281 research outputs found
Exploring within-person variability in qualitative negative and positive Emotional Granularity by means of Latent Markov Factor Analysis
Emotional granularity (EG) is an individual’s ability to describe their emotional experiences in a nuanced and specific way. In this paper, we propose that researchers adopt latent Markov factor analysis (LMFA) to investigate within-person variability in qualitative EG (i.e., variability in distinct granularity patterns between specific emotions across time). LMFA clusters measurement occasions into latent states according to state-specific measurement models. We argue that state-specific measurement models of repeatedly assessed emotion items can provide information about qualitative EG at a given point in time. Applying LMFA to the area of EG for negative and positive emotions separately by using data from an experience sampling study with 11,662 measurement occasions across 139 participants, we found three latent EG states for the negative emotions and three for the positive emotions. Momentary stress significantly predicted transitions between the EG states for both the negative and positive emotions. We further identified two and three latent classes of individuals who differed in state trajectories for negative and positive emotions, respectively. Neuroticism and dispositional mood regulation predicted latent class membership for negative (but not for positive) emotions. We conclude that LMFA may enrich EG research by enabling more fine-grained insights into variability in qualitative EG patterns
[18F]ZCDD083: a PFKFB3-targeted PET tracer for atherosclerotic plaque imaging
Copyright © 2020 American Chemical Society. Funding We thank the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie ITNEuropean Joint Doctorate MOGLYNET (grant agreement No. 675527).Peer reviewedPostprin
IL-10 Receptor Signaling Is Essential for T R 1 Cell Function In Vivo
Interleukin-10 (IL-10) is essential to maintain intestinal homeostasis. CD4+ T regulatory type 1 (TR1) cells produce large amounts of this cytokine and being therefore currently examined in clinical trials as T-cell therapy in patients with inflammatory bowel disease (IBD). However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified in order to optimize the efficiency and to ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo
The FERONIA Receptor Kinase Maintains Cell-Wall Integrity during Salt Stress through Ca2+ Signaling
Cells maintain integrity despite changes in their mechanical properties elicited during growth and environmental stress. How cells sense their physical state and compensate for cell-wall damage is poorly understood, particularly in plants. Here we report that FERONIA (FER), a plasma-membrane-localized receptor kinase from Arabidopsis, is necessary for the recovery of root growth after exposure to high salinity, a widespread soil stress. The extracellular domain of FER displays tandem regions of homology with malectin, an animal protein known to bind di-glucose in vitro and important for protein quality control in the endoplasmic reticulum. The presence of malectin-like domains in FER and related receptor kinases has led to widespread speculation that they interact with cell-wall polysaccharides and can potentially serve a wall-sensing function. Results reported here show that salinity causes softening of the cell wall and that FER is necessary to sense these defects. When this function is disrupted in the fer mutant, root cells explode dramatically during growth recovery. Similar defects are observed in the mur1 mutant, which disrupts pectin cross-linking. Furthermore, fer cell-wall integrity defects can be rescued by treatment with calcium and borate, which also facilitate pectin cross-linking. Sensing of these salinity-induced wall defects might therefore be a direct consequence of physical interaction between the extracellular domain of FER and pectin. FER-dependent signaling elicits cell-specific calcium transients that maintain cell-wall integrity during salt stress. These results reveal a novel extracellular toxicity of salinity, and identify FER as a sensor of damage to the pectin-associated wall
Asteroids' physical models from combined dense and sparse photometry and scaling of the YORP effect by the observed obliquity distribution
The larger number of models of asteroid shapes and their rotational states
derived by the lightcurve inversion give us better insight into both the nature
of individual objects and the whole asteroid population. With a larger
statistical sample we can study the physical properties of asteroid
populations, such as main-belt asteroids or individual asteroid families, in
more detail. Shape models can also be used in combination with other types of
observational data (IR, adaptive optics images, stellar occultations), e.g., to
determine sizes and thermal properties. We use all available photometric data
of asteroids to derive their physical models by the lightcurve inversion method
and compare the observed pole latitude distributions of all asteroids with
known convex shape models with the simulated pole latitude distributions. We
used classical dense photometric lightcurves from several sources and
sparse-in-time photometry from the U.S. Naval Observatory in Flagstaff,
Catalina Sky Survey, and La Palma surveys (IAU codes 689, 703, 950) in the
lightcurve inversion method to determine asteroid convex models and their
rotational states. We also extended a simple dynamical model for the spin
evolution of asteroids used in our previous paper. We present 119 new asteroid
models derived from combined dense and sparse-in-time photometry. We discuss
the reliability of asteroid shape models derived only from Catalina Sky Survey
data (IAU code 703) and present 20 such models. By using different values for a
scaling parameter cYORP (corresponds to the magnitude of the YORP momentum) in
the dynamical model for the spin evolution and by comparing synthetics and
observed pole-latitude distributions, we were able to constrain the typical
values of the cYORP parameter as between 0.05 and 0.6.Comment: Accepted for publication in A&A, January 15, 201
Cost-effectiveness of stereotactic body radiation therapy versus video assisted thoracic surgery in medically operable stage I non-small cell lung cancer: A modeling study
Objectives: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC. Materials and methods: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses. Results: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations. Conclusion: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations
In situ Biological Dose Mapping Estimates the Radiation Burden Delivered to ‘Spared’ Tissue between Synchrotron X-Ray Microbeam Radiotherapy Tracks
Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to ‘spared’ tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30–40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies
Switching on the Lights for Gene Therapy
Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application
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