bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of the Governing Equations, Computational Algorithms, and
Other Components of the Models-3 Community Multiscale Air Quality (CMAQ)
Modeling System
Authors: Byun Daewon , Schere Kenneth L.
Published: March 2006

This article describes the governing equations, computational algorithms, and other components entering into the Community Multiscale Air Quality (CMAQ) modeling system. This system has been designed to approach air quality as a whole by including state-of-the-science capabilities for modeling multiple air quality issues, including tropospheric ozone, fine particles, acid deposition, and visibility degradation. CMAQ was also designed to have multiscale capabilities so that separate models were not needed for urban and regional scale air quality modeling. By making CMAQ a modeling system that addresses multiple pollutants and different spatial scales, it has a “one-atmosphere” perspective that combines the efforts of the scientific community. To implement multiscale capabilities in CMAQ, several issues (such as scalable atmospheric dynamics and generalized coordinates), which depend on the desired model resolution, are addressed. A set of governing equations for compressible nonhydrostatic atmospheres is available to better resolve atmospheric dynamics at smaller scales. Because CMAQ is designed to handle scale-dependent meteorological formulations and a large amount of flexibility, its governing equations are expressed in a generalized coordinate system. This approach ensures consistency between CMAQ and the meteorological modeling system. The generalized coordinate system determines the necessary grid and coordinate transformations, and it can accommodate various vertical coordinates and map projections. The CMAQ modeling system simulates various chemical and physical processes that are thought to be important for understanding atmospheric trace gas transformations and distributions. The modeling system contains three types of modeling components (Models-3): a meteorological modeling system for the description of atmospheric states and motions, emission models for man-made and natural emissions that are injected into the atmosphere, and a chemistry-transport modeling system for simulation of the chemical transformation and fate. The chemical transport model includes the following process modules: horizontal advection, vertical advection, mass conservation adjustments for advection processes, horizontal diffusion, vertical diffusion, gas-phase chemical reactions and solvers, photolytic rate computation, aqueous-phase reactions and cloud mixing, aerosol dynamics, size distributions and chemistry, plume chemistry effects, and gas and aerosol deposition velocity estimation. This paper describes the Models-3 CMAQ system, its governing equations, important science algorithms, and a few application examples. This review article cites 114 references.
Particle-Turbulence Interaction in a Homogeneous, Isotropic Turbulent Suspension
Authors: Poelma Christian , Ooms Gijs
Published: March 2006

A review is given of numerical, analytical, and experimental research regarding the two-way coupling effect between particles and fluid turbulence in a homogeneous, isotropic turbulent suspension. The emphasis of this review is on the effect of the suspended particles on the spectrum of the carrier fluid, in order to explain the physical mechanisms that are involved. An important result of numerical simulations and analytical models (neglecting the effect of gravity) is that, for a homogeneous and isotropic suspension with particles with a response time much larger than the Kolmogorov time scale, the main effect of the particles is suppression of the energy of eddies of all sizes. However for a suspension with particles with a response time comparable to or smaller than the Kolmogorov time, the Kolmogorov length scale will decrease and the turbulence energy of (nearly) all eddy sizes increases. For a suspension with particles with a response time in between the two limiting cases mentioned above the energy of the larger eddies is suppressed, whereas the energy of the smaller ones is enhanced. Attention is paid to several physical mechanisms that were suggested in the literature to explain this influence of the particles on the turbulence. In some of the experimental studies, certain results from simulations and models have, indeed, been confirmed. However, in other experiments these results were not found. This is attributed to the role of gravity, which leads to turbulence production by the particles. Additional research effort is needed to fully understand the physical mechanisms causing the two-way coupling effect in a homogeneous, isotropic, and turbulently flowing suspension. This review contains 47 references.
Using a Dovetail Fixture to Study Fretting Fatigue and Fretting Palliatives
Authors: Conner B. P. , Nicholas T.
Published: March 2006

Fretting fatigue damage can reduce the service life of engineering components in contact. The attachment between blades and disks in the fan and compressor stages of gas turbine engines is often a dovetail geometry. As a result, normal and tangential cyclic contact loads are present. Results of fretting fatigue tests using a new dovetail fixture are detailed here. Dovetail specimens and three types of contact pads were all machined out of Ti−6A1−4V. Two types of palliatives are also examined: aluminum bronze coatings and low-plasticity burnishing. While the palliatives were effective in increasing the fatigue life, the three pad geometries produced essentially the same fatigue life.
Creep-Fatigue Life Evaluation for Sn-3.5Ag Solder
Authors: Nozaki Mineo , Sakane Masao , Tsukada Yutaka , Nishimura Hideo
Published: March 2006

This paper studies the creep-fatigue life evaluation of Sn-3.5Ag solder under push-pull loading using fast-fast, fast-slow, slow-fast, slow-slow, and strain-hold strain waves. Extensive creep-fatigue data were generated using these strain waves and the applicability of four conventional creep-fatigue damage rules, the linear damage rule, the frequency modified fatigue life, the ductility exhaustion model, and the strain range partitioning method, was examined. No conventional damage rules evaluated creep-fatigue lives accurately. Only the grain boundary sliding model, developed recently for solders, predicted creep-fatigue lives with a small scatter.
Effect of Cryogenic Temperature on the Fracture Toughness of Graphite/Epoxy Composites
Authors: Kalarikkal S. G. , Sankar B. V. , Ifju P. G.
Published: March 2006

The research presented in this paper is an effort to better understand the interlaminar fracture behavior of graphite/epoxy composite laminates in cryogenic conditions. Double cantilever beam tests were performed on different types of specimens, at room and cryogenic temperatures, and the fracture toughness was calculated from their load-displacement diagram. Additionally, the fracture toughness of some plain-weave textile composite specimens and specimens treated with nanoparticles (38nmAl2O3) were also measured. It was observed that all specimens, with the exception of woven composites, showed deterioration in fracture toughness at the liquid nitrogen temperature. Nanoparticle treated specimens showed an improvement in fracture toughness, both at room and cryogenic temperatures compared to the control specimens. The woven composite specimens showed an increase in fracture toughness at cryogenic temperature. The results indicate that woven fiber composites may have potential in lightweight cryogenic storage systems.
Uncertainty, Model Error, and Order Selection for Series-Expanded, Residual-Stress Inverse Solutions
Authors: Prime Michael B. , Hill Michael R.
Published: March 2006

Measuring the spatial variation of residual stresses often requires the solution of an elastic inverse problem such as a Volterra equation. Using a maximum likelihood estimate (least squares fit), a series expansion for the spatial distribution of stress or underlying eigenstrain can be an effective solution. Measurement techniques that use a series expansion inverse include incremental slitting (crack compliance), incremental hole drilling, a modified Sach’s method, and others. This paper presents a comprehensive uncertainty analysis and order selection methodology, with detailed development for the slitting method. For the uncertainties in the calculated stresses caused by errors in the measured data, an analytical formulation is presented which includes the usually ignored but important contribution of covariances between the fit parameters. Using Monte Carlo numerical simulations, it is additionally demonstrated that accurate uncertainty estimates require the estimation of model error, the ability of the chosen series expansion to fit the actual stress variation. An original method for estimating model error for a series expansion inverse solution is presented. Finally, it is demonstrated that an optimal order for the series expansion can usually be chosen by minimizing the estimated uncertainty in the calculated stresses.
Local Stress-Ratio Criterion for Incremental Hole-Drilling Measurements of Shot-Peening Stresses
Authors: Nobre J. P. , Dias A. M. , Gibmeier J. , Kornmeier M.
Published: March 2006

A criterion to evaluate the influence of the so-called plasticity effect on the final outcome of the incremental hole-drilling technique (IHD), for measuring residual stresses induced by mechanical surface treatments, is proposed here. In practice, it is currently accepted that residual stresses can be accurately determined by IHD if the residual stress level does not exceed about 60% of the material’s yield strength. However, this criterion is not appropriate when IHD is used to measure residual stresses in work-hardened surface layers, since the yield strength of these layers is very difficult to determine. The proposed criterion takes into account the strain-hardening effect and the local yield strength of work-hardened surface layers, using the concept of normalized hardness variation. The criterion was validated experimentally and numerically for shot-peening residual stress measurements.
Instrumented Microindentation of Nanoporous Alumina Films
Authors: Gall Ken , Liu Yiping , Routkevitch Dmitri , Finch Dudley S.
Published: March 2006

We examine the mechanical behavior of anodic alumina thin films with organized nanometer-scale porosity. The cylindrical pores in the alumina film are arranged perpendicular to the film thickness in a near-perfect triangular lattice. The films used in this work had pore diameters ranging from 35 to 75nm, and volume fractions ranging from 10% to 45%. Films with both amorphous and crystalline structures were considered. Mechanical properties of the thin films were studied using an instrumented indentor to measure the force-depth response of the films during indentation or the force-deflection response of micromachined beams in bending. The films showed increasing hardness/modulus with a decrease in pore volume fraction or transformation from amorphous to a polycrystalline alpha-alumina phase. The asymmetric films show higher hardness and modulus on their barrier side (with closed pores) relative to their open pore side. The force-depth response, measured with a spherical ball indentor, demonstrates fairly good agreement with an elastic Hertzian contact solution. The force-depth response, measured with a sharp Vickers indentor, shows an elastoplastic response. Microcracking at the corners of sharp indentations was not observed in amorphous nanoporous films, and rarely in harder, crystalline nanoporous films. High-resolution scanning electron microscopy revealed a collapse of the nanoporous structure beneath the indentor tip during sharp indentation. The results are discussed in light of continuum-based models for the elastic properties of porous solids. In general, the models are not capable of predicting the change in modulus of the films, given pore volume fraction and the properties of bulk crystalline alumina.
Determination of Mode of Damage During Creep-Fatigue Interaction
Authors: Hyder M. Javed
Published: March 2006

A technique has been developed using the reversing dc electrical potential method to determine the mode of damage taking place during creep-fatigue interaction. It is observed that the hysteresis loop created by plotting the stress verses electrical potential gives a clear indication whether the damage in process is creep dominated or fatigue-dominated. During the fatigue-dominated damage process the hysteresis loop of stress verses electrical potential changes the shape whereas during the creep-dominated damage process the hysteresis loop of stress verses electrical potential does not change the shape but moves in the direction of higher electrical potential values. These changes are observed well before any indication seen on the conventional hysteresis loop of stress verses strain. This identification of the damage mode is observed well before failure occurs. The conclusion has been confirmed through fractographs. Hence it can be said that this technique eliminates the need for fractographs when determining the mode of damage during creep-fatigue interaction.
Off-axis electric field of a ring of charge
Authors: Zypman Fredy R.
Published: March 2006

We consider the electric field produced by a charged ring and develop analytical expressions for the electric field based on intuition developed from numerical experiments. Our solution involves the approximation of elliptic integrals. Problems are suggested for an arbitrarily charged ring.
Surprises in the multipole description of macroscopic electrodynamics
Authors: de Lange O. L. , Raab R. E.
Published: March 2006

The theory of macroscopic electrodynamics (in its multipole form) for harmonic plane-wave electric and magnetic fields in linear anisotropic media yields constitutive relations and expressions for the material constants and other macroscopic observables. It is shown that the calculated dynamic material constants are unphysical: of the 36 elements of the constitutive tensor, 27 (comprising the inverse permeability and two magnetoelectric tensors) depend on the choice of coordinate origin, while the remaining 9 (the permittivity tensor) are physical at electric dipole order, but not beyond. Thus quantities such as the time average of the instantaneous Poynting vector have origin-dependent values. We use properties of the macroscopic Maxwell equations and the equation of wave propagation to show how physically acceptable results can be obtained in a relatively simple manner for both nonmagnetic and magnetic dissipative media. In doing so, it is essential to adhere to a certain hierarchy for the pairing of electric and magnetic multipoles∕polarizabilities. We also comment on the Post constraint in relation to this theory, and use the Buckingham effect to illustrate origin-dependent and origin-independent properties.
Research-inspired problems for electricity and magnetism
Authors: Parks Beth
Published: March 2006

I present several problems related to current research problems and techniques that are suitable for introductory and intermediate electricity and magnetism.
Dancing paperclips and the geometric influence on magnetization: A surprising result
Authors: Jackson David P.
Published: March 2006

An impressive demonstration of magnetism can be accomplished by placing some metal paperclips on a horizontal surface and then applying a vertical magnetic field. As the field is increased, the paperclips suddenly jump up, do a little dance, and then stand at attention. This behavior is related to the more common demonstration of paramagnetic and diamagnetic materials, which consists of hanging a small aluminum (paramagnetic) or glass (diamagnetic) cylinder horizontally in a strong horizontal magnetic field. A paramagnetic cylinder aligns its axis parallel to the applied field while a diamagnetic cylinder aligns its axis perpendicular to the field. This paper investigates these demonstrations by analyzing a magnetic spheroid in a uniform external field. Although this analysis explains the behavior of the paperclips, it predicts that both paramagnetic and diamagnetic cylinders will align themselves parallel to a uniform external field, in contrast to the common demonstration experiment.
Why is Ampère’s law so hard? A look at middle-division physics
Authors: Manogue Corinne A. , Browne Kerry , Dray Tevian , Edwards Barbara
Published: March 2006

Because mathematicians and physicists think differently about mathematics, they have different goals for their courses and teach different ways of thinking about the material. As a consequence, there are a number of capabilities that physics majors need in order to be successful that might not be addressed by any traditional course. The result is that the total cognitive load is too high for many students at the transition from the calculus and introductory physics sequences to upper-division courses for physics majors. We illustrate typical student difficulties in the context of an Ampère’s law problem.
DYNAMICAL PRESSURE ANISOTROPY IN LIQUID-GAS MODEL OF LATTICE-GAS
Authors: EBIHARA KEN-ICHI
Published: March 2006

A liquid-gas model of lattice-gas is made by adding long-range interaction to lattice-gas and can simulate phase separation similar to that in the van der Waals' liquid-gas theory. This liquid-gas model can generate a circular dense-phase in the rare phase. In this paper, the deformation of the circular dense-phase by external force is simulated using the two types of liquid-gas models of lattice-gas, which are distinguished by the type of long-range interaction. It is observed that one type of model shows the valid deformation and the other shows the unphysical deformation. It is found by numerical experiments that this difference of the deformation is caused by dynamical pressure anisotropy of the liquid-gas model of lattice-gas.
SELECTIVE ADVANTAGE OF RECOMBINATION IN EVOLVING PROTEIN POPULATIONS: A LATTICE MODEL STUDY
Authors: WILLIAMS PAUL D. , POLLOCK DAVID D. , GOLDSTEIN RICHARD A.
Published: March 2006

Recent research has attempted to clarify the contributions of several mutational processes, such as substitutions or homologous recombination. Simplistic, tractable protein models, which determine the compact native structure phenotype from the sequence genotype, are well-suited to such studies. In this paper, we use a lattice-protein model to examine the effects of point mutation and homologous recombination on evolving populations of proteins. We find that while the majority of mutation and recombination events are neutral or deleterious, recombination is far more likely to be beneficial. This results in a faster increase in fitness during evolution, although the final fitness level is not significantly changed. This transient advantage provides an evolutionary advantage to subpopulations that undergo recombination, allowing fixation of recombination to occur in the population.
TESTING THE PERFORMANCES OF DIFFERENT IMAGE REPRESENTATIONS FOR MASS CLASSIFICATION IN DIGITAL MAMMOGRAMS
Authors: ANGELINI E. , CAMPANINI R. , IAMPIERI E. , LANCONELLI N. , MASOTTI M. , ROFFILLI M.
Published: March 2006

The classification of tumoral masses and normal breast tissue is targeted. A mass detection algorithm which does not refer explicitly to shape, border, size, contrast or texture of mammographic suspicious regions is evaluated. In the present approach, classification features are embodied by the image representation used to encode suspicious regions. Classification is performed by means of a support vector machine (SVM) classifier. To investigate whether improvements can be achieved with respect to a previously proposed overcomplete wavelet image representation, a pixel and a discrete wavelet image representations are developed and tested. Evaluation is performed by extracting 6000 suspicious regions from the digital database for screening mammography (DDSM) collected by the University of South Florida (USF). More specifically, 1000 regions representing biopsy-proven tumoral masses (either benign or malignant) and 5000 regions representing normal breast tissue are extracted. Results demonstrate very high performance levels. The area Az under the receiver operating characteristic (ROC) curve reaches values of 0.973 ± 0.002, 0.948 ± 0.004 and 0.956 ± 0.003 for the pixel, discrete wavelet and overcomplete wavelet image representations, respectively. In particular, the improvement in the Az value with the pixel image representation is statistically significant compared to that obtained with the discrete wavelet and overcomplete wavelet image representations (two-tailed p-value < 0.0001). Additionally, 90% true positive fraction (TPF) values are achieved with false positive fraction (FPF) values of 6%, 11% and 7%, respectively.
A MODEL WITH INTERACTING COMPOSITES
Authors: HORTAÇSU M. , LÜTFÜOḠLU B. C.
Published: March 2006

We show that it is possible to construct a model in (3 + 1) dimensions where only composite scalars take place in physical processes as incoming and outgoing particles, whereas constituent spinors only act as intermediary particles. Hence while the spinor–spinor scattering goes to zero, the scattering of composites give nontrivial results.
MODELS OF LITTLE HIGGS AND ELECTROWEAK PRECISION TESTS
Authors: CHEN MU-CHUN
Published: March 2006

The little Higgs idea is an alternative to supersymmetry as a solution to the gauge hierarchy problem. Here we review various little Higgs models and their phenomenology with emphases on the precision electroweak constraints in these models.
NONLINEAR FEATURE EXTRACTION AND DIMENSION REDUCTION BY POLYGONAL PRINCIPAL CURVES
Authors: ZHANG FENG
Published: March 2006

In this article we propose a polygonal principal curve based nonlinear feature extraction method, which achieves statistical redundancy elimination without loss of information and provides more robust nonlinear pattern identification for high-dimensional data. Recognizing the limitations of linear statistical methods, this article integrates local principal component analysis (PCA) with a polygonal line algorithm to approximate the complicated nonlinear data structure. Experimental results demonstrate that the proposed algorithm can be implemented to reduce the computation complexity for nonlinear feature extraction in multivariate cases.
LOCALLY EFFICIENT AND RELIABLE A POSTERIORI ERROR ESTIMATORS FOR DIRICHLET PROBLEMS
Authors: SACCHI ROBERTA , VEESER ANDREAS
Published: March 2006

Considering the Dirichlet problem for Poisson's equation in two and three dimensions, we derive a posteriori error estimators for finite element solutions with interpolated boundary values. The estimators are reliable and (locally) efficient with respect to the energy norm error, also in the case of discontinuous boundary values and load terms that are not square-integrable due to singularities at the boundary of the underlying domain. Moreover, we propose an adaptive algorithm based upon these estimators and test it also in nonsmooth cases of the aforementioned type: its convergence rate is optimal.
NONLINEAR EVOLUTION GOVERNED BY ACCRETIVE OPERATORS IN BANACH SPACES: ERROR CONTROL AND APPLICATIONS
Authors: NOCHETTO RICARDO H. , SAVARÉ GIUSEPPE
Published: March 2006

Nonlinear evolution equations governed by m-accretive operators in Banach spaces are discretized via the backward or forward Euler methods with variable stepsize. Computable a posteriori error estimates are derived in terms of the discrete solution and data, and shown to converge with optimal order [Formula: see text]. Applications to scalar conservation laws and degenerate parabolic equations (with or without hysteresis) in L1, as well as to Hamilton–Jacobi equations in C0 are given. The error analysis relies on a comparison principle, for the novel notion of relaxed solutions, which combines and simplifies techniques of Benilan and Kružkov. Our results provide a unified framework for existence, uniqueness and error analysis, and yield a new proof of the celebrated Crandall–Liggett error estimate.
PARAMETRICALLY EXCITED INSTABILITY OF A CABLE UNDER TWO SUPPORT MOTIONS
Authors: YING Z. G. , NI Y. Q. , KO J. M.
Published: March 2006

A direct numerical approach for solving the instability problem of multi-degree-of-freedom dynamic systems with general period-parameter excitation is developed based on the Floquet theory, Fourier series and generalized eigenvalue analysis. The developed direct numerical approach to the instability is applied to an inclined stay cable with sag under periodic two-support-motion excitation. The partially differential equation for the parametrically excited vibration of the cable is derived by using the transformation of displacements and converted into ordinary differential equations according to the Galerkin method. The unstable regions for parametrically excited vibration of the damped cable system with multi-degree-of-freedom are obtained to illustrate its overall instability. The effects of each mode vibration and parameters of the cable on the unstable regions are analyzed. The developed direct numerical approach to the parametrically excited instability is applicable to more general periodic parameter-excited systems.
EVALUATION OF MULTIPLE DUAL TUNED MASS DAMPERS FOR STRUCTURES UNDER HARMONIC GROUND ACCELERATION
Authors: HAN B. K. , LI C. X.
Published: March 2006

The multiple dual tuned mass dampers, referred to as the MDTMD, consisting of several units of dual tuned mass dampers (DTMD) are proposed for the first time herein, aimed at the effectiveness and robustness of the system for suppressing the undesirable vibrations of structures under the ground acceleration. The total number of dampers can be arbitrary and their natural frequencies are uniformly distributed. Ten typical types of the MDTMD can be devised by varying the system parameters. Employing the criteria chosen for optimum searching, parametric studies were carried out to evaluate the performance of the MDTMD of Type I-1 for its convenience in manufacturing, in which the larger mass blocks (LMBs) are assumed to have identical stiffness, but unequal masses, and the smaller mass blocks (SMBs) have identical stiffness and damping coefficient, but unequal masses and damping ratios. By adopting the maximum dynamic magnification factor (DMF) for each LMB and SMB used in estimating the stroke, an evaluation is also made for the stroke of the MDTMD. The numerical results indicate that the MDTMD (I-1) can provide better effectiveness and higher robustness in comparison with the dual tuned mass dampers (DTMD) and other MTMD systems of similar complexities. However, the stroke of the MDTMD is greater than that of the DTMD and the stroke of each SMB in the MDTMD is larger than that of the mass blocks (MBs) in the arbitrary integer and odd number based MTMD.
A FIRM-LEVEL STUDY OF THE INTERNATIONAL COMPETITIVENESS: THEORETICAL ANALYSIS AND EMPIRICAL FINDINGS
Authors: MA N. , LIAO M.
Published: March 2006

An analytical framework for conceptualizing the issue of international competitiveness at the firm level is presented taking into account that the firms are increasingly being exposed to international competition. The model identifies three interdependent innovative capability dimensions, which offer insight into the sources of sustainable international competitive advantages over time: Technological capability, managerial capability and resource exploiting capability. The paper presents the challenges of these three components of innovative capability in an international context, and describes how a firm can develop and sustain competitiveness through the operation in the environment of globalization. Finally, based on data from 213 firms in the Beijing area, the paper proves that these three innovative capability components are closely related to international competitiveness. The study reinforces the importance of innovative capability composition in internationalization decision-making and suggests further research in this context.
"FUZZY FRONT END" PRACTICES IN INNOVATING JAPANESE COMPANIES
Authors: HERSTATT CORNELIUS , STOCKSTROM CHRISTOPH , VERWORN BIRGIT , NAGAHIRA AKIO
Published: March 2006

In this paper, we report on the results of a large-scale study about typical front-end-related innovation practices in 553 Japanese mechanical and electrical engineering companies. We explore typical activities concerning the generation and assessment of new product ideas, the reduction of technological as well as market uncertainty and front end planning. Finally, we report on the differences between successful and unsuccessful companies. Our study confirms earlier findings about the frequent use of creativity techniques in Japan during the process of idea generation. We also find companies to be intensively involved in upper management and customers on NPD projects. While integrating upper management is of vital importance for assessing new product ideas, integrating customers and users is primarily used to developing product ideas and concepts. We further find evidence that successful companies integrate their customers more frequently in the process of developing and assessing new product ideas than non-successful companies. In addition, the former integrate customer requirements into their product definitions more often and also translate these requirements into technical specifications more frequently than non-successful companies. Finally, successful companies more often systematically plan a project prior to its start than unsuccessful ones.
SQUARE INTEGRABLE PROJECTIVE REPRESENTATIONS AND SQUARE INTEGRABLE REPRESENTATIONS MODULO A RELATIVELY CENTRAL SUBGROUP
Authors: ANIELLO PAOLO
Published: March 2006

We introduce the notion of square integrable group representation modulo a relatively central subgroup and, establishing a link with square integrable projective representations, we prove a generalization of a classical theorem of Duflo and Moore. As an example, we apply the results obtained to the Weyl–Heisenberg group.
THE CONTINUUM LIMIT OF DISCRETE GEOMETRIES
Authors: REQUARDT MANFRED
Published: March 2006

In various areas of modern physics and in particular in quantum gravity or foundational space–time physics, it is of great importance to be in the possession of a systematic procedure by which a macroscopic or continuum limit can be constructed from a more primordial and basically discrete underlying substratum, which may behave in a quite erratic and irregular way. We develop such a framework within the category of general metric spaces by combining recent work of our own and ingeneous ideas of Gromov et al. developed in pure mathematics. A central role is played by two core concepts. For one, the notion of intrinsic scaling dimension of a (discrete) space or, in mathematical terms, the growth degree of a metric space at infinity, on the other hand, the concept of a metrical distance between general metric spaces and an appropriate scaling limit (called by us a geometric renormalization group) performed in this metric space of spaces. In doing this, we prove a variety of physically interesting results about the nature of this limit process, properties of the limit space, e.g., what preconditions qualify it as a smooth classical space–time and, in particular, its dimension.
QUANTUM MECHANICS AS A MEASUREMENT THEORY ON BICONFORMAL SPACE
Authors: ANDERSON LARA B. , WHEELER JAMES T.
Published: March 2006

Biconformal spaces contain the essential elements of quantum mechanics, making the independent imposition of quantization unnecessary. Based on three postulates characterizing motion and measurement in biconformal geometry, we derive standard quantum mechanics, and show how the need for probability amplitudes arises from the use of a standard of measurement. Additionally, we show that a postulate for unique, classical motion yields Hamiltonian dynamics with no measurable size changes, while a postulate for probabilistic evolution leads to physical dilatations manifested as measurable phase changes. Our results lead to the Feynman path integral formulation, from which follows the Schrödinger equation. We discuss the Heisenberg uncertainty relation and fundamental canonical commutation relations.
Biliverdin protects against polymicrobial sepsis by modulating inflammatory mediators
Authors: Overhaus Marcus , Moore Beverley A. , Barbato Joel E. , Behrendt Florian F. , Doering Julia G. , Bauer Anthony J.
Published: March 2006

Highly inducible heme oxygenase (HO)-1 is protective against acute and chronic inflammation. HO-1 generates carbon monoxide (CO), ferrous iron, and biliverdin. The aim of this study was to investigate the protective effects of biliverdin against sepsis-induced inflammation and intestinal dysmotility. Cecal ligation and puncture (CLP) was performed on Sprague-Dawley rats under isoflurane anesthesia with and without intraperitoneal biliverdin injections, which were done before, at the time of CLP, and after CLP. In vivo gastrointestinal transit was carried out with fluorescein-labeled dextran. Jejunal circular muscle contractility was quantified in vitro using organ bath-generated bethanechol dose-response curves. Neutrophilic infiltration into the muscularis externa was quantified. The jejunal muscularis was studied for cytokine mRNA expressions [interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, inducible nitric oxide synthase, cyclooxygenase-2, biliverdin, IL-10, and HO-1] using real-time RT-PCR. Biliverdin treatment prevented the sepsis-induced suppression of gastrointestinal muscle contractility in vivo and in vitro and significantly decreased neutrophilic infiltration into the jejunal muscularis. Inflammatory mRNA expressions for small bowel IL-6 and MCP-1 were significantly reduced after biliverdin treatment in CLP-induced septic animals compared with untreated septic animals. The anti-inflammatory mediator expression of small bowel IL-10 was significantly augmented after CLP at 3 h compared with untreated septic animals. These findings demonstrate that biliverdin attenuates sepsis-induced morbidity to the intestine by selectively modulating the inflammatory cascade and its subsequent sequelae on intestinal muscularis function.
Iron Imports. VI. HFE and regulation of intestinal iron absorption
Authors: Fleming Robert E. , Britton Robert S.
Published: March 2006

The majority of clinical cases of iron overload is caused by mutations in the HFE gene. However, the role that HFE plays in the physiology of intestinal iron absorption remains enigmatic. Two major models have been proposed: 1) HFE exerts its effects on iron homeostasis indirectly, by modulating the expression of hepcidin; and 2) HFE exerts its effects directly, by changing the iron status (and therefore the iron absorptive activity) of intestinal enterocytes. The first model places the primary role of HFE in the liver (hepatocytes and/or Kupffer cells). The second model places the primary role in the duodenum (crypt cells or villus enterocytes). These models are not mutually exclusive, and it is possible that HFE influences the iron status in each of these cell populations, leading to cell type-specific downstream effects on intestinal iron absorption and body iron distribution.
Influence of fibrillin-1 genotype on aortic stiffness in men: a note of caution
Authors: Yasmin  , Wilkinson Ian B. , O’Shaughnessy Kevin M.
Published: March 2006

Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28–81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G\?\T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype ( P = 0.005). Pulse pressure also was increased in the 2-3 genotype ( P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.
Vascular Proliferation Is Important for Clinical Progress of Endometrial Cancer
Authors: Stefansson Ingunn M. , Salvesen Helga B. , Akslen Lars A.
Published: March 2006

Angiogenesis is essential for tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/factor VIII staining) and the degree of pericyte coverage [by α-smooth muscle actin (α-SMA)/factor VIII staining], in a large and population-based series of endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D and basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the α-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of endometrial carcinoma. (Cancer Res 2006; 66(6): 3303-9)
Lysophosphatidic Acid Is Constitutively Produced by Human Peritoneal Mesothelial Cells and Enhances Adhesion, Migration, and Invasion of Ovarian Cancer Cells
Authors: Ren Juan , Xiao Yi-jin , Singh Lisam Shanjukumar , Zhao Xiaoxian , Zhao Zhenwen , Feng Li , Rose Tyler M. , Prestwich Glenn D. , Xu Yan
Published: March 2006

Lysophosphatidic acid (LPA) is both a potential marker and a therapeutic target for ovarian cancer. It is critical to identify the sources of elevated LPA levels in ascites and blood of patients with ovarian cancer. We show here that human peritoneal mesothelial cells constitutively produce LPA, which accounts for a significant portion of the chemotactic activity of the conditioned medium from peritoneal mesothelial cells to ovarian cancer cells. Both production of LPA by peritoneal mesothelial cells and the chemotactic activity in the conditioned medium can be blocked by HELSS [an inhibitor of the calcium-independent phospholipase A2 (iPLA2)] and AACOCF3 [an inhibitor of both cytosolic PLA2 (cPLA2) and iPLA2]. Moreover, cell-based enzymatic activity assays for PLA2 indicate that peritoneal mesothelial cells have strong constitutive PLA2 activity. Receptors for LPA, LPA2, and LPA3 are involved in the conditioned medium–induced chemotactic activity. Invasion of ovarian cancer cells into peritoneal mesothelial cells has also been analyzed and shown to require PLA2, LPA receptors, and the mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase signaling pathway. Thus, we show here, for the first time, that human peritoneal mesothelial cells constitutively produce bioactive lipid signaling molecules, such as LPA, via iPLA2 and/or cPLA2 activities. Conditioned medium from peritoneal mesothelial cells stimulate migration, adhesion, and invasion of ovarian cancer cells, and may play similar roles in vivo. (Cancer Res 2006; 66(6): 3006-14)
Nuclear Insulin-Like Growth Factor Binding Protein-3 Induces Apoptosis and Is Targeted to Ubiquitin/Proteasome–Dependent Proteolysis
Authors: Santer Frédéric R. , Bacher Nicole , Moser Barbara , Morandell Dieter , Ressler Sigrun , Firth Sue M. , Spoden Gilles A. , Sergi Consolato , Baxter Robert C. , Jansen-Dürr Pidder , Zwerschke Werner
Published: March 2006

Insulin-like growth factor binding protein-3 (IGFBP-3), the product of a tumor suppressor target gene, can modulate cell proliferation and apoptosis by IGF-I-dependent and IGF-I-independent mechanisms. IGFBP-3 controls the bioavailability of IGFs in the extracellular environment and is known to be subject to degradation by various extracellular proteases. Although nuclear localization and functions of IGFBP-3 have been described in the past, we show as the novel features of this study that the abundance of nuclear IGFBP-3 is directly regulated by ubiquitin/proteasome–dependent proteolysis. We show that IGFBP-3 degradation depends on an active ubiquitin-E1 ligase, specific 26S proteasome inhibitors can efficiently stabilize nuclear IGFBP-3, and the metabolic half-life of nuclear IGFBP-3 is strongly reduced relative to cytoplasmic IGFBP-3. Nuclear IGFBP-3 is highly polyubiquitinated at multiple lysine residues in its conserved COOH-terminal domain and stabilized through mutation of two COOH-terminal lysine residues. Moreover, we show that IGFBP-3, if ectopically expressed in the nucleus, can induce apoptotic cell death. These results suggest that ubiquitin/proteasome–mediated proteolysis of IGFBP-3 may contribute to down-regulation of apoptosis. (Cancer Res 2006; 66(6): 3024-33)
The Oncogenic Epidermal Growth Factor Receptor Variant Xiphophorus Melanoma Receptor Kinase Induces Motility in Melanocytes by Modulation of Focal Adhesions
Authors: Meierjohann Svenja , Wende Elisabeth , Kraiss Anita , Wellbrock Claudia , Schartl Manfred
Published: March 2006

One of the most prominent features of malignant melanoma is the fast generation of metastasizing cells, resulting in the poor prognosis of patients with this tumor type. For this process, cells must gain the ability to migrate. The oncogenic receptor Xmrk (Xiphophorus melanoma receptor kinase) from the Xiphophorus melanoma system is a mutationally activated version of the epidermal growth factor receptor that induces the malignant transformation of pigment cells. Here, we show that the activation of Xmrk leads to a clear increase of pigment cell motility in a fyn-dependent manner. Stimulation of Xmrk induces its interaction with the focal adhesion kinase (FAK) and the interaction of active, receptor-bound fyn with FAK. This results in changes in FAK activity and induces the modulation of stress fibers and focal adhesions. Overexpression of dominant-negative FAK shows that the activity of innate FAK and a receptor-induced focal adhesion turnover are a prerequisite for pigment cell migration. Our findings show that in our system, Xmrk is sufficient for the induction of pigment cell motility and underlines a role of the src family protein tyrosine kinase fyn in melanoma development and progression. (Cancer Res 2006; 66(6): 3145-52)
Activation of Stat3 in Human Melanoma Promotes Brain Metastasis
Authors: Xie Tong-xin , Huang Feng-Ju , Aldape Kenneth D. , Kang Shin-Hyuk , Liu Mingguang , Gershenwald Jeffrey E. , Xie Keping , Sawaya Raymond , Huang Suyun
Published: March 2006

Brain metastasis is a major cause of morbidity and mortality in patients with melanoma. The molecular changes that lead to brain metastasis remain poorly understood. In this study, we developed a model to study human melanoma brain metastasis and found that Stat3 activity was increased in human brain metastatic melanoma cells when compared with that in cutaneous melanoma cells. The expression of activated Stat3 is also increased in human brain metastasis specimens when compared with that in the primary melanoma specimens. Increased Stat3 activation by transfection with a constitutively activated Stat3 enhanced brain metastasis, whereas blockade of Stat3 activation by transfection with a dominant-negative Stat3 suppressed brain metastasis of human melanoma cells in animal models. Furthermore, altered Stat3 activity profoundly affected melanoma angiogenesis in vivo and melanoma cell invasion in vitro and significantly affected the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in vivo and in vitro. Finally, Stat3 activity transcriptionally regulated the promoter activity of bFGF in addition to VEGF and MMP-2 in human melanoma cells. These results indicated that Stat3 activation plays an important role in dysregulated expression of bFGF, VEGF, and MMP-2 as well as angiogenesis and invasion of melanoma cells and contributes to brain metastasis of melanoma. Therefore, Stat3 activation might be a new potential target for therapy of human melanoma brain metastases. (Cancer Res 2006; 66(6): 3188-96)
A Growth-Related Oncogene/CXC Chemokine Receptor 2 Autocrine Loop Contributes to Cellular Proliferation in Esophageal Cancer
Authors: Wang Bo , Hendricks Denver T. , Wamunyokoli Fred , Parker M. Iqbal
Published: March 2006

Growth-related oncogene (GRO), a member of the CXC chemokine subfamily, plays a major role in inflammation and wound healing. CXC chemokines have been found to be associated with tumorigenesis, angiogenesis, and metastasis. Although elevated expression of GRO has been reported in several human cancers, the expression and role of GRO and its receptor, CXCR2, in esophageal cancer are poorly understood. This study used real-time reverse transcription-PCR (RT-PCR) and immunohistochemical approaches to show that GROα, GROβ, and CXCR2 are up-regulated in esophageal tumor tissue. Furthermore, GROα, GROβ, and CXCR2 are constitutively expressed in WHCO1, an esophageal cancer cell line that was used as a model system here. GROβ enhances transcription of EGR-1, via the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which can be blocked by a specific antagonist of CXCR2 (SB 225002) or specific antibody to GROβ. WHCO1 cells treated with SB 225002 exhibited a 40% reduction in cell proliferation. A stable WHCO1 GROα RNA interference (RNAi) clone displayed a 43% reduction in GROα mRNA levels as determined by real-time RT-PCR, reduced levels of GROα by fluorescence microscopy, and a 60% reduction in the levels of phosphorylated ERK1/2. A stable clone expressing GROβ RNAi displayed >95% reduction in GROβ mRNA levels, reduced levels of GROβ by fluorescence microscopy, and an 80% reduction in the levels of phosphorylated ERK1/2. Moreover, these GROα RNAi- and GROβ RNAi-expressing clones displayed a 20% and 50% decrease in cell proliferation, respectively. Our results suggest that GROα-CXCR2 and GROβ-CXCR2 signaling contributes significantly to esophageal cancer cell proliferation and that this autocrine signaling pathway may be involved in esophageal tumorigenesis. (Cancer Res 2006; 66(6): 3071-7)