The functional interpretation of high throughput metabolomics by mass spectrometry is hindered by the identification of metabolites, a tedious and challenging task. We present a set of computational ...algorithms which, by leveraging the collective power of metabolic pathways and networks, predict functional activity directly from spectral feature tables without a priori identification of metabolites. The algorithms were experimentally validated on the activation of innate immune cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and ...management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report on the experimental observation of scaling in the time evolution following a sudden quench into the vicinity of a quantum critical point. The experimental system, a two-component Bose gas ...with coherent exchange between the constituents, allows for the necessary high level of control of parameters as well as the access to time-resolved spatial correlation functions. The theoretical analysis reveals that when quenching the system close to the critical point, the energy introduced by the quench leads to a short-time evolution exhibiting crossover reminiscent of the finite-temperature critical properties in the system's universality class. Observing the time evolution after a quench represents a paradigm shift in accessing and probing experimentally universal properties close to a quantum critical point and allows in a new way benchmarking of quantum many-body theory with experiments.
Detection of low abundance metabolites is important for de novo mapping of metabolic pathways related to diet, microbiome or environmental exposures. Multiple algorithms are available to extract m/z ...features from liquid chromatography-mass spectral data in a conservative manner, which tends to preclude detection of low abundance chemicals and chemicals found in small subsets of samples. The present study provides software to enhance such algorithms for feature detection, quality assessment, and annotation.
xMSanalyzer is a set of utilities for automated processing of metabolomics data. The utilites can be classified into four main modules to: 1) improve feature detection for replicate analyses by systematic re-extraction with multiple parameter settings and data merger to optimize the balance between sensitivity and reliability, 2) evaluate sample quality and feature consistency, 3) detect feature overlap between datasets, and 4) characterize high-resolution m/z matches to small molecule metabolites and biological pathways using multiple chemical databases. The package was tested with plasma samples and shown to more than double the number of features extracted while improving quantitative reliability of detection. MS/MS analysis of a random subset of peaks that were exclusively detected using xMSanalyzer confirmed that the optimization scheme improves detection of real metabolites.
xMSanalyzer is a package of utilities for data extraction, quality control assessment, detection of overlapping and unique metabolites in multiple datasets, and batch annotation of metabolites. The program was designed to integrate with existing packages such as apLCMS and XCMS, but the framework can also be used to enhance data extraction for other LC/MS data software.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Historically, the completeness of quantum theory has been questioned using the concept of bipartite continuous-variable entanglement. The non-classical correlations (entanglement) between the two ...subsystems imply that the observables of one subsystem are determined by the measurement choice on the other, regardless of the distance between the subsystems. Nowadays, continuous-variable entanglement is regarded as an essential resource, allowing for quantum enhanced measurement resolution, the realization of quantum teleportation and quantum memories, or the demonstration of the Einstein-Podolsky-Rosen paradox. These applications rely on techniques to manipulate and detect coherences of quantum fields, the quadratures. Whereas in optics coherent homodyne detection of quadratures is a standard technique, for massive particles a corresponding method was missing. Here we report the realization of an atomic analogue to homodyne detection for the measurement of matter-wave quadratures. The application of this technique to a quantum state produced by spin-changing collisions in a Bose-Einstein condensate reveals continuous-variable entanglement, as well as the twin-atom character of the state. Our results provide a rare example of continuous-variable entanglement of massive particles. The direct detection of atomic quadratures has applications not only in experimental quantum atom optics, but also for the measurement of fields in many-body systems of massive particles.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A major challenge in quantum metrology is the generation of entangled states with a macroscopic atom number. Here, we demonstrate experimentally that atomic squeezing generated via nonlinear dynamics ...in Bose-Einstein condensates, combined with suitable trap geometries, allows scaling to large ensemble sizes. We achieve a suppression of fluctuations by 5.3(5) dB for 12,300 particles, from which we infer that similar squeezing can be obtained for more than 10(7) atoms. With this resource, we demonstrate quantum-enhanced magnetometry by swapping the squeezed state to magnetically sensitive hyperfine levels that have negligible nonlinearity. We find a quantum-enhanced single-shot sensitivity of 310(47) pT for static magnetic fields in a probe volume as small as 90 μm3.
We experimentally demonstrate a nonlinear detection scheme exploiting time-reversal dynamics that disentangles continuous variable entangled states for feasible readout. Spin-exchange dynamics of ...Bose-Einstein condensates is used as the nonlinear mechanism which not only generates entangled states but can also be time reversed by controlled phase imprinting. For demonstration of a quantum-enhanced measurement we construct an active atom SU(1,1) interferometer, where entangled state preparation and nonlinear readout both consist of parametric amplification. This scheme is capable of exhausting the quantum resource by detecting solely mean atom numbers. Controlled nonlinear transformations widen the spectrum of useful entangled states for applied quantum technologies.
Many cold atom experiments rely on precise atom number detection, especially in the context of quantum-enhanced metrology where effects at the single particle level are important. Here, we ...investigate the limits of atom number counting via resonant fluorescence detection for mesoscopic samples of trapped atoms. We characterize the precision of these fluorescence measurements beginning from the single-atom level up to more than one thousand. By investigating the primary noise sources, we obtain single-atom resolution for atom numbers as high as 1200. This capability is an essential prerequisite for future experiments with highly entangled states of mesoscopic atomic ensembles.
We experimentally investigate the mixing and demixing dynamics of Bose-Einstein condensates in the presence of a linear coupling between two internal states. The observed amplitude reduction of the ...Rabi oscillations can be understood as a result of demixing dynamics of dressed states as experimentally confirmed by reconstructing the spatial profile of dressed state amplitudes. The observations are in quantitative agreement with numerical integration of coupled Gross-Pitaevskii equations without free parameters, which also reveals the criticality of the dynamics on the symmetry of the system. Our observations demonstrate new possibilities for changing effective atomic interactions and studying critical phenomena.
Ovine footrot caused by Dichelobacter nodosus (D nodosus) is an infectious disease affecting sheep worldwide. Switzerland plans a nationwide footrot eradication program, based on PCR-testing of ...interdigital swab samples. The aim of this study was to test for the presence of D nodosus in clinically footrot-free sheep flocks which had been subjected to different treatment strategies, to assess whether they were feasible for the eradication process, especially focussing on antimicrobial flock treatments. Clinical scoring and PCR-results were compared. Ten farms had used hoof bathing and hoof trimming without causing bleeding, ten had used individual treatments and flock vaccines to gain the free status and ten had become free through whole-flock systemic macrolide treatment. For every farm, three risk-based collected pool samples were analysed for the occurrence of virulent and benign D nodosus by PCR detection of aprV2/aprB2.
Six flocks from any treatment group tested positive for aprB2 in all pools. Clinical signs were absent at the time of sampling, but some flocks had experienced non-progressive interdigital inflammation previously. Two flocks tested aprV2-positive in the high-risk pool. One of them underwent a progressive footrot outbreak shortly after sampling. Individual retesting indicated, that virulent D nodosus most likely was reintroduced by a recently purchased ram. In the second flock, a ram was tested positive and treated before clinical signs occurred.
All treatment strategies eliminated the causative agent and were found to be suitable for implementation in the PCR-based eradication process. PCR-testing proved to be more sensitive than visual scoring, as it also detected clinically healthy carriers. It will be of benefit as a diagnostic tool in elimination and surveillance programs.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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