Project Overview: Cumulus Humilis Aerosol Processing Study (CHAPS): Proposed Summer 2007 ASP Field Campaign

This white paper presents the scientific motivation and preliminary logistical plans for a proposed ASP field campaign to be carried out in the summer of 2007. The primary objective of this campaign is to use the DOE Gulfstream-1 aircraft to make measurements characterizing the chemical, physical and optical properties of aerosols below, within and above large fields of fair weather cumulus and to use the NASA Langley Research Center’s High Spectral Resolution Lidar (HSRL) to make independent measurements of aerosol backscatter and extinction profiles in the vicinity of these fields. Separate from the science questions to be addressed by these observations will be information to add in the development of a parameterized cumulus scheme capable of including multiple cloud fields within a regional or global scale model. We will also be able to compare and contrast the cloud and aerosol properties within and outside the Oklahoma City plume to study aerosol processes within individual clouds. Preliminary discussions with the Cloud and Land Surface Interaction Campaign (CLASIC) science team have identified overlap between the science questions posed for the CLASIC Intensive Operation Period (IOP) and the proposed ASP campaign, suggesting collaboration would benefit both teams

Overnight Atmospheric Transport and Chemical Processing of Photochemically Aged Houston Urban and Petrochemical Industrial Plume

Overnight atmospheric transport and chemical evolution of photochemically aged Houston urban and petrochemical industrial plume were investigated in July 2005. We report here on the 26 July episode in which the aged plume was tagged 1.5 h before sunset with a pair of free-floating controlled meteorological balloons, which guided quasi-Lagrangian aircraft sampling in the plume as it was advected 300 km to the north over 8 h. The aged plume around sunset was well mixed within a 1600 m residual layer, and was characterized by enhanced levels of aerosol, O3, CO, olefins, acetaldehyde, total odd nitrogen compounds (NOy), and relatively small amounts (\u3c1 \u3eppbv) of NO x. The plume experienced appreciable shearing overnight due to the development of a low-altitude nocturnal jet between 300 and 500 m above mean sea level (MSL). However, the plume above 600 m MSL remained largely undiluted even after 8 h of transport due to lack of turbulent mixing above the jet. About 40-60% of the NOx present in the aged plume around sunset was found to be depleted over this 8 h period. A constrained plume modeling analysis of the quasi-Lagrangian aircraft observations suggested that by dawn this NO x was converted to nitric acid, organic nitrates, and peroxy acyl nitrates via reactions of NO3 radicals with enhanced levels of olefins and aldehydes in the plume. Sensitivity of NOx depletion to heterogeneous hydrolysis of N2O5 on aerosols was examined. These results have significant implications for the impacts of urban and industrial pollution on far downwind regions

Chemical Speciation of Sulfur in Marine Cloud Droplets and Particles: Analysis of Individual Particles from Marine Boundary Layer over the California Current

Detailed chemical speciation of the dry residue particles from individual cloud droplets and interstitial aerosol collected during the Marine Stratus Experiment (MASE) was performed using a combination of complementary microanalysis techniques. Techniques include computer controlled scanning electron microscopy with energy dispersed analysis of X-rays (CCSEM/EDX), time-of-flight secondary ionization mass spectrometry (TOF-SIMS), and scanning transmission X-ray microscopy with near edge X-ray absorption fine structure spectroscopy (STXM/NEXAFS). Samples were collected at the ground site located in Point Reyes National Seashore, approximately 1 km from the coast. This manuscript focuses on the analysis of individual particles sampled from air masses that originated over the open ocean and then passed through the area of the California current located along the northern California coast. Based on composition, morphology, and chemical bonding information, two externally mixed, distinct classes of sulfur containing particles were identified: chemically modified (aged) sea salt particles and secondary formed sulfate particles. The results indicate substantial heterogeneous replacement of chloride by methanesulfonate (CH3SO3-) and non-sea salt sulfate (nss-SO42-) in sea-salt particles with characteristic ratios of nss-S/Na>0.10 and CH3SO3-/nss-SO42->0.6

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

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

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

What do antenatal care providers understand and do about oral health care during pregnancy: a cross-sectional survey in New South Wales, Australia

BACKGROUND: There is mounting evidence to support the lack of awareness among pregnant women about health consequences and long term risks associated with poor oral hygiene during pregnancy. A recognised and important point of influence is their interaction with health professionals, particularly when receiving Antenatal Care. However, there is limited evidence about the perceptions of ANC providers in Australia toward the provision of perinatal oral healthcare. This study was undertaken to explore the knowledge, attitudes and practices of Antenatal Care (ANC) providers in New South Wales (NSW), Australia providing perinatal oral healthcare and to identify barriers to and predictors of their practices in this area. METHODS: A cross sectional survey was undertaken of ANC providers (general practitioners, obstetricians/gynaecologists and midwives) practising in NSW, Australia. Participants were recruited through their professional organisations via email, postal mail, and networking at conferences. The survey addressed the domains of knowledge, attitude, barriers and practices towards oral healthcare, along with demographics. Data was entered into SPSS software and analysed using descriptive and inferential statistics. RESULTS: A total of 393 surveys (17.6% response rate) were completed comprising 124 general practitioners, 74 obstetricians/gynaecologists and 195 midwives. The results showed limited knowledge among ANC providers regarding the impact of poor maternal oral health on pregnancy/infant outcomes. Most (99%) participants agreed that maternal oral health was important yet few were discussing the importance of oral health or advising women to visit a dentist (16.4–21.5%). Further, less than a third felt they had the skills to provide oral health advice during pregnancy. ANC providers who were more knowledgeable about maternal oral health, had training and information in this area and greater experience, were more likely to engage in practices addressing the oral health of pregnant women. CONCLUSION: The findings suggest that ANC providers in NSW are not focussing on oral health with pregnant women. ANC providers seem willing to discuss oral health if they have appropriate education/training and information in this area. Further research at a national level is required to confirm whether these findings are similar in all Australian states

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies