Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells

OBJECTIVE:Vascular smooth muscle cell (VSMC) hypertrophy and proliferation occur in response to strain-induced local and systemic inflammatory cytokines and growth factors which may contribute to hypertension, atherosclerosis, and restenosis. We hypothesize VSMC strain, modeling normotensive arterial pressure waveforms in vitro, results in attenuated proliferative and increased hypertrophic responses 48 hrs post-strain.METHODS:Using Flexcell Bioflex Systems we determined the morphological, hyperplastic and hypertrophic responses of non-strained and biomechanically strained cultured rat A7R5 VSMC. We measured secretion of nitric oxide, key cytokine/growth factors and intracellular mediators involved in VSMC proliferation via fluorescence spectroscopy and protein microarrays. We also investigated the potential roles of VEGF on VSMC strain-induced proliferation.RESULTS:Protein microarrays revealed significant increases in VEGF secretion in response to 18 hours mechanical strain, a result that ELISA data corroborated. Apoptosis-inducing nitric oxide (NO) levels also increased 43% 48 hrs post-strain. Non-strained cells incubated with exogenous VEGF did not reproduce the antimitogenic effect. However, anti-VEGF reversed the antimitogenic effect of mechanical strain. Antibody microarrays of strained VSMC lysates revealed MEK1, MEK2, phospo-MEK1T385, T291, T298, phospho-Erk1/2T202+Y204/T185+T187, and PKC isoforms expression were universally increased, suggesting a proliferative/inflammatory signaling state. Conversely, VSMC strain decreased expression levels of Cdk1, Cdk2, Cdk4, and Cdk6 by 25-50% suggesting a partially inhibited proliferative signaling cascade.CONCLUSIONS:Subjecting VSMC to cyclic biomechanical strain in vitro promotes cell hypertrophy while attenuating cellular proliferation. We also report an upregulation of MEK and ERK activation suggestive of a proliferative phenotype. Hhowever, the proliferative response appears to be aborogated by enhanced antimitogenic cytokine VEGF, NO secretion and downregulation of Cdk expression. Although exogenous VEGF alone is not sufficient to promote the quiescent VSMC phenotype, we provide evidence suggesting that strain is a necessary component to induce VSMC response to the antimitogenic effects of VEGF. Taken together these data indicate that VEGF plays a critical role in mechanical strain-induced VSMC proliferation and vessel wall remodeling. Whether VEGF and/or NO inhibit signaling distal to Erk 1/2 is currently under investigation.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Electron interaction with domain walls in antiferromagnetically coupled multilayers

For antiferromagnetically coupled Fe/Cr multilayers the low field contribution to the resistivity, which is caused by the domain walls, is strongly enhanced at low temperatures. The low temperature resistivity varies according to a power law with the exponent about 0.7 to 1. This behavior can not be explained assuming ballistic electron transport through the domain walls. It is necessary to invoke the suppression of anti-localization effects (positive quantum correction to conductivity) by the nonuniform gauge fields caused by the domain walls.Comment: 5 pages with 3 figure

Validation of the self regulation questionnaire as a measure of health in quality of life research

<p>Abstract</p> <p>Objectives</p> <p>Several epidemiological studies address psychosomatic 'self regulation' as a measure of quality of life aspects. However, although widely used in studies with a focus on complementary cancer treatment, and recognized to be associated with better survival of cancer patients, it is unclear what the 'self regulation' questionnaire exactly measures.</p> <p>Design and setting</p> <p>In a sample of 444 individuals (27% healthy, 33% cancer, 40% other internal diseases), we performed reliability and exploratory factor analyses, and correlated the 16-item instrument with external measures such as the Hospital Anxiety and Depression Scale, the Herdecke Quality of Life questionnaire, and autonomic regulation questionnaire.</p> <p>Results</p> <p>The 16-item pool had a very good internal consistency (Cronbach's alpha = 0.948) and satisfying/good (r_rt= 0.796) test-retest reliability after 3 months. Exploratory factor analysis indicated 2 sub-constructs: (1) Ability to change behaviour in order to reach goals, and (2) Achieve satisfaction and well-being. Both sub-scales correlated well with quality of life aspects, particularly with Initiative Power/Interest, Social Interactions, Mental Balance, and negatively with anxiety and depression.</p> <p>Conclusions</p> <p>The Self Regulation Questionnaire (SRQ) was found to be a valid and reliable tool which measures unique psychosomatic abilities. Self regulation deals with competence and autonomy and can be regarded as a problem solving capacity in terms of an active adaptation to stressful situations to restore wellbeing. The tool is an interesting option to be used particularly in complementary medicine research with a focus on behavioural modification.</p

Nanoconfined circular and linear DNA - equilibrium conformations and unfolding kinetics

Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of DNA from the circular to linear configuration as a light-induced double strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to which extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.Comment: 21 pages, 7 figures, 1 tabl

Generation of annotated multimodal ground truth datasets for abdominal medical image registration

Sparsity of annotated data is a major limitation in medical image processing tasks such as registration. Registered multimodal image data are essential for the diagnosis of medical conditions and the success of interventional medical procedures. To overcome the shortage of data, we present a method that allows the generation of annotated multimodal 4D datasets. We use a CycleGAN network architecture to generate multimodal synthetic data from the 4D extended cardiac-torso (XCAT) phantom and real patient data. Organ masks are provided by the XCAT phantom, therefore the generated dataset can serve as ground truth for image segmentation and registration. Realistic simulation of respiration and heartbeat is possible within the XCAT framework. To underline the usability as a registration ground truth, a proof of principle registration is performed. Compared to real patient data, the synthetic data showed good agreement regarding the image voxel intensity distribution and the noise characteristics. The generated T1-weighted magnetic resonance imaging (MRI), computed tomography (CT), and cone beam CT (CBCT) images are inherently co-registered. Thus, the synthetic dataset allowed us to optimize registration parameters of a multimodal non-rigid registration, utilizing liver organ masks for evaluation. Our proposed framework provides not only annotated but also multimodal synthetic data which can serve as a ground truth for various tasks in medical imaging processing. We demonstrated the applicability of synthetic data for the development of multimodal medical image registration algorithms.Comment: 12 pages, 5 figures. This work has been published in the International Journal of Computer Assisted Radiology and Surgery volum

Structural Invariance of Sunspot Umbrae Over the Solar Cycle: 1993-2004

Measurements of maximum magnetic flux, minimum intensity, and size are presented for 12 967 sunspot umbrae detected on the NASA/NSO spectromagnetograms between 1993 and 2004 to study umbral structure and strength during the solar cycle. The umbrae are selected using an automated thresholding technique. Measured umbral intensities are first corrected for a confirming observation of umbral limb-darkening. Log-normal fits to the observed size distribution confirm that the size spectrum shape does not vary with time. The intensity-magnetic flux relationship is found to be steady over the solar cycle. The dependence of umbral size on the magnetic flux and minimum intensity are also independent of cycle phase and give linear and quadratic relations, respectively. While the large sample size does show a low amplitude oscillation in the mean minimum intensity and maximum magnetic flux correlated with the solar cycle, this can be explained in terms of variations in the mean umbral size. These size variations, however, are small and do not substantiate a meaningful change in the size spectrum of the umbrae generated by the Sun. Thus, in contrast to previous reports, the observations suggest the equilibrium structure, as testified by the invariant size-magnetic field relationship, as well as the mean size (i.e. strength) of sunspot umbrae do not significantly depend on solar cycle phase.Comment: 17 pages, 6 figures. Published in Solar Physic