Spectral Mass Research Articles

Crystal structure and analytical profile of 1,2-diphenyl-2-pyrrolidin-1-ylethanone hydrochloride or `α-D2PV': a synthetic cathinone seized by law enforcement, along with its diluent sugar, myo-inositol.

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT-IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant complete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hydrochloride hemihydrate or 1-(2-oxo-1,2-diphenylethyl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+·Cl-·0.5H2O, (I), a synthetic cathinone called `α-D2PV', and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) interesting hydrogen bonding observed in pairwise interactions by the drug molecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π-π interactions in the case of the phenyl rings of the drug which are of two different types, namely, π-π stacking and edge-to-π. Finally, the inositol crystallizes with Z' = 2 and the resulting diastereoisomers were examined by overlay techniques.

Synthesis, crystal structure studies, characterization and study of novel heterocyclic thiadiazoles as caspase 3 inhibitors for anticancer activity

In the present study we have reported the synthesis of some novel heterocyclic derivatives comprising imidazole and 1,3,4-thiadiazole containing cyclopropyl moiety. Imidazothiadiazoles are of interest because of their diverse biological activities and clinical applications. Primarily docking studies are carried out with reference structure Pdb code:2DKO. We have reported the new series of 5,6 diaryl substituted with imidazo[2,1- b], , thiadiazoles analogs to target caspase family cysteine proteases. The reaction was monitored by Thin-layer chromatography using suitable mobile phase. The Rf values were compared and determined the melting point of synthesized compounds. Further these derivatives were characterized and confirmed by IR, 1H-NMR, 13C-NMR, and Mass spectral (MS) studies. For anticancer activity, all the selected compounds submitted to National Cancer Institute (NCI) for in vitro anticancer assay were evaluated for their anticancer activity. Primary one dose anticancer assay was performed in full NCI 60 cell panel in accordance with the protocol of the NCI, USA. The compounds and showed good activity against all cancer cell lines. The synthesized drugs were monitored with Caspase 3 inhibitor kit.(CASP3C-1KT)using colorimeteric assay.

Machine learning for identification of silylated derivatives from mass spectra

MotivationCompound structure identification is using increasingly more sophisticated computational tools, among which machine learning tools are a recent addition that quickly gains in importance. These tools, of which the method titled Compound Structure Identification:Input Output Kernel Regression (CSI:IOKR) is an excellent example, have been used to elucidate compound structure from mass spectral (MS) data with significant accuracy, confidence and speed. They have, however, largely focused on data coming from liquid chromatography coupled to tandem mass spectrometry (LC–MS).Gas chromatography coupled to mass spectrometry (GC–MS) is an alternative which offers several advantages as compared to LC–MS, including higher data reproducibility. Of special importance is the substantial compound coverage offered by GC–MS, further expanded by derivatization procedures, such as silylation, which can improve the volatility, thermal stability and chromatographic peak shape of semi-volatile analytes. Despite these advantages and the increasing size of compound databases and MS libraries, GC–MS data have not yet been used by machine learning approaches to compound structure identification.ResultsThis study presents a successful application of the CSI:IOKR machine learning method for the identification of environmental contaminants from GC–MS spectra. We use CSI:IOKR as an alternative to exhaustive search of MS libraries, independent of instrumental platform and data processing software. We use a comprehensive dataset of GC–MS spectra of trimethylsilyl derivatives and their molecular structures, derived from a large commercially available MS library, to train a model that maps between spectra and molecular structures. We test the learned model on a different dataset of GC–MS spectra of trimethylsilyl derivatives of environmental contaminants, generated in-house and made publicly available. The results show that 37% (resp. 50%) of the tested compounds are correctly ranked among the top 10 (resp. 20) candidate compounds suggested by the model. Even though spectral comparisons with reference standards or de novo structural elucidations are neccessary to validate the predictions, machine learning provides efficient candidate prioritization and reduction of the time spent for compound annotation.

In Vivo Crosslinking and Mass Spectral Analysis of the Yeast Nucleosomal Protein Interactome

Chromatin is essential for proper DNA storage and gene regulation. The repeating unit of chromatin, the nucleosome, is composed of DNA wrapped around an octameric core of histone proteins. Histones interact with DNA, but they also make contacts to chromosomal regulating proteins. Histones undergo an array of dynamic posttranslational modifications (PTMs), each having an essential role in chromosomal structuring, function, and maintenance. To understand how nucleosomes regulate chromatin processes and how the dynamic PTM landscape influences histone‐protein interactions, it is important to identify interacting partners. We use UV crosslinking unnatural amino acids that allow for site‐selective photo‐crosslinking from histones, in vivo. This allows for the study of chromatin protein‐protein interactive dynamics in the physiological environment of the nucleus. We pair crosslinking techniques with mass spectral (MS) analysis to identify histone interacting proteins from cell lysates providing an unbiased overview of the site‐specific interactome. Our assays reveal many well‐established chromatin partners; however, they also provided insight to nucleosomal contacts that have been less reported in the literature. Of interest, we identify several histone contacts to ribosomal subunits, both large and small. We are interested in the extra ribosomal function of these proteins and their roles in chromatin regulation. To verify MS hits, we crosslink in yeast strains harboring a C‐terminal fusion tag (Myc) to the gene of interest, while expressing the crosslinking histone with a separate tag (HA). Products are precipitated and analyzed via western blot by decorating with antibodies to the opposing tag. We have verified several histone‐ribosomal protein interactions, including Rpl7A, Rpl3, and Rpl10. Using this technique, we investigate PTM mutations and their effects on the ability to form crosslinked products, providing insight on sequestering and regulatory mechanisms. These initial investigations suggest that UV crosslinking paired with MS analysis is an effective tool for studying yeast nucleosomal protein contacts.

Synthesis of new 2,2-dimethyl-2H-chromen derivatives as potential anticancer agents

The synthesis of some new heterocyclic derivatives comprising imidazothaidiazole, diaryl ketone and chromen as starting compound has been reported. The new series of chromen analogues have been synthesized. The reaction has been monitored by Thin Layer Chromatography (TLC) using suitable mobile phase. The Rf values have been compared and the melting points of derivatives determined. Further, these derivatives have been characterized and confirmed by IR, 1H NMR and mass spectral (MS) studies. All the selected compounds submitted to National Cancer Institute (NCI) for in vitro anticancer assay have been evaluated for their anticancer activity.

Thermal Analysis of Ozonized Pinewood

The transformation of pinewood under the action of ozone is investigated via synchronous thermal analysis in combination with the mass spectral (MS) analysis of incondensable products of pyrolysis. TG/DTG and MS data are analyzed from the viewpoint of the conversion of wood lignin (LG), hemicelluloses (HCs), and cellulose (CL) in the composition of products of LG oxidation using different amounts of absorbed ozone. Results from TG/DTG analysis indicate the destruction of hemicelluloses during pinewood ozonation. The lower temperature of the thermal destruction of cellulose material (CM) produced from ozonized wood correlates with the lower LG content, the depolimerization of CL, and the formation of products of oxidation in biomass ozonation. Data from TG/DTG and MS analyses suggest that when wood is treated with ozone, aromatic lignin structures are not only destroyed but polymerized as well.

Antibacterial and Antifungal Activity of Three Monosaccharide Monomyristate Derivatives.

Microbial infections remains a serious challenge in food industries due to their resistance to some of the well-known antibacterial and antifungal agents. In this work, a novel monomyristoyl ester (fructosyl monomyristate) and two other derivatives (i.e., glucosyl and galactosyl monomyristates) were successfully synthesized from myristic acid and monosaccharides in two-step reactions. First, the myristic acid was converted to myristoyl chloride, and then the myristoyl chloride was reacted with fructose, glucose and galactose separately to produce the corresponding monosaccharide monomyristate derivatives. The structures of the synthesized products were confirmed by Fourier transform infrared (FTIR), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR), and mass spectral (MS) data. The monomyristates esters were obtained in reaction yields of 45.80%–79.49%. The esters were then evaluated for their antimicrobial activity using the disc diffusion test. It was found that the esters exhibited a medium antibacterial activity against gram-positive bacteria; however, they showed a weak antibacterial activity against gram-negative bacteria. Amongst the esters, galactosyl myristate yielded the highest antibacterial activity against Salmonella typhimurium, Staphylococcus aureus and Bacillus subtilis, while glucosyl monomyristate exhibited the highest antibacterial activity only against Escherichia coli. Additionally, all products showed remarkable antifungal activity against Candida albicans. These findings demonstrate that monosaccharide monomyristate derivatives are promising for use as biocompatible antimicrobial agents in the future.

Facile removal of 4-methoxybenzyl protecting group from selenocysteine.

Historically, methods to remove the 4-methoxybenzyl (Mob)-protecting group from selenocysteine (Sec) in peptides have used harsh and toxic reagents. The use of 2,2'-dithiobis-5-nitropyridine (DTNP) is an improvement over these methods; however, many wash steps are required to remove the by-product contaminant 5-nitro-2-thiopyridine. Even with many washes, excess DTNP adheres to the peptide. The final product needs excess purification to remove these contaminants. It was recently discovered by our group that hindered hydrosilanes could be used to reduce Cys(Mob). We sought to apply a similar methodology to reduce Sec(Mob), which we expected to be even more labile. Here, we present a gentle and facile method for deprotection of Sec(Mob) using triethylsilane (TES), phenol, and a variety of other scavengers often used in deprotection cocktails. The different cocktails were all incubated at 40 °C for 4 hours. The combination of TFA/TES/thioanisole (96:2:2) appeared to be the most efficient of the cocktails tested, providing complete deprotection and yielded peptide that was mainly in the diselenide form. This cocktail also showed no evidence of side reactions or significant contaminants in the high-performance liquid chromatography (HPLC) and mass spectral (MS) analyses. We envision that our new method will allow for a simple and gentle "one-pot" deprotection of Sec(Mob) following solid-phase peptide synthesis and will minimize the need for extensive purification steps.

A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry: Application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1–2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.

Structure investigation of solid ion pairs of three imidazole drugs-Rose Bengal using different spectroscopic techniques and Their Biological Activities

In the present work is concerned with preparation, separation and structure elucidation of solid ion-pairs of three antifungal drugs Fluconazole (FLZ), Voriconazole (VRZ) and Butoconazole nitrate (BTZ) with Rose Bengal (Rbeng). The solid ion-pairs were prepared and investigated using FT-IR, mass spectral (MS) and thermal analyses (TA), in addition to elemental analysis (EA). The general formulae of the prepared ion-pairs were determined. Moreover, the formulae of prepared ion-pairs were proposed and structurally identified. The biological activities of the separated solid ion-pairs towards five types of bacteria and one type fungi in comparison with their drugs were studied, and they were found to be biologically active more than their parent drugs.

Fall Creek Monitoring Station: Highly Resolved Temporal Sampling to Prioritize the Identification of Nontarget Micropollutants in a Small Stream.

The goal of this research was to comprehensively characterize the occurrence and temporal dynamics of target and nontarget micropollutants in a small stream. We established the Fall Creek Monitoring Station in March 2017 and collected daily composite samples for one year. We measured water samples by means of high-resolution mass spectrometry and developed and optimized a postacquisition data processing workflow to screen for 162 target micropollutants and group all mass spectral (MS) features into temporal profiles. We used hierarchical clustering analysis to prioritize nontarget MS features based their similarity to target micropollutant profiles and developed a high-throughput pipeline to elucidate the structures of prioritized nontarget MS features. Our analyses resulted in the identification of 31 target micropollutants and 59 nontarget micropollutants with varying levels of confidence. Temporal profiles of the 90 identified micropollutants revealed unexpected concentration-discharge relationships that depended on the source of the micropollutant and hydrological features of the watershed. Several of the nontarget micropollutants have not been previously reported including pharmaceutical metabolites, rubber vulcanization accelerators, plasticizers, and flame retardants. Our data provide novel insights on the temporal dynamics of micropollutant occurrence in small streams. Further, our approach to nontarget analysis is general and not restricted to highly resolved temporal data acquisitions or samples collected from surface water systems.

Experimental and theoretical spectroscopic studies in relation to molecular structure investigation of para chloro, para fluoro and para nitro maleanilinic acids

In the present work novel para chloro, para fluoro and para nitro maleanilic acid derivatives were prepared and investigated using FT-IR, thermal analyses (TA) measurements (TGA/DTG and DTA) in comparison with mass spectral (MS) fragmentation at 70 eV. The crystallographic structures of studied compounds were investigated by X-ray diffraction (XRD). The vibrational frequencies and the corresponding normal modes were evaluated at the optimized geometry. Vibrational modes were analyzed using GAUSSVIEW software. Experimental FT-IR and Raman spectra of the three newly prepared derivatives, namely, (E) – oxo -4- ((4- nitro phenyl) amino)-4- oxobut-2-enoic acid (p-NMA), (E) -4- ((4- chloro phenyl)amino)-4- oxobut -2- enoic acid (p-ClMA), (E) -4- ((4- fluoro phenyl) amino)- 4- oxobut -2- enoic acid (p-FMA) were compared with the theoretically calculated one. FT-IR and the observed vibrational frequencies were assigned; thermal analysis and mass spectrum measurements of the maleanilic acid derivatives were recorded and discussed. The computational calculations were carried out by DFT - B3LYP method with 6-311++G(d,p) basis sets and the corresponding results were tabulated. The alternations of structures of p-FMA, p-ClMA and p-NMA due to the subsequent substitutions were investigated. This correlation between experimental and theoretical calculations provided a good confirmation of the proposed structures of the newly prepared compounds. The derivatives were found to be highly effective against Hepatocellular carcinoma cells > Breast carcinoma cells > colon carcinoma cells. It was recognized, that cancer cells over expression promotes tumorigenic functions; can be suppressed by p-NMA > p-FMA > p-ClMA inhibitors.

Differentiation of key biomarkers in tea infusions using a target/nontarget gas chromatography/mass spectrometry workflow

Climatic conditions affect the chemical composition of edible crops, which can impact flavor, nutrition and overall consumer preferences. To understand these effects new data analysis software capable of tracking hundreds of compounds across years of samples under various environmental conditions is needed. Our recently developed mass spectral (MS) subtraction algorithms have been used with spectral deconvolution to efficiently analyze complex samples by 2-dimensional gas chromatography/mass spectrometry (GC-GC/MS). In this paper, we address the accuracy of identifying target and nontarget compounds by GC/MS. Findings indicate that Yunnan tea contains higher concentrations of floral compounds. In contrast, Fujian tea contains higher concentrations of compounds that exhibit fruity characteristics, but contains much less monoterpenes. Principal components analysis shows that seasonal changes in climate impact tea plants similarly despite location differences. For example, spring teas contained more of the sweet, floral and fruity compounds compared to summer teas, which had higher concentrations of green, woody, herbal compounds.

Metabolism of megestrol acetate in vitro and the role of oxidative metabolites

1. There is limited knowledge regarding the metabolism of megestrol acetate (MA), as it was approved by FDA in 1971, prior to the availability of modern tools for identifying specific drug-metabolizing enzymes. We determined the cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs) that metabolize MA, identified oxidative metabolites and determined pharmacologic activity at the progesterone, androgen and glucocorticoid receptors (PR, AR and GR, respectively).2. Oxidative metabolites were produced using human liver microsomes (HLMs), and isolated for mass spectral (MS) and nuclear magnetic resonance (NMR) analyses. We screened recombinant P450s using MA at 62 μM (HLM Km for metabolite 1; M1) and 28 μM (HLM Km for metabolite 2; M2). UGT isoforms were simultaneously incubated with UDPGA, nicotinamide adenine dinucleotide phosphate (NADPH), CYP3A4 and MA. Metabolites were evaluated for pharmacologic activity on the PR, AR and GR. CYP3A4 and CYP3A5 are responsible for oxidative metabolism of 62 μM MA.3. At 28 μM substrate concentration, CYP3A4 was the only contributing enzyme. Mass spectral and NMR data suggest metabolism of MA to two alcohols. After oxidation, MA is converted into two secondary glucuronides by UGT2B17 among other UGTs. MA, M1 and M2 had significant pharmacologic activity on the PR while only MA showed activity on the AR and GR.

Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu2+ play a major role in the oxidative stress mechanism of Alzheimer's disease.

Extensive research has linked the amyloid-beta (Aβ) peptide to neurological dysfunction in Alzheimer's disease (AD). Insoluble Aβ plaques in the AD patient brain contain high concentrations of advanced glycation end-products (AGEs) as well as transition metal ions. This research elucidated the roles of Aβ, sugars, and Cu2+ in the oxidative stress mechanism of AD at the molecular level. Mass spectral (MS) analysis of the reactions of Aβ with two representative sugars, ribose-5-phosphate (R5P) and methylglyoxal (MG), revealed Lys-16 and Arg-5 as the primary glycation sites. Quantitative analysis of superoxide [Formula: see text] production by a cyt c assay showed that Lys-16 generated four times as much [Formula: see text] as Arg-5. Lys-16 and Arg-5 in Aβ1-40 are both adjacent to histidine residues, which are suggested to catalyze glycation. Additionally, Lys-16 is close to the central hydrophobic core (Leu-17-Ala-21) and to His-13, both of which are known to lower the pKa of the residue, leading to increased deprotonation of the amine and an enhanced glycation reactivity compared to Arg-5. Gel electrophoresis results indicated that all three components of AD plaques-Aβ1-40, sugars, and Cu2+-are necessary for DNA damage. It is concluded that the glycation of Aβ1-40 with sugars generates significant amounts of [Formula: see text], owing to the rapid glycation of Lys-16 and Arg-5. In the presence of Cu2+, [Formula: see text] converts to hydroxyl radical (HO·), the source of oxidative stress in AD.

Fragmentation Pathway of Doxazosin Drug: Thermal Analysis, Mass Spectrometry and DFT Calculations and NBO Analysis

Doxazosin (C23H25N5O5) is α1-selective alpha blocker used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia (BPH). The doxazosin (DOX) drug was investigated using electron impact mass spectral (MS) fragmentation at 70 and 15 eV of electron energy, thermal analysis (TA) measurements and confirmed by molecular orbital calculations using density functional theory(DFT) calculations and natural bond orbital (NBO) analysis. The mass spectra and thermal analysis fragmentation pathways were proposed and compared to each other to select the most suitable scheme representing the correct fragmentation pathway of the drug in both techniques. The optimum molecular geometry and the total energy of the neutral and the positively charged DOX molecules were calculated by density functional theory method with 6-311G basis sets and natural bond orbitals (NBO) analysis. The molecular orbital calculations provides a base for fine distinction among sites of initial bond cleavage and subsequent fragmentation of drug molecule in both TA and MS techniques; consequently the choice of the correct pathway of such fragmentation knowing this structural session of bonds can be used to decide the active sites of this drug responsible for its chemical, biological and medical reactivity.

P3.02c-051 A Pre-Treatment Serum Test Based on Complement and IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel: Topic: IT

SUNRISE, a global, double-bind, Phase III trial of docetaxel (D) plus bavituximab (B) or D plus placebo (P) in previously treated non-squamous non-small cell lung cancer, demonstrated similar overall survival (OS) in both treatment arms. Mass spectrometry and correlative analysis were used to create a test able to identify a subgroup of patients benefitting from the addition of B to D. Pre-treatment serum samples were available for 197 of the first 200 subjects enrolled in the trial. Mass spectra could be generated for 193 samples using the Deep MALDI method (Duncan et al, ASMS 2013), processed and features (peaks) identified. Mass spectral (MS) features associated with various biological functions were identified using a gene set enrichment analysis approach. Analysis of scores based on these MS feature, subsets indicated that in patients with high complement activation outcome depended on IL-10 activation in D+B but not in D+P. A test using the MS features associated with these functions was created to reliably identify a patient subgroup associated with clinical benefit using modern machine learning methods. Complement activation, as assessed by a classifier trained using related MS features, was a prognostic factor in both treatment arms, with high activation associated with poorer clinical outcome (OS HR = 0.54, log-rank p = 0.013 for D+B; OS HR = 0.60, log-rank p = 0.040 for D+P). Within the subgroup with high complement activation [N=50 (D+B); N=54 (D+P)], a second classifier using features related to IL-10 activation was able to isolate a subgroup of patients showing numerical benefit from the addition of B [median OS 5.9 months (D+P), 12.5 months (D+B)]. The remaining subgroup showed no benefit from addition of B [median OS 10.4 months (D+P), 5.6 months (D+B)]. Blinded validation of the test in the remainder 397 patients randomized in SUNRISE is will be presented. Proteomic and correlative approaches identified complement activation and low IL-10 levels as important pathways for predicting improved outcomes of patient treatment with D+B, in line with preclinical work on B’s mechanism of action. The test resulting from this work will undergo blinded independent validation.

Evolution of metabolic divergence in Pseudomonas aeruginosa during long-term infection facilitates a proto-cooperative interspecies interaction.

The effect of polymicrobial interactions on pathogen physiology and how it can act either to limit pathogen colonization or to potentiate pathogen expansion and virulence are not well understood. Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens commonly found together in polymicrobial human infections. However, we have previously shown that the interactions between these two bacterial species are strain dependent. Whereas P. aeruginosa PAO1, a commonly used laboratory strain, effectively suppressed S. aureus growth, we observed a commensal-like interaction between the human host-adapted strain, DK2-P2M24-2003, and S. aureus. In this study, characterization by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) imaging mass spectrometry (IMS) and mass spectral (MS) molecular networking revealed a significant metabolic divergence between P. aeruginosa PAO1 and DK2-P2M24-2003, which comprised several virulence factors and signaling 4-hydroxy-2-alkylquinoline (HAQ) molecules. Strikingly, a further modulation of the HAQ profile was observed in DK2-P2M24-2003 during interaction with S. aureus, resulting in an area with thickened colony morphology at the P. aeruginosa–S. aureus interface. In addition, we found an HAQ-mediated protection of S. aureus by DK2-P2M24-2003 from the killing effect of tobramycin. Our findings suggest a model where the metabolic divergence manifested in human host-adapted P. aeruginosa is further modulated during interaction with S. aureus and facilitate a proto-cooperative P. aeruginosa–S. aureus relationship.

Analysis and quantitation of volatile organic compounds emitted from plastics used in museum construction by evolved gas analysis–gas chromatography–mass spectrometry

Construction materials used in museums for the display, storage, and transportation of artwork must be assessed for their tendency to emit harmful pollution that could potentially damage cultural treasures. Traditionally, a subjective metals corrosion test known as the Oddy test has been widely utilized in museums for this purpose. To augment the Oddy test, an instrumental sampling approach based on evolved gas analysis (EGA) coupled to gas chromatography (GC) with mass spectral (MS) detection has been implemented for the first time to qualitatively identify off-gassed pollutants under specific conditions. This approach is compared to other instrumental methods reported in the literature. This novel application of the EGA sampling technique yields several benefits over traditional testing, including rapidity, high sensitivity, and broad detectability of volatile organic compounds (VOCs). Furthermore, unlike other reported instrumental approaches, the EGA method was used to determine quantitatively the amount of VOCs emitted by acetate resins and polyurethane foams under specific conditions using both an external calibration method as well as surrogate response factors. EGA was successfully employed to rapidly characterize emissions from 12 types of common plastics. This analysis is advocated as a rapid pre-screening method to rule out poorly performing materials prior to investing time and energy in Oddy testing. The approach is also useful for rapid, routine testing of construction materials previously vetted by traditional testing, but which may experience detrimental formulation changes over time. As an example, a case study on batch re-orders of rigid expanded poly(vinyl chloride) board stock is presented.

Abstract 5304: A serum protein test for improved prognostic stratification of patients with myelodysplastic syndrome (MDS)

Abstract While existing scoring systems provide physicians with methods of assessing prognosis of patients with MDS and help with the choice of appropriate treatment regimens, some patients defined as lower risk still have poor outcomes and tests which can refine current stratifications are of clinical interest. Serum samples, clinical and survival data were available from 106 MDS patients with refractory anemia (RA) (n = 46), RA with excess blasts (n = 29), RA with ring sideroblasts (n = 14), and chronic myelomonocytic leukemia (n = 17). The international prognostic scoring system (IPSS) score distribution 0/0.5/1/>1 was n = 36/23/24/12. Matrix assisted laser desorption/ionization (MALDI) mass spectra were acquired from the samples using the deep MALDI method1, allowing a deep probing of the proteome. The spectra were preprocessed and spectral features defined. The integrated intensities of these features were combined with the survival data using deep learning based machine learning techniques to create classifiers able to stratify patients into groups with better and worse survival. Patients in the good prognosis group had median survival of 52 months, compared with 23 months in the poor prognosis group (hazard ratio = 0.37, p < 0.001). Within the subgroup of patients with refractory anemia (n = 46) it was possible to identify a group of patients with no death events before 30 months, while median survival in the other patients was only 25 months. Multivariate analysis stratified by MDS subtype found that the mass spectral (MS) classification was a significant independent predictor of survival even when adjusted for international prognostic scoring system (IPSS) score and cytogenetic status. MS classification was able to separate low to intermediate risk (IPSS 0-1) and good karyotype subgroups into groups with significantly better and worse survival. If validated in an independent dataset, this serum test would provide complementary information for physicians to consider in addition to existing scoring systems to aid in planning treatment for MDS patients. 1. M Duncan et al, Proceedings of the 61st ASMS Conference on Mass Spectrometry and Allied Topics. Minneapolis, MN June 8-9, 2013 MP 181. Citation Format: Joanna Roder, Judith Löffler-Ragg, Reinhard Stauder, Ulrich Germing, Wolfgang R. Sperr, Peter Valent, Heinrich Roder, Arni Steingrimsson, Heinz Zwierzina. A serum protein test for improved prognostic stratification of patients with myelodysplastic syndrome (MDS). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2015-5304