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NS - The Gay Simple Life.mp4

Microcystin (MC) peptides produced by cyanobacteria pose a hepatotoxic threat to human health upon ingestion from contaminated drinking water. While rapid MC identification and quantification in contaminated body fluids or tissue samples is important for patient treatment and outcomes, conventional immunoassay-based measurement strategies typically lack the specificity required for unambiguous determination of specific MC variants, whose toxicity can significantly vary depending on their structures. Furthermore, the unambiguous identification and accurate quantitation of MC variants using tandem mass spectrometry (MS/MS)-based methods can be limited due to a current lack of appropriate stable isotope-labeled internal standards. To address these limitations, we have systematically examined here the sequence and charge state dependence to the formation and absolute abundance of both "global" and "variant-specific" product ions from representative MC-LR, MC-YR, MC-RR, and MC-LA peptides, using higher-energy collisional dissociation (HCD)-MS/MS, ion-trap collision-induced dissociation (CID)-MS/MS and CID-MS3, and 193 nm ultraviolet photodissociation (UPVD)-MS/MS. HCD-MS/MS was found to provide the greatest detection sensitivity for both global and variant-specific product ions in each of the MC variants, except for MC-YR where a variant-specific product uniquely formed via UPVD-MS/MS was observed with the greatest absolute abundance. A simple methodology for the preparation and characterization of 18O-stable isotope-labeled MC reference materials for use as internal standards was also developed. Finally, we have demonstrated the applicability of the methods developed herein for absolute quantification of MC-LR present in human urine samples, using capillary scale liquid chromatography coupled with ultra-high resolution / accurate mass spectrometry and HCD-MS/MS.

NS - The Gay Simple Life.mp4

A new time of flight mass spectrometer (TOFMS) has been developed to study the absolute dissociative electron attachment (DEA) cross section using a relative flow technique of a wide variety of molecules in gas phase, ranging from simple diatomic to complex biomolecules. Unlike the Wiley-McLaren type TOFMS, here the total ion collection condition has been achieved without compromising the mass resolution by introducing a field free drift region after the lensing arrangement. The field free interaction region is provided for low energy electron molecule collision studies. The spectrometer can be used to study a wide range of masses (H- ion to few hundreds atomic mass unit). The mass resolution capability of the spectrometer has been checked experimentally by measuring the mass spectra of fragment anions arising from DEA to methanol. Overall performance of the spectrometer has been tested by measuring the absolute DEA cross section of the ground state SO2 molecule, and the results are satisfactory.

A methodology for the accurate calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays and its application in supporting microdose absolute bioavailability studies are reported for the first time. For simplicity, this calculation methodology and the strategy to minimize the isotopic interference are demonstrated using a simple molecule entity, then applied to actual development drugs. The exact isotopic interferences calculated with this methodology were often much less than the traditionally used, overestimated isotopic interferences simply based on the molecular isotope abundance. One application of the methodology is the selection of a stable isotopically labeled internal standard (SIL-IS) for an LC-MS/MS bioanalytical assay. The second application is the selection of an SIL analogue for use in intravenous (i.v.) microdosing for the determination of absolute bioavailability. In the case of microdosing, the traditional approach of calculating isotopic interferences can result in selecting a labeling scheme that overlabels the i.v.-dosed drug or leads to incorrect conclusions on the feasibility of using an SIL drug and analysis by LC-MS/MS. The methodology presented here can guide the synthesis by accurately calculating the isotopic interferences when labeling at different positions, using different selective reaction monitoring (SRM) transitions or adding more labeling positions. This methodology has been successfully applied to the selection of the labeled i.v.-dosed drugs for use in two microdose absolute bioavailability studies, before initiating the chemical synthesis. With this methodology, significant time and cost saving can be achieved in supporting microdose absolute bioavailability studies with stable labeled drugs.

We present a novel and highly sensitive ICP-MS approach for absolute quantification of all important target biomolecule containing P, S, Se, As, Br, and/or I (e.g., proteins and phosphoproteins, metabolites, pesticides, drugs), under the same simple instrumental conditions and without requiring any specific and/or isotopically enriched standard.

Tidal gravitational forces can modify the shape of galaxies and clusters of galaxies, thus correlating their orientation with the surrounding matter density field. We study the dependence of this phenomenon, known as intrinsic alignment (IA), on the mass of the dark matter haloes that host these bright structures, analysing the Millennium and Millennium-XXL N-body simulations. We closely follow the observational approach, measuring the halo position-halo shape alignment and subsequently dividing out the dependence on halo bias. We derive a theoretical scaling of the IA amplitude with mass in a dark matter universe, and predict a power law with slope βM in the range 1/3 to 1/2, depending on mass scale. We find that the simulation data agree with each other and with the theoretical prediction remarkably well over three orders of magnitude in mass, with the joint analysis yielding an estimate of β M = 0.36^+0.01_-0.01. This result does not depend on redshift or on the details of the halo shape measurement. The analysis is repeated on observational data, obtaining a significantly higher value, β M = 0.56^+0.05_-0.05. There are also small but significant deviations from our simple model in the simulation signals at both the high- and low-mass end. We discuss possible reasons for these discrepancies, and argue that they can be attributed to physical processes not captured in the model or in the dark matter-only simulations.

The growth of a planetary core by pebble accretion stops at the so-called pebble isolation mass, when the core generates a pressure bump that traps drifting pebbles outside its orbit. The value of the pebble isolation mass is crucial in determining the final planet mass. If the isolation mass is very low, gas accretion is protracted and the planet remains at a few Earth masses with a mainly solid composition. For higher values of the pebble isolation mass, the planet might be able to accrete gas from the protoplanetary disc and grow into a gas giant. Previous works have determined a scaling of the pebble isolation mass with cube of the disc aspect ratio. Here, we expand on previous measurements and explore the dependency of the pebble isolation mass on all relevant parameters of the protoplanetary disc. We use 3D hydrodynamical simulations to measure the pebble isolation mass and derive a simple scaling law that captures the dependence on the local disc structure and the turbulent viscosity parameter α. We find that small pebbles, coupled to the gas, with Stokes number τf

Childhood obesity prevalence has been increased and known to be related to various diseases and mortality in adult and body mass index (BMI) has been widely used as a screening tool in children with obesity. It is important to understand what BMI is and its limitations. BMI is a measure of weight adjusted for height. Weight scales to height with a power of about 2, is the basis of BMI (weight/height(2)) as the scaling of body weight to height across adults provides powers rounded to 2. BMI has the advantage of a simple and noninvasive surrogate measure of body fat, but it has limitation in differentiating body fat from lean (fat free) mass and low-moderate sensitivity is problematic for clinical applications. Among overweight children higher BMI levels can be a result of increased either fat or fat-free mass. BMI could be divided into fat-free mass index and fat mass index. Monitoring of the changes in body composition is important as distinguishing changes in each component occur with rapid growth in adolescents as it is occur in concert with changes in the hormonal environment. Reference values for each body composition indexes and chart created with selected percentiles of a normal adolescent population could be helpful in growth assessment and health risk evaluation.

Background and aims Proteome-based biomarker studies are targeting proteins that could serve as diagnostic, prognosis, and prediction molecules. In the clinical routine, immunoassays are currently used for the absolute quantification of such biomarkers, with the major limitation that only one molecule can be targeted per assay. The aim of our study was to test a mass spectrometry based absolute quantification method for the verification of plasma protein sets which might serve as reliable biomarker panels for the clinical practice. Methods Six EDTA plasma samples were analyzed after tryptic digestion using a high throughput data independent acquisition nano-LC Q-TOF UDMSE proteomics approach. Synthetic Escherichia coli standard peptides were spiked in each sample for the absolute quantification. Data analysis was performed using ProgenesisQI v2.0 software (Waters Corporation). Results Our method ensured absolute quantification of 242 non redundant plasma proteins in a single run analysis. The dynamic range covered was 105. 86% were represented by classical plasma proteins. The overall median coefficient of variation was 0.36, while a set of 63 proteins was found to be highly stable. Absolute protein concentrations strongly correlated with values reviewed in the literature. Conclusions Nano-LC Q-TOF UDMSE proteomic analysis can be used for a simple and rapid determination of absolute amounts of plasma proteins. A large number of plasma proteins could be analyzed, while a wide dynamic range was covered with low coefficient of variation at protein level. The method proved to be a reliable tool for the quantification of protein panel for biomarker verification in the clinical practice. PMID:29151793 041b061a72


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