Current and future approaches in the prevention and treatment of diabetic retinopathy

Diabetic retinopathy (DR) is a major cause of blindness worldwide and is the number one cause of blindness in working-age individuals in developed countries. We review the current literature and discuss the pathogenesis, modifying risk factors, genetics, and treatment of DR. Special focus is placed on the rationale and effectiveness of therapeutic modalities, both current and future

Interval Estimation and Monte Carlo Simulation of Digital Communication Systems

This work quantifies the accuracy of bit error rate (BER) estimates produced by Monte Carlo simulations by carefully applying confidence interval estimation techniques. Due to numerical difficulties, some previous work in this area has assumed that the BER statistic possessed a Gaussian distribution. This work demonstrates that in some important regions the estimate is decidedly non-Gaussian, and application of central limit theorem arguments can result in errors in excess of an order of magnitude. This work investigates the accuracy of common approximations and the feasibility of exact calculation of confidence intervals, and presents a novel polynomial class approximation. By combining the new approximation with more conventional approaches, an algorithm is developed for estimating confidence intervals of BER estimates. The algorithm is nonrecursive and numerically stable, requires a trivial amount of compute time to evaluate, has a small margin of error, and can be used for all error rates less than 0.5

Normalized solutions of L2L^2-supercritical NLS equations on compact metric graphs

This paper is devoted to the existence of non-trivial bound states of prescribed mass for the mass-supercritical nonlinear Schr\"odinger equation on compact metric graphs. The investigation is based upon a general variational principle which combines the monotonicity trick and a min-max theorem with second order information, and upon the blow-up analysis of bound states with prescribed mass and bounded Morse index

Conservative Confidence Intervals of Importance Sampling Estimates

Confidence intervals (CI) are used to gauge the accuracy of bit error rate (BER) estimates produced by Monte Carlo (MC) simulations. This work attempts to objectively evaluate the performance of Important Sampling (IS) simulations by applying the same statistical analysis tool. While it is not possible to evaluate the minimum size CI for arbitrary IS estimates, it is possible to over-bound the interval using a technique called conservative confidence interval (CCI) estimation. This bounding procedure is applied to a simple IS biasing technique. While the IS estimate may be superior to the MC estimate, the CCI fails to support this claim. Since there has been little previous work published in the area of CI of IS estimates, this document is offered as a starting point. Hopefully others will be able to develop tighter bounds for the CI of IS estimate

Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons: a potential role for mitochondrial permeability transition

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons

CFD Study of Turbo-Ramjet Interactions in Hypersonic Airbreathing Propulsion System

Advanced airbreathing propulsion systems used in Mach 4-6 mission scenarios, usually involve turbo-ramjet configurations. As the engines transition from turbojet to ramjet, there is an operational envelope where both engines operate simultaneously. In the first phase of our study, an over/under nozzle configuration was analyzed. The two plumes from the turbojet and ramjet interact at the end of a common 2-D cowl, where they both reach an approximate Mach 3.0 condition and then jointly expand to Mach 3.6 at the common nozzle exit plane. For the problem analyzed, the turbojet engine operates at a higher nozzle pressure ratio than the ramjet, causes the turbojet plume overpowers the ramjet plume, deflecting it approximately 12 degrees downward and in turn the turbojet plume is deflected 6 degrees upward. In the process, shocks were formed at the deflections and a shear layer formed at the confluence of the two jets. This particular case was experimentally tested and the data were used to compare with a computational fluid dynamics (CFD) study using the PARC2D code. The CFD results were in good agreement with both static pressure distributions on the cowl separator and on nozzle walls. The thrust coefficients were also in reasonable agreement. In addition, inviscid relationships were developed around the confluence point, where the two exhaust jets meet, and these results compared favorably with the CFD results. In the second phase of our study, a 3-D CFD solution was generated to compare with the 2-D solution. The major difference between the 2-D and 3-D solutions was the interaction of the shock waves, generated by the plume interactions, on the sidewall. When a shock wave interacts with a sidewall and sidewall boundary layer, it is called a glancing shock sidewall interaction. These interactions entrain boundary layer flow down the shockline into a vortical flow pattern. The 3-D plots show the streamlines being entrained down the shockline. The pressure of the flow also decreases slightly as the sidewall is approached. Other difference between the 2-D and 3-D solutions were a lowering of the nozzle thrust coefficient value from 0.9850 (2-D) to 0.9807 (3-D), where the experimental value was 0.9790. In the third phase of our study, a different turbo-ramjet configuration was analyzed. The confluence of a supersonic turbojet and a subsonic ramjet in the turbine based combined-cycle (TBCC) propulsion system was studied by a 2-D CFD code. In the analysis, Mach 1.4 primary turbojet was mixed with the subsonic ramjet secondary flow in an ejector mode operation. Reasonable agreements were obtained with the supplied I-D TBCC solutions. For low downstream backpressure, the Fabri choke condition (Break-Point condition) was observed in the secondary flow within mixing zone. For sufficient high downstream backpressure, the Fabri choke no longer exist, the ramjet flow was reduced and the ejector flow became backpressure dependent. Highly non-uniform flow at ejector exit were observed, indicated that for smooth downstream combustion, the mixing of the two streams probably required some physical devices

Bounded Palais-Smale sequences with Morse type information for some constrained functionals

In this paper, we study, for functionals having a mountain pass geometry on a constraint, the existence of bounded Palais-Smale sequences carrying Morse index type information.Comment: This version is the final one, corresponding to the paper now published in Transactions of the American Mathematical Societ

Modeling of minimum void ratio for sand–silt mixtures

Minimum void ratio or maximum packing density is an important soil property in geotechnical engineering. It correlates to the volume change tendency, the pore fluid conductivity, and the shear strength of the soil. In geotechnical engineering, it often requires to estimate the minimum void ratio for a sand–silt mixture with any amount of fines content, based only on few laboratory test results. The minimum void ratio for soil mixtures is usually estimated by methods based on, to some extent, an empirical approach, for example, the AASHTO coarse particle correction method. In this paper, based on a more fundamental approach using the concept of dominant particle network, we aim to develop a mathematical model that can predict the minimum void ratio for sand–silt mixtures with any amount of fines content. The developed model only requires two parameters for the prediction of minimum void ratios of soil mixtures with various fines contents. The developed model is evaluated by the experimental results on 33 types of soil mixtures available in the literature, including mixtures of sands (Ottawa sand, Nevada sand, Toyoura sand, Hokksund sand, etc), and silts (ATC silt, Nevada fines, crushed silica fines, grind Toyoura fines, etc). Comparisons of the results are discussed