bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Urban Development on Auto Ownership and Transit Use
Authors: Kain John F. , Fauth Gary R.
Published: October 2003

This study documents an investigation of how intermetropolitan differences in transit and highway service levels; as well as overall urban development patterns, affect auto ownership and use. Specifically, this paper presents models of the determinants of auto ownership and mode choice for 163,488 white, single‐worker households residing in the largest 125 SMSAs in 1970. Indices of highway capicity, transit service levels, and overall residential density for each SMSA together with each household's socio‐economic characteristics, workplace location, and residence choice, are used to explain each household's observed auto ownership status (0, one, or more than one car), and, given that auto ownership status, each household's worktrip mode (auto driver, auto passenger, bus, rail, or walk).

The models offer a framework for considering the effect of alternative urban development scenarios upon auto ownership and use, and for comparing alternative development and infrastructure policy options. Because the models have been estimated using households from different SMSAs, they are particularly appropriate for investigating changes in spatial structure.
FHA, Racial Discrimination and Urban Mortgages
Authors: Fullerton David J. , MacRae C. Duncan
Published: October 2003

The empirical validity of two propositions regarding FHA unsubsidized single‐family activity are explored at the neighborhood level in this paper. The propositions are first that FHA serves moderate‐to‐middle‐income families, not low‐income families who live in the inner city nor high‐income families who live in the outer suburbs; and second that all other things being equal, black owner‐occupants are more likely to have an FHA‐insured mortgage than are whites

Two methods of analysis are performed: mapping and regression. First, 1974 FHA activity in the Philadelphia metropolitan area is mapped by race—black and white—and program—203(b), 221(d)(2), and 223(e)—at the census tract level. Then, the FHA activity by race and by program is regressed on 1970 neighborhood housing and population characteristics, again, using the census tract as the unit of observation. The results of the analysis provide support for both propositions. In Philadelphia in 1974, FHA is to a degree a border program differentially serving blacks.
Confidence Intervals and the Evaluation of Regression Based Appraisal Models
Authors: Gloudemans Robert J.
Published: October 2003

Perhaps the most important technical development in assessment administration in recent years has been the application of multiple regression analysis. The technique offers an effective means of reappraising the large majority of single family residences each year or so at low costs per parcel. This paper addresses the issue of how to evaluate properly the accuracy or reliability of such models.
Major Developments in Residential Mortgage and Housing Markets Since the Hunt Commission
Authors: Seiders David F.
Published: October 2003

A number of important changes have been made to the mortgage finance system since the Hunt Commission filed its report, and the economic environment has been altered substantially. This paper examines shifts in the relative importance of public and private institutions in the residential mortgage markets during the past decade, within the context of Hunt Commission recommendations. Changes in the cyclical sensitivity of mortgage and housing activity, and the implications of rapid inflation for the growth of these markets, also are considered.
Standardizing Yields on Mortgages and other Securities
Authors: Kaufman George G. , Morgan George E.
Published: October 2003

The existence of a difference between the yield to maturity of a coupon bond and the expected holding period return on a coupon bond, referred to as coupon bias, is well recognized. This paper discusses the nature of coupon bias for mortgages, estimates the magnitude of the bias under different assumptions about the characteristics of the mortgage security and the term structure, and compares the magnitude of the coupon biases on mortgages and comparable coupon bonds. For a moderately upward sloping term structure at current levels of interest rates, coupon bias for a thirty‐year mortgage can be on the order of 75 basis points.
An Intertemporal Empirical Analysis of the Renter's Decision to Purchase a Home
Authors: Ihlanfeldt Keith Ray
Published: October 2003

In recent years a controversy has developed regarding the responses of different types of families to increases in the relative cost of homeownership. In order to provide evidence on this question, this study employs samples of renters from the Panel Study of Income Dynamics to estimate the marginal probability of home purchase and the conditional expectation of the house value to income ratio. These cross‐section estimations are performed for two separate time periods: 1968–70 and 1974–76. Among the conclusions reached (by analyzing intertemporal changes in predicted purchase probabilities and value to income ratios) are (1) that first‐time homebuyers have not stretched their housing budgets in response to inflationary expectations, and (2) that the probability of purchase by many of these families has declined over time, especially at low income levels.
A Model of Localized Mortgage Lending Behavior*
Authors: Clapp John M.
Published: October 2003

Loan administration costs and the costs of search for information about risk are found to be determinants of spatial interest rate differentials. These costs are independent of dollar loan size; therefore, rational lending policies can produce higher interest rates (or lower term to maturity) in low‐income communities. But the premium (lower maturity) should be related to lower loan size and risk differentials. Public policy should be directed toward compiling and verifying an information bank which would allow lenders to search efficiently for information about risk.

An empirical methodology designed to test for mortgage deficiency in minority areas was developed through case studies. This indicated the utility of specifying the supply and demand for mortgages at the neighborhood level of aggregation. Trends in neighborhood property values were identified as important and overlooked measures of lending risk. Further exploration of the hypothesis that Spanish‐speaking areas are mortgage deficient is suggested by the cases.
What A National Commission on Neighborhoods Could Do
Authors: Yin Robert K.
Published: October 2003

This paper addresses the problems to be faced by a national commission on neighborhoods. Legislation to create such a study group was introduced during the past year, in conjunction with renewed interest in neighborhood conservation and revitalization. However, there have been many earlier study groups that have already made most of the recommendations which might be expected from a new effort. The work of a new commission should therefore focus on the ways in which the study group conducts its activities. For instance, a new commission should explicitly assess existing programs (with a view toward reducing some of the less efficient or contradictory ones), should broaden its attempts to solicit the views of residents, should conduct advocate inquiries in addition to research analyses, should focus on the organizational problems of implementing any new recommendations, and should help neighborhoods to develop simple techniques for monitoring neighborhood change. This paper also points out some of the critical issues that any new study group must face, including the problem that the prime candidates for neighborhood preservation are not likely to be poverty neighborhoods. Therefore, neighborhood revitalization policies cannot easily serve both middle‐ and low‐income constituents.
Simulation Analysis of Alternative Mortgage Instruments
Authors: Field Al , Cassidy Henry J.
Published: October 2003

The widespread concern over the inadequacies of the standard fixed rate, level payment mortgage instrument, especially in inflationary periods, has prompted a number of proposals for alternative mortgage instruments (AMIs). In this study the individual characteristics and economic implications of a number of AMIs are analyzed by simulating their behavior over different types of economic conditions. Each instrument is evaluated on the basis of its relative efficiency in accomplishing its particular objectives. Most of the instruments appear suitable for certain types of borrowers and lenders. However, this limited analysis suggests that the graduated payment and variable rate mortgages have advantages over the other variants considered. Various forms of each are already in use and appear to be relevant and marketable for many of the country's borrowers and lenders.
FHA Mortgage Discount Points, House Prices and Consumer Behavior
Authors: Guntermann Karl L.
Published: October 2003

The allocation of FHA discount points between buyers and sellers has recently been the subject of empirical investigation. The research reported here examines this relationship in more detail. Regression equations were estimated for separate price categories of housing using dummy variables for the number of discount points being charged. Separate equations were also estimated for periods when points were rising and when they were falling. The results essentially are that sellers attempt to shift all of the discount points to buyers and frequently are successful. However, in certain situations the points are shared between buyers and seller.
Expected and Actual Effects of Housing Allowances on Housing Prices
Authors: Barnett C. Lance
Published: October 2003

Most analysts and policy makers expected fullscale housing allowance programs to substantially disturb local housing markets, causing housing prices tb increase sharply. This paper reviews conjectures about expected price effects, summarizes evidence from the Housing Assistance Supply Experiment, and explains why the program did not engender the expected price inflation.
The Incidence of Property Taxes on Single‐Family Housing*
Authors: Lewis W. Cris , McNutt Paul J.
Published: October 2003

The incidence of local property taxes, specifically the degree of capitalizing of property tax differentials in market prices, remains an unresolved question. The studies by Oates (1969) and McMillan and Carlson (1977), which come to contradictory conclusions typify the diversity of opinion on the question. Many of the previous studies suffer from research design problems including, the use of census data for market values and property tax levels on real property; failure to control for differences in public services quality among the cities samples; and use of assessed value as a proxy for market price.

A theoretical model in developed to explain the capitalization effect of property tax differentials within an urban area. Because the model is exactly identified, a single reduced from equation relating market value to a set of physical characteristics of the property and the level of property taxes can be estimated using ordinary least‐squares techniques. The function is estimated using data drawn from 107 residential property sales made during 1976. Estimated parameters for the other equations then are determined indirectly. Actual market price and property tax data for each parcel ware used.

It is found that property tax differentials on otherwise comparable properties are associated with significant market value differentials. Because the assessed value ranges from 7 to 20 percent of market value, the property tax procedure in the area studied appears to have randomly generated large capital gains for some and capital losses for others.

Because of the limited data base, the statistical results are only indicative; the model, howevfer, should have wide applicability in a variety of questions concerning the incidence of property taxes.
Alternative Methods of Variable Selection: An Application to Real Estate Assessment*
Authors: Richardson David H. , Thalheimer Richard
Published: October 2003

This article compares alternative methods of variable selection using data from a real estate assessment project. Various stepwise methods are compared with the all possible regression solution and a variable set selected on a priori considerations. The methods are evaluated by the predictive performance of the estimated regression equation in a holdout sample. One of the major conclusions of the study is that the most expensive and time consuming method, all possible regression, does not yield the best predictions. In addition, the variables selected judgmentally produced predictions that were not appreciably different from the other methods.
Hedonic Property Valuation Models: Are Subjective Measures of Neighborhood Amenities Needed?
Authors: Lang James R. , Jones Wesley H.
Published: October 2003

Common applications of hedonic residential property valuation models have relied on proxy measures of neighborhood amenities rather than directly measured subjective evaluations. While this approach simplifies data collection, there is reason to suspect that the use of proxy measures has degraded the accuracy of hedonic valuation models. The extent to which the use of proxy measures may decrease predictive accuracy, and fail to capture the effect of neighborhood amenities, has not been reported previously. The results presented here show that direct subjective measures yield only modest improvements in price prediction. Careful use of proxy measures for neighborhood amenities appears to be cost efficient for large‐scale appraisal work.
Assessment Ratios and Property Tax Burdens in Norfolk, Virginia, 1974–75*
Authors: Pearson Thomas D.
Published: October 2003

To examine the relationship between property taxes and neighborhood housing, this paper employed property tax assessment to sale price ratios (i.e. effective tax rates) of residential properties sold during the period beginning July 1, 1974 through June 30, 1975. The analysis was designed to question whether or not the property tax in Norfolk results in different tax burdens for neighborhoods with different income levels. The results indicate there are substantial variations in effective tax rates within neighborhoods as well as between neighborhoods. More interesting is the fact that the property tax appeared to be progressive, given the measure used. If inequities in administration did not exist, it would be much more progressive.

Such relationships indicate the existence of problems with the administration of the property tax in Norfolk. An examination of possible problems is conducted and some recommendations are made for potential corrective measures.
Simulations of Savings Associations Using Alternative Mortgage Instruments
Authors: Vernor James D.
Published: October 2003

This paper reports on the development and use of a deterministic, accounting identity, simulation computer model of a federally chartered savings and loan association to observe the effect upon earnings and net worth growth, over the 1964 to 1974 period, of the use of various alternative mortgage instruments. Experiments were conducted on several kinds of variable rate mortgages, graduated payment mortgages, and price level adjusted mortgages; various interest reference rates were tested along with alternative systems of constraining VRM changes, alternative graduation rates, and various systems for paying interest to savers.
North‐South Differences in Housing and the Housing and Community Development Act of 19771
Authors: Dahmann Donald C.
Published: October 2003

During the past two decades the South has experienced more vigorous urban development than the North. In response to this continuing trend, the Congress has recently enacted legislation that provides increased levels of Federal assistance to slower growing communities and those whose housing stocks are disproportionately old, thus providing increased benefits to northern cities. Data from the Annual Housing Survey are examined to establish differences between housing conditions in these two regions, and the potential of the newly‐established regionally targeted allocation schemes toward achieving national housing goals is discussed.
From ‘black‐balling’ to ‘marking’: the suburban origin of redlining in Canada, 1930s–1950s
Authors: Harris Richard
Published: October 2003

Redlining occurs where institutional mortgage lending is the norm and where lenders decline to loan in specific areas. The term originated during the 1930s in the United States, where it was promoted by federal agencies and acquired racial connotations. Recently, redlining has been uncommon in Canada, but contemporary reports, archival records and parliamentary debates show it was widespread from the 1930s to the 1950s. Contemporaries distinguished the ‘black‐balling’ of remote areas, where it was impossible to make loans, from the ‘marking’ of districts in urban areas where companies could lend but chose not to do so. Only the latter can be regarded as redlining. As defined by Canadian housing agencies, most ‘marked’ areas were in unregulated, owner‐built suburbs that lacked services. The suburban origin of redlining in Canada had little to do with the distribution of ethnic minorities. As long as it lasted, roughly until the late 1950s, it perpetuated social class diversity in Canadian suburbs.
Central Command is Capable of Modulating Sweating from Non‐Glabrous Human Skin
Authors: Shibasaki Manabu , Secher Niels H. , Selmer Christian , Kondo Narihiko , Crandall Craig G.
Published: October 2003

Isometric handgrip exercise (IHG) increases sweating rate without changing core or skin temperatures. The contribution of central command resulting in increases in sweating rate during IHG is unknown. To investigate this question, seven subjects performed IHG (35 % maximum voluntary contraction (MVC) for 2 min) followed by 2‐min of post‐exercise ischaemia (PEI), with and without partial neuromuscular blockade (PNB). PNB was performed to augment central command during the IHG bout. These trials were conducted while the subject was normothermic, mildly heated, and moderately heated. On the non‐exercising arm, forearm sweating rate was monitored over a microdialysis membrane perfused with neostigmine (acetylcholinesterase inhibitor), and at an adjacent untreated site. In normothermia with PNB, despite reduced force production during IHG (17 ± 9 versus 157 ± 13 N; P < 0.001), the elevation in sweating rate at the neostigmine‐treated site was greater relative to the control IHG bout (P < 0.05). During subsequent PEI, for the PNB trial mean arterial blood pressure (MAP) and sweating rate returned towards pre‐IHG levels, while during the control trial these variables remained elevated. During IHG while mildly heated, the elevation in sweating rate was greater during the PNB trial relative to the control trial. In contrast, during moderate heating sweating increased during IHG for both trials, however the elevation in sweating rate during the PNB trial was not greater than during the control trial. These results suggest that central command is capable of modulating sweating rate in all thermal conditions, however its effect is reduced when body temperatures and/or sweating rate are substantially elevated.
Nicotine is Highly Effective at Producing Desensitization of Rat α4β2 Neuronal Nicotinic Receptors
Authors: Paradiso K. G. , Steinbach Joe Henry
Published: October 2003

We examined desensitization by acetylcholine (ACh) and nicotine at the rat α4β2 neuronal nicotinic receptor stably expressed in HEK cells. For both agonists, the decay in response due to desensitization (‘onset’) was best fitted by the sum of two exponentials with the fast component dominant at concentrations > 1 μm. The time constants for onset were similar for both agonists, and showed little concentration dependence over the range of 0.1‐100 μm. Recovery from desensitization also showed two exponential components. In contrast to the similarity in onset, nicotine produced longer lasting desensitization, resulting from an increase in the proportion of receptors in the slowly recovering population and from an increase in the time constant for the slow recovery process. The proportion of receptors in the slowly recovering population increased as the duration of the desensitizing pulse increased. Desensitization was also induced by low concentrations of agonist, with no apparent macroscopic response. A 100 s application of 10 nm nicotine desensitized 70 % of the peak response, while 100 s of 10 nm ACh desensitized only 15 %. At higher concentrations of agonist, which result in a macroscopic response, desensitization in the absence of activation also can occur. Nicotine is a very potent and efficacious desensitizing agent at this neuronal nicotinic receptor.
The Internet Pilot to Physics: An Open Information System for Physics Research and Education
Authors: Karttunen Mikko , Holmlund Kenneth , Nowotny Günther
Published: October 2003

In this article we discuss the effort made by the Internet Pilot to Physics (TIPTOP) project to develop a uniform and open information infrastructure for physics research and education. We discuss concepts such as communication in research and education, the importance of distributed indexing and catalogs, and briefly the use of new technology such as VRML and Java. We also stress the importance of developing and using standardized protocols and formats such as the Summary Object Interchangeable Format (SOIF) and Thematic Uniform Resource Agents (TURA). TIPTOP has rapidly grown to be one of the most popular physics Internet knowledge servers, and the recently established collaboration with the European Physical Society is an important step forward in developing a stable framework of high quality information for researchers and educators.
World Wide Web Technology as a New Teaching and Learning Environment
Authors: Novak Gregor M. , Patterson Evelyn T.
Published: October 2003

Since the introduction in 1993 of the World Wide Web and the associated multimedia technologies numerous projects are underway introducing the new tool into introductory physics teaching. This paper will describe two such undertakings: The Cockpit Physics project at the United States Air Force Academy and the WebPhysics project at Indiana University Purdue University at Indianapolis.
Primality Test Via Quantum Factorization
Authors: Chau H. F. , Lo H.-K.
Published: October 2003

We consider a probabilistic quantum implementation of a variation of the Pocklington–Lehmer N - 1 primality test using Shor's algorithm. O ( log 3 N log log N log log log N) elementary q-bit operations are required to determine the primality of a number N, making it (asymptotically) the fastest known primality test. Thus, the potential power of quantum mechanical computers is once again revealed.
Mesoscopic Maxwell-Dissipative Finite Element Model for Crack Propagation
Authors: Heino Pekka , Kaski Kimmo
Published: October 2003

Dynamic fracture in viscoelastic solids has been studied computationally using a mesoscale Finite Element model. In order to study crack propagation in homogeneous or amorphous materials the locations of nodes are selected regularly or randomly, respectively. In both cases results show oscillations in crack velocity above a critical velocity of about one-half the Raleigh velocity. The complicated topology of cracks obeys the scaling law found in experimental works. Dissipative systems are found to bear a larger maximum strain than purely elastic systems before macroscopic fracture.
Quantum Lattice-Gas Models for the Many-Body Schrödinger Equation
Authors: Boghosian Bruce M. , Taylor Washington
Published: October 2003

A general class of discrete unitary models are described whose behavior in the continuum limit corresponds to a many-body Schrödinger equation. On a quantum computer, these models could be used to simulate quantum many-body systems with an exponential speedup over analogous simulations on classical computers. On a classical computer, these models give an explicitly unitary and local prescription for discretizing the Schrödinger equation. It is shown that models of this type can be constructed for an arbitrary number of particles moving in an arbitrary number of dimensions with an arbitrary interparticle interaction.
Error Analysis for the Interpolation-Supplemented Lattice-Boltzmann Equation Scheme
Authors: He Xiaoyi
Published: October 2003

The numerical error of the interpolation-supplemented lattice-Boltzmann equation (ISLBE) scheme is theoretically analyzed. The ISLBE is proved to recover the Navier–Stokes equation as long as a second order interpolation scheme is used and the flow domain is appropriately discretized. Using a linear interpolation scheme will inevitably generate the numerical diffusivity and viscosity, making the ISLBE scheme unable to simulate the Navier–Stokes equation correctly. The analysis is consistent with previous numerical experiments.
Finite Size Effect in Lattice-BGK Models
Authors: Qian Yue-Hong , Chen Shiyi
Published: October 2003

In this paper, we present numerical results of finite size effect in lattice-BGK models applied to liquid-gas phase transitions in one dimension. Several "pseudo-potentials" are used in simulations and the lattice size varies from 4 lattice sites to 4096 sites. Power law scaling is found and simple mean-field theory is used to explain the numerical finding.
Using Dissipative Particle Dynamics to Model Binary Immiscible Fluids
Authors: Novik Keir E. , Coveney Peter V.
Published: October 2003

We investigate the domain growth and phase separation of two-dimensional binary immiscible fluid systems using dissipative particle dynamics. Our results are compared with similar simulations using other techniques, and we conclude that dissipative particle dynamics is a promising method for simulating these systems.
IMD: A Software Package for Molecular Dynamics Studies on Parallel Computers
Authors: Stadler J. , Mikulla R. , Trebin H.-R.
Published: October 2003

We report on implementation and performance of the program IMD, designed for short range molecular dynamics simulations on massively parallel computers. After a short explanation of the cell-based algorithm, its extension to parallel computers as well as two variants of the communication scheme are discussed. We provide performance numbers for simulations of different sizes and compare them with values found in the literature. Finally we describe two applications, namely a very large scale simulation with more than 1.23×109 atoms, to our knowledge the largest published MD simulation up to this day and a simulation of a crack propagating in a two-dimensional quasicrystal.
The Influence of the Number of Different Stocks on the Levy–Levy–Solomon Model
Authors: Kohl R.
Published: October 2003

The stock market model of Levy, Levy, Solomon is simulated for more than one stock to analyze the behavior for a large number of investors. Small markets can lead to realistic looking prices for one and more stocks. A large number of investors leads to a semi-regular fashion simulating one stock. For many stocks, three of the stocks are semi-regular and dominant, the rest is chaotic. Aside from that we changed the utility function and checked the results.
Holonomic Links and Smale Principles for Multisingularities
Authors: Vassiliev Victor A.
Published: October 2003

A loop S1 → ℝn is holonomic if it is the (n - 1)-jet extension of a function S1 → ℝ1. We prove that for n = 3 any tame link in ℝn is isotopy equivalent to a holonomic one; for n > 3 the space of holonomic links is holotopy equivalent to the space of all differentiable links.
State-Sum Invariants of 4-Manifolds
Authors: Crane Louis , Kauffman Louis H. , Yetter David N.
Published: October 2003

We provide, with proofs, a complete description of the authors' construction of state-sum invariants announced in [CY], and its generalization to an arbitrary (artinian) semisimple tortile category. We also discuss the relationship of these invariants to generalizations of Broda's surgery invariants [Br1,Br2] using techniques developed in the case of the semi-simple sub-quotient of Rep(Uq(sl2)) (q a principal 4rth root of unity) by Roberts [Ro1]. We briefly discuss the generalizations to invariants of 4-manifolds equipped with 2-dimensional (co)homology classes introduced by Yetter [Y6] and Roberts [Ro2].
The Double Cover of S3 Branched along a Link
Authors: Brunner A. M.
Published: October 2003

Let L be an unsplittable link in S3 and let V denote the double cover of S3 branched along L. Starting with an arbitrary planar projection of L, it is shown how to construct a special presentation for the fundamental group π1V which encodes in a simple way geometric data from a (checkerboard) spanning surface obtained from the given projection, and which relates to the construction of Coxeter quotients of π1 (S3-L) previously studied by the author and Y. W. Lee.
Knot Energies by Ropes
Authors: Diao Y. , Ernst C. , van Rensburg E. J. Janse
Published: October 2003

An energy function for smooth knots is defined using the concept of thickness and proved to be a good indicator of the complexity of knots. This energy function has the advantage that it can be measured experimentally. We carry out an experiment to measure the energies for knots up to 8 crossings and compare our data with energies obtained elsewhere through numerical simulations.
Parabolic Representations of the Groups of Mutant Knots
Authors: Wada Masaaki
Published: October 2003

It is proved that the groups of the Kinoshita-Terasaka knot and the Conway's knot have the same number of parabolic representations in SL2(F) for every finite field F. Although the proof is based on the fact that the two knots are mutants of each other, it is also shown that the groups of mutant knots do not in general have the same number of parabolic representations.
Nucleon Resonances in Nuclei and Quark Levels
Authors: Giannini M. M. , Trovatore E.
Published: October 2003

The effect of the nuclear medium on the excitation mechanism of nucleon resonances is investigated in the framework of the constituent quark model (CQM). Calculations of the total strength of the M1 and E1 excitations in a two-nucleon system are performed by means of a two-centre quark potential model in which the intercluster barrier is allowed to vary with the relative distance. The results show that the resonance excitation in the deuteron is not modified with respect to the free nucleon case. In contrast, when the internucleon distance assumes typical nuclear values, the pattern of the quark levels leads to a ~ 10% damping of the D 13 resonance, leaving the Δ excitation unaffected, in agreement with the recent photoabsorption measurements.
Structural Configurations in an Extended Orbiting Cluster Model for Molecular Resonance States
Authors: Gupta Raj K. , Kumar Satish , Scheid Werner
Published: October 2003

An extended orbiting cluster model (EOCM), which includes structural configurations in terms of two-centre nuclear shapes, is studied. In all the representative reactions with observed resonances studied here, the relative separation distance Δ R between the surfaces of the two nuclei in the "equivalent" dinuclear molecular configuration is found to be less than 2 fm, the range of attractive nuclear forces. The moments of inertia for the equivalent dinuclear shapes are related with one full rotation of the intermediate composite systems. Applications are also made to reactions with no observed resonances.
Nuclear Localization of Endothelin-Converting Enzyme-1
Authors: Jafri Farahdiba , Ergul Adviye
Published: October 2003

Objective—

The biosynthesis of endothelin-1 (ET-1), the most potent vasoconstrictor with mitogenic properties, involves the processing of intermediate protein big ET-1 by a unique metalloprotease, endothelin-converting enzyme-1 (ECE-1). ECE-1 has 4 subisoforms that possess the same catalytic properties but different localization patterns on the plasma membrane and cytosol. We investigated the trafficking of ECE-1 subisoforms using green fluorescent protein–tagged recombinant enzymes in target and nontarget cells.

Methods and Results—

ECE-1 localization was studied using confocal microscopy, which provides evidence for the first time that both ET-1 and ECE-1a are also found in the nuclear compartment in transiently transfected cells as well as in native endothelial cells that endogenously possess the ET system. In cells maintained in high-glucose medium, ECE-1a–specific staining shifted from plasma membrane to intracellular compartments. ECE-1b subisoform, however, is mainly in the cytosolic compartment, indicating a subisoform specificity for nuclear localization.

Conclusions—

Our findings define a novel localization pattern for the ET system, which may be differentially regulated under pathophysiological conditions.
Matrix Metalloproteinase-2 and −9 Differentially Regulate Smooth Muscle Cell Migration and Cell-Mediated Collagen Organization
Authors: Johnson Chad , Galis Zorina S.
Published: October 2003

Objectives—

Smooth muscle cells (SMCs) produce both matrix metalloproteinase (MMP)-2 and MMP-9, enzymes with similar in vitro matrix degrading abilities. We compared the specific contributions of these enzymes to SMC-matrix interactions in vitro and in vivo.

Methods and Results—

Using genetic models of deficiency, we investigated MMP-2 and MMP-9 roles in SMC migration in vivo in the formation of intimal hyperplasia and in vitro. In addition, we investigated potential effects of MMP-2 and MMP-9 genetic deficiency on compaction and assembly of collagen by SMCs.

Conclusions—

MMP-2 and MMP-9 genetic deficiency decreased by 81% and 65%, respectively (

P

<0.01), SMC invasion in vitro and decreased formation of intimal hyperplasia in vivo (

P

<0.01). However, we found that MMP-9, but not MMP-2, was necessary for organization of collagen by SMCs. Likewise, we found that MMP-9 deficiency resulted in a 50% reduction of SMC attachment to gelatin (

P

<0.01), indicating that SMCs may use MMP-9 as a bridge between the cell surface and matrix. Furthermore, we found that the hyaluronan receptor, CD44, assists in attachment and utilization of MMP-9 by SMCs. Understanding the specific roles of these MMPs, generally thought to be similar, could improve the design of therapeutic interventions aimed at controlling vascular remodeling.
Sustained Expansion and Transgene Expression of Coagulation Factor VIII–Transduced Cord Blood–Derived Endothelial Progenitor Cells
Authors: Herder Christian , Tonn Torsten , Oostendorp Robert , Becker Sven , Keller Ulrich , Peschel Christian , Grez Manuel , Seifried Erhard
Published: October 2003

Objective—

Although hemophilia A seems particularly suitable for gene therapy because even low amounts of plasma coagulation factor VIII (FVIII) provide a significant clinical benefit to the patients, the ideal target cell for recombinant FVIII expression and gene therapy approaches remains to be identified. In this study, we tested the capacity of cord blood–derived endothelial progenitor cells (CBECs) for FVIII expression on stable lentiviral transduction.

Methods and Results—

CD34
+
endothelial progenitor cells (EPCs) from cord blood were differentiated into CBECs. Endothelial phenotype was characterized, and lentiviral transduction of early-passage CBECs with a vector encoding FVIII and EGFP did not alter their functional properties and proliferative potential. CBEC could be expanded by 5 to 9 orders of magnitude, thus allowing the expansion of up to 10
15
FVIII-secreting CBECs, starting from as little as 10
6
CD34
+
cells. CBECs proved to be highly suitable for FVIII secretion, with 0.35 to 0.39 IU FVIII:C/5×10
4
cells per 48 hours (7.0 to 7.8 IU FVIII:C/10
6
cells per 48 hours), which remained stable over the expansion period.

Conclusions—

Our data indicate that CBECs are attractive target cells for inherited coagulation disorders such as hemophilia A, which on lentiviral transduction can be readily expanded to large numbers of transplantable gene-modified cells in vitro.
Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With α
v
β
3
-Integrin–Targeted Nanoparticles
Authors: Winter Patrick M. , Morawski Anne M. , Caruthers Shelton D. , Fuhrhop Ralph W. , Zhang Huiying , Williams Todd A. , Allen John S. , Lacy Elizabeth K. , Robertson J. David , Lanza Gregory M. , Wickline Samuel A.
Published: October 2003

Background—

Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to plaque instability, however, cannot be detected directly with any current diagnostic modality.

Methods and Results—

Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for ≈80 days. α
v
β
3
-Integrin–targeted, paramagnetic nanoparticles were injected intravenously and provided specific detection of the neovasculature within 2 hours by routine magnetic resonance imaging (MRI) at a clinically relevant field strength (1.5 T). Increased angiogenesis was detected as a 47±5% enhancement in MRI signal averaged throughout the abdominal aortic wall among rabbits that received α
v
β
3
-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with α
v
β
3
-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the α
v
β
3
-targeted paramagnetic agent. MRI revealed a pattern of increased α
v
β
3
-integrin distribution within the atherosclerotic wall that was spatially heterogeneous along both transverse and longitudinal planes of the abdominal aorta. Histology and immunohistochemistry confirmed marked proliferation of angiogenic vessels within the aortic adventitia, coincident with prominent, neointimal proliferation among cholesterol-fed, atherosclerotic rabbits in comparison with sparse incidence of neovasculature in the control animals.

Conclusions—

This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.
Activation of Peroxisome Proliferator–Activated Receptor-α Protects the Heart From Ischemia/Reperfusion Injury
Authors: Yue Tian-li , Bao Weike , Jucker Beat M. , Gu Juan-li , Romanic Anne M. , Brown Peter J. , Cui Jianqi , Thudium Douglas T. , Boyce Rogely , Burns-Kurtis Cynthia L. , Mirabile Rosanna C. , Aravindhan Karpagam , Ohlstein Eliot H.
Published: October 2003

Background—

Peroxisome proliferator–activated receptor-α (PPAR-α) is expressed in the heart and regulates genes involved in myocardial fatty acid oxidation (FAO). The role of PPAR-α in acute ischemia/reperfusion myocardial injury remains unclear.

Methods and Results—

The coronary arteries of male mice were ligated for 30 minutes. After reperfusion for 24 hours, ischemic and infarct sizes were determined. A highly selective and potent PPAR-α agonist, GW7647, was administered by mouth for 2 days, and the third dose was given 1 hour before ischemia. GW7647 at 1 and 3 mg · kg
−1
· d
−1
reduced infarct size by 28% and 35%, respectively (
P
<0.01), and myocardial contractile dysfunction was also improved. Cardioprotection by GW7647 was completely abolished in PPAR-α–null mice. Ischemia/reperfusion downregulated mRNA expression of cardiac PPAR-α and FAO enzyme genes, decreased myocardial FAO enzyme activity and in vivo cardiac fat oxidation, and increased serum levels of free fatty acids. All of these changes were reversed by GW7647. Moreover, GW7647 attenuated ischemia/reperfusion-induced release of multiple proinflammatory cytokines and inhibited neutrophil accumulation and myocardial expression of matrix metalloproteinases-9 and -2. Furthermore, GW7647 inhibited nuclear factor-κB activation in the heart, accompanied by enhanced levels of inhibitor-κBα.

Conclusions—

Activation of PPAR-α protected the heart from reperfusion injury. This cardioprotection might be mediated through metabolic and antiinflammatory mechanisms. This novel effect of the PPAR-α agonist could provide an added benefit to patients treated with PPAR-α activators for dyslipidemia.
Thromboxane A
2
Regulates Vascular Tone via Its Inhibitory Effect on the Expression of Inducible Nitric Oxide Synthase
Authors: Yamada Takehiro , Fujino Takayuki , Yuhki Koh-ichi , Hara Akiyoshi , Karibe Hideji , Takahata Osamu , Okada Yuji , Xiao Chun-Yang , Takayama Koji , Kuriyama Shuhko , Taniguchi Takanobu , Shiokoshi Takahiro , Ohsaki Yoshinobu , Kikuchi Kenjiro , Narumiya Shuh , Ushikubi Fumitaka
Published: October 2003

Background—

Circulatory failure in sepsis arises from vascular hyporesponsiveness, in which nitric oxide (NO) derived from inducible NO synthase (iNOS) plays a major role. Details of the cross talk between thromboxane (TX) A
2
and the iNOS–NO system, however, remain unknown. We intended to clarify the role of TXA
2
, via the cross talk, in vascular hyporesponsiveness.

Methods and Results—

We examined cytokine-induced iNOS expression and NO production in cultured vascular smooth muscle cells (VSMCs) and cytokine-induced hyporesponsiveness of the aorta from mice lacking the TXA
2
receptor (TP
−/−
mice). The cytokine-induced iNOS expression and NO production observed in wild-type VSMCs were significantly augmented in TP
−/−
VSMCs, indicating an inhibitory effect of endogenous TXA
2
on iNOS expression. Furthermore, in indomethacin-treated wild-type VSMCs, U-46619, a TP agonist, inhibited cytokine-induced iNOS expression and NO production in a concentration-dependent manner, effects absent from TP
−/−
VSMCs. In an ex vivo system, the cytokine-induced hyporesponsiveness of aortas to phenylephrine was significantly augmented in TP
−/−
aorta but was almost completely canceled by aminoguanidine, an iNOS inhibitor. Accordingly, cytokine-induced NO production was significantly higher in TP
−/−
aorta than in wild-type aorta. Moreover, U-46619 significantly suppressed lipopolysaccharide-induced NO production in vivo only in wild-type mice.

Conclusions—

These results suggest that TXA
2
has a protective role against the development of vascular hyporesponsiveness via its inhibitory action on the iNOS–NO system under pathological conditions such as sepsis.
Gadolinium Cardiovascular Magnetic Resonance Predicts Reversible Myocardial Dysfunction and Remodeling in Patients With Heart Failure Undergoing β-Blocker Therapy
Authors: Bello David , Shah Dipan J. , Farah George M. , Di Luzio Silvia , Parker Michele , Johnson Maryl R. , Cotts William G. , Klocke Francis J. , Bonow Robert O. , Judd Robert M. , Gheorghiade Mihai , Kim Raymond J.
Published: October 2003

Background—

In some patients with heart failure, β-blockers can improve left ventricular (LV) function and reduce morbidity and mortality. We hypothesized that gadolinium-enhanced cardiovascular magnetic resonance imaging (CMR) can predict reversible myocardial dysfunction and remodeling in heart failure patients treated with β-blockers.

Methods and Results—

Forty-five patients with chronic heart failure underwent CMR. Contrast imaging using gadolinium was performed to obtain high-resolution spatial maps of myocardial scarring and viability. Cine imaging was performed to assess LV function and morphology and was repeated in 35 patients after 6 months of β-blockade. Gadolinium CMR demonstrated scarring in 30 of 45 patients (67%). Scarring was found in 100% of patients with ischemic cardiomyopathy (28 of 28) but in only 12% with nonischemic cardiomyopathy (2 of 17). In the 35 patients who were maintained on β-blockers and had a second study, there was an inverse relation between the extent of scarring at baseline and the likelihood of contractile improvement 6 months later (
P
<0.001). For instance, contractility improved in 56% (674 of 1207) of regions with no scarring but in only 3% with >75% scarring (8 of 232). Multivariate analysis showed that the amount of dysfunctional but viable myocardium by CMR was an independent predictor of the change in ejection fraction (
P
=0.01), mean wall motion score (
P
=0.0007), LV end-diastolic volume index (
P
=0.007), and LV end-systolic volume index (
P
≤0.0001).

Conclusions—

For heart failure patients treated with β-blockers, gadolinium-enhanced CMR predicts the response in LV function and remodeling.
Prognostic Significance of Small-Artery Structure in Hypertension
Authors: Rizzoni Damiano , Porteri Enzo , Boari Gianluca E.M. , De Ciuceis Carolina , Sleiman Intissar , Muiesan Maria Lorenza , Castellano Maurizio , Miclini Marco , Agabiti-Rosei Enrico
Published: October 2003

Background—

The presence of structural alterations in the microcirculation may be considered an important mechanism of organ damage; however, it is not currently known whether structural alterations of small arteries may predict fatal and nonfatal cardiovascular events.

Methods and Results—

One hundred twenty-eight patients were included in the present study. There were 59 patients with essential hypertension, 17 with pheochromocytoma, 20 with primary aldosteronism, 12 with renovascular hypertension, and 20 normotensive patients with non-insulin-dependent diabetes mellitus. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media-to-internal lumen ratio (M/L) was measured. The subjects were reevaluated after an average follow-up time of 5.4 years. Thirty-seven subjects had a documented fatal or nonfatal cardiovascular event (5.32 events/100 patients per year). In the subcutaneous small arteries of subjects with cardiovascular events, a smaller internal diameter and a clearly greater M/L was observed. Our subjects were subdivided according to the presence of an M/L greater or smaller than the mean and median values observed in the whole population (0.098) or mean value +2 SD of our normal subjects (0.11). Life-table analyses showed a significant difference in event-free survival between the subgroups. Cox’s proportional hazard model, considering all known cardiovascular risk factors, indicated that only pulse pressure (
P
=0.009) and M/L (
P
<0.0001) were significantly associated with the occurrence of cardiovascular events.

Conclusions—

Our results strongly indicate a relevant prognostic role of structural alterations in small resistance arteries of a high-risk population.
Blood Oxygen Level–Dependent Magnetic Resonance Imaging in Patients with Stress-Induced Angina
Authors: Friedrich Matthias G. , Niendorf Thoralf , Schulz-Menger Jeanette , Gross C. Michael , Dietz Rainer
Published: October 2003

Background—

Blood oxygen level–dependent (BOLD) MRI reflects tissue oxygenation and may be useful for the detection of myocardial ischemia in patients with suspected coronary artery disease.

Methods and Results—

We studied 25 patients with stress-induced angina using a T
2
*-sensitive echo planar imaging sequence before and during adenosine in a single-slice approach. BOLD-MRI results were compared with quantitative angiography and adenosine thallium single-photon emission computed tomography (SPECT). Although image quality was variable because of artifacts, no data were excluded from the analysis. During adenosine, a mean signal intensity decrease was observed for myocardial segments related to coronary stenoses >75%. On average, a nonsignificant increase was observed in the other segments. The angiographically determined stenosis was correlated with BOLD-MRI results. Including all segments and using BOLD-MRI signal intensity increase cutoff value of 1.2%, BOLD-MRI had a sensitivity of 88% and a specificity of 47% to correctly classify severe stenoses. Adenosine thallium SPECT data from distal segments of the same coronary territory were also correlated with BOLD-MRI. However, variability was substantial.

Conclusions—

In patients with stress-induced angina, adenosine BOLD-MRI detects myocardial ischemia in myocardial segments related to severe coronary stenoses. Its potential will increase with additional improvement of spatial coverage and image quality.