Mesenchymal stromal cells (MSC) hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC ...from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies.
We hypothesized that canine adipose tissue (AT) and bone marrow (BM) MSC (derived from the same dogs) will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1) proliferation rate, 2) cell surface marker expression, 3) DNA methylation levels, 4) potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5) immunomodulatory potency in vitro.
1) AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days) for passage (P) 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21). 2) Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3) Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4) Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-β3)-based induction medium. 5) Immunomodulatory capacity was equal regardless of cell source when tested in mitogen-stimulated lymphocyte reactions. Priming of MSC with pro-inflammatory factors interferon-gamma and/or tumour necrosis factor did not increase the lymphocyte suppressive properties of the MSC compared to untreated MSC.
No significant differences were found between AT- and BM-MSC with regard to their immunophenotype, progenitor, and non-progenitor functions. Both MSC populations showed strong adipogenic and osteogenic potential and poor chondrogenic potential. Both significantly suppressed stimulated peripheral blood mononuclear cells. The most significant differences found were the higher isolation success and proliferation rate of AT-MSC, which could be realized as notable benefits of their use over BM-MSC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It has been proposed that there could be a mirror copy of the standard model particles, restoring the parity symmetry in the weak interaction on the global level. Oscillations between a neutral ...standard model particle, such as the neutron, and its mirror counterpart could potentially answer various standing issues in physics today. Astrophysical studies and terrestrial experiments led by ultracold neutron storage measurements have investigated neutron to mirror-neutron oscillations and imposed constraints on the theoretical parameters. Recently, further analysis of these ultracold neutron storage experiments has yielded statistically significant anomalous signals that may be interpreted as neutron to mirror-neutron oscillations, assuming nonzero mirror magnetic fields. The neutron electric dipole moment collaboration performed a dedicated search at the Paul Scherrer Institute and found no evidence of neutron to mirror-neutron oscillations. Thereby, the following new lower limits on the oscillation time were obtained: τnn′>352 s at B′=0 (95% C.L.), τnn′>6s for 0.4μT<B′<25.7μT (95% C.L.), and τnn′/cosβ>9s for 5.0μT<B′<25.4μT (95% C.L.), where β is the fixed angle between the applied magnetic field and the local mirror magnetic field, which is assumed to be bound to the Earth. These new constraints are the best measured so far around B′∼10μT and B′∼20μT.
We present for the first time a detailed and comprehensive analysis of the experimental results that set the current world sensitivity limit on the magnitude of the electric dipole moment (EDM) of ...the neutron. We have extended and enhanced our earlier analysis to include recent developments in the understanding of the effects of gravity in depolarizing ultracold neutrons (UCN); an improved calculation of the spectrum of the neutrons; and conservative estimates of other possible systematic errors, which are also shown to be consistent with more recent measurements undertaken with the apparatus. We obtain a net result of $d_\mathrm{n} = -0.21 \pm 1.82 \times10^{-26}$ $e$cm, which may be interpreted as a slightly revised upper limit on the magnitude of the EDM of $3.0 \times10^{-26}$ $e$cm (90% CL) or $ 3.6 \times10^{-26}$ $e$cm (95% CL). This paper is dedicated by the remaining authors to the memory of Prof. J. Michael Pendlebury.
Abstract Objective To validate the diagnosis of hyperkinetic disorders (HD) in the Danish Psychiatric Central Research Registry (DPCRR) for children and adolescents aged 4 to 15 given in the years ...1995 to 2005. Method From a total of 4568 participants, a representative random subsample of n = 387 patients were used to validate the diagnosis. Patient files were systematically scored for the presence of ICD-10 criteria for HD and oppositional defiant disorder/conduct disorder (ODD/CD; F91). Further to this, an inter-rater reliability study was also conducted, whereby two experienced child and adolescent psychiatrists who were blind to patients discharge diagnoses, rated a random subsample of n = 101 participants. Results Information was available for 372 out of 387 patients. Out of n = 372 available files, n = 324 (86.8%) were evaluated to fulfil diagnostic criteria for HD. Due to missing information it was not possible to reach a conclusion for 5.1% of the cases, 3.8% of the diagnoses were registration errors, and in 4.3% of the files the diagnosis had to be rejected. Inter-rater agreement was high (κ = 0.83, z = 10.9, P < .001). The validity of hyperkinetic disorders, unspecified (F90.9) was lower and comorbid CD/ODD were under-diagnosed in the sample. All participants fulfilling HD criteria also fulfilled DSM-5-criteria for ADHD. Conclusion The risk of misclassification of patients with HD in the DPCRR is relatively low, with the exception of the diagnosis of hyperkinetic disorders, unspecified (F90.9).
Fundamental electronic principles underlying all transition metal compounds are the symmetry and filling of the d-electron orbitals and the influence of this filling on structural configurations and ...responses. Here we use a sensitive local structural technique, x-ray atomic pair distribution function analysis, to reveal the presence of fluctuating local-structural distortions at high temperature in one such compound, CuIr
S
. We show that this hitherto overlooked fluctuating symmetry-lowering is electronic in origin and will modify the energy-level spectrum and electronic and magnetic properties. The explanation is a local, fluctuating, orbital-degeneracy-lifted state. The natural extension of our result would be that this phenomenon is likely to be widespread amongst diverse classes of partially filled nominally degenerate d-electron systems, with potentially broad implications for our understanding of their properties.
We report on a search for ultralow-mass axionlike dark matter by analyzing the ratio of the spin-precession frequencies of stored ultracold neutrons and Hg199 atoms for an axion-induced oscillating ...electric dipole moment of the neutron and an axion-wind spin-precession effect. No signal consistent with dark matter is observed for the axion mass range 10−24≤ma≤10−17eV . Our null result sets the first laboratory constraints on the coupling of axion dark matter to gluons, which improve on astrophysical limits by up to 3 orders of magnitude, and also improves on previous laboratory constraints on the axion coupling to nucleons by up to a factor of 40.
We present the result of an experiment to measure the electric dipole moment (EDM) of the neutron at the Paul Scherrer Institute using Ramsey's method of separated oscillating magnetic fields with ...ultracold neutrons. Our measurement stands in the long history of EDM experiments probing physics violating time-reversal invariance. The salient features of this experiment were the use of a ^{199}Hg comagnetometer and an array of optically pumped cesium vapor magnetometers to cancel and correct for magnetic-field changes. The statistical analysis was performed on blinded datasets by two separate groups, while the estimation of systematic effects profited from an unprecedented knowledge of the magnetic field. The measured value of the neutron EDM is d_{n}=(0.0±1.1_{stat}±0.2_{sys})×10^{-26} e.cm.
To achieve a deeper understanding of the brain, scientists, and clinicians use electroencephalography (EEG) and magnetoencephalography (MEG) inverse methods to reconstruct sources in the cortical ...sheet of the human brain. The influence of structural and electrical anisotropy in both the skull and the white matter on the EEG and MEG source reconstruction is not well understood.
In this paper, we report on a study of the sensitivity to tissue anisotropy of the EEG/MEG forward problem for deep and superficial neocortical sources with differing orientation components in an anatomically accurate model of the human head.
The goal of the study was to gain insight into the effect of anisotropy of skull and white matter conductivity through the visualization of field distributions, isopotential surfaces, and return current flow and through statistical error measures. One implicit premise of the study is that factors that affect the accuracy of the forward solution will have at least as strong an influence over solutions to the associated inverse problem.
Major findings of the study include (1) anisotropic white matter conductivity causes return currents to flow in directions parallel to the white matter fiber tracts; (2) skull anisotropy has a smearing effect on the forward potential computation; and (3) the deeper a source lies and the more it is surrounded by anisotropic tissue, the larger the influence of this anisotropy on the resulting electric and magnetic fields. Therefore, for the EEG, the presence of tissue anisotropy both for the skull and white matter compartment substantially compromises the forward potential computation and as a consequence, the inverse source reconstruction. In contrast, for the MEG, only the anisotropy of the white matter compartment has a significant effect. Finally, return currents with high amplitudes were found in the highly conducting cerebrospinal fluid compartment, underscoring the need for accurate modeling of this space.
Contemporary β-lactam antibiotic dosing is debatable in severely ill patients, since the occurrence of pathophysiological changes in critical illness can result in great inter-individual variability. ...Therapeutic drug monitoring (TDM) is a commonly used dosing strategy to optimize exposure and thereby minimize toxicity and maximize the efficacy. Currently, TDM of β-lactam antibiotics is rarely performed, due to poor availability in clinical practice. We describe an ultrafast Hydrophilic-Interaction Chromatography (HILIC) based UPLC–MS/MS method for the determination of amoxicillin, benzylpenicillin, cefotaxime, cefuroxime, ceftazidime, flucloxacillin, imipenem, meropenem and piperacillin in human plasma. This method involves simple sample preparation steps and was comprehensively validated according to standard FDA guidelines. For all analytes, mean accuracy and precision values were within the acceptance value. The lower and upper limits of quantification were found to be sufficient to cover the therapeutic range for all antibiotics. Finally, the method was successfully applied in a large pharmacokinetic study performed in the intensive care setting, and the feasibility of the analytical procedure was demonstrated in routine clinical practice. To the best of our knowledge, we report here the first HILIC-based UPLC–MS/MS assay for the determination of β-lactam antibiotics in human plasma. This simple, sensitive and ultrafast assay requires small-volume samples and can easily be implemented in clinical laboratories to promote the TDM of β-lactam antibiotics.
ABSTRACT
The latest generation of Galactic Plane surveys is enhancing our ability to study the effects of galactic environment upon the process of star formation. We present the first data from CO ...Heterodyne Inner Milky Way Plane Survey 2 (CHIMPS2). CHIMPS2 is a survey that will observe the Inner Galaxy, the Central Molecular Zone (CMZ), and a section of the Outer Galaxy in 12CO, 13CO, and C18O $(J = 3\rightarrow 2)$ emission with the Heterodyne Array Receiver Program on the James Clerk Maxwell Telescope (JCMT). The first CHIMPS2 data presented here are a first look towards the CMZ in 12CO J = 3 → 2 and cover ${-}3^{\circ }\, \le \, \ell \, \le \, 5^{\circ }$ and $\mid {b} \mid \, \le \, 0{_{.}^{\circ}} 5$ with angular resolution of 15 arcsec, velocity resolution of 1 km s−1, and rms $\Delta \, T_A ^\ast =$ 0.58 K at these resolutions. Such high-resolution observations of the CMZ will be a valuable data set for future studies, whilst complementing the existing Galactic Plane surveys, such as SEDIGISM, the ${Herschel}$ infrared Galactic Plane Survey, and ATLASGAL. In this paper, we discuss the survey plan, the current observations and data, as well as presenting position–position maps of the region. The position–velocity maps detect foreground spiral arms in both absorption and emission.
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