Untargeted urine metabolite profiling by mass spectrometry aided by multivariate statistical analysis to predict prostate cancer treatment outcome.

Deciphering metabolomic networks has been demonstrated to provide valuable information for diagnosing and monitoring diseases. Herein, we report a technique to monitor untargeted urine metabolites to evaluate prostate cancer aggressiveness and treatment outcome. Direct chemical profiling of urine was achieved by a combined procedure of hyphenating laser diode thermal desorption with atmospheric pressure chemical ionization mass spectrometry (LDTD-APCI-MS). We describe a conceptually new approach to monitoring preoperative urinary metabolic alterations associated with prostate cancer recurrence. By evaluating mass/charge (m/z) ratios and peak intensities of ions detected by mass spectroscopy of urine samples, we revealed that intensities at m/z 313.2740 (±0.0003) and 341.3054 (±0.0006) attributable to monoacylglycerol backbone fragments from glycerides can be statistically correlated to disease progression.

Open-Space Vehicle Positioning Algorithm Based on Detection and Tracking in Video Sequences.

In on-street parking lots, it is very important to obtain the positions and license plate numbers of the vehicles for charging and management. Existing algorithms usually detect vehicles from an input image first, then localize their license plates, and finally recognize the license plate numbers. However, they are of high time and space complexity and cannot work if the vehicles or license plates are obscured. Therefore, this paper proposes an open-space vehicle positioning algorithm based on detection and tracking in video sequences. The work is as follows: (1) To reduce the time and space complexity, parallel detection of vehicles and license plates is carried out. Then, geometric matching is performed to accomplish the correspondences between them. (2) To track vehicles and license plates, this paper improves DeepSORT by combining with integrated voting based on the historical license plate library. (3) To accurately judge the vehicle behavior of entry or exit, a cumulative state detector is designed to increase the fault-tolerance of the proposed algorithm. The experimental results reveal that the proposed algorithm makes improvements in model parameters, inference speed, and tracking accuracy, demonstrating that it can be well applied to open-space vehicle positioning.

Low-Velocity Impact Localization on a Honeycomb Sandwich Panel Using a Balanced Projective Dictionary Pair Learning Classifier.

Carbon-fiber aluminum honeycomb sandwich panels are vulnerable to low-velocity impacts, which can cause structural damage and failures that reduce the bearing performance and reliability of the structure. Therefore, a method for locating such impacts through a sensor network is very important for structural health monitoring. Unlike composite laminates, the stress wave generated by an impact is damped rapidly in a sandwich panel, meaning that the signal qualities measured by different sensors vary greatly, thereby making it difficult to locate the impact. This paper presents a method for locating impacts on carbon-fiber aluminum honeycomb sandwich panels utilizing fiber Bragg grating sensors. This method is based on a projective dictionary pair learning algorithm and uses structural sparse representation for impact localization. The measurement area is divided into several sub-areas, and a corresponding dictionary is trained separately for each sub-area. For each dictionary, the sensors are grouped into main sensors within the sub-area and auxiliary sensors outside the sub-area. A balancing weight factor is added to optimize the proportion of the two types of sensor in the recognition model, and the algorithm for determining the balancing weight factor is designed to suppress the negative effects on the positioning of the sensors with poor signal quality. The experimental results show that on a 300 mm × 300 mm × 15 mm sandwich panel, the impact positioning accuracy of this method is 96.7% and the average positioning error is 0.85 mm, which are both sufficient for structural health monitoring.

LC-MS analysis of p-aminosalicylic acid under electrospray ionization conditions manifests a profound solvent effect.

Selected-ion recording (SIR) or multiple-reaction monitoring (MRM) protocols are widely employed for the quantification of targeted analytes by liquid chromatography-mass spectrometry (LC-MS). After chromatographic separation, analytes are desolvated and converted to gaseous ions usually by electrospray-ionization. The chromatographic peaks generated in this way are then integrated for quantification. It is generally assumed that the chromatographic peak intensities are dependent only on the selected MRM-transition protocols and the instrumental parameters set on the mass spectrometer. Using p-aminosalicylic acid (PAS) as a model compound, we demonstrate that the nature of the LC mobile phase exerts a significant effect on the chromatographic peak intensities. Under identical mass spectrometric conditions, chromatographic peak intensities recorded with methanol as the mobile phase were drastically different from those acquired using acetonitrile as the eluent. In fact, the product-ion mass spectra recorded with protonated PAS under different solvent conditions were qualitatively different. The observed differences were attributed to the existence of different protomers of PAS in the gas phase in dissimilar ratios under different solvent-spray conditions. Results from ion-mobility mass spectrometry experiments confirmed this hypothesis. For example, when PAS was sprayed from an acetonitrile solution, the arrival-time profile recorded from the mass-selected m/z 154 ion for protonated PAS showed essentially one arrival-time peak for the N-protonated tautomer. In contrast, the profile recorded from a methanolic PAS solution showed a different arrival-time peak for a more mobile protomer, which was recognized as the carbonyl-protonated PAS. The coexistence of protomers in different and variable ratios in an ensemble of ions generated by electrospray ionization of a single pure compound wields strong ramifications on the identification and quantification of analytes by LC-MS. However, the inclusion of an ion-mobility separator before the mass-selected ions are fragmented and detected by mass spectrometry ameliorates the complications rendered by the coexistence of different protomers and deprotomers.

Active Magnetic-Field Stabilization with Atomic Magnetometer.

A magnetically-quiet environment is important for detecting faint magnetic-field signals or nonmagnetic spin-dependent interactions. Passive magnetic shielding using layers of large magnetic-permeability materials is widely used to reduce the magnetic-field noise. The magnetic-field noise can also be actively monitored with magnetometers and then compensated, acting as a complementary method to the passive shielding. We present here a general model to quantitatively depict and optimize the performance of active magnetic-field stabilization and experimentally verify our model using optically-pumped atomic magnetometers. We experimentally demonstrate a magnetic-field noise rejection ratio of larger than ∼800 at low frequencies and an environment with a magnetic-field noise floor of ∼40 fT/Hz1/2 in unshielded Earth's field. The proposed model provides a general guidance on analyzing and improving the performance of active magnetic-field stabilization with magnetometers. This work offers the possibility of sensitive detections of magnetic-field signals in a variety of unshielded natural environments.

Evidence of Gas-Phase Attachment of Molecular Oxygen to Deprotonated Hydroquinone During Ion-Mobility Mass Spectrometry.

Gas-phase addition of dioxygen to certain ions is a well-known phenomenon in mass spectrometry. For this reaction to occur, the presence of a distonic radical site on the precursor ion is thought to be a prerequisite. Herein, we report that oxygen adduct formation can take place also with deprotonated hydroquinone, which in fact is an even-electron species without a radical site. When the product-ion spectrum of the m/z 109 ion, generated by electrospray ionization from a solution of hydroquinone in acetonitrile, was recorded under ion-mobility conditions, a new peak was observed at m/z 141. However, an analogous peak was not visible in the spectrum acquired under nonmobility conditions (i.e., without any gas introduced to the mobility cell). Presumably, traces of oxygen present in the collision gas instigate an ion-molecule reaction to produce an adduct of m/z 141, which upon activation results in CO and H2O loss to form a product ion of m/z 95. Isotope-labeling studies confirmed that one of the hydrogen atoms from the hydroxy group and another from the aromatic ring contribute to the water loss instigated from the m/z 141 adduct. Furthermore, computational methods indicated the three-dimensional structure of the ground-state deprotonated hydroquinone to be distinctly different from those of its 1,2- and 1,3-isomers. Calculations predicted that all atoms in the two m/z 109 ions generated from catechol and resorcinol lie on one plane. In contrast, the structure of the m/z 109 ion from hydroquinone was significantly different. Computations predicted that the hydrogen atom on the intact hydroxyl group of deprotonated hydroquinone protrudes out of plane from rest of the atoms. Consequently, the exposed OH group can interact with an incoming dioxygen molecule. Computations conducted at the CAM-B3LYP/6-311++g(2d,2p) level of theory detected a minimum energy crossing point (MECP) at -4.3 kJ mol-1 below the separated O2 + deprotonated hydroquinone triplet threshold. In contrast, similar calculations conducted for catechol and resorcinol yielded MECPs of +116.9 and +69.1 kJ mol-1, respectively, above the associated triplet thresholds. These results indicated that the curve crossing required to form singlet products upon reaction with triplet O2 is favorable in the case of hydroquinone and unfavorable in the cases of catechol and resorcinol. In practical terms, the selective oxygen addition appears to be a diagnostically useful reaction to differentiate hydroquinone from its ring isomers.

Fragmentation pathways of deprotonated ortho-hydroxybenzyl alcohol.

The ortho, meta, and para isomers of hydroxybenzyl alcohol can be unequivocally distinguished by the collision-induced dissociation mass spectra of their anions. The presence of a prominent peak at m/z 121 for an elimination of a dihydrogen molecule renders the ortho-isomer spectrum markedly different from those of its meta and para congeners. Investigations carried out with deuterium-labeled isotopologues of the ortho isomer verified that the labile hydrogen atom on the hydroxyl group and one of the benzylic hydrogen atoms are specifically removed in the formation of the m/z 121 ion. The ortho-isomer spectrum also showed a prominent peak at m/z 93. Experimental data indicated that the m/z 93 product ion originates either from a two-step H2 and CO elimination mechanism or from a direct loss of a HCHO molecule from the precursor anion. The intensity ratio of the m/z 93 and 94 peaks in the spectrum recorded from the m/z 124 ion generated from a sample of o-hydroxybenzyl alcohol dissolved in D2 O supported the notion that the direct HCHO loss is the more dominant pathway for the generation of the phenolate ion under low activation conditions. In contrast, the two-step mechanism becomes the more dominant pathway under high collisional activation conditions. The spectrum also showed a weak peak at m/z 105 for a water loss. Based on computational data, the m/z 105 ion generated in this way appears to be a composite generated from a common ion-neutral complex intermediate in which a hydroxyl anion is positioned equidistantly between one of the benzylic hydrogens and a nearby hydrogen atom of the benzene ring. Upon activation, the complex dissociates to form either a phenide or a quinone methide anion. The reaction forming a carbon dioxide adduct under ion-mobility conditions was used to support the proposed water-loss mechanism.

Impact of Ambient Vapors Present in an Electrospray Ionization Source on Gas-Phase Ion Structures.

According to current consensus, structures of protomeric (or deprotomeric) tautomers of gaseous ions generated by electrospray ionization depend primarily on the nature of the spray solvent. To probe the effect of the spray solvent on protonation, 4-aminobenzoic acid (PABA) has often been selected as the model compound. It is widely accepted that the protonation in the gas phase takes place primarily on the carbonyl oxygen atom when the sample is sprayed in methanol and on the nitrogen atom when acetonitrile is used as the spray solvent. Although this observation is valid, our current results indicate that the determination of the predominant protomer in the gas phase by the spray solvent is an indirect effect moderated by the solvent vapor molecules present in the ambient ion source. To investigate real-time changes in protomer distributions due to solvents, we used ion-mobility mass spectrometry (IM-MS). Initially, when a PABA solution in methanol was electrosprayed, the ion-mobility arrival-time profile recorded showed essentially one peak for the O-protomer. However, when acetonitrile or acetone vapors were introduced to the ambient-pressure ion source via the flowing desolvation gas, the intensity of the O-protomer peak diminished rapidly, and the N-protomer signal became dominant. The moment the acetonitrile (or acetone) vapors were removed from the ion source, the protomer-distribution signals began gradually reverting back to their original intensities. Furthermore, when PABA samples in methanol and acetonitrile were electrosprayed separately via a dual-sprayer setup, which allowed for the selective blocking of the gaseous ion-generation cascade of charged droplets from either sprayer, the predominant signal corresponded only to the N-protomer, irrespective of the position of the mechanical barrier. Because the mechanical barrier prevents only the gaseous ion formation, but not the physical access of solvent vapors to the ion source, it is evident that the solvent vapor that engulfs the ion source is the governing factor that decides the protomer distribution, not the nature of the spray solvent. Noticeably, acetonitrile wields a stronger effect on the manifested protomer distribution than many other solvents, including methanol, water, hexanes, and toluene. Apparently, the so-called "memory" of the solution-phase structures and the phenomenon described as "kinetic trapping" are both due to indirect effects caused by the solvent vapor engulfing the atmospheric-pressure ion source. Moreover, the so-called "memory" effect can either be "saved" or "erased" by exposing the initially formed gaseous ions to different solvent vapors from an alternative source.

Helium-Plasma-Ionization Mass Spectrometry of Metallocenes and Their Derivatives.

Ferrocene and its derivatives and nickelocene undergo facile ionization when exposed directly to the ionizing plasma of a helium-plasma ionization (HePI) source. Mass spectra recorded from such samples under ambient positive-ion-generating conditions show intense peaks for the respective molecular ions [M+•] and protonated species [(M + H)+]. The protonation process occurs most efficiently when traces of water are present in the heated nitrogen used as the "heating gas." In fact, the relative population of the two categories of ions generated in this way can be manipulated by regulating the heating-gas flow. Moreover, rapid and highly efficient gas-phase hydrogen-deuterium exchange (HDX) reactions can be performed in the ion source by passing the heating gas through a vial with D2O before it reaches the HePI source. Moreover, the ionized species generated in this way can be subjected to in-source CID fragmentation in the QDa-HePI source very efficiently by varying the sampling-cone voltage. By this procedure, ions generated from ferrocene and nickelocene could be stripped so far as to ultimately generate the bare-metal cation. Other typical fragment-ions produced from protonated metallocenes included the M(cp)1+ ions (M = Fe or Ni), by elimination of a cyclopentadiene molecule, or the molecular cation, by loss of a H• radical. Moreover, H/D exchanges and subsequent tandem mass spectrometric analysis indicated that the central metal core participates in the initial protonation process of ferrocene under HePI conditions. However, in compounds such as ferrocene carboxaldehyde and ferrocene boronic acid, the protonation takes place at the peripheral functional group.

Therapeutic prognosis of prostate cancer using surface-enhanced Raman scattering of patient urine and multivariate statistical analysis.

Surface-enhanced Raman scattering (SERS) is highly sensitive and label-free analytical technique based on Raman spectroscopy aided by field-multiplying plasmonic nanostructures. We report the use of SERS measurements of patient urine in conjunction with biostatistical algorithms to assess the treatment response of prostate cancer (PCa) in 12 recurrent (Re) and 63 nonrecurrent (NRe) patient cohorts. Multiple Raman spectra are collected from each urine sample using monodisperse silver nanoparticles (AgNPs) for Raman signal enhancement. Genetic algorithms-partial least squares-linear discriminant analysis (GA-PLS-LDA) was employed to analyze the Raman spectra. Comprehensive GA-PLS-LDA analyses of these Raman spectral features (p = 3.50 × 10-16 ) yield an accuracy of 86.6%, sensitivity of 86.0%, and specificity 87.1% in differentiating the Re and NRe cohorts. Our study suggests that SERS combined with multivariate GA-PLS-LDA algorithm can potentially be used to detect and monitor the risk of PCa relapse and to aid with decision-making for optimal intermediate secondary therapy to recurred patients.

Formation of Protonated ortho-Quinonimide from ortho-Iodoaniline in the Gas Phase by a Molecular-Oxygen-Mediated, ortho-Isomer-Specific Fragmentation Mechanism.

Upon collisional activation under mass spectrometric conditions, protonated 2-, 3-, and 4-iodoanilines lose an iodine radical to generate primarily dehydroanilinium radical cations (m/z 93), which are the distonic counterparts of the conventional molecular ion of aniline. When briefly accumulated in the Trap region of a Triwave cell in a SYNAPT G2 instrument, before being released for ion-mobility separation, these dehydroanilinium cations react readily with traces of oxygen present in the mobility gas to form peroxyl radical cations. Although all three isomeric dehydroanilinium ions showed avid affinity for O2, their reactivities were distinctly different. For example, the product-ion spectra recorded from mass-selected m/z 93 ion from 3- and 4-iodoanilines showed a peak at m/z 125 for the respective peroxylbenzenaminium ion. In contrast, an analogous peak at m/z 125 was absent in the spectrum of the 2-dehydroanilinium ion generated from 2-iodoaniline. Evidently, the 2-peroxylbenzenaminium ion generated from the 2-dehydroanilinium ion immediately loses a •OH to form protonated ortho-quinonimide (m/z 108).

Recording brain activities in unshielded Earth's field with optically pumped atomic magnetometers.

Understanding the relationship between brain activity and specific mental function is important for medical diagnosis of brain symptoms, such as epilepsy. Magnetoencephalography (MEG), which uses an array of high-sensitivity magnetometers to record magnetic field signals generated from neural currents occurring naturally in the brain, is a noninvasive method for locating the brain activities. The MEG is normally performed in a magnetically shielded room. Here, we introduce an unshielded MEG system based on optically pumped atomic magnetometers. We build an atomic magnetic gradiometer, together with feedback methods, to reduce the environment magnetic field noise. We successfully observe the alpha rhythm signals related to closed eyes and clear auditory evoked field signals in unshielded Earth's field. Combined with improvements in the miniaturization of the atomic magnetometer, our method is promising to realize a practical wearable and movable unshielded MEG system and bring new insights into medical diagnosis of brain symptoms.

Fortuitous Ion-Molecule Reaction Enables Enumeration of Metal-Hydrogen Bonds Present in Gaseous Ions.

Upon mass selection and ion activation under mass spectrometric conditions, gaseous formate adducts of many metal formates undergo decarboxylation and form product ions that bear metal-hydrogen bonds. Fortuitously, we noted that negative-ion spectra of several such formate adducts showed many peaks that could not be rationalized by the conventional fragmentation pathways attributed to the precursor ion. Subsequent experimentation proved that these enigmatic peaks are due to an ion-molecule reaction that takes place between traces of adventitious water vapor in the collision gas and the in situ formed product anions bearing metal-hydrogen bonds, generated by the fragmentation of the formate adducts. Results show that metal-hydrogen bonds of the group 2 elements are particularly susceptible to this reaction. For example, in the product-ion spectrum of [Sr(η2-O2CH)3]-, the peak at m/z 91 for SrH3 - was accompanied by three peaks at higher m/z ratios. These peaks, at m/z 107, 123, and 139, represented SrH2(OH)1 -, SrH1(OH)2 -, and Sr(OH)3 -, respectively. These satellite peaks, which were separated by 16 m/z units, were attributed to adducts formed due to the high affinity of gas-phase anions bearing metal-hydrogen bonds to water. Although undesired, these peaks are diagnostically useful to determine the number of metal-hydrogen bonds present in a precursor ion. Even though the peaks were less pronounced, analogous reactions were noted from the adducts of the group 1 elements as well. Moreover, Gibbs free energy values computed for the interaction of [H-Mg(η2-O2CH)2]- with water to form [HO-Mg(η2-OCOH)2]- and H2 indicated that this is an exergonic reaction.

Brimstone chemistry under laser light assists mass spectrometric detection and imaging the distribution of arsenic in minerals.

Singly charged As2n+1 ion clusters (n = 2-11) were generated from elemental arsenic by negative-ion laser-ablation mass spectrometry. The overall abundance of the gaseous As ions generated upon laser irradiation was enhanced nearly a hundred times when As-bearing samples were admixed with sulfur. However, sulfur does not act purely as an inert matrix: irradiating arsenic-sulfur mixtures revealed a novel pathway to generate and detect a series of [AsSn]- clusters (n = 2-6). Intriguingly, the spectra recorded from As2O3, NaAsO2, Na3AsO4, cacodylic acid and 3-amino-4-hydroxyphenylarsonic acid together with sulfur as the matrix were remarkably similar to that acquired from an elemental arsenic and sulfur mixture. This result indicated that arsenic sulfide cluster-ions are generated directly from arsenic compounds by a hitherto unknown pathway. The mechanism of elemental sulfur extracting chemically bound arsenic from compounds and forming [AsSn]- clusters is enigmatic; however, this discovery has a practical value as a general detection method for arsenic compounds. For example, the method was employed for the detection of As in its minerals, and for the imaging of arsenic distribution in minerals such as domeykite. LDI-MS data recorded from a latent image imprinted on a piece of paper from a flat mineral surface, and wetting the paper with a solution of sulfur, enabled the localization of arsenic in the mineral. The distribution of As was visualized as false-color images by extracting from acquired data the relative intensities of m/z 139 (AsS2-) and m/z 171 (AsS3-) ions.

Periodic Trends Manifested through Gas-Phase Generation of Anions Such as [AlH4]-, [GaH4]-, [InH4]-, [SrH3]-, [BaH3]-, [Ba(0)(η2-O2CH)1]-, [Pb(0)H]-, [Bi(I)H2]-, and Bi- from Formates.

Metal-hydride anions of main group elements, such as BaH3 - and InH4 -, were generated by dissociating formate adducts of the respective metal formates. Upon activation, these adducts fragment by formate-ion ejection or by decarboxylation. For adducts of alkali-metal formates, the formate-ion ejection is the preferred pathway, whereas for those of alkaline-earth and group 13-15 metals, the expulsion of CO2 is the more favorable pathway. Decarboxylation is deemed to yield a metal-hydrogen bond presumably by a hydride transfer to the metal atom. For example, the decarboxylation of Al(η-OCOH)4 - and Ga(η-OCOH)4 - generated AlH4 - and GaH4 -, respectively. The initial fragment-ion with a H-M bond formed in this way from adducts of the heavier metals of group 13 (Ga, In, and Tl) undergo a unimolecular reductive elimination, ascribable to the "inert-pair" effect, to lower the metal-ion oxidation state from +3 to +1. As group 13 is descended, the tendency for this reductive elimination process increases. PbH3 -, generated from the formate adduct of lead formate, reductively eliminated H2 to form PbH-, in which Pb is in oxidation state zero. In the energy-minimized structure [H-Pb(η2-H2)]-, proposed as an intermediate for the process, a H2 molecule is coordinated with PbH- as a dihapto ligand. The formate adducts of strontium and barium produce monoleptic ions such as [M(0)(η2-O2CH)1]-, in which the formate ion is chelated to a neutral metal atom. The bismuth formate adduct undergoes a double reductive elimination process whereby the oxidation state of Bi is reduced from +3 to +1 and then to -1. Upon activation, the initially formed [H-Bi-H]- ion transforms to an anionic η2-H2 complex, which eliminates dihydrogen to form the bismuthide anion (Bi-).