beam corrections and reflection parameters, may be added in a modular manner.Comment: 18 pages + 3 for appendices. 13 figures. Accepted to MNRA

Avoiding the Next Silent Spring: Our Chemical Past, Present, and Future

Rachel Carson's Silent Spring,1 published just over 60 years ago, outlined how the indiscriminate use of dichlorodiphenyltrichloroethane (DDT), a potent, environmentally persistent insecticide, was damaging the world's ecosystems, animals and food supply. There were many other chemicals more persistent than DDT accumulating in the environment when Carson was writing, including per- and polyfluoroalkyl substances (PFAS). Whilst man-made, PFAS were not intended to cause harm, contrary to pesticides such as DDT. Today, ambient PFAS levels are contaminating rain, soil and drinking water resources worldwide to such an extent that they have caused substantial, irreversible health and environmental damage.2 Like DDT, PFAS were long in use by the time Rachel Carson was writing Silent Spring (see Figure 1). However, their environmental presence went unnoticed by Carson and other contemporary environmental researchers. PFAS were entering the environment under the radar, except to those who were manufacturing and emitting them.

Bactobolin Resistance Is Conferred by Mutations in the L2 Ribosomal Protein

Burkholderia thailandensis produces a family of polyketide-peptide molecules called bactobolins, some of which are potent antibiotics. We found that growth of B. thailandensis at 30°C versus that at 37°C resulted in increased production of bactobolins. We purified the three most abundant bactobolins and determined their activities against a battery of bacteria and mouse fibroblasts. Two of the three compounds showed strong activities against both bacteria and fibroblasts. The third analog was much less potent in both assays. These results suggested that the target of bactobolins might be conserved across bacteria and mammalian cells. To learn about the mechanism of bactobolin activity, we isolated four spontaneous bactobolin-resistant Bacillus subtilis mutants. We used genomic sequencing technology to show that each of the four resistant variants had mutations in rplB, which codes for the 50S ribosome-associated L2 protein. Ectopic expression of a mutant rplB gene in wild-type B. subtilis conferred bactobolin resistance. Finally, the L2 mutations did not confer resistance to other antibiotics known to interfere with ribosome function. Our data indicate that bactobolins target the L2 protein or a nearby site and that this is not the target of other antibiotics. We presume that the mammalian target of bactobolins involves the eukaryotic homolog of L2 (L8e)