bluuebunny/crossref_metadata_2025 huggingface dataset:
Borrower Attitudes Toward Alternative Mortgage Instruments*
Authors: Colton Kent W. , Lessard Donald R. , Solomon Arthur P.
Published: October 2003

Much of the existing literature on homeownership assumes that financial markets work well enough to allow households to translate permanent income into effective demand. However, transaction costs, imperfections, and uncertainties all constrain the markets' operation so that people are often forced to choose a quantity of housing stock that diverges from their desired consumption level. Instead of being able to borrow against future income for the down payment or to make monthly payments in a pattern that matches future income, young families in their early years may be constrained from purchasing the size house they desire, and older households may remain in homes larger than they need. In light of these market imperfections, housing and tenure decisions depend not only on permanent income and the relative price of housing services, but also on such mortgage parameters as monthly payment patterns, down payment, and rate of equity accumulation.

Models of the demand for housing and homeownership described in the existing literature do not include these parameters of mortgage finance. Mortgage terms are important factors in housing consumption and investment decisions. Because the standard mortgage no longer seems appropriate for all households under all economic conditions, the extent to which alternative mortgage instruments meet the requirements and preferences of different segments of the market becomes an important issue.
A Research Note on Factors Associated with Troubled Residential Construction Loans
Authors: Lusht Kenneth M. , Leidenberger Bruce E.
Published: October 2003

Several factors considered significant in determining the level of construction lending risk were tested for association with samples of troubled and good residential construction loans. Generally, a priori expectations were confirmed. The strongest associations with risk were found for unavailability of materials, followed by inflationary cost overruns and borrower experience.

Interest rates on the sample of troubled loans did not significantly differ from the rates on the sample of good loans, suggesting the lender did not adequately recognize elements of lending risk, or that those risks were ignored.
Transnational geographies: Indian immigration to Canada
Authors: Walton‐Roberts Margaret
Published: October 2003

Immigration from the Asia and Pacific area now accounts for over 50 percent of all Canadian immigration. Therefore, any consideration of Canada's linkages with Asia must address this issue. While much work has debated the impact of immigration in Canada's urban centres, less has been directed to understanding the transnational nature of such population movements, or their specific transnational geographies. In this paper, I consider the geography of immigration from India to Canada. Immigration from India has traditionally been tightly regionalised, with the majority of immigrants originating from the Doaba area of Punjab. Settlement in Canada is also highly concentrated at the provincial, metropolitan and suburban scales. Drawing upon a range of qualitative and quantitative data collected in both India and Canada, I illustrate the geography of immigration from India and highlight some of the processes that contribute to creating transnational networks between these sites.
Shaping the excitability of human motor cortex with premotor rTMS
Authors: Rizzo Vincenzo , Siebner Hartwig R. , Modugno Nicola , Pesenti Alessandra , Münchau Alexander , Gerschlager Willibald , Webb Ruth M. , Rothwell John C.
Published: October 2003

Recent studies have shown that low‐frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsal premotor cortex has a lasting influence on the excitability of specific neuronal subpopulations in the ipsilateral primary motor hand area (M1HAND). Here we asked how these premotor to motor interactions are shaped by the intensity and frequency of rTMS and the orientation of the stimulating coil. We confirmed that premotor rTMS at 1 Hz and an intensity of 90% active motor threshold (AMT) produced a lasting decrease in corticospinal excitability probed with single‐pulse TMS over the left M1HAND. Reducing the intensity to 80% AMT increased paired‐pulse excitability at an interstimulus interval (ISI) of 7 ms. Opposite effects occurred if rTMS was given at 5 Hz: at 90% AMT, corticospinal excitability increased; at 80% AMT, paired‐pulse excitability at ISI = 7 ms decreased. No effects were seen if rTMS was applied at the same intensities to prefrontal or primary motor cortices. These findings indicate that the intensity of premotor rTMS determines the net effect of conditioning on distinct populations of neurones in the ipsilateral M1HAND, but it is the frequency of rTMS that determines the direction of the induced change. By selecting the appropriate intensity and frequency, premotor rTMS allows to induce a predictable up‐ or down‐regulation of the excitability in distinct neuronal circuits of human M1HAND.
Calcium Mobilisation and CCK Secretion Induced by Modified Fatty Acids and Latex Microspheres Reveal Dual Receptor Mechanisms for Lipid Stimulation of STC‐1 Cells
Authors: Kazmi S. , Sidhu S. S. , Donohoe T. J. , Wickham M. , Jones M. N. , Thompson D. G. , Case R. M. , Benson R. S. P.
Published: October 2003

How fatty acids stimulate enteroendocrine cells to release cholecystokinin (CCK) is largely unknown. Recently, we proposed that the murine enteroendocrine cell line, STC‐1, responds to insoluble fatty acid aggregates rather than fatty acid monomers in solution. This hypothesis led to two testable predictions. First, other insoluble particles of similar size but unrelated to fatty acid may be able to stimulate STC‐1 cells in a similar fashion to dodecanoic acid and second, fatty acid sensing in STC‐1 cells should be fairly insensitive to chemical modifications of the fatty acid as long as these modifications do not greatly alter the ability of the molecule to form insoluble aggregates. We used several analogues of dodecanoic acid and several varieties of latex microsphere (varying in size and surface charge) to see whether the predictions of our model hold. We found that while there was at least one latex microsphere that could induce CCK secretion and calcium mobilisation in STC‐1 cells, there was a very poor correlation between the presence of insoluble aggregates and a cellular response. Instead the most important property, determining the potency of fatty acid analogues as stimulants of CCK secretion, was their amphipathicity. Removal of either the polar head or lipophilic tail completely abolished the ability of a given fatty acid analogue to stimulate STC‐1 cells. These data suggested that while fatty acids can stimulate cells as aggregates, they may also be acting in monomeric form with the oil:water partitioning coefficient playing a crucial role. We finally resolved this issue with the observation that the sulfate ion greatly altered the response of STC‐1 cells to monomeric dodecanoic acid. In the presence of sulfate, STC‐1 cells will only respond to dodecanoic acid aggregates whereas when sulfate is replaced with chloride the cells clearly respond to dodecanoic acid monomers which are completely in solution. In summary, we propose that dodecanoic acid can stimulate STC‐1 cells via two separate pathways one involving fatty acid monomers in solution and one involving fatty acid aggregates. Which pathway dominates depends on the presence of sulfate in the extracellular medium.
Algorithms for New Product Development: An Exercise in Thought Dynamics
Authors: Goldenberg Y. , Horowitz R. , Mazursky D. , Solomon S.
Published: October 2003

We generate new product ideas using algorithms which manipulate formally conceptual structures. These structures are abstract closed configurations composed of discrete elements which represent parts or properties of the products and of their immediate environment. The algorithms are assembled of a very limited number of fundamental operations acting on the elements. We present some successful field applications of the method carried out in leading international companies as well as an experiment providing quantitative proof of its superiority over usual ideas search.
Structure of Liquid–Vapor Interfaces in the Ising Model
Authors: Moseley L. L.
Published: October 2003

The asymptotic behavior of the density profile of the fluid-fluid interface is investigated by computer simulation and is found to be better described by the error function than by the hyperbolic tangent in three dimensions. For higher dimensions the hyperbolic tangent is a better approximation.
Effect of Shear on Droplets in a Binary Mixture
Authors: Wagner Alexander J. , Yeomans J. M.
Published: October 2003

In this article we use a lattice-Boltzmann simulation to examine the effects of shear flow on an equilibrium droplet in a phase separated binary mixture. We find that large drops break up as the shear is increased but small drops dissolve. We also show how the tip-streaming, observed for deformed drops, leads to a state of dynamic equilibrium.
Rapid Close-to-Optimum Optimization by Genetic Algorithms
Authors: Hackl R. , Morgenstern I.
Published: October 2003

In this article we consider the optimization of np-complete problems with a genetic algorithm. For "real word" problems we regard it to be sufficient to get close to the optimal solution without any guarantee of ever hitting it. Our algorithm was tested on two problem classes: the traveling salesman problem and the product ordering problem; the first is a standard problem, the latter a problem we were confronted with in a practical application. For all investigated problem instances we found very good solutions (<0.2% above optimum) in each run and even the global optimum in some runs on a Pentium/100 MHz-PC. For one instance of the TSP problem we could verify that the time spent to find the optimum follows a logarithmic normal distribution.
Noncommutativity of the Moving D2-brane Worldvolume
Authors: Kamani Davoud
Published: October 2003

In this paper we study the noncommutativity of a moving membrane with background fields. The open string variables are analyzed. Some scaling limits are studied. The equivalence of the magnetic and electric noncommutativities is investigated. The conditions for equivalence of noncommutativity of the T-dual theory in the rest frame and noncommutativity of the original theory in the moving frame are obtained.
Growth of Nd-Ca-Ba-Cu-O Tetragonal Superconductors by Liquid-Phase Epitaxy
Authors: Kita R. , Suzuki T.
Published: October 2003

Nd-Ca-Ba-Cu-O thick films with a tetragonal structure have been successfully grown on NdGaO 3 (110) single crystals by a liquid-phase epitaxy (LPE) technique using a Nd-BaCu-O powder as a solute, BaCuO 2 -CuO powder as a flux and CaO as a crucible. The films epitaxially grown at temperatures between 1173 K and 1273 K showed perfect a-axis orientated growth. The chemical composition of the grown film was found to be Nd 0.81 Ca 0.18 Ba 2.1 Cu 3.0 O y. The film showed a sharp superconducting transition with T c (onset) = 79.5 K and a transition width of 0.5 K. The a-axis orientated film showed a very smooth surface.
Neon Bulbs and the Unknotting of ARCS in Manifolds
Authors: Hass Joel , Thompson Abigail
Published: October 2003

We give several generalizations of the light bulb trick. These show that in a variety of settings there is a unique isotopy class of arcs connecting two points.
Genus One Knots with Unknotting Tunnels and Unknotting Operations
Authors: Goda Hiroshi
Published: October 2003

We show that every tunnel number 1 genus 1 knot can be changed into a genus 3 fibered knot by a crossing change.
Link Colorability, Covering Spaces and Isotopy
Authors: Nanyes Ollie
Published: October 2003

In this paper we modify the concept of link diagram colorability and branched cyclic covering spaces to the study of links under the piecewise linear isotopy equivalence relation. We then show that all mod B colorings of a link diagram (B an abelian group) are determined completely by the "nullity corrected" Goeritz matrix developed by Traldi.
The Structure and Verification of Plan-Based Joint Intentions
Authors: Balzer Wolfgang , Tuomela Raimo
Published: October 2003

Tuomela's philosophical account of joint intentions is formalized in a special setting in which fully specified plans are available for the execution of the intended joint action. Using additional modal logical assumptions the definition is simplified and used to investigate how the presence of a joint intention can be efficiently checked.
Minimization in Cooperative Response to Failing Database Queries
Authors: Godfrey Parke
Published: October 2003

When a query fails, it is more cooperative to identify the cause of failure, rather than just to report the empty answer set. When there is not a cause per se for the query's failure, it is then worthwhile to report the part of the query which failed. To identify a Minimal Failing Subquery (MFS) of the query is the best way to do this. (This MFS is not unique; there may be many of them.) Likewise, to identify a Maximal Succeeding Subquery (XSS) can help a user to recast a new query that leads to a non-empty answer set.

Database systems do not provide the functionality of these types of cooperative responses. This may be, in part, because algorithmic approaches to finding the MFSs and the XSSs to a failing query are not obvious. The search space of subqueries is large. Despite work on MFSs in the past, the algorithmic complexity of these identification problems had remained uncharted.

This paper shows the complexity profile of MFS and XSS identification. It is shown that there exists a simple algorithm for finding an MFS or an XSS by asking N subsequent queries, in which N is the length of the query. To find more MFSs (or XSSs) can be hard. It is shown that to find N MFSs (or XSSs) is NP-hard. To find k MFSs (or XSSs), for a fixed k, remains polynomial.

An optimal algorithm for enumerating MFSs and XSSs, ISHMAEL, is developed and presented. The algorithm has ideal performance in enumeration, finding the first answers quickly, and only decaying toward intractability in a predictable manner as further answers are found.

The complexity results and the algorithmic approaches given in this paper should allow for the construction of cooperative facilities which identify MFSs and XSSs for database systems. These results are relevant to a number of problems outside of databases too, and may find further application.
Semantic Query Processing in the VENUS Environment
Authors: Cardiff John , Catarci Tiziana , Santucci Giuseppe
Published: October 2003

Recent years have seen the publication of several methodologies for query processing in a Multidatabase (MDB) environment. Whilst different approaches are pertinent to specific CIS architectures, the issue of efficiency of processing has received relatively little attention. This is somewhat surprising considering the potentially large costs associated with MDB queries.

In this paper, we consider the efficiency of processing queries in the VENUS (Esprit 6398) environment. The goal of this system is to allow a user to query multiple data sources by interacting with a conceptually single database, and by providing a query interface based on the use of visual formalisms. This system takes advantage of existing multidatabase query processing strategies, and deals with optimization issues by considering the exploitation of inter- and intra-schema semantics. We present a methodology which harnesses knowledge of the set-theoretic relationships between classes participating in a query, and demonstrate that significant saving can be made in MDB query processing.

The methodology presented here is based on a powerful data model, the Graph Model, which we argue is suitable as the canonical model of a MDB. We also introduce a logic language to formally express interdependencies between classes belonging to different schemas. These assertions form the "backbone" of the MDB and, we may benefit in several ways from the possibility of reasoning about them, specifically by applying them in MDB query processing.
Reversal of Atrial Mechanical Dysfunction After Cardioversion of Atrial Fibrillation
Authors: Sanders Prashanthan , Morton Joseph B. , Kistler Peter M. , Vohra Jitendra K. , Kalman Jonathan M. , Sparks Paul B.
Published: October 2003

Background—

Atrial mechanical “stunning” develops after cardioversion of atrial fibrillation (AF) and is implicated in the genesis of thromboembolic complications. However, the mechanisms responsible for this phenomenon are poorly understood. Whether atrial mechanical dysfunction caused by AF can be reversed by pacing at increased rates or by pharmacological agents is unknown.

Methods and Results—

Twenty-six patients with AF undergoing cardioversion were dichotomized prospectively on the basis of the duration of arrhythmia as short-duration (1 to 6 months) or long-duration (≥3 years) AF. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AF, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol. In patients with short-duration AF, LAAEV decreased (42.0±2.7 to 18.5±2.0 cm/s;
P
<0.0001) and LASEC increased (0.9±0.3 to 2.2±0.3;
P
<0.01) with termination of AF; pacing increased LAAEV (48.3±4.1 cm/s;
P
<0.0001) and decreased LASEC (1.5±0.3;
P
<0.01); isoproterenol increased LAAEV (73.3±7.8 cm/s;
P
<0.0001) and decreased LASEC (0.3±0.2;
P
<0.01); and the postpacing pause increased LAAEV (68.3±3.8 cm/s;
P
<0.0001). In contrast, patients with long-duration AF demonstrated a significantly attenuated response of atrial mechanical function at each time point. With termination of AF, LAAEV decreased (19.1±2.6 to 8.2±1.0 cm/s;
P
=0.003) and LASEC increased (2.0±0.2 to 3.3±0.2;
P
<0.01); pacing increased LAAEV (18.4±2.7 cm/s;
P
<0.0001) and decreased LASEC (2.3±0.2;
P
<0.01); isoproterenol increased LAAEV (26.1±3.9 cm/s;
P
=NS to equivalent atrial rate) and decreased LASEC (1.0±0.3;
P
<0.01); and the postpacing pause increased LAAEV (27.2±2.4 cm/s;
P
=0.007).

Conclusions—

Atrial pacing at increased rates and isoproterenol can reverse atrial mechanical stunning associated with short-duration AF. In contrast, long-duration AF is associated with an attenuated response to these maneuvers. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium caused by AF; however, with longer durations of AF, additional factors may determine atrial mechanical function.
Aldosterone Regulates Vascular Reactivity
Authors: Liu Selina L. , Schmuck Saskia , Chorazcyzewski Jozef Z. , Gros Robert , Feldman Ross D.
Published: October 2003

Background—

There is increasing evidence for rapid nongenomic effects of aldosterone. Therefore, we studied the immediate effects of aldosterone on vascular reactivity in rat aortic ring segments and on endothelial and vascular smooth muscle cellular responses.

Methods and Results—

In endothelium-intact ring segments, aldosterone attenuated phenylephrine-mediated constriction (maximal reduction, 25±4% below control phenylephrine-mediated constriction). In contrast, in endothelium-denuded vessels, aldosterone mediated a monophasic dose-dependent enhancement of vasoconstrictor response. In endothelial cells, aldosterone caused a phosphatidylinositol 3-kinase (PI3K)–dependent increase in nitric oxide synthase activity as well as PI3K-dependent activation of extracellular signal–regulated kinase 1/2 and p70 S6 kinase.

Conclusions—

Overall, these data support a novel effect of aldosterone on vascular endothelial and smooth muscle cell function. These rapid effects of aldosterone might be important in both the short- and long-term regulation of peripheral vascular resistance. Furthermore, in the setting of endothelial dysfunction, alterations in aldosterone’s short-term vascular responses might contribute to its pathophysiological effects in cardiovascular disease.
Two-Pore Domain K Channel, TASK-1, in Pulmonary Artery Smooth Muscle Cells
Authors: Gurney A.M. , Osipenko O.N. , MacMillan D. , McFarlane K.M. , Tate R.J. , Kempsill F.E.J.
Published: October 2003

Pulmonary vascular tone is strongly influenced by the resting membrane potential of smooth muscle cells, depolarization promoting Ca
2+
influx, and contraction. The resting potential is determined largely by the activity of K
+
-selective ion channels, the molecular nature of which has been debated for some time. In this study, we provide strong evidence that the two-pore domain K
+
channel, TASK-1, mediates a noninactivating, background K
+
current (
I
KN
), which sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells (PASMCs). TASK-1 mRNA was found to be present in PASMCs, and the membranes of PASMCs contained TASK-1 protein. Both
I
KN
and the resting potential were found to be exquisitely sensitive to extracellular pH, acidosis inhibiting the current and causing depolarization. Moreover,
I
KN
and the resting potential were enhanced by halothane (1 mmol/L), inhibited by Zn
2+
(100 to 200 μmol/L) and anandamide (10 μmol/L), but insensitive to cytoplasmic Ca
2+
. These properties are all diagnostic of TASK-1 channels and add to previously identified features of
I
KN
that are shared with TASK-1, such as inhibition by hypoxia, low sensitivity to 4-aminopyridine and quinine and insensitivity to tetraethylammonium ions. It is therefore concluded that TASK-1 channels are major contributors to the resting potential in pulmonary artery smooth muscle. They are likely to play an important role in mediating pulmonary vascular responses to changes in extracellular pH, and they could be responsible for the modulatory effects of pH on hypoxic pulmonary vasoconstriction.
Does Nitric Oxide Mediate the Vasodilator Activity of Nitroglycerin?
Authors: Kleschyov Andrei L. , Oelze Matthias , Daiber Andreas , Huang Yale , Mollnau Hanke , Schulz Eberhard , Sydow Karsten , Fichtlscherer Birgit , Mülsch Alexander , Münzel Thomas
Published: October 2003

Nitroglycerin (glyceryl trinitrate, GTN) relaxes blood vessels primarily via activation of the soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK-I) pathway. Although the precise mechanism of sGC activation by GTN in the vascular wall is unknown, the mediatory role of nitric oxide (NO) has been postulated. We tested the GTN/NO hypothesis in different types of isolated rat and rabbit blood vessels using two novel approaches: (1) EPR spin trapping using colloid Fe(DETC)
2
and (2) analysis of cGK-I–dependent phosphorylation of the vasodilator-stimulated phosphoprotein at Ser239 (P-VASP). For comparison, another organic nitrate, isosorbide dinitrate (ISDN), and endothelium-dependent vasodilator, calcium ionophore A23187, were tested. We found a marked discrepancy between GTN’s strong vasoactivity (vasodilation and augmentation of P-VASP) and its poor NO donor properties. In aortas precontracted with phenylephrine, GTN, ISDN, and A23187 induced nearly full relaxations (>80%) and doubling of vascular P-VASP content at concentrations of 100 nmol/L, 100 μmol/L, and 1 μmol/L, respectively. GTN applied in vasorelaxant concentrations (10 to 1000 nmol/L) did not significantly increase the basal vascular NO production, in contrast to ISDN and A23187. The absence of GTN-derived NO was confirmed in rabbit vena cava and renal artery. A significant increase in vascular NO formation was observed only at suprapharmacological GTN concentrations (>10 μmol/L). The concentration dependency of NO formation from GTN was comparable to that of ISDN, although the latter exhibits 100-folds lower vasorelaxant potency. We conclude that GTN activates the sGC/cGMP/cGK-I pathway and induces vasorelaxation without intermediacy of the free radical NO. The full text of this article is available online at http://www.circresaha.org.
Cholesterol Depletion Impairs Vascular Reactivity to Endothelin-1 by Reducing Store-Operated Ca
2+
Entry Dependent on TRPC1
Authors: Bergdahl Andreas , Gomez Maria F. , Dreja Karl , Xu Shang-Zhong , Adner Mikael , Beech David J. , Broman Jonas , Hellstrand Per , Swärd Karl
Published: October 2003

The reactivity of the vascular wall to endothelin-1 (ET-1) is influenced by cholesterol, which is of possible importance for the progression of atherosclerosis. To elucidate signaling steps affected, the cholesterol acceptor methyl-β-cyclodextrin (mβcd, 10 mmol/L) was used to manipulate membrane cholesterol and disrupt caveolae in intact rat arteries. In endothelium-denuded caudal artery, contractile responsiveness to 10 nmol/L ET-1 (mediated by the ET
A
receptor) was reduced by mβcd and increased by cholesterol. Neither ligand binding nor colocalization of ET
A
and caveolin-1 was affected by mβcd. Ca
2+
inflow via store-operated channels after depletion of intracellular Ca
2+
stores was reduced in mβcd-treated caudal arteries, as shown by Mn
2+
quench rate and intracellular [Ca
2+
] response. Expression of TRPC1, 3, and 6 was detected by reverse transcriptase–polymerase chain reaction, and colocalization of TRPC1 with caveolin-1 was reduced by mβcd, as seen by immunofluorescence. Part of the contractile response to ET-1 was inhibited by Ni
2+
(0.5 mmol/L) and by a TRPC1 blocking antibody. In the basilar artery, exhibiting less store-operated channel activity than the caudal artery, ET-1–induced contractions were insensitive to the TRPC1 blocking antibody and to mβcd. Increased store-operated channel activity in basilar arteries after organ culture correlated with increased sensitivity of ET-1 contraction to mβcd. These results suggest that cholesterol influences vascular reactivity to ET-1 by affecting the caveolar localization of TRPC1.
Apoptosis Signal-Regulating Kinase 1 Plays a Pivotal Role in Angiotensin II–Induced Cardiac Hypertrophy and Remodeling
Authors: Izumiya Yasuhiro , Kim Shokei , Izumi Yasukatsu , Yoshida Kaoru , Yoshiyama Minoru , Matsuzawa Atsushi , Ichijo Hidenori , Iwao Hiroshi
Published: October 2003

Multiple lines of evidence establish that angiotensin II (Ang II) induces not only hypertension but also directly contributes to cardiac diseases. Apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, plays a key role in stress-induced cellular responses. However, nothing is known about the role of ASK1 in cardiac hypertrophy and remodeling in vivo. In this study, by using mice deficient in ASK1 (ASK1
−/−
mice), we investigated the role of ASK1 in cardiac hypertrophy and remodeling induced by Ang II. Left ventricular (LV) ASK1 was activated by Ang II infusion in wild-type mice, which was mediated by angiotensin II type 1 receptor and superoxide. Although Ang II-induced hypertensive effect was comparable to wild-type and ASK1
−/−
mice, LV ASK1 activation by Ang II was not detectable in ASK1
−/−
mice, and p38 and c-Jun N-terminal kinase (JNK) activation was lesser in ASK
−/−
mice than in wild-type mice. Elevation of blood pressure by continuous Ang II infusion was comparable between ASK1
−/−
and wild-type mice. However, Ang II–induced cardiac hypertrophy and remodeling, including cardiomyocyte hypertrophy, cardiac hypertrophy–related mRNA upregulation, cardiomyocyte apoptosis, interstitial fibrosis, coronary arterial remodeling, and collagen gene upregulation, was significantly attenuated in ASK1
−/−
mice compared with wild-type mice. These results provided the first in vivo evidence that ASK1 is the critical signaling molecule for Ang II–induced cardiac hypertrophy and remodeling. Thus, ASK1 is proposed to be a potential therapeutic target for cardiac diseases.
Interhemispheric Asymmetries of Motor Cortex Excitability in the Postacute Stroke Stage
Authors: Cicinelli Paola , Pasqualetti Patrizio , Zaccagnini Marina , Traversa Raimondo , Oliveri Massimiliano , Rossini Paolo Maria
Published: October 2003

Background and Purpose—

Changes in the intracortical inhibition (ICI) and facilitation (ICF) of motor cortex paired-pulse transcranial magnetic stimulation were reported in the affected (AH) and unaffected (UH) hemispheres of stroke patients and reflect some of the mechanisms related to motor cortex plasticity and different degrees of functional recovery. The interhemispheric differences of the ICI/ICF slopes have been found to have a nearly identical time course in the 2 hemispheres of healthy subjects, and whether such symmetry is modified after monohemispheric stroke has not yet been examined. Our goal was to investigate the interhemispheric asymmetries of the time course of ICI/ICF between the AH and UH of stroke patients in the postacute phase of recovery.

Methods—

ICI/ICF recovery curves to subthreshold-conditioning suprathreshold-test magnetic stimuli were recorded from the paretic and nonparetic hand muscles of 10 well-recovered stroke patients and compared with those of a population of 10 control subjects.

Results—

In the healthy subjects, ICI/ICF showed a symmetrical time evolution between the 2 hemispheres. In stroke patients, the ICI/ICF slopes were significantly different between the UH and AH; the intracortical inhibition was reduced in the AH and normal in the UH.

Conclusions—

The defective AH ICI associated with the effective UH ICI could represent a marker of poststroke cortical plasticity implicated as a mechanism relevant to functional recovery. Analysis of the interhemispheric asymmetries of the ICI/ICF recovery curves might provide a valuable neurophysiological parameter in the prognosis and follow-up of patients with monohemispheric stroke.
Practical Aspects of the Agent's Role in Cases Before the International Court
Authors:   Matheson
Published: October 2003

No Abstract
International Justice and Developing Countries (Continued): A Qualitative Analysis
Authors:   Romano
Published: October 2003

No Abstract
Offender Interaction With Victims in Homicide
Authors: Salfati C. Gabrielle
Published: October 2003

Homicide grows out of a transaction between individuals. This transaction is a product of the individuals and their relationship. More may therefore be understood about different “styles” of homicide by examining how an offender acts toward a victim during the crime. The analysis of the actual behaviors used by offenders at 247 single offender–single victim homicide crime scenes indicated a pattern of frequencies that follow a continuum from where the offender reacts in an impulsive way toward the emotions engendered through the conflicted interpersonal relationship with the victim, to where the offender interacts with the victim much more at a removed level, both physically and emotionally. Behaviors can thus be seen to follow a thematic pattern that can be related to underlying psychological principles, which closely relate to how an offender interacts with the victim at the crime scene.
Strategies of Coping Among Adolescents Experiencing Interparental Violence
Authors: Goldblatt Hadass
Published: October 2003

This article presents findings of a qualitative study, using a phenomenological perspective, aimed at understanding the meaning of interparental violence for adolescents. The professional literature emphasizes the negative effects of exposure to interparental violence. Yet coping with these effects has been largely overlooked. Whereas most knowledge is based on information about young children, adolescents’ perception of their experience has rarely been addressed. The study sample was composed of 21 Israeli-born Jewish youths, males and females, aged 13 to 18. All participants were interviewed using an in-depth semistructured interview format. Thematic content analysis of the data was performed, revealing coping strategies that serve as (a) a mode of action to survive in a violent ecology and (b) a positive outcome of life in spite of negative influences. The meaning of these coping strategies for the youths at present and for their future development is discussed. Implications for further research and intervention are proposed.
Multiple-Precursor Scenarios
Authors: Marcus Robert F. , Swett Bruce
Published: October 2003

The objectives of this research were to identify an extensive set of precursors (risk and prevention) to interpersonal violence on campus and to develop a measure to predict patterns of violence potential on campus with greater specificity. The method involved a study of 451 college students on two campuses and tested the predictive capabilities of the Violence Risk Assessment measure. The results showed that specific situational and gender patterns of violence exist, as well as significant effects of alcohol consumption and peer influence. Implications of results for prevention of violence and directions for further research are discussed.
Highly efficient expression of transgenic proteins by naked DNA-transfected dendritic cells through terminal differentiation
Authors: Larregina Adriana T. , Morelli Adrian E. , Tkacheva Olga , Erdos Geza , Donahue Cara , Watkins Simon C. , Thomson Angus W. , Falo Louis D.
Published: October 2003

Dendritic cells (DCs) play a key role in the induction and control of immunity. Genetic engineering of DCs is a promising approach for the development of a broad range of immunomodulatory strategies, for purposes ranging from genetic immunization to tolerance induction. The development of DC-based immunotherapies is limited by the inability to efficiently transfect DCs using naked DNA. Here we demonstrate that after plasmid DNA delivery, the transgene expression level controlled by the human immediate-early cytomegalovirus promoter (hIE-CMVp) is higher in mature DCs than in immature DCs and is further increased after terminal differentiation of DCs by agonist anti-CD40 monoclonal antibody (mAb) or after DC interaction with CD4+ T cells. CD40 signaling of DCs resulted in nuclear translocation of the transcription factors nuclear factor-κB (NF-κB), activator of protein-1 (AP-1), and cyclic adenosine monophosphate (cAMP)–responsive element, necessary for the activation of hIE-CMVp. Transgene expression by DCs diminished after the inhibition of these transcription factors or the blockade of adhesion molecules involved in the DC–T-cell synapse. Importantly, CD40 signaling of DCs results in the highly efficient expression and presentation of transgenic antigens and the induction of “in vivo” cytotoxic T-cell (CTL) responses specific for transgenic antigen peptides, demonstrating the functional potential of genetically engineered DCs.
Adoptive transfer of ex vivo immune-programmed NKT lymphocytes alleviates immune-mediated colitis
Authors: Shibolet Oren , Kalish Yossef , Klein Athalia , Alper Ruslana , Zolotarov Lydia , Thalenfeld Barbara , Engelhardt Dean , Rabbani Elazar , Ilan Yaron
Published: October 2003

T lymphocyte-expressing natural killer (NK) cell markers (NKT cells) play a role in immune regulation. Our aim was to evaluate the in vivo effect of adoptive transfer of immune-programmed NKT cells. Colitis was induced in C57/B6 mice by 2,4,6-trinitrobenzenesulfonic acid. NKT, CD4, CD8 lymphocytes, and dendritic cells (DC) were prepared from spleens of naive mice, animals with colitis, and animals with colitis that were orally tolerized. Subsets of splenocytes, NKT, CD4, and CD8 and NKT+CD4, NKT+CD8, and NKT+DC lymphocytes were prepared. Assessment of the T helper cell type 1 (Th1)/Th2 cytokine secretion paradigm in vitro was performed before and following exposure to the antigen. Adoptive transfer of ex vivo immune-programmed lymphocytes from each group was performed into recipient mice, followed by colitis induction. Ex vivo exposure of NKT cells harvested from mice with colitis-to-colitis proteins [colitis-extracted proteins (CEP)] led to a Th2 cytokine shift. The interleukin (IL)-4/interferon-γ (IFN-γ) ratio increased for NKT harvested from colitis-harboring mice following exposure to CEP. Adoptive transfer of NKT lymphocytes harvested from colitis-harboring mice, which were ex vivo-educated, significantly alleviated experimental colitis in vivo. Intrahepatic NKT lymphocytes increased significantly in mice transplanted with NKT lymphocytes harvested from colitis-harboring donor mice, which were ex vivo-exposed to CEP, similar to mice transplanted with NKT lymphocytes harvested from tolerized donors. Exposure of NKT cells to the disease-target antigen induced a significant increase in the IL-4/IFN-γ cytokine ratio. Adoptive transfer of a relatively small number of immune-programmed NKT cells induced a systemic Th1 to Th2-immune shift and alleviated immune-mediated colitis.
Regulation of Collagen Synthesis in Mouse Skin Fibroblasts by Distinct Angiotensin II Receptor Subtypes
Authors: Min Li-Juan , Cui Tai-Xing , Yahata Yoko , Yamasaki Kenshi , Shiuchi Tetsuya , Liu Hong-Wei , Chen Rui , Li Jian-Mei , Okumura Midori , Jinno Toyohisa , Wu Lan , Iwai Masaru , Nahmias Clara , Hashimoto Koji , Horiuchi Masatsugu
Published: October 2003

We examined the possibility of whether angiotensin (Ang) II type 1 (AT1) and type 2 (AT2) receptor stimulation differentially regulates collagen production in mouse skin fibroblasts. Both AT1 and AT2 receptors were expressed in neonatal skin fibroblasts prepared from wild-type mice to a similar degree, and the AT1a receptor was exclusively expressed as opposed to the AT1b receptor. In wild-type fibroblasts, Ang II increased collagen synthesis accompanied by an increase in expression of tissue inhibitor of metalloproteinase (TIMP)-1, and these increases were inhibited by valsartan, an AT1 receptor blocker, but augmented by PD123319, an AT2 receptor antagonist. Ang II decreased basal and IGF-I-induced collagen production and inhibited TIMP-1 expression in neonatal skin fibroblasts prepared from AT1a knockout (KO) mice. These Ang II-mediated inhibitory effects on collagen production and TIMP-1 expression observed in AT1a KO fibroblasts were attenuated by the addition of PD123319 or a tyrosine phosphatase inhibitor, sodium orthovanadate, but not affected by a serine/threonine phosphatase inhibitor, okadaic acid. Moreover, we demonstrated that transfection of a catalytically inactive, dominant negative SHP-1 (Src homology 2-containing protein-tyrosine phosphatase-1) mutant inhibited the Ang II-mediated inhibitory effect on both collagen synthesis and TIMP-1 expression in AT1a KO fibroblasts. These results suggest that AT1a receptor stimulation increases collagen production in skin fibroblasts at least in part due to the inhibition of collagen degradation via the increase in TIMP-1 expression, whereas AT2 receptor stimulation exerts inhibitory effects on TIMP-1 expression, which is mediated at least partially by the activation of SHP-1, thereby possibly inhibiting collagen production.
Attenuating effect of mexiletine hydrochloride on herpetic pain in mice infected with herpes simplex virus
Authors: Asano Kazuhito , Sameshima Tatsuo , Shirasawa Hiroshi , Hisamitsu Tadashi
Published: October 2003

The influence of mexiletine hydrochloride on herpes-related pain responses was examined using mice infected with herpes virus. BALB/c mice were inoculated with herpes simplex virus (HSV; 1 times 106 plaque-forming units) on the right hind paw, and the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using electric von fray meter. BALB/c mice inoculated with HSV showed a decrease in nociceptive threshold. Intraperitoneal administration of mexiletine prevented the decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was firstly observed at a dose of 15.0 mg kg−1, and peaked at doses more than 17.5 mg kg−1. This antinociceptive effect of mexiletine attained peaks at 60–90 min after administration and declined gradually to non-treated levels by 150 min. Intraperitoneal administration of mexiletine at a dose of 17.5 mg kg−1 (but not 10.0 mg kg−1) caused significant increase in β-endorphin levels in the mid brain and hypothalamus of HSV-inoculated mice. However, mexiletine scarcely affected noradrenaline (norepinephrine) levels in the pons and medulla oblongata, even when HSV-inoculated mice were treated with 17.5 mg kg−1 mexiletine. These results strongly suggested that mexiletine exerts antinociceptive effects on herpes-related pain through enhancement of β-endorphin levels in the central nervous system in HSV-inoculated mice. It is also suggested that mexiletine will be a good candidate for an antinociceptive drug in the treatment of acute herpetic pain in man.
Synthesis and biological activity of pyridinium-type acetylcholinesterase inhibitors
Authors: Alptüzün Vildan , Kapková Petra , Baumann Knut , Erciyas Ercin , Holzgrabe Ulrike
Published: October 2003

A novel series of bispyridinium-type acetylcholinesterase (AChE) inhibitors derived from obidoxime, being active in the lower micromolar range, has been reported recently. According to the hypothesis that shorter pyridinium compounds should exhibit higher activity, a new series of compounds was synthesized that has 2,6-dichlorobenzyl, 2-chlorobenzyl and phthalimidomethyl moieties, respectively, at one end of the molecule and that are systematically shortened from the contralateral end. The concentration inhibiting the AChE and butyrylcholinesterase (BChE) by 50% (IC50) was evaluated by means of Ellman's test. Compounds characterized by a phenylpropyl residue at the contralateral end (3) were found to have IC50 values comparable with tacrine. In addition, the affinity of 3c toward the BChE was lower, indicating a lower degree of side effects.
Effects of L-carnitine treatment on oxidant/antioxidant state and vascular reactivity of streptozotocin-diabetic rat aorta
Authors: Irat Ali Murat , Aktan Fügen , Ozansoy Gülgün
Published: October 2003

In this study, the effects of L-carnitine treatment on lipids, lipid peroxidation of plasma, reactivity and antioxidant enzyme activity of aorta were evaluated in streptozotocin (STZ)-diabetic rats. Treatment with L-carnitine (0.6 g kg−1 daily, i.p.) was started 8 weeks after the induction of diabetes and continued for 2 weeks. Diabetes was induced by a single injection of streptozotocin (45 mg kg−1, i.p.). Plasma cholesterol, triglyceride and thiobarbituric acid reactive substance (TBARS) levels and blood glucose levels were significantly increased, although free carnitine levels were markedly decreased in diabetic rats. L-Carnitine treatment completely normalized plasma cholesterol, triglyceride, free carnitine and TBARS levels but partially restored blood glucose levels of diabetic rats. STZ-diabetes caused a significant reduction in the endothelium-dependent relaxation response to acetylcholine (ACh). In diabetic aorta, TBARS levels and catalase (CAT) activity were significantly increased but glutathione peroxidase (GSH-Px) activity was unchanged. Treatment of diabetic rats with L-carnitine resulted in partial restoration of the endothelium-dependent relaxation response to ACh and completely normalized the oxidant/antioxidant state. These results suggested that the beneficial effects of L-carnitine treatment partially improve vascular reactivity and antioxidant property beyond its reduction of plasma lipids and it may have an important therapeutic approach in the treatment of diabetic vascular complications.
A sensitive enzyme-linked immunosorbent assay for evaluating the concentration of bee venom in rat plasma
Authors: Xing Liu , Liping Xie , Rongqing Zhang , Dawei Chen , Lan Shao
Published: October 2003

A simple and reproducible enzyme-linked immunosorbent assay (ELISA) was developed to determine the concentration of bee venom in rat plasma. The intra- and inter-assay coefficients of variation for the ELISA were less then 3% between 0.1 and 1000 ng mL−1 venom, and the sensitivity of the detection was 0.1 ng mL−1. Total recovery of the bee venom added to rat plasma was determined. Using this ELISA, serum levels of bee venom were easily determined. The rats were administered a single intravenous injection or oral dose of bee venom (1 mg kg−1 of body weight). The bioavailability of the bee venom under the two administrations was compared using pharmacokinetic parameters. Results showed that intravenous administration of bee venom produced high plasma concentrations with a short half-life. The area under the curve for oral administration was 10 times lower than for intravenous administration. This loss of bee venom may be due to the degradation that occurs in the enzymatic and acidic environment of the gastrointestinal tract.
Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and requiretfap2afor expression of the neurotransmitter phenotype
Authors: Holzschuh Jochen , Barrallo-Gimeno Alejandro , Ettl Anne-Kathrin , Dürr Katrin , Knapik Ela W. , Driever Wolfgang
Published: October 2003

Tfap2a is a transcriptional activator expressed in many different cell types, including neurons, neural crest derivatives and epidermis. We show that mutations at the zebrafish locus previously called mont blanc(mob) or lockjaw (low) encode tfap2a. The mutant phenotype reveals that tfap2a is essential for the development of hindbrain noradrenergic (NA) neurons of the locus coeruleus, medulla and area postrema, as well as for sympathetic NA neurons, epibranchial placode derived visceral sensory ganglia, and craniofacial and trunk crest derivatives. We focus our analysis on the role of tfap2a NA differentiation in the CNS. In the locus coeruleus, Phox2a and Tfap2a are co-expressed and are both required for NA development. By contrast, in the medulla Phox2a and Tfap2a are expressed in adjacent overlapping domains, but only tfap2a activity is required for NA differentiation, as NA neurons develop normally in soulless/phox2a mutant medulla. phox2a and tfap2a do not appear to affect each others expression. Our studies show that two distinct inductive mechanisms control NA development in the zebrafish hindbrain. For the posterior hindbrain, we identify retinoic acid as an important signal to induce NA differentiation in the medulla oblongata and area postrema, where it expands the tfap2aexpression domain and thus acts upstream of tfap2a. By contrast,previous work revealed Fgf8 to be involved in specification of NA neurons in the locus coeruleus. Thus, although the inductive signals may be distinct,hindbrain NA neurons of the locus coeruleus and the posterior groups both require Tfap2a to establish their noradrenergic identity.
ESR Detection of the Isotopic-site-preference in the Jahn–Teller Distorted Benzene Cation Radicals Produced in MCM-41, Silica Gel, and Halocarbons
Authors: Toriyama Kazumi , Okazaki Masaharu
Published: October 2003

Isotopic-site-preference was detected in partially-deuterated benzene cation radicals, which were distorted by the Jahn–Teller effect to the D2h symmetry. In all cases, C–H bonds tend to occupy the positions with higher spin densities in the distorted cation.
Support Effect of Silica on Photocatalytic Degradation of Dibutyl Phthalate by TiO2 Nanoparticles in Water Containing Chloride Anion
Authors: Yoshida Hisao , Nishimoto Jun-ichi , Miyashita Yoshinori , Ooka Chihiro , Komai Shin-ichi , Satsuma Atsushi , Hattori Tadashi
Published: October 2003

Employing silica as a support of TiO2 reduced the inhibition effect of chloride anion on photocatalytic activity for degradation of dibutyl phthalate in water. This support effect was largely observed in the cases of silica having larger surface area and of smaller TiO2 particles.
Specific Binding of Vanadyl Ion (VO2+) with Thiolate of the Cysteine-34 Residue in Serum Albumin, Demonstrated by CD Spectroscopy and Kinetic Property
Authors: Yasui Hiroyuki , Kunori Yasuo , Sakurai Hiromu
Published: October 2003

Binding feature of the vanadyl ion (VO2+) with bovine serum albumin (BSA) was studied with CD spectrometry based on comparisons with that of Cu2+. The strong positive CD band at 590 nm in the VO2+–albumin system was assigned to the binding of VO2+ and thiolate of Cys-34 in BSA.