CSU radiation budget pilot study for TOGA COARE

July 1993.Funding agencies: National Oceanic and Atmospheric Administration, Office of Naval Research

Interplay between ESR1/PIK3CA codon variants, oncogenic pathway alterations and clinical phenotype in patients with metastatic breast cancer (MBC): Comprehensive circulating tumor DNA (ctDNA) analysis

BACKGROUND: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice. METHODS: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored. RESULTS: The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases. CONCLUSIONS: The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making

Hyperspectral Imager for the Coastal Ocean (HICO): Overview, Operational Updates, and Coastal Ocean Applications

The Hyperspectral Imager for the Coastal Ocean (HICO) was built to measure inwater properties of complex coastal regions. HICO enables synoptic coverage; 100meter spatial resolution for sampling the variability and spatial irregularity of coastal waters; and high spectral resolution to untangle the signals from chlorophyll, colored dissolved organic matter, suspended sediments and varying bottom types. HICO was built by the Naval Research Laboratory, installed on the International Space Station (ISS) in September 2009, and operated for ONR for the first three years. In 2013, NASA assumed sponsorship of operations in order to leverage HICO's ability to address their Earth monitoring mission. This has opened up access of HICO data to the broad research community. Over 8000 images are now available on NASA's Ocean Color Website (http://oceancolor.gsfc.nasa.gov/cgi/browse.pl?sen=hi). Oregon State University's HICO website (http://hico.coas.oregonstate.edu) remains the portal for researchers to request new collections and access their requested data. We will present updates on HICO's calibration and improvements in geolocation and show examples of the use of HICO data to address issues in the coastal ocean and Great Lakes

Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer

BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology. METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies. FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P \u3c 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q \u3c 0.05). INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment. FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422

The Social Psychology of Religion and Wellbeing: Is a Belief in a God, Good for one’s Wellbeing? An Empirical Inquiry

Objectives: The correlations between religion, age, education, ethnicity, social class, and subjective psychological wellbeing (SWB) of Jamaicans were examined and the predictability of those selected predisposing conditions on SWB were determined.Method: Analysis of the data was by bivariate and multivariate analyses, taken from a nationally representative survey of 1,338 Jamaican adults ≥18 years. The survey was conducted between July and August 2006 by the Centre of Leadership and Governance (CLG), Department of Government, the University of the West Indies, Mona-Jamaica.Findings: The findings indicated that religiosity was positively correlated with SWB as well as ethnicity, education and social class, and that gender was negatively related to SWB. It can be generalized, using multiple regressions, that religiosity, race, gender, education and social class can explain 7.7% of the variance in SWB of Jamaicans. Religiosity was found to be a weak predictor of subjective wellbeing (SWB), (1%), with race contributing 0.4% and gender at 0.3% been among the least suppliers to the model. However, self-reported social class made the most significant contribution to SWB - (3.9%) - along with years of schooling which contributed 2.2%.Conclusion: The study showed that religion provides for a different psychological state for its practitioners as well as influences the general state of wellbeing

High-throughput allele-specific expression across 250 environmental conditions

Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response to drug treatment and pathogen exposure. However, eQTL mapping approaches are infeasible for large-scale analysis of multiple cellular environments. Recently, allele-specific expression (ASE) analysis emerged as a powerful tool to identify GxE interactions in gene expression patterns by exploiting naturally occurring environmental exposures. Here we characterized genetic effects on the transcriptional response to 50 treatments in five cell types. We discovered 1455 genes with ASE (FDR \u3c 10%) and 215 genes with GxE interactions. We demonstrated a major role for GxE interactions in complex traits. Genes with a transcriptional response to environmental perturbations showed sevenfold higher odds of being found in GWAS. Additionally, 105 genes that indicated GxE interactions (49%) were identified by GWAS as associated with complex traits. Examples include GIPR–caffeine interaction and obesity and include LAMP3–selenium interaction and Parkinson disease. Our results demonstrate that comprehensive catalogs of GxE interactions are indispensable to thoroughly annotate genes and bridge epidemiological and genome-wide association studies

Separability of Black Holes in String Theory

We analyze the origin of separability for rotating black holes in string theory, considering both massless and massive geodesic equations as well as the corresponding wave equations. We construct a conformal Killing-Stackel tensor for a general class of black holes with four independent charges, then identify two-charge configurations where enhancement to an exact Killing-Stackel tensor is possible. We show that further enhancement to a conserved Killing-Yano tensor is possible only for the special case of Kerr-Newman black holes. We construct natural null congruences for all these black holes and use the results to show that only the Kerr-Newman black holes are algebraically special in the sense of Petrov. Modifying the asymptotic behavior by the subtraction procedure that induces an exact SL(2)^2 also preserves only the conformal Killing-Stackel tensor. Similarly, we find that a rotating Kaluza-Klein black hole possesses a conformal Killing-Stackel tensor but has no further enhancements.Comment: 27 page

Comparison of in situ measurements of cirrus cloud ice water content

Aircraft-based in situ measurements of cirrus cloud ice water content (IWC) are important for cloud microphysical/radiative modeling and satellite validation studies, yet the measurements have proven challenging due, in part, to the large dynamic range of IWC values present in cirrus clouds. To date, three instruments designed for the measurement of IWC have been flown aboard the NASA WB-57F research aircraft: the University of Colorado closed-path laser hygrometer, the Droplet Measurement Technologies Cloud Spectrometer and Impactor, and the Harvard University Lyman-a total water photofragment-fluorescence hygrometer. This paper compares IWC measurements from these three instruments taken during the Midlatitude Cirrus Experiment (MidCiX) in 2004. At larger values of IWC (IWC > 10 mg m¯³), the three instruments agree, on average, to within 20%, which is of the order of their estimated instrumental uncertainties. At smaller IWC values (<10 mg m¯³), the agreement is worse, in part due to increasing instrument uncertainties. These results have implications for measurements in thin and subvisual cirrus. Particle sampling and evaporation, instrument background levels, and hysteresis are not found to be significant contributors to discrepancies among the measurements. For remote sensing validation studies where IWC data are vertically integrated to obtain ice water path, the agreement between the instruments is better than 20% for thick cirrus (τ > 1), implying that IWC measurements in thicker clouds are of sufficient accuracy for validation studies