APPLICATION OF THE KHOKHLOV-ZABOLOTSKAYA-KUZNETSOV EQUATION TO MODELING HIGH-INTENSITY FOCUSED ULTRASOUND BEAMS

High-intensity focused ultrasound is a form of therapeutic ultrasound which uses high amplitude acoustic waves to heat and ablate tissue. HIFU employs acoustic amplitudes that are high enough that nonlinear propagation effects are important in the evolution of the sound field. A common model for HIFU beams is the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation which accounts for nonlinearity, diffraction, and absorption. The KZK equation models diffraction using the parabolic or paraxial approximation. Many HIFU sources have an aperture diameter similar to the focal length and the paraxial approximation may not be appropriate. Here, results obtained using the “Texas code,” a time-domain numerical solution to the KZK equation, were used to assess when the KZK equation can be employed. In a linear water case comparison with the O’Neil solution, the KZK equation accurately predicts the pressure field in the focal region. The KZK equation was also compared to simulations of the exact fluid dynamics equations (no paraxial approximation). The exact equations were solved using the Fourier-Continuation (FC) method to approximate derivatives in the equations. Results have been obtained for a focused HIFU source in tissue. For a low focusing gain transducer (focal length 50λ and radius 10λ), the KZK and FC models showed excellent agreement, however, as the source radius was increased to 30λ, discrepancies started to appear. Modeling was extended to the case of tissue with the appropriate power law using a relaxation model. The relaxation model resulted in a higher peak pressure and a shift in the location of the peak pressure, highlighting the importance of employing the correct attenuation model. Simulations from the code that were compared to experimental data in water showed good agreement through the focal plane.

Kinetic Analysis of Ester Hydrolysis

A two-week multi-step experiment that introduces students to mechanistic organic chemistry and substituent effects. A simple preparation of differentially substituted para-nitrophenyl benzoates is followed by ester hydrolysis with monitoring by UV-Vis spectroscopy to provide rate data for the reaction.

Smooth Multirate Multicast Congestion Control

A significant impediment to deployment of multicast services is the daunting technical complexity of developing, testing and validating congestion control protocols fit for wide-area deployment. Protocols such as pgmcc and TFMCC have recently made considerable progress on the single rate case, i.e. where one dynamic reception rate is maintained for all receivers in the session. However, these protocols have limited applicability, since scaling to session sizes beyond tens of participants necessitates the use of multiple rate protocols. Unfortunately, while existing multiple rate protocols exhibit better scalability, they are both less mature than single rate protocols and suffer from high complexity. We propose a new approach to multiple rate congestion control that leverages proven single rate congestion control methods by orchestrating an ensemble of independently controlled single rate sessions. We describe SMCC, a new multiple rate equation-based congestion control algorithm for layered multicast sessions that employs TFMCC as the primary underlying control mechanism for each layer. SMCC combines the benefits of TFMCC (smooth rate control, equation-based TCP friendliness) with the scalability and flexibility of multiple rates to provide a sound multiple rate multicast congestion control policy.

Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

Exogenous-Loss Awareness in Queue Management: Toward Global Fairness

For a given TCP flow, exogenous losses are those occurring on links other than the flow's bottleneck link. Exogenous losses are typically viewed as introducing undesirable "noise" into TCP's feedback control loop, leading to inefficient network utilization and potentially severe global unfairness. This has prompted much research on mechanisms for hiding such losses from end-points. In this paper, we show through analysis and simulations that low levels of exogenous losses are surprisingly beneficial in that they improve stability and convergence, without sacrificing efficiency. Based on this, we argue that exogenous loss awareness should be taken into account in any AQM design that aims to achieve global fairness. To that end, we propose an exogenous-loss aware Queue Management (XQM) that actively accounts for and leverages exogenous losses. We use an equation based approach to derive the quiescent loss rate for a connection based on the connection's profile and its global fair share. In contrast to other queue management techniques, XQM ensures that a connection sees its quiescent loss rate, not only by complementing already existing exogenous losses, but also by actively hiding exogenous losses, if necessary, to achieve global fairness. We establish the advantages of exogenous-loss awareness using extensive simulations in which, we contrast the performance of XQM to that of a host of traditional exogenous-loss unaware AQM techniques.

Object Detection at the Optimal Scale with Hidden State Shape Models

Hidden State Shape Models (HSSMs) [2], a variant of Hidden Markov Models (HMMs) [9], were proposed to detect shape classes of variable structure in cluttered images. In this paper, we formulate a probabilistic framework for HSSMs which provides two major improvements in comparison to the previous method [2]. First, while the method in [2] required the scale of the object to be passed as an input, the method proposed here estimates the scale of the object automatically. This is achieved by introducing a new term for the observation probability that is based on a object-clutter feature model. Second, a segmental HMM [6, 8] is applied to model the "duration probability" of each HMM state, which is learned from the shape statistics in a training set and helps obtain meaningful registration results. Using a segmental HMM provides a principled way to model dependencies between the scales of different parts of the object. In object localization experiments on a dataset of real hand images, the proposed method significantly outperforms the method of [2], reducing the incorrect localization rate from 40% to 15%. The improvement in accuracy becomes more significant if we consider that the method proposed here is scale-independent, whereas the method of [2] takes as input the scale of the object we want to localize.

Adaptive Neural Models of Queuing and Timing in Fluent Action

Temporal structure in skilled, fluent action exists at several nested levels. At the largest scale considered here, short sequences of actions that are planned collectively in prefrontal cortex appear to be queued for performance by a cyclic competitive process that operates in concert with a parallel analog representation that implicitly specifies the relative priority of elements of the sequence. At an intermediate scale, single acts, like reaching to grasp, depend on coordinated scaling of the rates at which many muscles shorten or lengthen in parallel. To ensure success of acts such as catching an approaching ball, such parallel rate scaling, which appears to be one function of the basal ganglia, must be coupled to perceptual variables, such as time-to-contact. At a fine scale, within each act, desired rate scaling can be realized only if precisely timed muscle activations first accelerate and then decelerate the limbs, to ensure that muscle length changes do not under- or over-shoot the amounts needed for the precise acts. Each context of action may require a much different timed muscle activation pattern than similar contexts. Because context differences that require different treatment cannot be known in advance, a formidable adaptive engine-the cerebellum-is needed to amplify differences within, and continuosly search, a vast parallel signal flow, in order to discover contextual "leading indicators" of when to generate distinctive parallel patterns of analog signals. From some parts of the cerebellum, such signals controls muscles. But a recent model shows how the lateral cerebellum, such signals control muscles. But a recent model shows how the lateral cerebellum may serve the competitive queuing system (in frontal cortex) as a repository of quickly accessed long-term sequence memories. Thus different parts of the cerebellum may use the same adaptive engine system design to serve the lowest and the highest of the three levels of temporal structure treated. If so, no one-to-one mapping exists between levels of temporal structure and major parts of the brain. Finally, recent data cast doubt on network-delay models of cerebellar adaptive timing.