ABSTRACT
Two camera systems are installed on the DIII-D tokamak at the toroidal positions of 90° (90° system) and 225° (225° system), respectively. The cameras have two types of relay optics, namely, a coherent optical fiber bundle and a periscope system. The periscope system provides absolute intensity calibration stability while sacrificing resolution (10 lp/mm), while the fiber system provides high resolution (16 lp/mm) while sacrificing calibration stability. The periscope is available only for the 90° system. The optics of the 225° system were designed for view stability, repeatability, and easy maintenance. The cameras are located inside optimized neutron, x ray and magnetic shielding in order to reduce electronics damage, reboots, and magnetic and neutron interference, increasing the overall system reliability. An automated filter wheel, providing remote filter change, allows for remote wavelength selection. A software suite automates camera acquisition and data storage, allowing for remote operation and reduced operator involvement. System metadata is used to streamline the data analysis workflow, particularly for intensity calibration. The spatial calibration uses multiple observable wall features, resulting in a reconstruction accuracy ≤2 cm.
ABSTRACT
PURPOSE: To investigate the mRNA expression of B-MYB and MDM2 together with their p53 relatedness in clear cell renal cell carcinoma (ccRCC). METHODS: Genes were screened for their mRNA expression from 529 patients in a publicly available ccRCC cohort (TCGA). A cohort of 101 patients with ccRCC served as validation by qRT-PCR mRNA tissue expression analysis. RESULTS: Expression: B-MYB expression was significantly higher in high-grade tumours (p < 0.0001 and p = 0.048) and in advanced stages (p = 0.005 and p = 0.037) in both cohorts. Correlation: p53-B-MYB as well as MDM2-B-MYB showed significant correlations in local and low-grade ccRCCs, but not in high grade tumours or advanced stages (r < 0.3 and/or p > 0.05). Survival: Multivariable Cox regression of the TCGA cohort revealed B-MYB upregulation and low MDM2 expression as predictors for an impaired overall survival (OS) (HR 1.97; p = 0.0003; HR 2.94, p < 0.0001) and progression-free survival (PFS) (HR 2.86; p = 0.0005; HR 1.58, p = 0.046). In the validation cohort, the results were confirmed for OS by univariable, but not multivariable regression: high B-MYB expression (HR = 3.05, p = 0.035) and low MDM2 expression (HR 3.81, p value 0.036). CONCLUSION: In ccRCC patients with high-grade tumours and advanced stages, high B-MYB expression is common and is associated with poorer OS and PFS. These patients show a loss of their physiological B-MYB-p53 network correlation, suggesting an additional, alternative regulatory, oncogenic mechanism. Assuming further characterization of its signalling pathways, B-MYB could be a potential therapy target for ccRCC.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/pathology , Cell Cycle Proteins/metabolism , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/pathology , Trans-Activators/metabolism , Tumor Suppressor Protein p53/metabolism , Aged , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Cell Cycle Proteins/genetics , Disease Progression , Female , Follow-Up Studies , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Male , Middle Aged , Prognosis , Survival Rate , Trans-Activators/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
Since its discovery in 1945, methotrexate has become a standard therapy for number of diseases, including oncological, inflammatory and pulmonary ones. Major physiological interactions of methotrexate include folate pathway, adenosine, prostaglandins, leukotrienes and cytokines. Methotrexate is used in treatment of pulmonary sarcoidosis as a second line therapy and is drug of choice in patients who are not candidates for corticosteroid therapy, with recommended starting weekly dose of 5-15 mg. Number of studies dealt with methotrexate use in rheumatoid arthritis and oncological patients. Authors are conducting research on oral methotrexate use and pharmacokinetics in chronic sarcoidosis patients and have performed literature research to better understand molecular mechanisms of methotrexate action as well as high level pharmacokinetic considerations. Polyglutamation of methotrexate affects its pharmacokinetic and pharmacodynamic properties and prolongs its effect. Bile excretion plays significant role due to extensive enterohepatic recirculation, although majority of methotrexate is excreted through urine. Better understanding of its pharmacokinetic properties in sarcoidosis patients warrant optimizing therapy when corticosteroids are contraindicated in these patients.
Subject(s)
Methotrexate/metabolism , Methotrexate/pharmacology , Methotrexate/pharmacokinetics , Antirheumatic Agents , Arthritis, Rheumatoid/metabolism , Cytokines/metabolism , Humans , Polyglutamic Acid/metabolism , Polyglutamic Acid/pharmacology , Prostaglandin-Endoperoxide Synthases/metabolism , Sarcoidosis/drug therapy , Tetrahydrofolate Dehydrogenase/metabolismABSTRACT
Hyperosmolar micromilieu has been observed in physiologic (kidney medulla, lymphatic tissue) and pathologic (renal allorejection, solid tumors) conditions. Hyperosmolarity can modulate gene expression and alter the stimulatory profile of macrophages and dendritic cells. We have reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection. Moreover, we showed that a hyperosmotic microenvironment affects the cross-priming capacity of dendritic cells. Using ovalbumin as a model antigen, we showed that exposure of dendritic cells to hyperosmolarity strongly inhibits activation of antigen-specific T cells despite enhancement of antigen uptake, processing, and presentation; it can reduce dendritic cell-T cell contact time. We have identified TRIF as key mediator of this phenomenon. Moreover, we detected a hyperosmolarity-triggered, TRIF-dependent clustering of MHC class Iantigen complexes, but not of unloaded MHCI molecules, providing a possible explanation for a reduced T cell activation. Our findings identify dendritic cells as important players in hyperosmolarity-triggered immune imbalance and suggest that targeting local hyperosmolarity in tumor micromilieu may contribute to an enhanced specific anti-tumor immune response.
Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Dendritic Cells , Histocompatibility Antigens Class I , Cross-Priming , Dendritic Cells/drug effects , Dendritic Cells/immunology , Histocompatibility Antigens Class I/metabolism , Humans , Lymphocyte Activation , Osmoregulation , Ovalbumin/immunology , T-LymphocytesABSTRACT
A portable Runaway Electron Imaging and Spectrometry System (REIS) was developed in ENEA-Frascati to measure synchrotron radiation spectra from in-flight runaway electrons in tokamaks. The REIS is a wide-angle optical system collecting simultaneously visible and infrared emission spectra using an incoherent bundle of fibers, in a spectral range that spans from 500 nm to 2500 nm, and visible images using a CCD color microcamera at a rate of 25 frames/s. The REIS system is supervised and managed using a dedicated LabVIEW program to acquire data simultaneously from three spectrometers every 20 ms (configurable down to 10 ms). An overview of the REIS architecture and acquisition system and resulting experimental data obtained in FTU are presented and discussed in this paper.
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In investigation of (patho)physiological processes, cells represent frequently used analyte as an exceptional source of information. However, spectroscopic analysis of live cells is still very seldom in clinics, as well as in research studies. Among others, the reasons are long acquisition time during which autolysis process is activated, necessity of specified technical equipment, and inability to perform analysis in a moment of sample preparation. Hence, an optimal method of preserving cells in the existing state is of extreme importance, having in mind that selection of fixative is cell lineage dependent. In this study, two commonly used chemical fixatives, formaldehyde and methanol, are used for preserving primary mesenchymal stem cells extracted from periodontal ligament, which are valuable cell source for reconstructive dentistry. By means of Raman spectroscopy, cell samples were probed and the impact of these fixatives on their Raman response was analyzed and compared. Different chemical mechanisms are the core processes of formaldehyde and methanol fixation and certain Raman bands are shifted and/or of changed intensity when Raman spectra of cells fixed in that manner are compared. In order to get clearer picture, comprehensive statistical analysis was performed.
Subject(s)
Fixatives/chemistry , Formaldehyde/chemistry , Mesenchymal Stem Cells/chemistry , Methanol/chemistry , Spectrum Analysis, Raman/methods , Tissue Fixation/methods , Cell Separation , Cells, Cultured , Humans , Mesenchymal Stem Cells/cytology , Periodontal Ligament/chemistry , Periodontal Ligament/cytologyABSTRACT
We have employed micro-Raman spectroscopy to get insight into intrinsic biomolecular profile of individual mesenchymal stem cell isolated from periodontal ligament. Furthermore, these cells were stimulated towards adipogenic, chondrogenic, and osteogenic lineages and their status of differentiation was assessed using micro-Raman spectroscopy. In both cases, glass coverslips were used as substrates, due to their wide availability and cost effectiveness. In all sample groups, the same type of behavior was observed, manifested as changes in Raman spectra: the increase of relative intensity of protein/lipid bands and decrease of nucleic acid bands. Comprehensive statistical analysis in the form of principal component analysis was performed, which revealed noticeable grouping of cells with the similar features. Despite the inhomogeneity of primary stem cells and their differentiated lineages, we demonstrated that micro-Raman spectroscopy is sufficient for distinguishing cells' status, which can be valuable for medical and clinical application.
Subject(s)
Cell Differentiation , Mesenchymal Stem Cells/cytology , Spectrum Analysis, Raman/methods , Adolescent , Adult , Cell Lineage , Cells, Cultured , Humans , Microspectrophotometry , Periodontal Ligament/cytology , Principal Component Analysis , Young AdultABSTRACT
We report on the magnetic properties of HoCo dimers as a model system for the smallest intermetallic compound of a lanthanide and a transition metal atom. The dimers are adsorbed on ultrathin MgO(100) films grown on Ag(100). New for 4f elements, we detect inelastic excitations with scanning tunneling spectroscopy and prove their magnetic origin by applying an external magnetic field. In combination with density functional theory and spin Hamiltonian analysis, we determine the magnetic level distribution, as well as sign and magnitude of the exchange interaction between the two atoms. In contrast to typical 4f-3d bulk compounds, we find ferromagnetic coupling in the dimer.
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Polarized Raman scattering spectra of the K x Co2-y Se2 single crystals reveal the presence of two phonon modes, assigned as of the A 1g and B 1g symmetry. The absence of additional modes excludes the possibility of vacancy ordering, unlike in K x Fe2-y Se2. The ferromagnetic (FM) phase transition at [Formula: see text] K leaves a clear fingerprint on the temperature dependence of the Raman mode energy and linewidth. For [Formula: see text] the temperature dependence looks conventional, driven by the thermal expansion and anharmonicity. The Raman modes are rather broad due to the electron-phonon coupling increased by the disorder and spin fluctuation effects. In the FM phase the phonon frequency of both modes increases, while an opposite trend is seen in their linewidth: the A 1g mode narrows in the FM phase, whereas the B 1g mode broadens. We argue that the large asymmetry and anomalous frequency shift of the B 1g mode is due to the coupling of spin fluctuations and vibration. Our density functional theory (DFT) calculations for the phonon frequencies agree rather well with the Raman measurements, with some discrepancy being expected since the DFT calculations neglect the spin fluctuations.
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Polarized Raman scattering spectra of superconducting K(x)Fe(2-y)Se2 and non-superconducting K0.8Fe1.8Co0.2Se2 single crystals were measured in the temperature range from 10 K up to 300 K. Two Raman active modes from the I4/mmm phase and seven from the I4/m phase are observed in the frequency range from 150 to 325 cm(-1) in both compounds, suggesting that the K0.8Fe1.8Co0.2Se2 single crystal also has a two-phase nature. The temperature dependence of the Raman mode energy is analyzed in terms of lattice thermal expansion and phonon-phonon interaction. The temperature dependence of the Raman mode linewidth is dominated by temperature-induced anharmonic effects. It is shown that the change in Raman mode energy with temperature is dominantly driven by thermal expansion of the crystal lattice. An abrupt change of the A1g mode energy near T(C) was observed in K(x)Fe(2-y) Se2, whereas it is absent in non-superconducting K0.8Fe1.8Co0.2Se2. Phonon energy hardening at low temperatures in the superconducting sample is a consequence of superconductivity-induced redistribution of the electronic states below the critical temperature.
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We report the low-temperature Raman scattering study of racemic ibuprofen. Detailed analysis of the racemic ibuprofen crystal symmetry, related to the vibrational properties of the system, has been presented. The first principle calculations of a single ibuprofen molecule dynamical properties are compered with experimental data. Nineteen, out of 26 modes expected for the spectral region below 200cm(-1), have been observed.
Subject(s)
Analgesics, Non-Narcotic/chemistry , Ibuprofen/chemistry , Cold Temperature , Models, Molecular , Spectrum Analysis, Raman/methodsABSTRACT
We developed a full symmetry implementing method, based on classical molecular dynamics with the Brenner-Tersoff potential, for determining the optimal configuration of homogeneously deformed infinitely long single-wall carbon nanotubes. All nanotubes with diameter less than 1.3 nm are studied. Systematic analysis of the coupling between different types of deformation shows that, in the tubes with chiral angle close to zero and 30°, the torsion-induced circumferential strain is opposite to the induced axial strain. Also, torsion in zigzag tubes induces larger circumferential strain, but in armchair tubes it yields a larger axial strain. The influence of diameter on axial-stretching-induced torsion becomes significant only for narrow tubes. Finally, significant deviation from the linear dependence of axial-strain-induced radial deformation is found for zigzag tubes. The presented results are important for the calculation of electro-optical properties of nanotubes under strain.
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We have measured the magnetization of undoped and Fe(2+/3+) doped CeO(2-y) nanocrystals at various temperatures and magnetic fields. The Stoner condition N(0)I > 1 is multiply fulfilled in the case of nano-CeO(2-y), favoring the band ferromagnetism approach. In the case of Fe-doped samples, the magnetization versus magnetic field dependence is well fitted with a weighted Langevin function. A blocking temperature of about 20 K is obtained both from the ZFC/FC curves and from the coercive field against temperature dependence. The temperature and field dependence of the magnetization clearly shows the presence of nanosized particles which exhibit superparamagnetic behavior.
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The lattice dynamics of FeSb(2) is investigated by first-principles density functional theory calculations and Raman spectroscopy. All Raman- and infrared-active phonon modes are properly assigned. The calculated and measured phonon energies are in good agreement. We have observed strong mixing of the A(g) symmetry modes, with the intensity exchange in the temperature range 210 and 260 K. The A(g) mode repulsion increases by doping FeSb(2) with Co, with no signatures of the electron-phonon interaction for these modes.
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The phonon properties of CoSb(2) have been investigated by Raman scattering spectroscopy and lattice dynamics calculations. Sixteen out of eighteen Raman active modes predicted by factor-group analysis are experimentally observed and assigned. The calculated and measured phonon energies at the Γ point are in very good agreement. The temperature dependence of the A(g) symmetry modes is well represented by phonon-phonon interactions without contribution from any other phonon or electron related interactions.
Subject(s)
Antimony/chemistry , Cobalt/chemistry , Phonons , Crystallography, X-Ray , Electrons , Models, Chemical , Spectrum Analysis, Raman , Temperature , VibrationABSTRACT
BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) exhibit a difference in left ventricular outflow tract (LVOT) obstruction, independently of basal septal thickness (BST). Some patients with HCM have a steeper left ventricle to aortic root angle than controls. OBJECTIVE: To test the predictors of the LV-aortic root angle and the association between LV-aortic root angle and LVOT obstruction using three-dimensional imaging. PATIENTS: 153 consecutive patients with HCM (mean (SD) age 46 (14) years, 68% men) and 62 patients with hypertensive heart disease of the elderly (all >65 years of age, 73 (6) years, 34% men) who underwent whole-heart three-dimensional cardiac magnetic resonance (CMR) angiography (1.5 T) and Doppler echocardiography. Forty-two controls (age 43 (11) years, 38% men) who underwent contrast-enhanced multidetector computed tomography and were free of cardiovascular pathology were also studied. MAIN OUTCOMES: LV-aortic root angle, BST and maximal non-exercise LVOT gradient were measured in patients with HCM and in hypertensive-elderly patients. Additionally, LV-aortic root angle and BST were measured in controls. RESULTS: The mean (SD) LV-aortic root angle was significantly different (p<0.001) in the three groups: HCM (134 (10) degrees ), hypertensive-elderly (128 (10) degrees ), control (140 (7) degrees ). There was an inverse correlation between age and LV-aortic root angle in the three groups (all p<0.001): HCM (r = -0.56), hypertensive-elderly (r = -0.35), control (r = -0.48). On univariate analysis, in the HCM group, LV-aortic root angle (beta = -0.34, p<0.001), age (beta = 0.23, p = 0.01) and end-systolic volume index (beta = -0.20, p = 0.02), but not BST (beta = 0.02, p = 0.8), were associated with LVOT gradient. On multivariate analysis, only LV-aortic root angle was associated with LVOT gradient. CONCLUSIONS: Patients with HCM have a steeper LV-aortic root angle than controls. In patients with HCM, a steeper LV-aortic root angle predicts dynamic LVOT obstruction, independently of BST.
Subject(s)
Aorta, Thoracic/pathology , Cardiomyopathy, Hypertrophic/pathology , Heart Ventricles/pathology , Ventricular Outflow Obstruction/pathology , Aged , Cardiomyopathy, Hypertrophic/complications , Case-Control Studies , Female , Humans , Imaging, Three-Dimensional , Male , Ventricular Outflow Obstruction/etiologyABSTRACT
The design of electromagnetic invisibility cloaks is based on singular mappings prescribing zero or infinite values for material parameters on the inner surface of the cloak. Since this is only approximately feasible, an asymptotic analysis is necessary for a sound description of cloaks. We adopt a simple and effective approach for analyzing electromagnetic cloaks - instead of the originally proposed singular mapping, nonsingular mappings asymptotically approaching the ideal one are considered. Scattering and radiation from this type of imperfect cylindrical cloaks is solved analytically and the results are confirmed by full-wave finite element simulations. Our analysis sheds more light on the influence of this kind of imperfection on the cloaking performance and further explores the physics of cloaking devices.
Subject(s)
Algorithms , Electromagnetic Fields , Models, Theoretical , Radiometry/methods , Security Measures , Computer Simulation , Radiation Dosage , Scattering, RadiationABSTRACT
BACKGROUND: Heart failure patients who are candidates for CRT frequently display longitudinal rotation (LR) - a swinging motion of the heart when imaged in a horizontal long-axis plane. OBJECTIVES: To identify the magnitude and predictors of LR in patients with ischaemic (ICM) and idiopathic dilated (DCM) cardiomyopathy, and to assess predictive value of LR in patients undergoing cardiac resynchronisation therapy (CRT). DESIGN AND SETTING: A retrospective study in a tertiary heart care setting. METHODS: Echocardiography was performed in 45 ICM and 41 DCM patients who were CRT candidates and 16 control subjects. Global LR, segmental strains and segmental LR were assessed from echocardiograms using speckle tracking. Repeat echocardiography >40 days after the beginning of CRT was performed in 64 patients. RESULTS: While DCM patients with QRS duration of both <130 ms and > or =130 ms displayed significant clockwise LR (p<0.001 for both vs 0), ICM patients and control subjects had LR that did not differ from 0. The most significant LR predictor was end-diastolic volume (p<0.001) followed by the absence of ischaemia (p<0.001) and QRS duration (p = 0.05). DCM patients with prominent clockwise LR had lower septal but higher lateral strains than DCM patients with minimal LR, or ICM patients with counterclockwise LR. LR correlated with decrease of end-systolic volume in DCM (r = 0.49, p = 0.004), while no relationship was observed in ICM. CONCLUSION: Clockwise LR is linked to presence of DCM, with the small impact of QRS duration. LR is a moderately strong predictor of end-systolic volume decrease during CRT in DCM.
Subject(s)
Cardiomyopathy, Dilated/diagnostic imaging , Echocardiography, Doppler/methods , Image Processing, Computer-Assisted/methods , Movement/physiology , Aged , Cardiac Pacing, Artificial/methods , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/therapy , Diastole/physiology , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Prognosis , Rotation , Stroke Volume/physiology , Systole/physiologyABSTRACT
BACKGROUND: Abnormal papillary muscles (PM) are often found in hypertrophic cardiomyopathy (HCM). OBJECTIVE: To assess the relationship between morphological alterations of PM in patients with HCM and left ventricular outflow tract (LVOT) obstruction, using magnetic resonance imaging (MRI) and echocardiography. METHODS: Fifty-six patients with HCM (mean age 42 years (interquartile range 27, 51), 70% male) and 30 controls (mean age (42 (30, 53) years, 80% male) underwent MRI on a 1.5 T scanner (Siemens, Erlangen, Germany). Standard cine images were obtained in short-axis (base to apex), along with two-, three- and four-chamber views. The presence of bifid PM (none, one or both) and anteroapical displacement of anterolateral PM was recorded by MRI and correlated with resting LVOT gradients obtained by echocardiography. RESULTS: Double bifid PM (70% vs 17%) and anteroapical displacement of anterolateral PM (77% vs 17%) were more prevalent in patients with HCM than in controls (p<0.001). Subjects with anteroapically displaced PM and double bifid PM had higher resting LVOT gradients than controls (45 (6, 81) vs 12 (0, 12) mm Hg (p<0.01) and 42 (6, 64) vs 11 (0, 17) mm Hg (p = 0.02), respectively. In patients with HCM, the odds ratio of having significant (>or=30 mm Hg) peak resting gradient was 7.1 (95% CI 1.4 to 36.7) for anteroapically displaced anterolateral PM and 10.4 (95% CI 1.2 to 91.2) for double bifid PM (both p = 0.005), independent of septal thickness, use of beta-blockers and/or calcium blockers and resting heart rate. CONCLUSIONS: Patients with HCM with abnormal PM have a higher degree of resting LVOT gradient, which is independent of septal thickness.