No abstract

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. In this study, we present theoretical arguments that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Our theoretical analysis suggests that this opposition to motion increases rapidly as the cargo approaches the wall. We find that having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus minimizes the effects of any opposition to transport. Even if microtubules are randomly placed in axons, we find that the higher density of microtubules found in small-caliber axons increases the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. The boundary effect is not a factor in transport in large-caliber axons where the microtubule density is lower.

The CEBAF Large Acceptance Spectrometer for operation at 12 GeV beam energy (CLAS12) in Hall B at Jefferson Laboratory is used to study electro-induced nuclear and hadronic reactions. This spectrometer provides efficient detection of charged and neutral particles over a large fraction of the full solid angle. CLAS12 has been part of the energy-doubling project of Jefferson Lab's Continuous Electron Beam Accelerator Facility, funded by the United States Department of Energy. An international collaboration of over 40 institutions contributed to the design and construction of detector hardware, developed the software packages for the simulation of complex event patterns, and commissioned the detector systems. CLAS12 is based on a dual-magnet system with a superconducting torus magnet that provides a largely azimuthal field distribution that covers the forward polar angle range up to 35 • , and a solenoid magnet and detector covering the polar angles from 35 • to 125 • with full azimuthal coverage. Trajectory reconstruction in the forward direction using drift chambers and in the central direction using a vertex tracker results in momentum resolutions of <1% and <3%, respectively. Cherenkov counters, time-of-flight scintillators, and electromagnetic calorimeters provide good particle identification. Fast triggering and high data-acquisition rates allow operation at a luminosity of 10 35 cm −2 s −1 . These capabilities are being used in a broad program to study the structure and interactions of nucleons, nuclei, and mesons, using polarized and unpolarized electron beams and targets for beam energies up to 11 GeV. This paper gives a general description of the design, construction, and performance of CLAS12.

Background The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single photon emission computed tomography (SPECT). Methods Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve K1=Ftrue(1−Aexptrue(−BFtrue)true) for K1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH3 PET. The flow dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. Results The estimated flow extraction parameters for 99mTc-tefrofosmin was found to be A=0.91±0.11, B=0.34±0.20 (R2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The PS for 99mTc-tefrofosmin was (0.091 ± 0.10) * MBF = (0.32 ± 0.16). Conclusions Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.