XCMS-MRM and METLIN-MRM: a cloud library and public resource for targeted analysis of small molecules.

We report XCMS-MRM and METLIN-MRM ( http://xcmsonline-mrm.scripps.edu/ and http://metlin.scripps.edu/ ), a cloud-based data-analysis platform and a public multiple-reaction monitoring (MRM) transition repository for small-molecule quantitative tandem mass spectrometry. This platform provides MRM transitions for more than 15,500 molecules and facilitates data sharing across different instruments and laboratories.

METLIN: A Technology Platform for Identifying Knowns and Unknowns.

METLIN originated as a database to characterize known metabolites and has since expanded into a technology platform for the identification of known and unknown metabolites and other chemical entities. Through this effort it has become a comprehensive resource containing over 1 million molecules including lipids, amino acids, carbohydrates, toxins, small peptides, and natural products, among other classes. METLIN's high-resolution tandem mass spectrometry (MS/MS) database, which plays a key role in the identification process, has data generated from both reference standards and their labeled stable isotope analogues, facilitated by METLIN-guided analysis of isotope-labeled microorganisms. The MS/MS data, coupled with the fragment similarity search function, expand the tool's capabilities into the identification of unknowns. Fragment similarity search is performed independent of the precursor mass, relying solely on the fragment ions to identify similar structures within the database. Stable isotope data also facilitate characterization by coupling the similarity search output with the isotopic m/ z shifts. Examples of both are demonstrated here with the characterization of four previously unknown metabolites. METLIN also now features in silico MS/MS data, which has been made possible through the creation of algorithms trained on METLIN's MS/MS data from both standards and their isotope analogues. With these informatic and experimental data features, METLIN is being designed to address the characterization of known and unknown molecules.

Data Streaming for Metabolomics: Accelerating Data Processing and Analysis from Days to Minutes.

The speed and throughput of analytical platforms has been a driving force in recent years in the "omics" technologies and while great strides have been accomplished in both chromatography and mass spectrometry, data analysis times have not benefited at the same pace. Even though personal computers have become more powerful, data transfer times still represent a bottleneck in data processing because of the increasingly complex data files and studies with a greater number of samples. To meet the demand of analyzing hundreds to thousands of samples within a given experiment, we have developed a data streaming platform, XCMS Stream, which capitalizes on the acquisition time to compress and stream recently acquired data files to data processing servers, mimicking just-in-time production strategies from the manufacturing industry. The utility of this XCMS Online-based technology is demonstrated here in the analysis of T cell metabolism and other large-scale metabolomic studies. A large scale example on a 1000 sample data set demonstrated a 10 000-fold time savings, reducing data analysis time from days to minutes. Further, XCMS Stream has the capability to increase the efficiency of downstream biochemical dependent data acquisition (BDDA) analysis by initiating data conversion and data processing on subsets of data acquired, expanding its application beyond data transfer to smart preliminary data decision-making prior to full acquisition.

Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses.

Active data screening is an integral part of many scientific activities, and mobile technologies have greatly facilitated this process by minimizing the reliance on large hardware instrumentation. In order to meet with the increasingly growing field of metabolomics and heavy workload of data processing, we designed the first remote metabolomic data screening platform for mobile devices. Two mobile applications (apps), XCMS Mobile and METLIN Mobile, facilitate access to XCMS and METLIN, which are the most important components in the computer-based XCMS Online platforms. These mobile apps allow for the visualization and analysis of metabolic data throughout the entire analytical process. Specifically, XCMS Mobile and METLIN Mobile provide the capabilities for remote monitoring of data processing, real time notifications for the data processing, visualization and interactive analysis of processed data (e.g., cloud plots, principle component analysis, box-plots, extracted ion chromatograms, and hierarchical cluster analysis), and database searching for metabolite identification. These apps, available on Apple iOS and Google Android operating systems, allow for the migration of metabolomic research onto mobile devices for better accessibility beyond direct instrument operation. The utility of XCMS Mobile and METLIN Mobile functionalities was developed and is demonstrated here through the metabolomic LC-MS analyses of stem cells, colon cancer, aging, and bacterial metabolism.

Characterization of priority substances in effluents from an integrated steelworks in the United Kingdom.

In the Water Framework Directive, a list of priority substances that are deemed to be persistent, toxic, and liable to bioaccumulate have been identified. Within this list, a range of polycyclic aromatic hydrocarbons (PAHs) and certain trace metals are relevant to the steel industry. This study summarizes work carried out by Tata Steel Europe (Rotherham, U.K.) to characterize the emissions of PAHs and trace metals from wastewater streams at one of its main integrated steelworks in the United Kingdom over a 3-year period (2010 to 2012). The emissions inventory revealed that PAH emissions to water were almost entirely attributable to the cokemaking process, with emissions factors ranging from 20 to 55 mg/tonne of coke. Furthermore, analysis of the PAH distribution in coke oven effluents revealed that medium- and high-molecular-weight PAHs were associated with the suspended solids (particle-bound). Regarding trace metals, both ironmaking and steelmaking processes were the most important emission sources.

Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.

INTRODUCTION: Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). OBJECTIVES: Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. METHODS: We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. RESULTS: Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.

The METLIN small molecule dataset for machine learning-based retention time prediction.

Machine learning has been extensively applied in small molecule analysis to predict a wide range of molecular properties and processes including mass spectrometry fragmentation or chromatographic retention time. However, current approaches for retention time prediction lack sufficient accuracy due to limited available experimental data. Here we introduce the METLIN small molecule retention time (SMRT) dataset, an experimentally acquired reverse-phase chromatography retention time dataset covering up to 80,038 small molecules. To demonstrate the utility of this dataset, we deployed a deep learning model for retention time prediction applied to small molecule annotation. Results showed that in 70[Formula: see text] of the cases, the correct molecular identity was ranked among the top 3 candidates based on their predicted retention time. We anticipate that this dataset will enable the community to apply machine learning or first principles strategies to generate better models for retention time prediction.

Fluorinated Gold Nanoparticles for Nanostructure Imaging Mass Spectrometry.

Nanostructure imaging mass spectrometry (NIMS) with fluorinated gold nanoparticles (f-AuNPs) is a nanoparticle assisted laser desorption/ionization approach that requires low laser energy and has demonstrated high sensitivity. Here we describe NIMS with f-AuNPs for the comprehensive analysis of metabolites in biological tissues. F-AuNPs assist in desorption/ionization by laser-induced release of the fluorocarbon chains with minimal background noise. Since the energy barrier required to release the fluorocarbons from the AuNPs is minimal, the energy of the laser is maintained in the low µJ/pulse range, thus limiting metabolite in-source fragmentation. Electron microscopy analysis of tissue samples after f-AuNP NIMS shows a distinct "raising" of the surface as compared to matrix assisted laser desorption ionization ablation, indicative of a gentle desorption mechanism aiding in the generation of intact molecular ions. Moreover, the use of perfluorohexane to distribute the f-AuNPs on the tissue creates a hydrophobic environment minimizing metabolite solubilization and spatial dislocation. The transfer of the energy from the incident laser to the analytes through the release of the fluorocarbon chains similarly enhances the desorption/ionization of metabolites of different chemical nature, resulting in heterogeneous metabolome coverage. We performed the approach in a comparative study of the colon of mice exposed to three different diets. F-AuNP NIMS allows the direct detection of carbohydrates, lipids, bile acids, sulfur metabolites, amino acids, nucleotide precursors as well as other small molecules of varied biological origins. Ultimately, the diversified molecular coverage obtained provides a broad picture of a tissue's metabolic organization.

Subfractionation, characterization and photooxidation of crude oil resins.

Resins of five crude oils were obtained using SARA fractionation. The maltenic fraction of Blend Arabian Light, was further separated into six polar fractions. These fractions which are the constituents of the resins were analysed by FTIR spectroscopy. They appeared to be more oxidized, more aliphatic and less aromatic than asphaltenes. Photooxidation of resins showed that they are easily oxidizable and much more influenced by photooxidation than asphaltenes. The principal effect of photooxidation are: (i) increase of carbonyl group amounts and particularly formation of carboxylic groups, (ii) oxidation of sulfoxide in sulfone group, (iii) oxidation of alkyl chains and of aromatic rings (quinone structures).

Influence of n-alkanes and petroleum on fatty acid composition of a hydrocarbonoclastic bacterium: Marinobacter hydrocarbonoclasticus strain 617.

This study concerns the effects of various long-chain n-alkanes, n-alkane mixtures and Arabian Light crude oil on the fatty acid (FA) composition of a sedimentary marine bacteria (Marinobacter hydrocarbonoclasticus strain 617), growing under aerobic conditions. The cultures with n-alkanes, as compared with soluble carbon sources, led to greater amounts of saturated and methyl branched FA (mainly belonging to a delta10 series). We observed the appearance or increase of saturated and unsaturated FA with the same carbon chain length (CCL) as the n-alkane carbon source (maximum for n-alkane CCL corresponding to the 'range' of the de novo synthesized fatty acids). We also observed a strong control of the oddness/evenness of the CCL of the FA by the oddness/evenness of the n-alkane. A n-alkane utilization index, (saturated + branched)/monounsaturated fatty acids (SAFA + BFA/MUFA) enabled discriminating between soluble carbon sources and hydrocarbons.

Race and gender as components of the working self-concept.

A sample of 78 U.S. students carried beepers for 1 week and reported in situ on their awareness of gender and race. The participants to whom gender and race were more important were more aware of those characteristics, and their awareness of gender and race was more variable across situations. Awareness was higher in public than in private settings; it was also higher during athletic than during academic involvement. The White participants were more aware of race when they were in the racial minority; the non-White participants were more aware of race when they were in the racial majority. All the participants were more aware of gender when they were in the gender minority.

The importance of ethnicity in the development of identity of black adolescents.

Ego-identity status was examined in 20 male and 20 female black junior and senior high school students. Ego-identity was assessed by a semistructured interview measuring questioning and commitment in the traditional areas of occupation, ideology (religion and politics), sexual-interpersonal attitudes and behavior, and the newly added area of ethnicity. The greatest questioning and commitment occurred in the area of ethnicity. Ethnicity was most predictive of over-all identity-status and was seen as most important to self-definition. The other area of central importance was occupation. While the ideological and sexual-interpersonal areas have been found in previous research to have central importance for white adolescents, they were found in this sample of black adolescents to show the lowest concordance with over-all identity and to be cited as having least importance in self-definition. The lowest amount of questioning and commitment occurred in these areas.

Studies into the formation of PBDEs and PBDD/Fs in the iron ore sintering process.

Polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) were detected in stack emissions from UK sinter plants. The sum of 36 PBDE congeners was measured at a mean concentration of 295 ng/N m(3) with a standard deviation of 96 ng/N m(3). The mean PBDD/F concentrations were 0.14 ng WHO-TEQ/m(3) (range=0.03-0.39). PBDD/F emission concentrations were approximately ten times lower than their PCDD/F homologues. To understand the possible formation mechanisms of brominated organic species in iron ore sintering, both full-scale and laboratory experiments using an experimental sintering process were carried out. A complete PBDE mass balance was undertaken for a full scale sinter plant showing that PBDEs were already present in the raw materials such as iron ores and coke breeze and that a significant proportion of the PBDE inputs were actually destroyed during the process. A number of controlled experiments were conducted using a laboratory-scale sintering apparatus (sinter pot). These were designed to investigate: (a) mass balance of PBDEs during sintering, (b) the relationship between the availability of bromide (as KBr) and PBDE emissions, and (c) the influence of the availability of both bromide and PBDEs on PBDD/F formation. As observed in the full scale plant, the PBDEs already present in the raw materials were mostly destroyed during the process (79-96%) for all sinter pot experiments. Increasing amounts of KBr in the raw sinter mix did not result in a significant increase in PBDE formation suggesting that there was no PBDE formation in sintering via de novo synthesis. No relationship was observed between PBDE inputs and PBDD/F emissions indicating that PBDEs did not act as precursors for PBDD/Fs formation. Finally, PBDD/F formation was enhanced substantially with increasing amounts of KBr suggesting that their formation mechanism was similar to that of PCDD/Fs via de novo synthesis.