Sensitivity-analysis method for inverse simulation application

An important criticism of traditional methods of inverse simulation that are based on the Newton–Raphson algorithm is that they suffer from numerical problems. In this paper these problems are discussed and a new method based on sensitivity-analysis theory is developed and evaluated. The Jacobian matrix may be calculated by solving a sensitivity equation and this has advantages over the approximation methods that are usually applied when the derivatives of output variables with respect to inputs cannot be found analytically. The methodology also overcomes problems of input-output redundancy that arise in the traditional approaches to inverse simulation. The sensitivity- analysis approach makes full use of information within the time interval over which key quantities are compared, such as the difference between calculated values and the given ideal maneuver after each integration step. Applications to nonlinear HS125 aircraft and Lynx helicopter models show that, for this sensitivity-analysis method, more stable and accurate results are obtained than from use of the traditional Newton–Raphson approach

Coalignment of plasma membrane channels and protrusions (fibripositors) specifies the parallelism of tendon

The functional properties of tendon require an extracellular matrix (ECM) rich in elongated collagen fibrils in parallel register. We sought to understand how embryonic fibroblasts elaborate this exquisite arrangement of fibrils. We show that procollagen processing and collagen fibrillogenesis are initiated in Golgi to plasma membrane carriers (GPCs). These carriers and their cargo of 28-nm-diam fibrils are targeted to previously unidentified plasma membrane (PM) protrusions (here designated “fibripositors”) that are parallel to the tendon axis and project into parallel channels between cells. The base of the fibripositor lumen (buried several microns within the cell) is a nucleation site of collagen fibrillogenesis. The tip of the fibripositor is the site of fibril deposition to the ECM. Fibripositors are absent at postnatal stages when fibrils increase in diameter by accretion of extracellular collagen, thereby maintaining parallelism of the tendon. Thus, we show that the parallelism of tendon is determined by the late secretory pathway and interaction of adjacent PMs to form extracellular channels

A Dynamic Programming Approach to Adaptive Fractionation

We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl

All Vacuum Near-Horizon Geometries in DD-dimensions with (D−3)(D-3) Commuting Rotational Symmetries

We explicitly construct all stationary, non-static, extremal near horizon geometries in $D$ dimensions that satisfy the vacuum Einstein equations, and that have $D-3$ commuting rotational symmetries. Our work generalizes [arXiv:0806.2051] by Kunduri and Lucietti, where such a classification had been given in $D=4,5$. But our method is different from theirs and relies on a matrix formulation of the Einstein equations. Unlike their method, this matrix formulation works for any dimension. The metrics that we find come in three families, with horizon topology $S^2 \times T^{D-4}$, or $S^3 \times T^{D-5}$, or quotients thereof. Our metrics depend on two discrete parameters specifying the topology type, as well as $(D-2)(D-3)/2$ continuous parameters. Not all of our metrics in $D \ge 6$ seem to arise as the near horizon limits of known black hole solutions.Comment: 22 pages, Latex, no figures, title changed, references added, discussion of the parameters specifying solutions corrected, amended to match published versio

Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

Metal-Insulator Transitions in Degenerate Hubbard Models and Ax_xC60_{60}

Mott-Hubbard metal-insulator transitions in $N$-fold degenerate Hubbard models are studied within the Gutzwiller approximation. For any rational filling with $x$ (integer) electrons per site it is found that metal-insulator transition occurs at a critical correlation energy $U_c(N,x)=U_c(N,2N-x)=\gamma(N,x)|\bar{\epsilon}(N,x)|$, where $\bar{\epsilon}$ is the band energy per particle for the uncorrelated Fermi-liquid state and $\gamma(N,x)$ is a geometric factor which increases linearly with $x$. We propose that the alkali metal doped fullerides $A_xC_{60}$ can be described by a 3-fold degenerate Hubbard model. Using the current estimate of band width and correlation energy this implies that most of ${\rm A_xC_{60}}$, at integer $x$, are Mott-Hubbard insulators and ${\rm A_3C_{60}}$ is a strongly correlated metal.Comment: 10 pages, Revte

Immunogenicity and protective efficacy of nanoparticle formulations of L-SseB against Salmonella infection

Salmonella enterica, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, S. enterica causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the Salmonella pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic E. coli to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined via challenging the mice with S. enterica serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from S. enterica challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against S. enterica

Testing in the incremental design and development of complex products

Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested

Free field realization of superstring theory on AdS3

The Coulomb gas representation of expectation values in SU(2) conformal field theory developed by Dotsenko is extended to the SL(2,R) WZW model and applied to bosonic string theory on AdS3 and to Type II superstrings on AdS3 x N. The spectral flow symmetry is included in the free field realization of vertex operators creating superstring states of both Ramond and Neveu-Schwarz sectors. Conjugate representations for these operators are constructed and a background charge prescription is designed to compute correlation functions. Two and three point functions of bosonic and fermionic string states in arbitrary winding sectors are calculated. Scattering amplitudes that violate winding number conservation are also discussed.Comment: 40 pages, typos corrected, references added, minor changes in presentation and details completed in the calculation of the R sector 2-point function. Version to appear in JHE

Renormalization-Scale-Invariant PQCD Predictions for R_e+e- and the Bjorken Sum Rule at Next-to-Leading Order

We discuss application of the physical QCD effective charge $\alpha_V$, defined via the heavy-quark potential, in perturbative calculations at next-to-leading order. When coupled with the Brodsky-Lepage-Mackenzie prescription for fixing the renormalization scales, the resulting series are automatically and naturally scale and scheme independent, and represent unambiguous predictions of perturbative QCD. We consider in detail such commensurate scale relations for the $e^+e^-$ annihilation ratio $R_{e^+e^-}$ and the Bjorken sum rule. In both cases the improved predictions are in excellent agreement with experiment.Comment: 13 Latex pages with 5 figures; to be published in Physical Review