Multiplatform Approach Research Articles

A Multiplatform Metabolomics Approach to Characterize Plasma Levels of Phenylalanine and Tyrosine in Phenylketonuria.

Different pathophysiological mechanisms have been described in phenylketonuria (PKU) but the indirect metabolic consequences of metabolic disorders caused by elevated Phe or low Tyr concentrations remain partially unknown. We used a multiplatform metabolomics approach to evaluate the metabolic signature associated with Phe and Tyr. We prospectively included 10 PKU adult patients and matched controls. We analysed the metabolome profile using GC-MS (urine), amino-acid analyzer (urine and plasma) and nuclear magnetic resonance spectroscopy (urine). We performed a multivariate analysis from the metabolome (after exclusion of Phe, Tyr and directly derived metabolites) to explain plasma Phe and Tyr concentrations, and the clinical status. Finally, we performed a univariate analysis of the most discriminant metabolites and we identified the associated metabolic pathways. We obtained a metabolic pattern from 118 metabolites and we built excellent multivariate models to explain Phe, Tyr concentrations and PKU diagnosis. Common metabolites of these models were identified: Gln, Arg, succinate and alpha aminobutyric acid. Univariate analysis showed an inverse correlation between Arg, alpha aminobutyric acid and Phe and a positive correlation between Arg, succinate, Gln and Tyr (p < 0.0003). Thus, we highlighted the following pathways: Arg and Pro, Ala, Asp and Glu metabolism. We obtain a specific metabolic signature related to Tyr and Phe concentrations. We confirmed the involvement of different pathophysiological mechanisms previously described in PKU such as protein synthesis, energetic metabolism and oxidative stress. The metabolomics approach is relevant to explore PKU pathogenesis.

Radiative rates for forbidden M1 and E2 transitions of astrophysical interest in doubly ionized iron-peak elements

Aims. Accurate and reliable atomic data for lowly ionized Fe-peak species (Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) are of paramount importance for analyzing the high-resolution astrophysical spectra currently available. The third spectra of several iron group elements have been observed in different galactic sources, such as Herbig-Haro objects in the Orion Nebula and stars like Eta Carinae. However, forbidden M1 and E2 transitions between low-lying metastable levels of doubly charged iron-peak ions have been investigated very little so far, and radiative rates for those lines remain sparse or nonexistent. We attempt to fill that gap and provide transition probabilities for the most important forbidden lines of all doubly ionized iron-peak elements. Methods. We carried out a systematic study of the electronic structure of doubly ionized Fe-peak species. The magnetic dipole (M1) and electric quadrupole (E2) transition probabilities were computed using the pseudo-relativistic Hartree-Fock (HFR) code of Cowan and the central Thomas-Fermi-Dirac-Amaldi potential approximation implemented in AUTOSTRUCTURE. This multiplatform approach allowed for consistency checks and intercomparison and has proven very useful in many previous works for estimating the uncertainties affecting the radiative data. Results. We present transition probabilities for the M1 and E2 forbidden lines depopulating the metastable even levels belonging to the 3dk and 3dk−14s configurations in Sc III (k = 1), Ti III (k = 2), V III (k = 3), Cr III (k = 4), Mn III (k = 5), Fe III (k = 6), Co III (k = 7), and Ni III (k = 8).

Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal

The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms – gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) – to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1–86% for GC-MS and 0.9–42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2–97% for the positive and 4–69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a multi-platform metabolomics approach followed by multivariate and univariate data analysis for a broad-scale screen of the individual metabolome, particularly for studies using repeated measures to determine dietary response phenotype.

Abstract C56: Platinum containing anti-cancer agents as targeted therapeutics

Abstract Cisplatin and its analogs are one of the most widely used family of cancer chemotherapeutics. However, despite a diverse array of analogs having been synthesized over the past decades, the underlying assumption has been that they all work similarly by damaging DNA. Utilizing a unique multi-platform genetic approach we show that this is not the case, and that small modifications to the core structure of cisplatin can produce unexpected changes in mechanism of action. Specifically, we found oxaliplatin and a subset of mono-functional cisplatin analogs closely resembled transcription and translation inhibitors. This set of platinum-based agents do not rely on traditional cisplatin repair and tolerance pathways such as nucleotide excision repair, homologous recombination and inter-strand cross-link repair. Instead, we've demonstrated oxaliplatin treatment kills cells by eliciting a ribosome biogenesis stress response. Additionally, across a panel of human cell lines, we've shown that higher expression of ribosomal proteins correlates with resistance to these transcription/translation inhibitor-like platinum agents. From this analysis, and by analyzing and comparing human patient tumor expression data, we've concluded that oxaliplatin treatment is best applied in tumors that have developed a heightened dependence on translation. Thus, while commonly regarded as “blunt weapons”, our current arsenal of genotoxic anti-cancer agents utilizes surprisingly diverse mechanisms that suggest new paradigms for their application in patients. Citation Format: Peter M. Bruno, Ga Young Park, Junko Murai, Yunpeng Liu, Justin Pritchard, Yves Pommier, Stephen J. Lippard, Michael T. Hemann. Platinum containing anti-cancer agents as targeted therapeutics. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C56.

Developing clinically relevant biomarkers in inflammatory arthritis: A multiplatform approach for serum candidate protein discovery.

To identify candidate biomarkers that have the potential to distinguish between patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) and explore the value of combining different protein discovery platforms for the development of a multiplexed protein biomarker panel. Serum samples from 32 patients (PsA; n = 16 and RA; n = 16) defined as active, early onset, and treatment naïve were analyzed using unbiased label-free LC-MS/MS, a microsphere bead-based immunoassay (Luminex xMAP) and an aptamer-based assay (SOMAscan). LC-MS/MS was used to quantify 324 proteins, while the Luminex xMAP targeted 48 proteins and SOMAscan supported the measurement of 1129 proteins. The combined data from these techniques gave reproducible quantification of 1501 proteins in total. Of these, 42 (LC-MS/MS), 3 (Luminex xMAP), and 127 (SOMAscan) proteins were found to be differentially expressed between PsA and RA (p < 0.05). Using three different and potentially complementary proteomic platforms we identified a total of 172 proteins that are differentially expressed in patients with PsA compared to RA. These proteins collectively represent candidates for inclusion in a protein signature that could be developed as a diagnostic test to discriminate patients with PsA from RA and therefore be of clinical utility.

PTPS-01MOLECULAR PROFILING ANALYSIS OF SELECT PEDIATRIC NEUROEPITHELIAL TUMORS OF THE CENTRAL NERVOUS SYSTEM

BACKGROUND: Pediatric neuroepithelial tumors of the central nervous system (CNS) comprise a vast group of cancers where optimal treatments may be limited or non-existent given the rarity of these tumors in the pediatric population. As molecular oncology continues identifying novel treatments in adult cancers, a need exists to do the same in the pediatric population. The goal of this study is to retrospectively analyze pediatric tumors profiled at our facility to identify novel chemotherapeutic or targeted options in these diseases. METHODS: A retrospective evaluation of 44 neuroepithelial CNS tumors (e.g. astrocytic tumors, ependymal tumors, tumors with neuroblastic/glioblastic elements) tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) was performed. Testing consisted of gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (CISH/FISH). RESULTS: Patients were between the ages of 1 and 14 (mean = 7.4 years), with medulloblastoma (n = 10), glioblastoma multiforme (n = 7), and ependymoma (n = 6) being the most common histologies. In a comparison of three major subtypes, astrocytic tumors had the most gene aberrations (i.e. gene amplification or mutation) with abnormalities detected in APC, BRCA2, BRAF, EGFR, ERBB4, KDR, MGMT, and TP53. By contrast, few gene aberrations were found in ependymal tumors and neuroblastic/glioblastic tumors. Interestingly, an ALK abnormality was detected in one ependymoma. Protein evaluation by IHC yielded the most potential targets in all groups. CONCLUSION: Multiplatform tumor profiling identified several targets in molecular profiles of neuroepithelial tumors of the CNS. Astrocytic tumors, comprising anaplastic astrocytoma and glioblastoma multiforme, have the greatest number of potential targets. Ependymoma could potentially be targeted with ALK-targeted therapy capable of crossing the blood-brain barrier. Given the lack of mutations detected, a multiplatform approach may be advisable to identify the best targets in this patient population. Further studies are needed for this underserved patient population.

Evaluation of onion as a functional ingredient in the prevention of metabolic impairments associated to diet-induced hypercholesterolaemia using a multiplatform approach based on LC-MS, CE-MS and GC-MS

The preventive and modulating effects of onion in metabolites affected by a high-cholesterol diet and related to molecular pathway dysfunction were examined. Plasma obtained from 24 male Wistar rats after seven weeks of experimental feeding was analysed through a non-targeted multiplatform metabolomics approach based on LC-MS, CE-MS and GC-MS methods. A cross-comparison of the three metabolic profiles [I) control (C) group, II) high-cholesterol (HC) group and III) high-cholesterol enriched with onion (HCO) group] pointed out two sulphur metabolites, S-methyl-L-cysteine and S-methylcysteine sulphoxide, as markers of onion intake and evidenced the possibilities to regulate key metabolites. Thus, the methylation cycle, arginine and tryptophan pathways, the modulation of 3-methylhistidine, as well as the routes involved in the glycerophospholipids transformation have been highlighted. This study suggests that onion's biologically active compounds take a prominent role in ameliorating hypercholesterolaemia and related complications through the regulation of altered metabolic pathways.

A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women.

Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV include 2-hydroxyisovalerate and γ-hydroxybutyrate (GHB), but not succinate, which is produced by both Lactobacillus crispatus and BV-associated anaerobes in vitro. Biomarkers associated with high diversity and clinical BV are independent of pregnancy status, and were validated in a blinded replication cohort from Tanzania (n = 45), where we predicted clinical BV with 91% accuracy. Correlations between the metabolome and microbiota identified Gardnerella vaginalis as a putative producer of GHB, and we demonstrate production by this species in vitro. This work illustrates how changes in community structure alter the chemical composition of the vagina, and identifies highly specific biomarkers for a common condition.

Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants.

BackgroundRecent progress toward the elucidation of benzylisoquinoline alkaloid (BIA) metabolism has focused on a small number of model plant species. Current understanding of BIA metabolism in plants such as opium poppy, which accumulates important pharmacological agents such as codeine and morphine, has relied on a combination of genomics and metabolomics to facilitate gene discovery. Metabolomics studies provide important insight into the primary biochemical networks underpinning specialized metabolism, and serve as a key resource for metabolic engineering, gene discovery, and elucidation of governing regulatory mechanisms. Beyond model plants, few broad-scope metabolomics reports are available for the vast number of plant species known to produce an estimated 2500 structurally diverse BIAs, many of which exhibit promising medicinal properties.ResultsWe applied a multi-platform approach incorporating four different analytical methods to examine 20 non-model, BIA-accumulating plant species. Plants representing four families in the Ranunculales were chosen based on reported BIA content, taxonomic distribution and importance in modern/traditional medicine. One-dimensional 1H NMR-based profiling quantified 91 metabolites and revealed significant species- and tissue-specific variation in sugar, amino acid and organic acid content. Mono- and disaccharide sugars were generally lower in roots and rhizomes compared with stems, and a variety of metabolites distinguished callus tissue from intact plant organs. Direct flow infusion tandem mass spectrometry provided a broad survey of 110 lipid derivatives including phosphatidylcholines and acylcarnitines, and high-performance liquid chromatography coupled with UV detection quantified 15 phenolic compounds including flavonoids, benzoic acid derivatives and hydroxycinnamic acids. Ultra-performance liquid chromatography coupled with high-resolution Fourier transform mass spectrometry generated extensive mass lists for all species, which were mined for metabolites putatively corresponding to BIAs. Different alkaloids profiles, including both ubiquitous and potentially rare compounds, were observed.ConclusionsExtensive metabolite profiling combining multiple analytical platforms enabled a more complete picture of overall metabolism occurring in selected plant species. This study represents the first time a metabolomics approach has been applied to most of these species, despite their importance in modern and traditional medicine. Coupled with genomics data, these metabolomics resources serve as a key resource for the investigation of BIA biosynthesis in non-model plant species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-015-0594-2) contains supplementary material, which is available to authorized users.

P02.02 Another digi-gap! integrating multifaceted triaging approaches to assist and speed technological transition to electronic medical documentation and booking systems

<h3>&nbsp;Introduction</h3> Recognising and harnessing cultural and technological shifts in both client and healthcare provider arenas are crucial to optimising clinic wide responses to STI education and care. As methods of client-to-service engagement evolve, healthcare providers and their documentation systems must change as well. This is crucial to optimising clinical care and interaction for potential sexual health clients, especially when incorporating mandatory area health service and ministry directives into daily practice. Northern Sydney Sexual Health Service (NSSHS) triage has long allowed for telephone and walk-in enquiries. NSSHS has modified the existing service website to allow for online booking enquiries. This allows a potential patient to perform basic self-triage while engaging with sexual health services in a safe, non-confronting manner. At the same time, this reduces telephone wait times for clients and improves engagement. <h3>Results</h3> 75% of all website enquiries are appropriate for Clinic 16 services. A significant increase in appointments made via our website enquiry system for priority populations has occurred since initiation in November 2014, including with men who have sex with men (MSM) and youth. By improving our priority population engagement, there is a marked improvement in Occasions of Services and a projected improvement in Activity Based Funding (ABF) capture via the new electronic medical record system, Community Health and Outpatient Care system (CHOC). <h3>Conclusion</h3> By integrating a multi-platform approach to patient engagement, NSSHS is growing to fit client needs while incorporating Local Health District and Ministry of Health mandated electronic medical record changes. This improves ABF capture, patient documentation and above all, improves engagement of priority populations with sexual health services. <h3>Disclosure statement</h3> Northern Sydney Sexual Health Service is funded by the Northern Sydney Local Health District. No grants were received in the development of this study or project.

The human saliva metabolome

Saliva is a clear, watery biofluid produced by the salivary glands to protect and lubricate the oral cavity. While mostly composed of water (99 %), the chemical composition of saliva is known to change quite dramatically in response to a variety of different physiological states, stimuli, insults and stressors. Unfortunately, among the human biofluids typically used in medical testing (such as blood and urine), saliva is rarely used. Given that saliva is the most easily accessible and readily obtained biofluid, this is rather unfortunate. Part of the reluctance to use saliva in medical testing likely has to do with the fact that its chemical composition is not well known. Here, a comprehensive characterization of the human saliva metabolome is presented. Multiple analytical platforms including nuclear magnetic resonance spectroscopy, gas chromatography mass spectrometry, direct flow injection/liquid chromatography mass spectrometry, inductively coupled plasma mass spectrometry, and high performance liquid chromatography were employed to quantify the metabolites that can be commonly detected in human saliva. Using this multiplatform approach, we were able to quantify and/or identify 308 salivary metabolites or metabolite species in human saliva. This experimental work was complemented with computer-aided literature mining that led to the identification and annotation of another 708 salivary metabolites. The combined collection of 853 non-redundant salivary metabolites or metabolite species together with their concentrations, related literature references, and links to their known disease associations are freely available at http://www.hmdb.ca/ .

A systematic and detailed investigation of radiative rates for forbidden transitions of astrophysical interest in doubly ionized iron peak elements

AbstractWe carried out a systematic study of the electronic structure of doubly-ionized Fe-peak species, from Sc III to Ni III. The magnetic dipole (M1) and electric quadrupole (E2) transition probabilities were computed using the pseudo-relativistic Hartree-Fock (HFR) method and the central Thomas-Fermi-Dirac-Amaldi potential approximation implemented in the AUTOSTRUCTURE code. This multi-platform approach allowed for consistency checks and intercomparison and has proven very useful in many previous works for estimating the uncertainties affecting the radiative data.

A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.

There is a rising resistance against antimony drugs, the gold-standard for treatment until some years ago. That is a serious problem due to the paucity of drugs in current clinical use. In a research to reveal how these drugs affect the parasite during treatment and to unravel the underlying basis for their resistance, we have employed metabolomics to study treatment in Leishmania infantum promastigotes. This was accomplished first through the untargeted analysis of metabolic snapshots of treated and untreated parasites both resistant and responders, utilizing a multiplatform approach to give the widest as possible coverage of the metabolome, and additionally through novel monitoring of the origin of the detected alterations through a 13C traceability experiment. Our data stress a multi-target metabolic alteration with treatment, affecting in particular the cell redox system that is essential to cope with detoxification and biosynthetic processes. Additionally, relevant changes were noted in amino acid metabolism. Our results are in agreement with other authors studying other Leishmania species.

Multiplatform characterization of dynamic changes in breast milk during lactation.

The multicomponent analysis of human breast milk (BM) by metabolic profiling is a new area of study applied to determining milk composition, and is capable of associating BM composition with maternal characteristics, and subsequent infant health outcomes. A multiplatform approach combining HPLC‐MS and ultra‐performance LC‐MS, GC‐MS, CE‐MS, and 1H NMR spectroscopy was used to comprehensively characterize metabolic profiles from seventy BM samples. A total of 710 metabolites spanning multiple molecular classes were defined. The utility of the individual and combined analytical platforms was explored in relation to numbers of metabolites identified, as well as the reproducibility of the methods. The greatest number of metabolites was identified by the single phase HPLC‐MS method, while CE‐MS uniquely profiled amino acids in detail and NMR was the most reproducible, whereas GC‐MS targeted volatile compounds and short chain fatty acids. Dynamic changes in BM composition were characterized over the first 3 months of lactation. Metabolites identified as altering in abundance over lactation included fucose, di‐ and triacylglycerols, and short chain fatty acids, known to be important for infant immunological, neurological, and gastrointestinal development, as well as being an important source of energy. This extensive metabolic coverage of the dynamic BM metabolome provides a baseline for investigating the impact of maternal characteristics, as well as establishing the impact of environmental and dietary factors on the composition of BM, with a focus on the downstream health consequences this may have for infants.

Errata: Development of an integrated multiplatform approach for assessing brush management conservation efforts in semiarid rangelands

Millions of dollars have been spent on brush management, or removal of unwanted woody vegetation, as a conservation practice to control the presence of woody species. Land managers need an inexpensive means of monitoring the effects of brush management conser- vation methods for decreasing degradation in rangeland systems. In this study, free, publically available, high-resolution (1 m) imagery from the National Agricultural Imagery Program (NAIP) and moderate-resolution (30 m) Landsat-5 Thematic Mapper (TM) imagery were com- bined to produce a large-scale technique for mapping woody cover. High-resolution imagery- based estimates of woody cover were found to be reasonable (RMSE ¼ 3.8%, MAE ¼ 2.9%) surrogates for ground-based woody cover. An equation for TM-derived woody cover was developed. TM scenes of woody cover (TMWC) were produced and validated using NAIP and ground-based data. Results showed that the developed relation produced viable (RMSE ¼ 8.5%, MAE ¼ 6.4%) maps of woody cover that could be used to successfully track the occurrence of brush removal, as well as monitor the presence or lack of subsequent reemergence. This work provides land managers with an operational means of determining where to allocate resources to implement brush management, as well as a cost-effective method of monitoring the effects of their efforts. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. (DOI: 10.1117/1.JRS.9

Remake, Remodel: Women's Magazines in the Digital AgeBrooke ErinDuffy. Champaign: University of Illinois Press, 2013.

Remake, Remodel: Women's Magazines in the Digital Age Brooke Erin Duffy. Champaign: University Illinois Press, 2013.What is a magazine ? Recent changes in publishing have complicated this seemingly obvious question, and Brooke Erin Duffy details these developments in her timely study the magazine industry. Remake, Remodel: Women's Magazines in the Digital Age examines the ways in which an expanding digital marketplace has prompted a reimagining the mission, format, and strategies women's magazines. Duffy's research, based on in-depth interviews with magazine producers, trade press reports, and firsthand observation, offers a critical recalibration an industry attempting to redefine itself in the face technological evolution.the opening chapters, Duffy provides a flyover view central topics within the field magazine studies: audience research, industry studies, and the examination circuits production and consumption. Using concise, readable prose, she introduces key media theorists (Henry Jenkins, Raymond Williams) as well as a range scholars whose work has shaped the field women's magazine research (Ien Ang, Betty Frie dan, Joke Hermes, Angela McRobbie), before delving into the history the industry. Readers learn the early days magazine production and how it was that women came to hold positions as both creators and consumers these popular texts, which were understood to be and of women. Duffy describes an era in which magazines were tangible, recognizable, and purchasable.Much has changed. While the digital revolution the late twentieth and early twenty-first centuries gave rise to new resources, such as desktop publishing and digital imaging platforms, it also spawned an array virtual competitors who could work quickly and cheaply, forcing publishing houses to adapt. When the 2008 recession hit, worries mounted that a financially strapped readership would not spare what little disposable income it had for magazines when similar content could be found free online. Indeed, many titles folded. Those that persevered adopted a two-fold response, celebrating the importance and uniqueness the magazine itself while repositioning the magazine as a cross-platform brand (41).Today, Duffy argues, many titles envision their product not only, or even primarily, as a printed entity but as a brand. Publishers are scrambling to insert those brands into audiences' lives by aligning themselves with fashion companies and pop-up shops, iPhone apps, and blogs. This multi-platform approach has, Duffy writes, transformed circuits magazine production and consumption. …

A Multiplatform Approach Using MODIS Sensors to Cross-Calibrate the HJ-1A/CCD1 Sensors Over Aquatic Environments

A cross-calibration model is developed for calibrating the reflectance of HJ-1A/CCD1 sensor to MODIS/Terra sensor in the post-launch era. The vicarious cross-calibration models are initialized using the image pairs of HJ-1A/CCD1 and MODIS/Terra sensors collected from two testing sites, Nam Co Lake and Qinghai Lake, China. Our results show the cross-calibration model produced good performance in calibrating reflectance of HJ-1A/CCD1 sensor to MODIS/Terra sensor, whose mean relative error do not exceed 8.5 % for three visible channels of HJ-1A/CCD1 sensor. Moreover, the theoretical difference between the MODIS/Terra and HJ-1A/CCD1 reflectance are simulated using the 6S code. The results indicate that it would cause a pronounced difference. Therefore, it necessary to reinitialize the coefficients of the water color remote sensing models, when those models with HJ-1A/CCD1 band were applied to the vicarious cross-calibration data.

Multiplatform biomarker analysis on non-sun exposed mucosal melanoma.

9042 Background: Mucosal melanoma is a rare malignancy, notoriously resistant to conventional chemotherapy, with few treatment options. Because of their origin, they do not receive screening and, hence, are detected in advanced stages where prognosis and curative rates are poor. The purpose of this study is to identify novel, potential targets and therapeutic options for this disease, utilizing a multiplatform approach. Methods: In total, 93 mucosal melanoma specimenswere tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and/or gene amplification (CISH or FISH). Conjunctival melanoma was excluded. Results: Notable protein overexpression rates included co-expression of PD-1 and PD-L1 (71.4%, 5/7) and cKIT (42.4%, 14/33). Percent agreement between c-KIT by IHC and sequencing was 62% (16/26). Overall, sequencing revealed the highest mutation rates in TP53 (...

Drug efflux pump expression in 50,000 molecularly-profiled cancer patients.

11108 Background: The multidrug resistance (MDR) phenotype reduces the efficacy of various chemotherapies. MDR is linked to the overexpression of ATP-binding cassette (ABC) transporters in cancer cells, including P-glycoprotein (PGP/ABCB1), multidrug resistance protein (MRP1/ABCC1) and breast cancer resistance protein (BCRP/ABCG2). We assessed protein expression patterns of the drug efflux pumps across all tumor types for insight on how to exploit MDR status to circumvent treatment dilemmas. Methods: 51,939 patients molecularly profiled with a commercial multiplatform approach (Caris Life Sciences) were evaluated. Protein expression by IHC was assessed. The Caris Registry was queried for patients in this analysis with available clinical outcomes. Results: Across all tumors profiled (n = 51,939), MRP1 positivity (pos.) was highest at 81% (19935/24682), BCRP at 66% (8849/13409) and PGP the lowest at 23% (11969/51313). GI cancers exhibited the most abundant expression of all three drug pumps (80%, 90%, 53%), with highest average combined expression observed in liver cancers (81%). In contrast, brain, thymic and head and neck cancers exhibited the lowest average combined expression of all 3 drug pumps (39%, 40% and 42%, respectively). 6,002 patients were evaluable for co-expression with 29% (1728/6002) exhibiting pos. for all 3 drug pumps (ABC+) (highest frequencies in colon, pancreas, ovary, breast and lung), 42% (2494/6002) pos. for 2/3 drug pumps and 21% (1263/6002) pos. for 1/3 drug pumps. Only 9% (517/6002) exhibited negative status for all 3 drug pumps (ABC-) (highest frequencies in breast, lung, ovary, skin and endometrial). To determine the prognostic role of the drug pumps on patient survival, we assessed the differences in median survival between a cohort of ABC+ (n = 31) and ABC – (n = 27) patients with breast (n = 6, 2), ovary (n = 12, 6) and lung cancers (n = 13,19). Median survival since specimen used for profiling was collected for ABC + was 596 days compared to 855 days for ABC – patients. Conclusions: Tumors show broad and overlapped expression patterns for drug efflux pumps. Further study is needed to determine how transporter expression may impact clinical outcomes (e.g. ABC - status is more favorable than ABC + status).

Revealing important nocturnal and day‐to‐day variations in fire smoke emissions through a multiplatform inversion

AbstractWe couple airborne, ground‐based, and satellite observations; conduct regional simulations; and develop and apply an inversion technique to constrain hourly smoke emissions from the Rim Fire, the third largest observed in California, USA. Emissions constrained with multiplatform data show notable nocturnal enhancements (sometimes over a factor of 20), correlate better with daily burned area data, and are a factor of 2–4 higher than a priori estimates, highlighting the need for improved characterization of diurnal profiles and day‐to‐day variability when modeling extreme fires. Constraining only with satellite data results in smaller enhancements mainly due to missing retrievals near the emissions source, suggesting that top‐down emission estimates for these events could be underestimated and a multiplatform approach is required to resolve them. Predictions driven by emissions constrained with multiplatform data present significant variations in downwind air quality and in aerosol feedback on meteorology, emphasizing the need for improved emissions estimates during exceptional events.