Showing papers by "Agilent Technologies published in 2020"
University of Illinois at Chicago1, Case Western Reserve University2, Indian Institute of Technology Bombay3, The Chinese University of Hong Kong4, Beijing University of Posts and Telecommunications5, Peking University6, University of Oklahoma7, University of Warwick8, Shanghai Jiao Tong University9, University of North Carolina at Chapel Hill10, Zhejiang University11, Sun Yat-sen University12, University of Hong Kong13, Medical University of Vienna14, Loughborough University15, Royal Institute of Technology16, Carnegie Mellon University17, University of Illinois at Urbana–Champaign18, Vietnam National University, Ho Chi Minh City19, Sejong University20, Indian Institute of Technology Madras21, University of California, Berkeley22, Hong Kong University of Science and Technology23, Islamic Azad University24, RWTH Aachen University25, University of Science and Technology of China26, University of Lübeck27, Agilent Technologies28, Shenzhen University29, Nanjing University of Science and Technology30, Tata Consultancy Services31, Korea University32, Polytechnic University of Valencia33, Old Dominion University34, Jadavpur University35, University of Castilla–La Mancha36, Cognizant37, Xiamen University38, Tongji University39
TL;DR: Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics as well as heavy data augmentation in the MoNuSeg 2018 challenge.
Abstract: Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated. Contestants were given a training set with 30 images from seven organs with annotations of 21,623 individual nuclei. A test dataset with 14 images taken from seven organs, including two organs that did not appear in the training set was released without annotations. Entries were evaluated based on average aggregated Jaccard index (AJI) on the test set to prioritize accurate instance segmentation as opposed to mere semantic segmentation. More than half the teams that completed the challenge outperformed a previous baseline. Among the trends observed that contributed to increased accuracy were the use of color normalization as well as heavy data augmentation. Additionally, fully convolutional networks inspired by variants of U-Net, FCN, and Mask-RCNN were popularly used, typically based on ResNet or VGG base architectures. Watershed segmentation on predicted semantic segmentation maps was a popular post-processing strategy. Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics.
251 citations
TL;DR: The results showed that green synthesized (biogenic) AgNPs possess higher antimicrobial potency than chemically produced AgNPS, and confirm a more significant antimicrobial effect of the biogenic AgNps maintaining low-cytotoxicity than theAgNPs produced chemically.
Abstract: The scientific community is exploiting the use of silver nanoparticles (AgNPs) in nanomedicine and other AgNPs combination like with biomaterials to reduce microbial contamination. In the field of nanomedicine and biomaterials, AgNPs are used as an antimicrobial agent. One of the most effective approaches for the production of AgNPs is green synthesis. Lysiloma acapulcensis (L. acapulcensis) is a perennial tree used in traditional medicine in Mexico. This tree contains abundant antimicrobial compounds. In the context of antimicrobial activity, the use of L. acapulcensis extracts can reduce silver to AgNPs and enhance its antimicrobial activity. In this work, we demonstrate such antimicrobial activity effect employing green synthesized AgNPs with L. acapulcensis. The FTIR and LC–MS results showed the presence of chemical groups that could act as either (i) reducing agents stabilizing the AgNPs or (ii) antimicrobial capping agents enhancing antimicrobial properties of AgNPs. The synthesized AgNPs with L. acapulcensis were crystalline with a spherical and quasi-spherical shape with diameters from 1.2 to 62 nm with an average size diameter of 5 nm. The disk diffusion method shows the magnitude of the susceptibility over four pathogenic microorganisms of clinical interest. The antimicrobial potency obtained was as follows: E. coli ≥ S. aureus ≥ P. aeruginosa > C. albicans. The results showed that green synthesized (biogenic) AgNPs possess higher antimicrobial potency than chemically produced AgNPs. The obtained results confirm a more significant antimicrobial effect of the biogenic AgNPs maintaining low-cytotoxicity than the AgNPs produced chemically.
202 citations
TL;DR: High plasma levels of several inflammatory cytokines and chemokines, including GM‐CSF, IL‐18, CCL2, CXCL10, and osteopontin, finally confirm the importance of monocytes in COVID‐19 immunopathogenesis.
Abstract: In patients infected by SARS-CoV-2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood monocytes from patients with COVID-19 pneumonia and found that these cells show signs of altered bioenergetics and mitochondrial dysfunction, had a reduced basal and maximal respiration, reduced spare respiratory capacity and decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting reduced capability to perform aerobic glycolysis. Although COVID-19 monocytes had a reduced ability to perform oxidative burst, they were still capable of producing TNF and IFN-g,in vitro. A significantly high amount of monocytes had depolarized mitochondria and abnormal mitochondrial ultrastructure. A redistribution of monocyte subsets, with a significant expansion of intermediate/pro-inflammatory cells, and high amounts of immature monocytes were found, along with a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints like PD-1/PD-L1. High plasma levels of several inflammatory cytokines and chemokines, including GM-CSF, IL-18, CCL2, CXCL10 and osteopontin, finally confirm the importance of monocytes in COVID-19 immunopathogenesis.
119 citations
TL;DR: A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories offers a view of the current state-of-the-art for biologic glyCosylation measurement and suggests a clear need for harmonization of gly cosylation analysis methods.
81 citations
TL;DR: This work provides much-needed empirical data on the abundances, morphologies, and types of MPs that oysters are exposed to in the Mississippi Sound, although how much of these MPs are ingested and their impacts on the organisms deserves further scrutiny.
Abstract: Much of the seafood that humans consume comes from estuaries and coastal areas where microplastics (MPs) accumulate, due in part to continual input and degradation of plastic litter from rivers and runoff. As filter feeders, oysters (Crassostrea virginica) are especially vulnerable to MP pollution. In this study, we assessed MP pollution in water at oyster reefs along the Mississippi Gulf Coast when: (1) historic flooding of the Mississippi River caused the Bonnet Carre Spillway to remain open for a record period of time causing major freshwater intrusion to the area and deleterious impacts on the species and (2) the spillway was closed, and normal salinity conditions resumed. Microplastics (~25 µm–5 mm) were isolated using a single-pot method, preparing samples in the same vessel (Mason jars) used for their collection right up until the MPs were transferred onto filters for analyses. The MPs were quantified using Nile Red fluorescence detection and identified using laser direct infrared (LDIR) analysis. Concentrations ranged from ~12 to 381 particles/L and tended to decrease at sites impacted by major freshwater intrusion. With the spillway open, average MP concentrations were positively correlated with salinity (r = 0.87, p = 0.05) for sites with three or more samples examined. However, the dilution effect on MP abundances was temporary, and oyster yields suffered from the extended periods of lower salinity. There were no significant changes in the relative distribution of MPs during freshwater intrusions; most of the MPs (>50%) were in the lower size fraction (~25–90 µm) and consisted mostly of fragments (~84%), followed by fibers (~11%) and beads (~5%). The most prevalent plastic was polyester, followed by acrylates/polyurethanes, polyamide, polypropylene, polyethylene, and polyacetal. Overall, this work provides much-needed empirical data on the abundances, morphologies, and types of MPs that oysters are exposed to in the Mississippi Sound, although how much of these MPs are ingested and their impacts on the organisms deserves further scrutiny. This paper is believed to be the first major application of LDIR to the analysis of MPs in natural waters.
67 citations
TL;DR: Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddCFDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.
Abstract: Background After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient's circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection. Methods From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms. Results Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P = 0.017), acute tubular necrosis (P = 0.011) and acute pyelonephritis (P = 0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection. Conclusions Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.
59 citations
TL;DR: In this paper, a 16-well plate containing sensing electrodes was pre-coated with receptor binding domain (RBD) of SARS-CoV-2 spike protein, and subsequently tested with samples of anti-SARS CoV2 monoclonal antibody CR3022.
Abstract: Emerging novel human contagious viruses and pathogens put humans at risk of hospitalization and possibly death due to the unavailability of vaccines and drugs which may take years to develop. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was classified as a pandemic by the World Health Organization and has caused over 550,000 deaths worldwide as of July 2020. Accurate and scalable point-of-care devices would increase screening, diagnosis, and monitoring of COVID-19 patients. Here, we demonstrate rapid label-free electrochemical detection of SARS-CoV-2 antibodies using a commercially available impedance sensing platform. A 16-well plate containing sensing electrodes was pre-coated with receptor binding domain (RBD) of SARS-CoV-2 spike protein, and subsequently tested with samples of anti-SARS-CoV-2 monoclonal antibody CR3022 (0.1 μg/ml, 1.0 μg/ml, 10 μg/ml). Subsequent blinded testing was performed on six serum specimens taken from COVID-19 and non-COVID-19 patients (1:100 dilution factor). The platform was able to differentiate spikes in impedance measurements from a negative control (1% milk solution) for all CR3022 samples. Further, successful differentiation and detection of all positive clinical samples from negative control was achieved. Measured impedance values were consistent when compared to standard ELISA test results showing a strong correlation between them (R2 = 0:9). Detection occurs in less than five minutes and the well-based platform provides a simplified and familiar testing interface that can be readily adaptable for use in clinical settings.
59 citations
TL;DR: It is found that glycan expression profiles were dynamically regulated during postnatal developments and high levels of diversity in a glycosylation program underlying brain region specificity and age dependency may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
Abstract: Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale “omics” studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
56 citations
TL;DR: The need to better understand the breadth of environmental chemicals that reach the placenta and cord blood, as well as the linkages between prenatal exposures, mechanisms of toxicity, and subsequent health outcomes, is indicated.
55 citations
TL;DR: Lipid Annotator enables analysis of large sample cohorts and improves data-processing throughput as compared to previous lipidomics software, and validate annotation accuracy against lipid standards and other lipidomicsSoftware.
Abstract: Lipidomics has great promise in various applications; however, a major bottleneck in lipidomics is the accurate and comprehensive annotation of high-resolution tandem mass spectral data. While the number of available lipidomics software has drastically increased over the past five years, the reduction of false positives and the realization of obtaining structurally accurate annotations remains a significant challenge. We introduce Lipid Annotator, which is a user-friendly software for lipidomic analysis of data collected by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). We validate annotation accuracy against lipid standards and other lipidomics software. Lipid Annotator was integrated into a workflow applying an iterative exclusion MS/MS acquisition strategy to National Institute of Standards and Technology (NIST) SRM 1950 Metabolites in Frozen Human Plasma using reverse phase LC-HRMS/MS. Lipid Annotator, LipidMatch, and MS-DIAL produced consensus annotations at the level of lipid class for 98% and 96% of features detected in positive and negative mode, respectively. Lipid Annotator provides percentages of fatty acyl constituent species and employs scoring algorithms based on probability theory, which is less subjective than the tolerance and weighted match scores commonly used by available software. Lipid Annotator enables analysis of large sample cohorts and improves data-processing throughput as compared to previous lipidomics software.
54 citations
TL;DR: Overall analysis times and drift time measurement precision were found to be unaffected between standard and HRdm processed data sets, which allowed statistically identical collision cross section values to be directly determined from all ion mobility spectra.
Abstract: A combined data acquisition and data processing strategy for improving the sensitivity and resolution of ion mobility measurements is described. This strategy is implemented on a commercially avail...
University of Utah1, Landstuhl Regional Medical Center2, Thermo Fisher Scientific3, Ludwig Maximilian University of Munich4, Academy of Sciences of the Czech Republic5, Technische Universität München6, Singapore–MIT alliance7, Agilent Technologies8, National University of Singapore9, Celgene10, Massachusetts Institute of Technology11
TL;DR: Iron normalizes ms 2 t 6 A37 and proinsulin lysine incorporation, restoring insulin content and secretion in Irp2 −/− β cells and reveals a previously unidentified link between insulin processing and cellular iron deficiency that may have relevance to type 2 diabetes in humans.
Abstract: Regulation of cellular iron homeostasis is crucial as both iron excess and deficiency cause hematological and neurodegenerative diseases. Here we show that mice lacking iron-regulatory protein 2 (Irp2), a regulator of cellular iron homeostasis, develop diabetes. Irp2 post-transcriptionally regulates the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-storage protein ferritin, and dysregulation of these proteins due to Irp2 loss causes functional iron deficiency in β cells. This impairs Fe–S cluster biosynthesis, reducing the function of Cdkal1, an Fe–S cluster enzyme that catalyzes methylthiolation of t6A37 in tRNALysUUU to ms2t6A37. As a consequence, lysine codons in proinsulin are misread and proinsulin processing is impaired, reducing insulin content and secretion. Iron normalizes ms2t6A37 and proinsulin lysine incorporation, restoring insulin content and secretion in Irp2−/− β cells. These studies reveal a previously unidentified link between insulin processing and cellular iron deficiency that may have relevance to type 2 diabetes in humans. Iron metabolism is linked to type 2 diabetes. Here the authors describe a mechanism through which cellular iron deficiency caused by loss of Irp2 impairs Cdkal1 function, resulting in inaccurate proinsulin translation, impaired proinsulin processing and reduced insulin secretion.
Leiden University1, University of Geneva2, University of Liège3, Leiden University Medical Center4, University of Birmingham5, Phoenix House6, Agilent Technologies7, Institut Universitaire de France8, Université Paris-Saclay9, University of Strasbourg10, University of Orléans11, Innsbruck Medical University12, University of Montpellier13, CEU San Pablo University14, University of Pannonia15, University of Debrecen16, McMaster University17, University of Maryland, College Park18
TL;DR: This Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics by employing effective electrophoretic mobility (μeff) as the key parameter in comparison to the relative migration time (RMT) approach.
Abstract: Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and less reproducible, notably for migration time. The latter is key for a reliable comparison of metabolic profiles and for unknown biomarker identification that is complementary to high resolution MS/MS. In this work, we present the results of a Metabo-ring trial involving 16 CE-MS platforms among 13 different laboratories spanning two continents. The goal was to assess the reproducibility and identification capability of CE-MS by employing effective electrophoretic mobility (μeff) as the key parameter in comparison to the relative migration time (RMT) approach. For this purpose, a representative cationic metabolite mixture in water, pretreated human plasma, and urine samples spiked with the same metabolite mixture were used and distributed for analysis by all laboratories. The μeff was determined for all metabolites spiked into each sample. The background electrolyte (BGE) was prepared and employed by each participating lab following the same protocol. All other parameters (capillary, interface, injection volume, voltage ramp, temperature, capillary conditioning, and rinsing procedure, etc.) were left to the discretion of the contributing laboratories. The results revealed that the reproducibility of the μeff for 20 out of the 21 model compounds was below 3.1% vs 10.9% for RMT, regardless of the huge heterogeneity in experimental conditions and platforms across the 13 laboratories. Overall, this Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics.
TL;DR: In this article, the authors investigated the impact of human activities on the isotope composition of aerosols by synthesizing published Cu and Zn isotope compositions in aerosols and natural and anthropogenic sources.
Abstract: The stable isotope compositions of Cu and Zn in major geochemical reservoirs are increasingly studied with the aim to develop these isotope systems as tools to investigate the global biogeochemical cycles of these trace metals. The objectives of the present study were (i) to expand the range of Cu, Zn, and Pb isotope compositions of mineral dust by analyzing samples from major mineral dust sources in Asia and Africa (Chinese Loess Plateau, Chinese deserts, Thar desert, Sahel region) and (ii) to assess the potential impact of human activities on the isotope composition of aerosols by synthesizing published Cu and Zn isotope compositions in aerosols and natural and anthropogenic sources. For the newly analyzed mineral dust areas in Asia and Africa, δ^{65}Cu_{NIST-976} values range from −0.54 to +0.52‰, δ^{66}Zn_{JMC-Lyon} values from −0.07 to +0.57‰, and {206}^Pb/{204}^Pb values from 18.522 to 19.696. We find a significant geographic control with samples from the Thar Desert having the heaviest isotopic compositions (δ^{65}Cu_{NIST-976} = +0.48 ± 0.06‰, δ^{66}ZN_{JMC-Lyon} = +0.49 ± 0.11‰) and samples from the Sahel and the Badain Jaran desert having the lightest Zn isotope composition (δ^{66}ZN_{JMC-Lyon} = +0.19 ± 0.15‰ and +0.07 ± 0.07‰, respectively). We find important variations in the isotope signatures between particle size fractions with heavier isotopic compositions in the smallest and largest particle size fractions and lighter isotopic compositions in the mid particle size fractions. Associations with the mineralogical composition are less clear. Newly analyzed aerosol samples for Beijing and Xi'an show δ^{65}Cu_{NIST-976} values of +0.29 ± 0.19‰ and +0.16 ± 0.04‰, δ^{66}Zn_{JMC-Lyon} values of −0.36 ± 0.04‰ and +0.02 ± 0.06‰, and {206}^PB/{204}Pb values of 18.129 ± 0.003 and 18.031 ± 0.003, respectively. Based on a synthesis of published and novel data, we suggest improved ranges and mean values for the isotopic composition of mineral dust from selected locations in Asia and Africa and of anthropogenic sources such as non-exhaust traffic emissions, combustion, electroplating and galvanization. This should serve as a valuable reference for future studies using these isotope systems. This paper demonstrates univocally that human activity introduces a wide range of Zn isotope compositions into the atmospheric environment and, thus, impacts the biogeochemical cycle of Zn.
TL;DR: A unique drift tube IM-MS (DTIM-MS) platform is reported, which combines high-energy source optics for improved collision induced unfolding (CIU) experiments and an electromagnetostatic cell for electron capture dissociation (ECD) experiments, allowing for comprehensive unfolding of large multiprotein complex ions as well as interplatform CIU comparisons.
Abstract: Native ion mobility-mass spectrometry (IM-MS) is capable of revealing much that remains unknown within the structural proteome, promising such information on refractory protein targets. Here, we report the development of a unique drift tube IM-MS (DTIM-MS) platform, which combines high-energy source optics for improved collision induced unfolding (CIU) experiments and an electromagnetostatic cell for electron capture dissociation (ECD). We measured a series of high precision collision cross section (CCS) values for protein and protein complex ions ranging from 6-1600 kDa, exhibiting an average relative standard deviation (RSD) of 0.43 ± 0.20%. Furthermore, we compare our CCS results to previously reported DTIM values, finding strong agreement across similarly configured instrumentation (average RSD of 0.82 ± 0.73%), and systematic differences for DTIM CCS values commonly used to calibrate traveling-wave IM separators (-3% average RSD). Our CIU experiments reveal that the modified DTIM-MS instrument described here achieves enhanced levels of ion activation when compared with any previously reported IM-MS platforms, allowing for comprehensive unfolding of large multiprotein complex ions as well as interplatform CIU comparisons. Using our modified DTIM instrument, we studied two protein complexes. The enhanced CIU capabilities enable us to study the gas phase stability of the GroEL 7-mer and 14-mer complexes. Finally, we report CIU-ECD experiments for the alcohol dehydrogenase tetramer, demonstrating improved sequence coverage by combining ECD fragmentation integrated over multiple CIU intermediates. Further improvements for such native top-down sequencing experiments were possible by leveraging IM separation, which enabled us to separate and analyze CID and ECD fragmentation simultaneously.
TL;DR: A liquid chromatography-mass spectrometry-based targeted metabolomics method is developed to study the chemical profiles of 60 flavonoids and 11 anthraquinones in 40 seed cultivars (groats and hulls), providing new insights into differences in polyphenols among tartary buckwheat seeds with different color and shape.
TL;DR: The abilities of in silico spectra are shown to correctly identify true positives in complex samples (at rates comparable to those observed with reference spectra), and efficiently filter large numbers of potential false positives from further consideration.
Abstract: High-resolution mass spectrometry (HRMS) enables rapid chemical annotation via accurate mass measurements and matching of experimentally derived spectra with reference spectra. Reference libraries are generated from chemical standards and are therefore limited in size relative to known chemical space. To address this limitation, in silico spectra (i.e., MS/MS or MS2 spectra), predicted via Competitive Fragmentation Modeling-ID (CFM-ID) algorithms, were generated for compounds within the U.S. Environmental Protection Agency’s (EPA) Distributed Structure-Searchable Toxicity (DSSTox) database (totaling, at the time of analysis, ~ 765,000 substances). Experimental spectra from EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT) mixtures (n = 10) were then used to evaluate the performance of the in silico spectra. Overall, MS2 spectra were acquired for 377 unique compounds from the ENTACT mixtures. Approximately 53% of these compounds were correctly identified using a commercial reference library, whereas up to 50% were correctly identified as the top hit using the in silico library. Together, the reference and in silico libraries were able to correctly identify 73% of the 377 ENTACT substances. When using the in silico spectra for candidate filtering, an examination of binary classifiers showed a true positive rate (TPR) of 0.90 associated with false positive rates (FPRs) of 0.10 to 0.85, depending on the sample and method of candidate filtering. Taken together, these findings show the abilities of in silico spectra to correctly identify true positives in complex samples (at rates comparable to those observed with reference spectra), and efficiently filter large numbers of potential false positives from further consideration.
TL;DR: HoloPy makes it easy for experimentalists to use modern, sophisticated inference methods to analyze holograms by wrapping low-level scattering codes and taking advantage of Python's data analysis ecosystem.
Abstract: A holographic microscope captures interference patterns, or holograms, that encode three-dimensional (3-D) information about the object being viewed. Computation is essential to extract that 3-D information. By wrapping low-level scattering codes and taking advantage of Python's data analysis ecosystem, HoloPy makes it easy for experimentalists to use modern, sophisticated inference methods to analyze holograms. The resulting data can be used to understand how small particles or microorganisms move and interact. The project illustrates how computational tools can enable experimental methods and new experiments.
TL;DR: Low energy electron ionisation (EI) coupled with GC-quadrupole time-of-flight (GC-QTOF) was applied to achieve improved molecular ion signal intensity and reproducibility across five compounds, which resulted in good linearity and lowered detection levels.
TL;DR: It was found that CWA-related phenylarsenic chemicals (Clark I, Clark II and Adamsite) and sulfur mustard are released to the sediments and undergo environmental degradation to chemicals, of which some remain toxic.
TL;DR: EPSFs were found to be marker compounds for stored GT and showed potential anti-inflammatory activity by regulating the NF-κB signaling pathway in lipopolysaccharide-stimulated macrophages.
Abstract: Fresh green tea (GT) is commonly considered to have better sensory flavor and higher commercial value than long-term-stored GT; however, the chemical variations during storage are unclear. In this study, the chemical profiles of stored GT were surveyed among time-series samples from 0 to 19 months using a nontargeted metabolomics method. Seven N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) increased from 0.022 ± 0.019 to 3.212 ± 0.057 mg/g within 19 months (correlation coefficients with storage duration ranging from 0.936 to 0.965), and they were the most significantly increased compounds among the 127 identified compounds. Two representative EPSFs (R-EGCG-cThea and S-EGCG-cThea) possess potential anti-inflammatory properties by suppressing the expression, phosphorylation, and nuclear translocation of nuclear factor kappa-B (NF-κB) p65 in lipopolysaccharide-stimulated macrophages based on western blotting and immunofluorescence results. In conclusion, EPSFs were found to be marker compounds for stored GT and showed potential anti-inflammatory activity by regulating the NF-κB signaling pathway.
Takeda Pharmaceutical Company1, Center for Devices and Radiological Health2, University of Glasgow3, Fraunhofer Society4, Johnson & Johnson5, Bristol-Myers Squibb6, University of Michigan7, Center for Drug Evaluation and Research8, National Center for Toxicological Research9, Novartis10, Agilent Technologies11
TL;DR: Implementation of best practices should enhance the clinical translation of hSC-CM-based cell and tissue preparations in drug safety evaluations and support their growing role in regulatory filings.
TL;DR: Data indicate that digital image analysis offers an objective and quantifiable means of verifying IHC staining parameters as a part of laboratory quality assurance systems.
Abstract: With immunohistochemical (IHC) staining increasingly being used to guide clinical decisions, variability in staining quality and reproducibility are becoming essential factors in generating diagnoses using IHC tissue preparations. The current study tested a method to track and quantify the interrun, intrarun, and intersite variability of IHC staining intensity. Our hypothesis was that staining precision between laboratory sites, staining runs, and individual slides may be verified quantitatively, efficiently and effectively utilizing algorithm-based, automated image analysis. To investigate this premise, we tested the consistency of IHC staining in 40 routinely processed (formalin-fixed, paraffin-embedded) human tissues using 10 common antibiomarker antibodies on 2 Dako Omnis instruments at 2 locations (Carpinteria, CA: 30 m above sea level and Longmont, CO: 1500 m above sea level) programmed with identical, default settings and sample pretreatments. Digital images of IHC-labeled sections produced by a whole slide scanner were analyzed by a simple commercially available algorithm and compared with a board-certified veterinary pathologist's semiquantitative scoring of staining intensity. The image analysis output correlated well with pathology scores but had increased sensitivity for discriminating subtle variations and providing reproducible digital quantification across sites as well as within and among staining runs at the same site. Taken together, our data indicate that digital image analysis offers an objective and quantifiable means of verifying IHC staining parameters as a part of laboratory quality assurance systems.
TL;DR: Ion-exchange stationary phase and polar additives mixed with organic modifiers enabled separation of small ionic molecules using SFC, and may be considered an alternative separation technique to improve the separation of polar analytes.
TL;DR: This work has developed a Python script, the ion mobility-mass spectrometry image creation script (IM-MSIC), which interfaces Agilent's Mass Hunter Mass Profiler software with the MacCoss lab's Skyline software and generates drift time and mass-to-charge-selected ion images.
TL;DR: The freeze-drying procedure affords fecal SCFA stability, even with storage at room temperature for 3 d, and allows reliable SCFA measurements without labour-intensive processes, and can be applied in basic, clinical, and epidemiological studies.
TL;DR: It was reported that dissolved organic matter (DOM) reduced the transformation rate of CYN by inhibiting the transformation of oxidation intermediates, demonstrating that CO3•- played an important role in CYN attenuation under non-acidic environmentally relevant conditions.
Abstract: Cylindrospermopsin (CYN) is one of the most important cyanobacterial toxins frequently found in surface waters. We reported the detailed kinetics and pathways for the reaction of CYN with carbonate radicals (CO3•-). The rate constants of neutral and deprotonated CYN with CO3•- were found to be (1.2 ± 0.7) × 107 M-1 s-1 and (3.0 ± 0.4) × 108 M-1 s-1, respectively. The transformation products for the oxidation of CYN by CO3•- were identified by high-resolution mass spectrometry, illustrating that the guanidine and bridged hydroxyl portions were the primary moieties attacked by CO3•-. Thus, three transformation pathways, including cleavage of the hydroxymethyluracil moiety, hydroxylation, and oxidation of the bridged hydroxyl group, are proposed for the CO3•- oxidation of CYN. Moreover, this study reported that dissolved organic matter (DOM) reduced the transformation rate of CYN by inhibiting the transformation of oxidation intermediates. Finally, the role of CO3•- in CYN degradation was estimated in both sunlit surface waters and advanced oxidation processes (AOPs), demonstrating that CO3•- played an important role in CYN attenuation under nonacidic environmentally relevant conditions. The kinetic parameters and product information obtained in this study will be of considerable interest for the application of AOPs and predicting the environmental fate of CYN.
TL;DR: Higher levels of SCCPs were found in the air than polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ether (PBDEs), suggesting that the production and use of S CCPs were much higher than prohibited or restricted persistent organic pollutants (e.g., PCBs, OCPs, and PBDEs).
TL;DR: Comparison of glycosylated aroma molecules in Riesling and Muscat of Alexandria grapes showed that the two varieties were distinguishable based on relative abundances of shared glycosides and the presence of Glycosides unique to a single variety.
Abstract: Ultrahigh performance liquid chromatography (UHPLC) accurate mass tandem mass spectrometry (MS/MS) is a powerful tool for identifying and profiling plant metabolites. Here, we describe an approach ...
TL;DR: The phytosteroid ecdysterone was recently reported to enhance performance in sports and may thus be considered as a substance of relevance in anti-doping control to assess its integration into initial testing procedures (ITP) in doping control laboratories.
Abstract: The phytosteroid ecdysterone was recently reported to enhance performance in sports and may thus be considered as a substance of relevance in anti-doping control. To trace back an administration of ecdysterone from urine samples, analytical properties have been investigated to assess its integration into initial testing procedures (ITP) in doping control laboratories. Analytical properties of ecdysterone were evaluated using gas chromatography-quadrupole/time-of-flight-mass spectrometry (GC–QTOF–MS) and liquid chromatography (LC)–QTOF–MS. Its metabolism and elimination in human were studied using urines collected after administration. The detectability of ecdysterone by GC–MS (after derivatization) and/or LC–MS(/MS) has been demonstrated and sample preparation methods were evaluated. Dilute-and-inject for LC–MS(/MS) or solid phase extraction using Oasis HLB for GC–MS or LC–MS were found most suitable, while liquid–liquid extraction was hampered by the high polarity of ecdysteroids. Most abundantly, ecdysterone was detected in the post administration urines as parent compound besides the metabolite desoxy-ecdysterone. Additionally, desoxy-poststerone was tentatively assigned as minor metabolite, however, further investigations are needed. An administration of ecdysterone can be targeted using existing procedures of anti-doping laboratories. Ecdysterone and desoxy-ecdysterone appeared as suitable candidates for integration in ITP. Using dilute-and-inject a detection of the parent compound was possible for more than 2 days after the administration of a single dose of ~ 50 mg.