In Vivo Imaging of Vesicular Monoamine Transporters in Human Brain Using [ 11 C]Tetrabenazine and Positron Emission Tomography

The pharmacokinetics of [ 11 CJtetrabenazine, a high-affinity radioligand for the monoamine vesicular transporter, were determined in living human brain using in vivo imaging by positron emission tomography (PET). The radiotracer showed high brain uptake and rapid washout from all brain regions with relatively slower clearance from regions of highest concentrations of monoamine vesicular transporters (striatum), resulting in clear differential visualization of these structures at short intervals after injection (10–20 min). As the first human PET imaging study of a vesicular neurotransmitter transporter, these experiments demonstrate that external imaging of vesicular transporters forms a new and valuable approach to the in vivo quantification of monoaminergic neurons, with potential application to the in vivo study of neurodegenerative disorders such as Parkinson's disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65743/1/j.1471-4159.1993.tb03521.x.pd

Formation energy and interaction of point defects in two-dimensional colloidal crystals

The manipulation of individual colloidal particles using optical tweezers has allowed vacancies to be created in two-dimensional (2d) colloidal crystals, with unprecedented possibility of real-time monitoring the dynamics of such defects (Nature {\bf 413}, 147 (2001)). In this Letter, we employ molecular dynamics (MD) simulations to calculate the formation energy of single defects and the binding energy between pairs of defects in a 2d colloidal crystal. In the light of our results, experimental observations of vacancies could be explained and then compared to simulation results for the interstitial defects. We see a remarkable similarity between our results for a 2d colloidal crystal and the 2d Wigner crystal (Phys. Rev. Lett. {\bf 86}, 492 (2001)). The results show that the formation energy to create a single interstitial is $12$ lower than that of the vacancy. Because the pair binding energies of the defects are strongly attractive for short distances, the ground state should correspond to bound pairs with the interstitial bound pairs being the most probable.Comment: 5 pages, 2 figure

Determination of pulsation periods and other parameters of 2875 stars classified as MIRA in the All Sky Automated Survey (ASAS)

We have developed an interactive PYTHON code and derived crucial ephemeris data of 99.4% of all stars classified as 'Mira' in the ASAS data base, referring to pulsation periods, mean maximum magnitudes and, whenever possible, the amplitudes among others. We present a statistical comparison between our results and those given by the AAVSO International Variable Star Index (VSX), as well as those determined with the machine learning automatic procedure of Richards et al. 2012. Our periods are in good agreement with those of the VSX in more than 95% of the stars. However, when comparing our periods with those of Richards et al, the coincidence rate is only 76% and most of the remaining cases refer to aliases. We conclude that automatic codes require still more refinements in order to provide reliable period values. Period distributions of the target stars show three local maxima around 215, 275 and 330 d, apparently of universal validity, their relative strength seems to depend on galactic longitude. Our visual amplitude distribution turns out to be bimodal, however 1/3 of the targets have rather small amplitudes (A $<$ 2.5$^{m}$) and could refer to semi-regular variables (SR). We estimate that about 20% of our targets belong to the SR class. We also provide a list of 63 candidates for period variations and a sample of 35 multiperiodic stars which seem to confirm the universal validity of typical sequences in the double period and in the Petersen diagramsComment: 14 pages, 14 figures, and 8 tables. Accepted to The Astrophysical Journal Supplement Series, September 201

Synthesis of [11C]tetrabenazine, a vesicular monoamine uptake inhibitor, for PET imaging studies

Tetrabenazine (TBZ), a high affinity and specific inhibitor of the vesicular monoamine transporter, has been labeled with carbon-11 as a potential probe for in vivo positron emission tomographic imaging of monoaminergic neuronal losses in neurodegenerative diseases. [11C]TBZ was synthesized by O-[11C]methylation of the 9-O-desmethylTBZ using [11C]methyl iodide in the presence of tetrabutyl-ammonium hydroxide. The radiochemical yields were 35-55% (decay corrected) and the synthesis time 32-37 min from EOB. [11C]TBZ was obtained with specific activities of 2000-2500 Ci/mmol (EOS) and radiochemical and chemical purities were &gt;95%. [11C]Tetrabenazine is a promising new radioligand for the in vivo study of monoaminergic neurons using PET.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30889/1/0000558.pd

Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

<p>Abstract</p> <p>Background</p> <p>Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE) release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ) rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function.</p> <p>Methods</p> <p>Cardiac sympathetic nervous integrity was investigated <it>in vivo </it>via biodistribution of the positron emission tomography radiotracer and NE analogue [¹¹C]<it>meta-</it>hydroxyephedrine ([¹¹C]HED). Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET) expression were evaluated as correlative measurements.</p> <p>Results</p> <p>The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [¹¹C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle.</p> <p>Conclusions</p> <p>Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system signaling in the absence of systolic impairment.</p

Charged Particle Pseudorapidity Distributions in Au+Al, Cu, Au, and U Collisions at 10.8 A⋅\cdotGeV/c

We present the results of an analysis of charged particle pseudorapidity distributions in the central region in collisions of a Au projectile with Al, Cu, Au, and U targets at an incident energy of 10.8~GeV/c per nucleon. The pseudorapidity distributions are presented as a function of transverse energy produced in the target or central pseudorapidity regions. The correlation between charged multiplicity and transverse energy measured in the central region, as well as the target and projectile regions is also presented. We give results for transverse energy per charged particle as a function of pseudorapidity and centrality.Comment: 31 pages + 12 figures (compressed and uuencoded by uufiles), LATEX, Submitted to PR

Two-pion correlations in Au+Au collisions at 10.8 GeV/c per nucleon

Two-particle correlation functions for positive and negative pions have been measured in Au+Au collisions at 10.8~GeV/c per nucleon. The data were analyzed using one- and three-dimensional correlation functions. From the results of the three-dimensional fit the phase space density of pions was calculated. It is consistent with local thermal equilibrium.Comment: 5 pages RevTeX (including 3 Figures