Extrapolated High-Order Propagators for Path Integral Monte Carlo Simulations

We present a new class of high-order imaginary time propagators for path-integral Monte Carlo simulations by subtracting lower order propagators. By requiring all terms of the extrapolated propagator be sampled uniformly, the subtraction only affects the potential part of the path integral. The negligible violation of positivity of the resulting path integral at small time steps has no discernable affect on the accuracy of our method. Thus in principle arbitrarily high order algorithms can be devised for path-integral Monte Carlo simulations. We verify this claim is by showing that fourth, sixth, and eighth order convergence can indeed be achieved in solving for the ground state of strongly interacting quantum many-body systems such as bulk liquid $^4$He.Comment: 9 pages and 3 figures. Submitted to J. Chem. Phy

Chemometric analysis for extraction of individual fluorescence spectrum and lifetimes from a target mixture

The present invention is a system for chemometric analysis for the extraction of the individual component fluorescence spectra and fluorescence lifetimes from a target mixture. The present invention combines a processor with an apparatus for generating an excitation signal to transmit at a target mixture and an apparatus for detecting the emitted signal from the target mixture. The present invention extracts the individual fluorescence spectrum and fluorescence lifetime measurements from the frequency and wavelength data acquired from the emitted signal. The present invention uses an iterative solution that first requires the initialization of several decision variables and the initial approximation determinations of intermediate matrices. The iterative solution compares the decision variables for convergence to see if further approximation determinations are necessary. If the solution converges, the present invention then determines the reduced best fit error for the analysis of the individual fluorescence lifetime and the fluorescence spectrum before extracting the individual fluorescence lifetime and fluorescence spectrum from the emitted signal of the target mixture

Signal generation and mixing electronics for frequency-domain lifetime and spectral fluorometry

The present invention additionally comprises a method and apparatus for generating and mixing signals for frequency-domain lifetime and spectral fluorometry. The present invention comprises a plurality of signal generators that generate a plurality of signals where the signal generators modulate the amplitude and/or the frequency of the signals. The present invention uses one of these signals to drive an excitation signal that the present invention then directs and transmits at a target mixture, which absorbs the energy from the excitation signal. The property of fluorescence causes the target mixture to emit an emitted signal that the present invention detects with a signal detector. The present invention uses a plurality of mixers to produce a processor reference signal and a data signal. The present invention then uses a processor to compare the processor reference signal with the data signal by analyzing the differences in the phase and the differences in the amplitude between the two signals. The processor then extracts the fluorescence lifetime and fluorescence spectrum of the emitted signal from the phase and amplitude information using a chemometric analysis

Retrieving Aerosol in a Cloudy Environment: Aerosol Availability as a Function of Spatial and Temporal Resolution

The challenge of using satellite observations to retrieve aerosol properties in a cloudy environment is to prevent contamination of the aerosol signal from clouds, while maintaining sufficient aerosol product yield to satisfy specific applications. We investigate aerosol retrieval availability at different instrument pixel resolutions, using the standard MODIS aerosol cloud mask applied to MODIS data and a new GOES-R cloud mask applied to GOES data for a domain covering North America and surrounding oceans. Aerosol availability is not the same as the cloud free fraction and takes into account the technqiues used in the MODIS algorithm to avoid clouds, reduce noise and maintain sufficient numbers of aerosol retrievals. The inherent spatial resolution of each instrument, 0.5x0.5 km for MODIS and 1x1 km for GOES, is systematically degraded to 1x1 km, 2x2 km, 4x4 km and 8x8 km resolutions and then analyzed as to how that degradation would affect the availability of an aerosol retrieval, assuming an aerosol product resolution at 8x8 km. The results show that as pixel size increases, availability decreases until at 8x8 km 70% to 85% of the retrievals available at 0.5 km have been lost. The diurnal pattern of aerosol retrieval availability examined for one day in the summer suggests that coarse resolution sensors (i.e., 4x4 km or 8x8 km) may be able to retrieve aerosol early in the morning that would otherwise be missed at the time of current polar orbiting satellites, but not the diurnal aerosol properties due to cloud cover developed during the day. In contrast finer resolution sensors (i.e., 1x1 km or 2x2 km) have much better opportunity to retrieve aerosols in the partly cloudy scenes and better chance of returning the diurnal aerosol properties. Large differences in the results of the two cloud masks designed for MODIS aerosol and GOES cloud products strongly reinforce that cloud masks must be developed with specific purposes in mind and that a generic cloud mask applied to an independent aerosol retrieval will likely fail

Anti-proliferative but not anti-angiogenic tyrosine kinase inhibitors enrich for cancer stem cells in soft tissue sarcoma.

BackgroundIncreasing studies implicate cancer stem cells (CSCs) as the source of resistance and relapse following conventional cytotoxic therapies. Few studies have examined the response of CSCs to targeted therapies, such as tyrosine kinase inhibitors (TKIs). We hypothesized that TKIs would have differential effects on CSC populations depending on their mechanism of action (anti-proliferative vs. anti-angiogenic).MethodsWe exposed human sarcoma cell lines to sorafenib, regorafenib, and pazopanib and assessed cell viability and expression of CSC markers (ALDH, CD24, CD44, and CD133). We evaluated survival and CSC phenotype in mice harboring sarcoma metastases after TKI therapy. We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.ResultsAfter functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P < 0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P < 0.05). In contrast, we observed negligible effects on viability and CSC sub-populations with pazopanib. At low doses, there was progressive CSC enrichment in vitro after longer term exposure to sorafenib although the anti-proliferative effects were attenuated. In vivo, sorafenib improved median survival by 11 days (P < 0.05), but enriched ALDHbright cells 2.5 - 2.8 fold (P < 0.05). Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib and regorafenib with a corresponding increase in ALDHbright cells (P < 0.05). Again, negligible effects from pazopanib were observed. TMA analysis of archived specimens from sarcoma patients treated with sorafenib demonstrated significant enrichment for ALDHbright cells in the post-treatment resection specimen (P < 0.05), whereas clinical specimens obtained longitudinally from a patient treated with pazopanib showed no enrichment for ALDHbright cells (P > 0.05).ConclusionsAnti-proliferative TKIs appear to enrich for sarcoma CSCs while anti-angiogenic TKIs do not. The rational selection of targeted therapies for sarcoma patients may benefit from an awareness of the differential impact of TKIs on CSC populations

Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model

Objective: This study investigates whether 99mTc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. Methods: High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat\u27s hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with 99mTc PYP. The radiotracer\u27s temporal behavior among the experimental groups was compared using curve fitting of time-activity curves from the dynamic image data. Results: The washout kinetics of 99mTc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, 99mTc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered 99mTc PYP washout less than poloxamer-188 treatment. Conclusions: Behavior of 99mTc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of 99mTc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, 99mTc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury. © 2006 Elsevier Ltd and ISBI

Large-Scale Gravitational Instability and Star Formation in the Large Magellanic Cloud

Large-scale star formation in disk galaxies is hypothesized to be driven by global gravitational instability. The observed gas surface density is commonly used to compute the strength of gravitational instability, but according to this criterion star formation often appears to occur in gravitationally stable regions. One possible reason is that the stellar contribution to the instability has been neglected. We have examined the gravitational instability of the Large Magellanic Cloud (LMC) considering the gas alone, and considering the combination of collisional gas and collisionless stars. We compare the gravitationally unstable regions with the on-going star formation revealed by Spitzer observations of young stellar objects. Although only 62% of the massive young stellar object candidates are in regions where the gas alone is unstable, some 85% lie in regions unstable due to the combination of gas and stars. The combined stability analysis better describes where star formation occurs. In agreement with other observations and numerical models, a small fraction of the star formation occurs in regions with gravitational stability parameter Q > 1. We further measure the dependence of the star formation timescale on the strength of gravitational instability, and quantitatively compare it to the exponential dependence expected from numerical simulations.Comment: Accepted for publication in ApJ, 10 pages, 5 figure

Trajectory Optimization of Electric Aircraft Subject to Subsystem Thermal Constraints

Electric aircraft pose a unique design challenge in that they lack a simple way to reject waste heat from the power train. While conventional aircraft reject most of their excess heat in the exhaust stream, for electric aircraft this is not an option. To examine the implications of this challenge on electric aircraft design and performance, we developed a model of the electric subsystems for the NASA X-57 electric testbed aircraft. We then coupled this model with a model of simple 2D aircraft dynamics and used a Legendre-Gauss-Lobatto collocation optimal control approach to find optimal trajectories for the aircraft with and without thermal constraints. The results show that the X-57 heat rejection systems are well designed for maximum-range and maximum-efficiency flight, without the need to deviate from an optimal trajectory. Stressing the thermal constraints by reducing the cooling capacity or requiring faster flight has a minimal impact on performance, as the trajectory optimization technique is able to find flight paths which honor the thermal constraints with relatively minor deviations from the nominal optimal trajectory