Development of an ex vivo model for the study of cerebrovascular function utilizing isolated mouse olfactory artery

OBJECTIVE: Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. METHODS: The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately -500 µm in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). RESULTS: We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin PGH(2). Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. CONCLUSION: Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models

Suppressed dependence of polarization on epitaxial strain in highly polar ferroelectrics

A combined experimental and computational investigation of coupling between polarization and epitaxial strain in highly polar ferroelectric PbZr_0.2Ti_0.8O_3 (PZT) thin films is reported. A comparison of the properties of relaxed (tetragonality c/a = 1.05) and highly-strained (c/a = 1.09) epitaxial films shows that polarization, while being amongst the highest reported for PZT or PbTiO_3 in either film or bulk forms (P_r = 82 microC/cm^2), is almost independent of the epitaxial strain. We attribute this behavior to a suppressed sensitivity of the A-site cations to epitaxial strain in these Pb-based perovskites, where the ferroelectric displacements are already large, contrary to the case of less polar perovskites, such as BaTiO_3. In the latter case, the A-site cation (Ba) and equatorial oxygen displacements can lead to substantial polarization increases.Comment: 4 pages, 3 figure

Monte Carlo calculation of the current-voltage characteristics of a two dimensional lattice Coulomb gas

We have studied the nonlinear current-voltage characteristic of a two dimensional lattice Coulomb gas by Monte Carlo simulation. We present three different determinations of the power-law exponent $a(T)$ of the nonlinear current-voltage characteristic, $V \sim I^{a(T)+1}$. The determinations rely on both equilibrium and non-equilibrium simulations. We find good agreement between the different determinations, and our results also agree closely with experimental results for Hg-Xe thin film superconductors and for certain single crystal thin-film high temperature superconductors.Comment: late

Resistance scaling at the Kosterlitz-Thouless transition

We study the linear resistance at the Kosterlitz-Thouless transition by Monte Carlo simulation of vortex dynamics. Finite size scaling analysis of our data show excellent agreement with scaling properties of the Kosterlitz-Thouless transition. We also compare our results for the linear resistance with experiments. By adjusting the vortex chemical potential to an optimum value, the resistance at temperatures above the transition temperature agrees well with experiments over many decades.Comment: 7 pages, 4 postscript figures included, LATEX, KTH-CMT-94-00

Robotic Bronchoscopy: Review of Three Systems

Robotic bronchoscopy (RB) has been shown to improve access to smaller and more peripheral lung lesions, while simultaneously staging the mediastinum. Pre-clinical studies demonstrated extremely high diagnostic yields, but real-world RB yields have yet to fully matched up in prospective studies. Despite this, RB technology has rapidly evolved and has great potential for lung-cancer diagnosis and even treatment. In this article, we review the historical and present challenges with RB in order to compare three RB systems

Clinical Experience With Angiotensin II Receptor Antagonists

This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case. Am J Hypertens 1992;5:243S-246

Monte Carlo calculation of the linear resistance of a three dimensional lattice Superconductor model in the London limit

We have studied the linear resistance of a three dimensional lattice Superconductor model in the London limit London lattice model by Monte Carlo simulation of the vortex loop dynamics. We find excellent finite size scaling at the phase transition. We determine the dynamical exponent $z = 1.51$ for the isotropic London lattice model.Comment: 4 pages, RevTeX with 3 postscript figures include

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

The Stellar and Gaseous Contents of the Orion Dwarf Galaxy

We present new KPNO 0.9-m optical and VLA HI spectral line observations of the Orion dwarf galaxy. This nearby (D ~ 5.4 Mpc), intermediate-mass (M_dyn = 1.1x10^10 Solar masses) dwarf displays a wealth of structure in its neutral ISM, including three prominent "hole/depression" features in the inner HI disk. We explore the rich gas kinematics, where solid-body rotation dominates and the rotation curve is flat out to the observed edge of the HI disk (~6.8 kpc). The Orion dwarf contains a substantial fraction of dark matter throughout its disk: comparing the 4.7x10^8 Solar masses of detected neutral gas with estimates of the stellar mass from optical and near-infrared imaging (3.7x10^8 Solar masses) implies a mass-to-light ratio of ~13. New H alpha observations show only modest-strength current star formation (~0.04 Solar masses per year); this star formation rate is consistent with our 1.4 GHz radio continuum non-detection.Comment: Astronomical Journal, in press. Full-resolution version available from http://www.macalester.edu/~jcannon/pubs.htm