bluuebunny/crossref_metadata_2025 huggingface dataset:
Gleevec inhibits β-amyloid production but not Notch cleavage
Authors: Netzer William J. , Dou Fei , Cai Dongming , Veach Darren , Jean Stephanie , Li Yueming , Bornmann William G. , Clarkson Bayard , Xu Huaxi , Greengard Paul
Published: October 2003

Amyloid-β (Aβ) peptides, consisting mainly of 40 and 42 aa (Aβ40 and Aβ42, respectively), are metabolites of the amyloid precursor protein and are believed to be major pathological determinants of Alzheimer's disease. The proteolytic cleavages that form the Aβ N and C termini are catalyzed by β-secretase and γ-secretase, respectively. Here we demonstrate that γ-secretase generation of Aβ in an N2a cell-free system is ATP dependent. In addition, the Abl kinase inhibitor imatinib mesylate (Gleevec, or STI571), which targets the ATP-binding site of Abl and several other tyrosine kinases, potently reduces Aβ production in the N2a cell-free system and in intact N2a cells. Both STI571 and a related compound, inhibitor 2, also reduce Aβ production in rat primary neuronal cultures and
in vivo
in guinea pig brain. STI571 does not inhibit the γ-secretase-catalyzed S3 cleavage of Notch-1. Furthermore, production of Aβ and its inhibition by STI571 were demonstrated to occur to similar extents in both
Abl
-/-
and WT mouse fibroblasts, indicating that the effect of STI571 on Aβ production does not involve Abl kinase. The efficacy of STI571 in reducing Aβ without affecting Notch-1 cleavage may prove useful as a basis for developing novel therapies for Alzheimer's disease.
The near attack conformation approach to the study of the chorismate to prephenate reaction
Authors: Hur Sun , Bruice Thomas C.
Published: October 2003

Standard free energies (ΔG
N
°) for formation of near attack conformers, those ground state conformers that can convert directly to the transition state, were calculated for the Claisen rearrangement of chorismate to prephenate in six different environments: water, wild-type enzymes from
Bacillus subtilis
and
Escherichia coli
, their Arg90Cit and Glu52Ala mutants, and the 1F7 catalytic antibody. Values of the calculated ΔG
N
°s and the experimentally determined activation energies (ΔG
‡
) are linearly related with the slope of ≈1. This demonstrates that the relative rate of the chorismate → prephenate reaction is overwhelmingly dependent on the efficiency of formation of near attack conformers in the ground state.
Coarse-grained stochastic models for tropical convection and climate
Authors: Khouider Boualem , Majda Andrew J. , Katsoulakis Markos A.
Published: October 2003

Prototype coarse-grained stochastic parametrizations for the interaction with unresolved features of tropical convection are developed here. These coarse-grained stochastic parametrizations involve systematically derived birth/death processes with low computational overhead that allow for direct interaction of the coarse-grained dynamical variables with the smaller-scale unresolved fluctuations. It is established here for an idealized prototype climate scenario that, in suitable regimes, these coarse-grained stochastic parametrizations can significantly impact the climatology as well as strongly increase the wave fluctuations about an idealized climatology.
Protective immunity against
Helicobacter
is characterized by a unique transcriptional signature
Authors: Mueller Anne , O'Rourke Jani , Chu Pauline , Kim Charles C. , Sutton Philip , Lee Adrian , Falkow Stanley
Published: October 2003

Immunization with a whole-cell sonicate vaccine of
Helicobacter felis
in conjunction with cholera toxin as a mucosal adjuvant induces long-term protective immunity in a majority of laboratory mice. We have combined gene expression profiling and immunohistochemical analysis on a set of immunized animals to better understand the mechanism of protection. The stomachs of protected animals exhibited a strikingly different transcriptional profile compared with those of nonprotected or control mice, indicating that vaccination targets the appropriate site and leaves a molecular signature. Among the genes whose up-regulation is significantly correlated with protection are a number of adipocyte-specific factors. These include the fat-cell-specific cytokines adipsin, resistin, and adiponectin and the adipocyte surface marker CD36. Interestingly, potentially protective T and B lymphocytes can be found embedded in the adipose tissue surrounding protected stomachs but never in control or unprotected stomachs. Adipsin-specific immunohistochemical staining of protected stomach sections further revealed molecular cross-talk between adjacent lymphoid and adipose cell populations. We propose a mechanism of protection that involves the effector responses of either or both lymphocyte subclasses as well as the previously unappreciated paracrine functions of adipose tissue surrounding the resident lymphocytes.
Phosphoinositide 3-kinase(p110α) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy
Authors: McMullen Julie R. , Shioi Tetsuo , Zhang Li , Tarnavski Oleg , Sherwood Megan C. , Kang Peter M. , Izumo Seigo
Published: October 2003

An unresolved question in cardiac biology is whether distinct signaling pathways are responsible for the development of pathological and physiological cardiac hypertrophy in the adult. Physiological hypertrophy is characterized by a normal organization of cardiac structure and normal or enhanced cardiac function, whereas pathological hypertrophy is associated with an altered pattern of cardiac gene expression, fibrosis, cardiac dysfunction, and increased morbidity and mortality. The elucidation of signaling cascades that play distinct roles in these two forms of hypertrophy will be critical for the development of more effective strategies to treat heart failure. We examined the role of the p110α isoform of phosphoinositide 3-kinase (PI3K) for the induction of pathological hypertrophy (pressure overload-induced) and physiological hypertrophy (exercise-induced) by using transgenic mice expressing a dominant negative (dn) PI3K(p110α) mutant specifically in the heart. dnPI3K transgenic mice displayed significant hypertrophy in response to pressure overload but not exercise training. dnPI3K transgenic mice also showed significant dilation and cardiac dysfunction in response to pressure overload. Thus, PI3K(p110α) appears to play a critical role for the induction of physiological cardiac growth but not pathological growth. PI3K(p110α) also appears essential for maintaining contractile function in response to pathological stimuli.
The case of the missing NO– hemoglobin: Spectral changes suggestive of heme redox reactions reflect changes in NO– heme geometry
Authors: Fago Angela , Crumbliss Alvin L. , Peterson Jim , Pearce Linda L. , Bonaventura Celia
Published: October 2003

When low levels of gaseous nitric oxide (NO) are equilibrated with deoxygenated Hb, all NO added can be accounted for in terms of hexacoordinate and pentacoordinate forms of NO–Hb, despite recent reports on NO disappearance from heme groups to form nitroxyl anions or S-nitrosated Hb at low ratios of NO to Hb. We demonstrate that a fraction of the spectral signature of fully nitrosylated (largely hexacoordinate) Hb disappears as the pentacoordinate state forms and reappears when pentacoordinate NO–Hb is reconverted to the hexacoordinate condition. We show that the spectral changes associated with these reversible shifts in NO– heme geometry can be remarkably well approximated as variations in the contributions from fully nitrosylated Hb and oxidized Hb (MetHb). As a result, increases in the level of pentacoordinate NO–Hb that occur at low NO to Hb ratios can be misinterpreted as increases in MetHb levels associated with NO-dependent heme oxidation. Conversely, any decrease in levels of pentacoordinate NO–Hb can be misinterpreted as a disappearance of MetHb associated with NO-dependent heme reduction. Transitions between pentacoordinate and hexacoordinate forms of NO–Hb with spectral changes suggestive of changes in levels of heme-bound NO are sensitive to the protein's quaternary conformation and can be brought about by alterations in anion levels or the degree of heme saturation with either O
2
or NO.
Biomolecular hydration: From water dynamics to hydrodynamics
Authors: Halle Bertil , Davidovic Monika
Published: October 2003

Thermally driven rotational and translational diffusion of proteins and other biomolecules is governed by frictional coupling to their solvent environment. Prediction of this coupling from biomolecular structures is a longstanding biophysical problem, which cannot be solved without knowledge of water dynamics in an interfacial region comparable to the dry protein in volume. Efficient algorithms have been developed for solving the hydrodynamic equations of motion for atomic-resolution biomolecular models, but experimental diffusion coefficients can be reproduced only by postulating hundreds of rigidly bound water molecules. This static picture of biomolecular hydration is fundamentally inconsistent with magnetic relaxation dispersion experiments and molecular dynamics simulations, which both reveal a highly dynamic interface where rotation and exchange of nearly all water molecules are several orders of magnitude faster than biomolecular diffusion. Here, we resolve this paradox by means of a dynamic hydration model that explicitly links protein hydrodynamics to hydration dynamics. With the aid of this model, bona fide structure-based predictions of global biomolecular dynamics become possible, as demonstrated here for a set of 16 proteins for which accurate experimental rotational diffusion coefficients are available.
Noise and stochastic resonance in voltage-gated ion channels
Authors: Adair Robert K.
Published: October 2003

Using Monte Carlo techniques, I calculate the effects of internally generated noise on information transfer through the passage of action potential spikes along unmyelinated axons in a simple nervous system. I take the Hodgkin–Huxley (HH) description of Na and K channels in squid giant axons as the basis of the calculations and find that most signal transmission noise is generated by fluctuations in the channel open and closed populations. To bring the model closer to conventional descriptions in terms of thermal noise energy,
kT
, and to determine gating currents, I express the HH equations in the form of simple relations from statistical mechanics where the states are separated by a Gibbs energy that is modified by the action of the transmembrane potential on dipole moments held by the domains. Using the HH equations, I find that the output response (in the probability of action potential spikes) from small input potential pulses across the cell membrane is increased by added noise but falls off when the input noise becomes large, as in stochastic resonance models. That output noise response is sharply reduced by a small increase in the membrane polarization potential or a moderate increase in the channel densities. Because any reduction of noise incurs metabolic and developmental costs to an animal, the natural noise level is probably optimal and any increase in noise is likely to be harmful. Although these results are specific to signal transmission in unmyelinated axons, I suggest that the conclusions are likely to be general.
Zinc-finger protein-targeted gene regulation: Genomewide single-gene specificity
Authors: Tan Siyuan , Guschin Dmitry , Davalos Albert , Lee Ya-Li , Snowden Andrew W. , Jouvenot Yann , Zhang H. Steven , Howes Katherine , McNamara Andrew R. , Lai Albert , Ullman Chris , Reynolds Lindsey , Moore Michael , Isalan Mark , Berg Lutz-Peter , Campos Bradley , Qi Hong , Spratt S. Kaye , Case Casey C. , Pabo Carl O. , Campisi Judith , Gregory Philip D.
Published: October 2003

Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for the study and treatment of disease. Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome. A ZFP TF repressor that binds an 18-bp recognition sequence within the promoter of the endogenous
CHK2
gene gives a >10-fold reduction in
CHK2
mRNA and protein. This level of repression was sufficient to generate a functional phenotype, as demonstrated by the loss of DNA damage-induced CHK2-dependent p53 phosphorylation. We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (
CHK2
) within the monitored genome in two different cell types. These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics.
α
1E
-Containing Ca
2+
channels are involved in synaptic plasticity
Authors: Breustedt J. , Vogt K. E. , Miller R. J. , Nicoll R. A. , Schmitz D.
Published: October 2003

Long-term potentiation (LTP) is the most prominent model for the molecular and cellular mechanisms of learning and memory. Two main forms of LTP have been distinguished. The
N
-methyl-
d
-aspartate-receptor-dependent forms of LTP have been studied most extensively, whereas much less is known about
N
-methyl-
d
-aspartate-receptor-independent forms of LTP. This latter type of LTP was first described at the mossy fiber synapses in the hippocampus and subsequently at parallel fiber synapses in the cerebellum as well as at corticothalamic synapses. These presynaptic forms of LTP require a rise in the intraterminal calcium concentration, but the channel through which calcium passes has not been identified. By using pharmacological tools as well as genetic deletion, we demonstrate here that α
1E
-containing voltage-dependent calcium channels (VDCCs) shift the threshold for mossy fiber LTP. The channel is not involved in the expression mechanism, but it contributes to the calcium influx during the induction phase. Indeed, optical recordings directly show the presence and the function of α
1E
-containing VDCCs at mossy fiber terminals. Hence, a previously undescribed role for α
1E
-containing VDCCs is suggested by these results.
Inhibition of NF-κB by ZAS3, a zinc-finger protein that also binds to the κB motif
Authors: Hong Joung-Woo , Allen Carl E. , Wu Lai-Chu
Published: October 2003

The ZAS proteins are large zinc-finger transcriptional proteins implicated in growth, signal transduction, and lymphoid development. Recombinant ZAS fusion proteins containing one of the two DNA-binding domains have been shown to bind specifically to the κB motif, but the endogenous ZAS proteins or their physiological functions are largely unknown. The κB motif, GGGACTTTCC, is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth. The Rel family of NF-κB, predominantly p65.p50 and p50.p50, are transcription factors well known for inducing gene expression by means of interaction with the κB motif during acute-phase responses. A functional link between ZAS and NF-κB, two distinct families of κB-binding proteins, stems from our previousin vitrostudies that show that a representative member, ZAS3, associates with TRAF2, an adaptor molecule in tumor necrosis factor signaling, to inhibit NF-κB activation. Biochemical and genetic evidence presented herein shows that ZAS3 encodes major κB-binding proteins in B lymphocytes, and that NF-κB is constitutively activated in ZAS3-deficient B cells. The data suggest that ZAS3 plays crucial functions in maintaining cellular homeostasis, at least in part by inhibiting NF-κB by means of three mechanisms: inhibition of nuclear translocation of p65, competition for κB gene regulatory elements, and repression of target gene transcription.
Cooperative domains define a unique host cell-targeting signal in
Plasmodium falciparum
-infected erythrocytes
Authors: Lopez-Estraño Carlos , Bhattacharjee Souvik , Harrison Travis , Haldar Kasturi
Published: October 2003

When the malaria parasite
Plasmodium falciparum
infects an erythrocyte, it resides in a parasitophorous vacuole and remarkably exports proteins into the periphery of its host cell. Two of these proteins, the histidine-rich proteins I and II (PfHRPI and PfHRPII), are exported to the erythrocyte cytoplasm. PfHRPI has been linked to cell-surface “knobby” protrusions that mediate cerebral malaria and are a frequent cause of death. PfHRPII has been implicated in (
i
) the production of hemozoin, the black pigment associated with disease, as well as (
ii
) interactions with the erythrocyte cytoskeleton. Here we show that a tripartite signal that is comprised of an endoplasmic reticulum-type signal sequence followed by a bipartite vacuolar translocation signal derived from HRPII and HRPI exports GFP from the parasitophorous vacuole to the host cytoplasm. The bipartite vacuolar translocation signal is comprised of unique, peptidic (≈40-aa) sequences. A domain within it contains the signal for export to “cleft” transport intermediates in the host erythrocyte and may thereby regulate the pathway of export to the host cytoplasm. A signal for posttranslational, vacuolar exit of proteins has hitherto not been described in eukaryotic secretion.
Mutations in
bone morphogenetic protein receptor 1B
cause brachydactyly type A2
Authors: Lehmann Katarina , Seemann Petra , Stricker Sigmar , Sammar Marai , Meyer Birgit , Süring Katrin , Majewski Frank , Tinschert Sigrid , Grzeschik Karl-Heinz , Müller Dietmar , Knaus Petra , Nürnberg Peter , Mundlos Stefan
Published: October 2003

Brachydactyly (BD) type A2 is an autosomal dominant hand malformation characterized by shortening and lateral deviation of the index fingers and, to a variable degree, shortening and deviation of the first and second toes. We performed linkage analysis in two unrelated German families and mapped a locus for BD type A2 to 4q21-q25. This interval includes the gene
bone morphogenetic protein receptor 1B
(
BMPR1B
), a type I transmembrane serinethreonine kinase. In one family, we identified a T599 → A mutation changing an isoleucine into a lysine residue (I200K) within the glycine/serine (GS) domain of BMPR1B, a region involved in phosphorylation of the receptor. In the other family we identified a C1456 → T mutation leading to an arginine-to-tryptophan amino acid change (R486W) in a highly conserved region C-terminal of the BMPR1B kinase domain. An
in vitro
kinase assay showed that the I200K mutation is kinase-deficient, whereas the R486W mutation has normal kinase activity, indicating a different pathogenic mechanism. Functional analyses with a micromass culture system revealed a strong inhibition of chondrogenesis by both mutant receptors. Overexpression of mutant
chBmpR1b in vivo
in chick embryos by using a retroviral system resulted either in a BD phenotype with shortening and/or missing phalanges similar to the human phenotype or in severe hypoplasia of the entire limb. These findings imply that both mutations identified in human
BMPR1B
affect cartilage formation in a dominant-negative manner.
PPARγ coactivator 1β/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity
Authors: Kamei Yasutomi , Ohizumi Hiroshi , Fujitani Yasushi , Nemoto Tomoyuki , Tanaka Toshiya , Takahashi Nobuyuki , Kawada Teruo , Miyoshi Masamitsu , Ezaki Osamu , Kakizuka Akira
Published: October 2003

A well balanced body energy budget controlled by limitation of calorie uptake and/or increment of energy expenditure, which is typically achieved by proper physical exercise, is most effective against obesity and diabetes mellitus. Recently, peroxisome proliferator-activated receptor (PPAR) γ, a member of the nuclear receptor, and its cofactors have been shown to be involved in lipid metabolism and in the control of energy expenditure. Here we show that PPARγ coactivator 1 (PGC-1) β functions as ERRL1 (for
ERR l
igand
1
), which can bind and activate orphan ERRs (estrogen receptor-related receptors)
in vitro
. Consistently, PGC-1β/ERRL1 transgenic mice exhibit increased expression of the medium-chain acyl CoA dehydrogenase, a known ERR target and a pivotal enzyme of mitochondrial β-oxidation in skeletal muscle. As a result, the PGC-1β/ERRL1 mice show a state similar to an athlete; namely, the mice are hyperphagic and of elevated energy expenditure and are resistant to obesity induced by a high-fat diet or by a genetic abnormality. These results demonstrate that PGC-1β/ERRL1 can function as a protein ligand of ERR, and that its level contributes to the control of energy balance
in vivo
, and provide a strategy for developing novel antiobesity drugs.
Transforming Growth Factor (TGF)-β1–producing Regulatory T Cells Induce Smad-mediated Interleukin 10 Secretion That Facilitates Coordinated Immunoregulatory Activity and Amelioration of TGF-β1–mediated Fibrosis
Authors: Kitani Atsushi , Fuss Ivan , Nakamura Kazuhiko , Kumaki Fumiyuki , Usui Takashi , Strober Warren
Published: October 2003

Interleukin (IL)-10 and transforming growth factor (TGF)-β1 are suppressor cytokines that frequently occur together during a regulatory T cell response. Here we used a one gene doxycycline (Dox)-inducible plasmid encoding TGF-β1 to analyze this association and test its utility. In initial studies, we showed that intranasal administration of this plasmid (along with Dox) led to the appearance of TGF-β1–producing cells (in spleen and lamina propria) and the almost concomitant appearance of IL-10–producing cells. Moreover, we showed that these cells exert Dox-regulated suppression of the T helper cell (Th)1-mediated inflammation in trinitrobenzene sulfonic acid colitis. In subsequent in vitro studies using retroviral TGF-β1 expression, we established that IL-10 production by Th1 cells occurs after exposure to TGF-β1 from either an endogenous or exogenous source. In addition, using a self-inactivating retrovirus luciferase reporter construct we showed that TGF-β1 induces Smad4, which then binds to and activates the IL-10 promoter. Furthermore, intranasal TGF-β1 plasmid administration ameliorates bleomycin-induced fibrosis in wild-type but not IL-10–deficient mice, strongly suggesting that the amelioration is IL-10 dependent and that IL-10 protects mice from TGF-β1–mediated fibrosis. Taken together, these findings suggest that the induction of IL-10 by TGF-β1 is not fortuitous, but instead fulfills important requirements of TGF-β1 function after its secretion by regulatory T cells.
Movements near the Gate of a Hyperpolarization-activated Cation Channel
Authors: Rothberg Brad S. , Shin Ki Soon , Yellen Gary
Published: October 2003

Hyperpolarization-activated cation (HCN) channels regulate pacemaking activity in cardiac cells and neurons. Like the related depolarization-activated K+ channels (Kv channels), HCN channels use an intracellular activation gate to regulate access to an inner cavity, lined by the S6 transmembrane regions, which leads to the selectivity filter near the extracellular surface. Here we describe two types of metal interactions with substituted cysteines in the S6, which alter the voltage-controlled movements of the gate. At one position (L466), substitution of cysteine in all four subunits allows Cd2+ ions at nanomolar concentration to stabilize the open state (a “lock-open” effect). This effect depends on native histidines at a nearby position (H462); the lock-open effect can be abolished by changing the histidines to tyrosines, or enhanced by changing them to cysteines. Unlike a similar effect in Kv channels, this effect depends on a Cd2+ bridge between 462 and 466 in the same subunit. Cysteine substitution at another position (Q468) produces two effects of Cd2+: both a lock-open effect and a dramatic slowing of channel activation—a “lock-closed” effect. The two effects can be separated, because the lock-open effect depends on the histidine at position 462. The novel lock-closed effect results from stabilization of the closed state by the binding of up to four Cd2+ ions. During the opening conformational change, the S6 apparently moves from one position in which the 468C cysteines can bind four Cd2+ ions, possibly as a cluster of cysteines and cadmium ions near the central axis of the pore, to another position (or flexible range of positions) where either 466C or 468C can bind Cd2+ in association with the histidine at 462.
Income inequality between skilled individuals
Authors: Svizzero Serge , Tisdell Clem
Published: October 2003

It is widely agreed that income inequality has increased in OECD countries over the past two decades. Most of the debate has focused on the distinction between skilled and unskilled workers. However inequality increased not only among those with different observable traits but also within groups of workers with the same characteristics such as gender, race, education and experience. This poses a challenge for theories that try to explain the rise in overall earnings inequality. Indeed, is income inequality within groups explained by the same reasons that have led to income inequality between groups? It appears that some reasons are specific to inequality within groups. For instance, greater access to education has led to some confusion about the standard associated with the same educational level. Consequently, innate ability plays an increasing part in the determination of workers’ rewards. Similarly, the reduction of the size of the public sector may have contributed to the rise of the variability of the demand for skills. However, the central reason – innovation, notably the introduction of new technologies – is common to both types of inequality but it acts on within‐group income inequality through specific channels. Among the latter are the role of innate ability, the shift toward a decentralised wage determination system, and the changes of the demand for skills. Therefore, the explanations of within‐group inequality are complementary to the ones associated with between‐group inequality and thus help to explain the rise in overall earnings inequality.
Measuring franchisees’ satisfaction: theoretical considerations and empirical testing
Authors: Gauzente Claire
Published: October 2003

Franchisees’ satisfaction is key to a franchise network’s continuance over the years. However, at the moment, no robust scale exists in order to assess franchisees’ satisfaction. The aim of the present study is to fill this gap by providing a reflection on the nature of franchisee satisfaction. In particular, we favor a managerial approach to satisfaction which should provide franchisers with an appropriate tool for assessing the satisfaction of their franchisees and provide a basis for guaranteeing long‐term survival of their network. The study was conducted in France over a representative sample of 401 franchises representing 32 franchise networks and covering all sectors. After a pre‐test phase, exploratory and confirmatory factor analyses were performed. The results led to a short, robust and predictive scale of franchisee job satisfaction.
Cultural complexity: a new epistemological perspective
Authors: Browaeys Marie‐Joëlle , Baets Walter
Published: October 2003

Culture is a complex process. Many authors show the importance of the concept of culture in organizations. The question which arises is how to approach the cultural problematic of organizations. The paper proposes that the traditional ways – based on the Cartesian epistemology – do not match with the cultural complexity, since it simplifies too much to be satisfying. This paper proposes a new paradigm called “complexity thinking” which seems to be more appropriate for studying culture in organizations. Furthermore, the paper outlines the concepts and principles of this epistemology that could be seen more as a strategy than a ready‐for‐use method in approaching culture in learning organizations.
House Buying Behavior: An Empirical Study in Cross‐Cultural Buyer Behavior
Authors: Hempel Donald J. , Jain Subhash C.
Published: October 2003

Some preliminary findings concerning experience, motivation, and search are presented from a cross‐cultural study of buyer behavior in housing markets. Data were obtained from probability samples of 652 households in Connecticut and Northwest England. The results include comparative analyses of several dimensions of external search, five aspects of experience, reasons for moving, and husband‐wife reasons for buying. Predictive models of search are developed with multivariate regression techniques. The findings indicate that the experience and motivational variables are not very powerful predictors of search. Significant cultural differences do occur in the level of many variables, but there are some interesting similarities in the underlying factor structure.
Inflation and Real Estate Investment Value
Authors: Lusht Kenneth M.
Published: October 2003

It is demonstrated that the inflation rate must be reflected in the anticipated benefit flows used in investment value models. When flows are left unadjusted, a biased value estimate results. It is also shown that the actual effects of the inflation rate on investment value will depend on the relationships of original cost, the debt/equity ratio, and the level of depreciation expense. Inflation has a fundamentally negative impact on value traceable to capital gains and depreciation effects. This can be offset by the use of debt financing.
The Correct use of Confidence Intervals and Regression Analysis in Determining the Value of Residential Homes
Authors: Epley Donald R. , Burns William
Published: October 2003

This paper shows that (1) the principle of substitution has been misinterpreted in regression analysis on residential homes by the misuse of the confidence interval; (2) the proper confidence interval to judge the accuracy of the equation is the mean CI; and (3) the accuracy of the equation can be improved by applying factor analysis to the entire data set rather than a predetermined neighborhood. These results are illustrated in a sample of 571 residential sales in Northwest Arkansas during 1975. The data are divided into clusters, and a regression equation is computed for each. The results show that the mean confidence interval is the correct application of the principle of substitution. The correct decision rule to determine the superiority of the multi‐equation or the single equation model compares the explained to the unexplained variation. These results should allow the appraiser to select properties that are better suited for comparison. This will improve the accuracy of the regression analysis and resulting estimates of property value.
The Land Development Corporation: A System for Selling Rural Real Estate
Authors: Stroud Hubert B.
Published: October 2003

This research illustrates ways in which rural real estate is converted into potential vacation home sites by large land development corporations. The individual and previously disorganized approach to selling property is replaced by an organized framework that is designed to create a demand for rural real estate.

Unfortunately, development is progressing without serious or adequate consideration being given to a number of specific problems. Developers and local governmental officials often fail to consider the environmental impact of these developments, the adequacy of service facilities being provided or the direct and indirect public costs associated with this type of developmental activity. Because of these shortcomings and others, serious questions arise concerning the desirability of this kind of developmental activity for rural areas.
Multifamily Housing Demand: 1980–2000
Authors: Sternlieb George , Burchell Robert W.
Published: October 2003

Using Annual Housing Survey data on multifamily structure occupancy by household type for 1975, together with number of household projections from the Department of Agriculture, a gross level of multifamily housing demand is projected. Allowance is made for a 2 percent replacement rate of the total stock as well as a 5 percent vacancy figure for new household demand. Assuming that: (1) there is no massive shift away from one‐family ownership to multifamily units, and (2) the present level of conversions from one‐family units to multiple occupancy continues to offset the trend of conversion from rental multifamily units to condominium status, then total future demand for multifamily rental units is well within current construction levels.

We are presently building one and one‐half times the demand of 416,000 units per year projected for 1975–80.

The demand from 1980 to 1990 decreases to 367,000 new units annually.

This is further reduced to 335,000 units annually for the period 1990–2000.

The major determinants of future demand will focus on the scrap‐page rate of extant facilities and the regional shifts of population.

The future supply of multifamily structures depends on an abatement of construction costs and interest rates, and/or massive levels of Government subsidy.

There is evidence that operating cost rises are challenging the financial integrity of multifamily structures. This is manifested by the HUD and private market mortgage delinquency and foreclosure rates.

Policy focus for the future should emphasize the minimization of both construction and operating costs rather than augmented delivery rates.
A Regional Model of Multifamily Housing Starts
Authors: Rosen Kenneth T.
Published: October 2003

This paper presents a regional time series model of multifamily housing activity. The theoretical model, based on a profit‐maximizing builder or investor is used as a basis for estimating housing start and completion equations for each of the four Census regions and the U.S. as a whole. The empirical estimates show that new housing construction is highly responsive to profitability consideration, with the elasticity being between 5 and 14. The empirical estimates also demonstrate that there is substantial variance between regions in terms of parameter estimates.
Community Growth Around Nuclear Power Plants
Authors: Gamble Hays B. , Downing Roger H. , Sauerlender Owen H.
Published: October 2003

This study analyzes the growth rates of 64 municipalities around 4 nuclear power plants in the Northeastern United States, as reflected by changes in equalized total real property market values from 1960 to 1976. Annual growth rates were inversely related to distance from the plant, and were higher after the plants became operational. Growth rates for the host municipalities were greater than those for the regions around them. Although it was not possible to isolate the specific effects of nuclear power plants on growth rates, the empirical results suggest that at least until 1976 there were positive growth effects in the host communities.
Residential Mortgage Markets: Current Developments and Future Prospects
Authors: Kaplan Donald M. , Hartzog B.G.
Published: October 2003

Historical developments as well as current innovations have generated significant changes in the structure and operation of the residential mortgage market. General economic stability, a low inflation rate, growth of savings and loan associations, and strong consumer demand marked the fifteen‐year period immediately following World War II. In contrast, the decade of the sixties was characterized by increased competition in the mortgage market, a series of credit crunches, and increased governmental activity. In reaction to these and related developments, current innovations affecting the mortgage market focus on design of new mortgage instruments, improvements in market efficiency, and reform of financial institutions. If history is a guide, it suggests that the residential mortgage market responds flexibly to adverse conditions.
The Changing Spatial Relationship Between Residences and Worksites in the New York Metropolitan Region: Implications for Public Policy
Authors: Kamer Pearl
Published: October 2003

In recent decades, most new metropolitan population and job growth has occurred in the suburbs. Conventional wisdom suggests that because of the selective nature of suburban labor market development, most metropolitan workers currently live further from their jobs. Distance, in turn, fragments urban labor markets and creates physical and informational barriers to employment.

This article examines the selective pattern of central city‐suburban labor market development within the New York Metropolitan Region between 1960 and 1975 and analyzes the extent to which worker residences have adapted to spatial shifts in employment.
Flexible citizens? Transnationalism and citizenship amongst economic immigrants in Vancouver
Authors: Waters Johanna
Published: October 2003

This paper contributes to current theoretical debates surrounding concepts of transnationalism and citizenship through an in‐depth, qualitative analysis of ‘astronaut families’ and ‘satellite kids’ in Vancouver, Canada. Specifically, it asks whether the emergence of these ostensibly transnational households amongst Hong Kong and Taiwanese groups indicates a form of ‘instrumental citizenship’(Ip, Inglis and Wu 1997). The circumstances surrounding these family arrangements indeed point to a strategic use of migration, wherein one or both adults planned prior to emigration that they would return, imminently, to the country of origin to work, optimising financial opportunities. The children would remain in Vancouver to obtain an education, during which time the family would be able to acquire Canadian citizenship. Such depictions of a strategising, ‘hypermobile’(Skeldon 1995) Chinese cohort fail, however, to capture an important aspect of the transnational experience, wherein research participants clearly undergo settlement over time and, for want of a better term, a degree of acculturation. This paper suggests that the ‘mobility’ of the Chinese diaspora has been often over emphasised in recent accounts of contemporary migration patterns, too hastily rejecting outright traditional conceptions of immigrant settlement experience.
A Genetic Screen in
Drosophila
for Metastatic Behavior
Authors: Pagliarini Raymond A. , Xu Tian
Published: October 2003

A genetic screen was designed in
Drosophila
to interrogate its genome for mutations sufficient to cause noninvasive tumors of the eye disc to invade neighboring or distant tissues. We found that cooperation between oncogenic

Ras
V12

expression and inactivation of any one of a number of genes affecting cell polarity leads to metastatic behavior, including basement membrane degradation, loss of E-cadherin expression, migration, invasion, and secondary tumor formation. Inactivation of these cell polarity genes cannot drive metastatic behavior alone or in combination with other tumor-initiating alterations. These findings suggest that the oncogenic background of tissues makes a distinct contribution toward metastatic development.
Numerical Algorithms for Application to Time-Dependent Problems in Quantum Chemistry
Authors: Mazzone A. M.
Published: October 2003

This study illustrates the application of Monte Carlo methods of quantum mechanical type and of direct numerical integration to the solution of a multi-particle, time-dependent Schrödinger equation of the type used for the evaluation of molecular properties. In this study the algorithms are presented and a comparison is made with ab initio and semi-empirical calculations.
Probability Distribution and Sizes of Spanning Clusters at the Percolation Thresholds
Authors: Sen Parongama
Published: October 2003

For random percolation at pc, the probability distribution P (n) of the number of spanning clusters (n) has been studied in large-scale simulations. The results are compatible with P(n) ~ exp (-an2) for all dimensions. We also study the variation of the average size (mass) of the spanning clusters when there are more than one spanning cluster. While the average size of the spanning clusters scales as usual with LD where D=d-β/ν for any number of clusters, it shows a smooth decrease as the number of spanning clusters increases.
K-System Generator of Pseudorandom Numbers on Galois Field
Authors: Athanasiu G. G. , Floratos E. G. , Savvidy G. K.
Published: October 2003

We analyze the structure of the periodic trajectories of the K-system generator of pseudorandom numbers on a rational sublattice which coincides with the Galois field GF[p]. The period of the trajectories increases as a function of the lattice size p and the dimension of the K-matrixd. We emphasize the connection of this approach with the one which is based on primitive matrices over Galois fields.
Search for Asymptotic Death in Game of Life
Authors: Gibbs P. , Stauffer D.
Published: October 2003

Simulations with more than 4 × 1010 sites confirm that the density of active sites in Game of Life cellular automata approaches a positive limit, of about 2.87 per cent.
Immiscible Lattice Gas with Long-Range Interaction
Authors: Tsumaya Akira , Ohashi Hirotada
Published: October 2003

We developed a new LGA model which has the applicability for simulation of immiscible two phases with wide difference in density. We introduced long-range interparticle forces into the Rothman and Keller's ILG model to represent density difference between phases. We attempted some simulations of phase separation using our new model. Two-phase interfaces are stably made with density distribution coinciding with particle color distribution. Furthermore, the two-phase interface is clearer than that obtained by the Appert and Zaleski's LG model.
Shock Fitting and Numerical Modeling of Detonation Waves
Authors: Akram Muhammad , Ali Farhad
Published: October 2003

Numerical modelling of detonation using shock fitting is described in detail. A complete set of jump conditions that hold across the detonation front is presented in a simple form. Validity and accuracy of the model has been established by comparison with published results and results of another model utilizing the method of integral relations. A brief description of the later model is given to highlight its validity and limitations.
Quantum SU(3) Invariant of 3-Manifolds via Linear Skein Theory
Authors: Ohtsuki Tomotada , Yamada Shuji
Published: October 2003

The linear skein theory for the Kauffman bracket was introduced by Lickorish [11,12]. It gives an elementary construction of quantum SU(2) invariant of 3-manifolds. In this paper we prove basic properties of the linear skein theory for quantum SU(3) invariant. By using them we give an elementary construction of quantum SU(3) invariant of 3-manifolds and prove topological invariance of the invariant along the construction.
Three-Dimensional Representations of Punctured Torus Bundles
Authors: Mangum Brian , Shanahan Patrick
Published: October 2003

In this paper, we construct a complex curve of irreducible [Formula: see text] representations of the fundamental group of a once punctured torus bundle over the circle. These representations are different from those obtained by composing representations in [Formula: see text] with the unique irreducible representation of [Formula: see text] in [Formula: see text]. Moreover, infinitely many of these representations are conjugate to SU(3) representations. We conclude the paper with a computation of the curve in the case that the bundle is the figure-eight knot complement, and we show that for infinitely many Dehn surgeries on the figure-eight knot, there is a representation from this curve that descends to a representation of the fundamental group of the surgered manifold.
Approximate Chiral Symmetry, in Medium Pion Mass, and the PI-Abnormal Nuclear State
Authors: Zhang Qi-Ren , Greiner Walter
Published: October 2003

In an approximately chiral symmetric nuclear model consistent with the empirical nuclear data, we find that the medium pion mass approaches zero when the nuclear density approaches a critical value. At this critical density a chiral rotation occurs. The binding energy pernucleon jumps from about 16 MeV to 85 MeV. Since the chiral angle is not zero, we call this new state the pi-abnormal nuclear state. In this new state the pion mass becomes about 140 MeV again. Then it decreases with further increase of the nuclear density until it reaches another critical point. At this second point, the chiral angle reaches π. The pion mass starts rising. We identify this phase with the Lee–Wick's abnormal nuclear state.
A Logical Framework for Security Enforcement in CapBasED-AMS
Authors: Hung Patrick C. K. , Karlapalem Kamalakar
Published: October 2003

The CapBasED-AMS (Capability-based and Event-driven Activity Management System) deals with the management and execution of activities. A Problem Solving Agent (PSA) is a human, or a hardware system, or a software system having an ability to execute activities. An activity consists of multiple inter-dependent tasks that need to be coordinated, scheduled and executed by a set of PSAs. Since security is essential and integral part of activities, the activity management system has to manage and execute the activities in a secure way. In the CapBasED-AMS, threats, such as, unauthorized access or modification are identified as events. In this paper, we develop a logical framework for security enforcement in CapBasED-AMS by taking into consideration the system infrastructure, secure match-making under security constraints, security policies and secure PSA, the task coordination model for security enforcement during activity execution.
Insulin-Like Growth Factor-1 Receptor Activation Inhibits Oxidized LDL-Induced Cytochrome C Release and Apoptosis via the Phosphatidylinositol 3 Kinase/Akt Signaling Pathway
Authors: Li Yangxin , Higashi Yusuke , Itabe Hiroyuki , Song Yao-Hua , Du Jie , Delafontaine Patrice
Published: October 2003

Objective—

We have shown previously that oxidized LDL decreases insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells and that IGF-1 and IGF-1 receptor expression are reduced in the deep intima of early atherosclerotic lesions. Because oxidized LDL is potentially important for the depletion of vascular smooth muscle cells contributing to plaque destabilization, we studied the role of IGF-1 in oxidized LDL-induced apoptosis.

Methods and Results—

We provide evidence that oxidized LDL-induced apoptosis is caused by decreased mitochondrial membrane potential and increased cytochrome C release in human aortic vascular smooth muscle cells. Overexpression of the IGF-1 receptor by using an adenovirus completely abrogated these effects. The antiapoptotic function of the IGF-1 receptor was associated with increased Akt kinase activity and increased expression of phosphorylated Bad. Moreover, a dominant-negative p85 phosphatidylinositol 3-kinase adenovirus blocked the capacity of the IGF-1 receptor to prevent oxidized LDL-induced apoptosis.

Conclusions—

Our data demonstrate that IGF-1 receptor activation inhibits oxidized LDL-induced cytochrome C release and apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway and suggest that genetic or pharmacological activation of the IGF-1 receptor may be a useful strategy to stabilize atherosclerotic plaques.