Dynamic range and mass accuracy of wide-scan direct infusion nanoelectrospray fourier transform ion cyclotron resonance mass spectrometry-based metabolomics increased by the spectral stitching method

Direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry (DI nESI FT-ICR MS)offers high mass accuracy and resolution for analyzing complex metabolite mixtures. High dynamic range across a wide mass range, however, can only be achieved at the expense of mass accuracy, since the large numbers of ions entering the ICR detector induce adverse spacecharge effects. Here we report an optimized strategy for wide-scan DI nESI FT-ICR MS that increases dynamic range but maintains high mass accuracy. It comprises the collection if multiple adjacent selected ion monitoring (SIM) windows that are stitched together using novel algorithms. The final SIM-stitching method, derived from several optimization experiments, comprises 21 adjoining SIM windows each of width m/z 30 (from m/z 70 to 500; adjacent windows overlap by m/z 10) with an automated gain control (AGC) target of 1 105 charges. SIMstitching and wide-scan range (WSR; Thermo Electron)were compared using a defined standard to assess mass accuracy and a liver extract to assess peak count and dynamic range. SIM-stitching decreased the maximum mass error by 1.3- and 4.3-fold, and increased the peak count by 5.3- and 1.8-fold, versus WSR (AGC targets of 1 x 105 and 5 x 105, respectively). SIM-stitching achieved an rms mass error of 0.18 ppm and detected over 3000 peaks in liver extract. This novel approach increases metabolome coverage, has very high mass accuracy, and at 5.5 min/sample is conducive for high- throughput metabolomics

Computer-assisted orthopedic training system for fracture fixation

Background: Surgical training has been greatly affected by the challenges of reduced training opportunities, shortened working hours, and financial pressures. There is an increased need for the use of training systems in developing psychomotor skills of the surgical trainee. Aims: To develop the training system for fracture fixation and validate its effectiveness in a cohort of junior orthopedic trainees. Training System: Computer-navigated training system uses the 2 sets of images from the c-arm while the registration phantom is placed in the fluoroscopic imaging space which permits determination of the position of the x-ray source and the image plane that then guides the trainee to navigate the surgical instruments into the three-dimensional space. No further c-arm exposures are taken during the entire procedure. Materials and Method: The training system was developed to simulate dynamic hip screw fixation. Twelve orthopedic senior house officers performed dynamic hip screw fixation before and after the training on the training system. The results were assessed based on the scoring system that included the amount of time taken, accuracy of guidewire placement, and the number of exposures requested to complete the procedure. Results: The result shows a significant improvement in the amount of time taken, accuracy of fixation, and the number of exposures after the training on the simulator system. The paired student t-test was used and statistically significant results were obtained (p-value< 0.05). Conclusion: Computer-navigated training system appears to be a good training tool for young orthopedic trainees. This system can be used to augment training in the operating room and trainees acquire their skills in a "nonthreatening and unhurried environment." The system has the potential to be used in various other orthopedic procedures for learning of technical skills in a manner aimed at ensuring a smooth escalation in task complexity leading to the better performance of procedures in the operating theater

Direct infusion mass spectrometry metabolomics dataset: a benchmark for data processing and quality control

Direct-infusion mass spectrometry (DIMS) metabolomics is an important approach for characterising molecular responses of organisms to disease, drugs and the environment. Increasingly large-scale metabolomics studies are being conducted, necessitating improvements in both bioanalytical and computational workflows to maintain data quality. This dataset represents a systematic evaluation of the reproducibility of a multi-batch DIMS metabolomics study of cardiac tissue extracts. It comprises of twenty biological samples (cow vs. sheep) that were analysed repeatedly, in 8 batches across 7 days, together with a concurrent set of quality control (QC) samples. Data are presented from each step of the workflow and are available in MetaboLights. The strength of the dataset is that intra- and inter-batch variation can be corrected using QC spectra and the quality of this correction assessed independently using the repeatedly-measured biological samples. Originally designed to test the efficacy of a batch-correction algorithm, it will enable others to evaluate novel data processing algorithms. Furthermore, this dataset serves as a benchmark for DIMS metabolomics, derived using best-practice workflows and rigorous quality assessment

First test of a high voltage feedthrough for liquid Argon TPCs connected to a 300 kV power supply

Voltages above a hundred kilo-volt will be required to generate the drift field of future very large liquid Argon Time Projection Chambers. The most delicate component is the feedthrough whose role is to safely deliver the very high voltage to the cathode through the thick insulating walls of the cryostat without compromising the purity of the argon inside. This requires a feedthrough that is typically meters long and carefully designed to be vacuum tight and have small heat input. Furthermore, all materials should be carefully chosen to allow operation in cryogenic conditions. In addition, electric fields in liquid argon should be kept below a threshold to reduce risks of discharges. The combination of all above requirements represents significant challenges from the design and manufacturing perspective. In this paper, we report on the successful operation of a feedthrough satisfying all the above requirements. The details of the feedthrough design and its manufacturing steps are provided. Very high voltages up to unprecedented voltages of -300 kV could be applied during long periods repeatedly. A source of instability was observed, which was specific to the setup configuration which was used for the test and not due to the feedthrough itself.Comment: 13 pages, 9 figure

The metabolic response of marine copepods to environmental warming and ocean acidification in the absence of food

Marine copepods are central to the productivity and biogeochemistry of marine ecosystems. Nevertheless, the direct and indirect effects of climate change on their metabolic functioning remain poorly understood. Here, we use metabolomics, the unbiased study of multiple low molecular weight organic metabolites, to examine how the physiology of Calanus spp. is affected by end-of-century global warming and ocean acidification scenarios. We report that the physiological stresses associated with incubation without food over a 5-day period greatly exceed those caused directly by seawater temperature or pH perturbations. This highlights the need to contextualise the results of climate change experiments by comparison to other, naturally occurring stressors such as food deprivation, which is being exacerbated by global warming. Protein and lipid metabolism were up-regulated in the food-deprived animals, with a novel class of taurine-containing lipids and the essential polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid and docosahexaenoic acid, changing significantly over the duration of our experiment. Copepods derive these PUFAs by ingesting diatoms and flagellated microplankton respectively. Climate-driven changes in the productivity, phenology and composition of microplankton communities, and hence the availability of these fatty acids, therefore have the potential to influence the ability of copepods to survive starvation and other environmental stressors

NMR-Based Metabolomic Investigations on the Differential Responses in Adductor Muscles from Two Pedigrees of Manila Clam Ruditapes philippinarum to Cadmium and Zinc

Manila clam Ruditapes philippinarum is one of the most important economic species in shellfishery in China due to its wide geographic distribution and high tolerance to environmental changes (e.g., salinity, temperature). In addition, Manila clam is a good biomonitor/bioindicator in “Mussel Watch Programs” and marine environmental toxicology. However, there are several pedigrees of R. philippinarum distributed in the marine environment in China. No attention has been paid to the biological differences between various pedigrees of Manila clams, which may introduce undesirable biological variation in toxicology studies. In this study, we applied NMR-based metabolomics to detect the biological differences in two main pedigrees (White and Zebra) of R. philippinarum and their differential responses to heavy metal exposures (Cadmium and Zinc) using adductor muscle as a target tissue to define one sensitive pedigree of R. philippinarum as biomonitor for heavy metals. Our results indicated that there were significant metabolic differences in adductor muscle tissues between White and Zebra clams, including higher levels of alanine, glutamine, hypotaurine, phosphocholine and homarine in White clam muscles and higher levels of branched chain amino acids (valine, leucine and isoleucine), succinate and 4-aminobutyrate in Zebra clam muscles, respectively. Differential metabolic responses to heavy metals between White and Zebra clams were also found. Overall, we concluded that White pedigree of clam could be a preferable bioindicator/biomonitor in marine toxicology studies and for marine heavy metals based on the relatively high sensitivity to heavy metals

First operation and performance of a 200 lt double phase LAr LEM-TPC with a 40x76 cm^2 readout

In this paper we describe the design, construction, and operation of a first large area double-phase liquid argon Large Electron Multiplier Time Projection Chamber (LAr LEM-TPC). The detector has a maximum drift length of 60 cm and the readout consists of a $40\times 76$ cm$^2$ LEM and 2D projective anode to multiply and collect drifting charges. Scintillation light is detected by means of cryogenic PMTs positioned below the cathode. To record both charge and light signals, we have developed a compact acquisition system, which is scalable up to ton-scale detectors with thousands of charge readout channels. The acquisition system, as well as the design and the performance of custom-made charge sensitive preamplifiers, are described. The complete experimental setup has been operated for a first time during a period of four weeks at CERN in the cryostat of the ArDM experiment, which was equipped with liquid and gas argon purification systems. The detector, exposed to cosmic rays, recorded events with a single-channel signal-to-noise ratio in excess of 30 for minimum ionising particles. Cosmic muon tracks and their $\delta$-rays were used to assess the performance of the detector, and to estimate the liquid argon purity and the gain at different amplification fields.Comment: 23 pages, 21 figure

Problemas globales que impactan a Singapur: terrorismo, migraciones y cambio climático: Global problems impacting Singapore: terrorism, migration and climate change

Los problemas contemporáneos globales van aparejados al propio desarrollo del sistema capitalista y afectan con diferentes grados de intensidad a los actores internacionales. Los Estados son sujetos de estos procesos con independencia de sus dimensiones o posicionamiento geoestratégico, tal es el caso de la Ciudad Estado sudeste asiática Singapur, también urgida de revertir esa afectación en su política interna y exterior. El carácter transfronterizo de estos asuntos referidos a la migración, el terrorismo y el cambio climático, ha demandado una respuesta coordinada e implementación de políticas con el fin de contrarrestar el impacto y las consecuencias de los citados fenómenos, mediante proyecciones y articulaciones consensuadas con otros actores soberanos también en el ámbito regional e internacional