bluuebunny/crossref_metadata_2025 huggingface dataset:
THE DYNAMICS OF FRACTALS
Authors: BAK PER , PACZUSKI MAYA
Published: July 2003

Fractals are formed by avalanches, driving the system toward a critical state. This critical state is a fractal in d spatial plus one temporal dimension. Long range spatial and temporal properties are described by different cuts in this fractal attractor. We unify the origin of fractals, 1/f noise, Hurst exponents, Levy flights, and punctuated equilibria in terms of avalanche dynamics, and elucidate their relationships through analytical and numerical studies of simple models.
THE EVIDENCE FOR SELF-ORGANIZED CRITICALITY IN SANDPILE DYNAMICS
Authors: FEDER J.
Published: July 2003

Self-organized criticality (SOC) is thought to describe avalanche dynamics in sandpiles. Experiments on the dynamics of “sandpiles” fall in two broad categories. Sandpiles in rotating drums exhibit periodic large avalanches, which is inconsistent with SOC. Other experiments study sandpiles on a circular support driven by the addition of grains of sand at a low rate from above and centered with respect to the support. The mass of avalanches that drop sand off the support is typically measured by a balance. It has been claimed that the observed avalanche statistics is consistent with SOC. However, I find that experiments described in the literature all have avalanche-size distributions that can be very well described by stretched-exponential distributions. Since the stretched-exponential distribution has a characteristic size, I conclude that the experiments described in the literature are inconsistent with SOC.
DISTRIBUTIONS OF STRUCTURAL PROPERTIES FOR PERCOLATION CLUSTERS
Authors: HOVI J.-P. , AHARONY AMNON
Published: July 2003

The distributions of structural properties, which span between two terminals on percolation clusters, are studied using the “H-cell” renormalization group (RG). The RG iteration for these distributions is directly related to a simple Galton-Watson branching process, and we therefore apply theorems developed in the mathematical literature to obtain exact expressions for the asymptotic distribution functions. Distributions of the minimal path lengths, average edge-to-edge self-avoiding walk lengths, and of the masses of percolation clusters are found, and we derive exact exponential forms for the asymptotic tail behavior of the scaled probability densities at both small and large arguments. We also find new results for the multifractal distribution of wave functions on these clusters.
MAPPING OF A DETERMINISTIC DYNAMICS WITH QUENCHED VARIABLES INTO A STOCHASTIC PROBLEM WITH COGNITIVE MEMORY
Authors: CAFIERO R. , GABRIELLI A. , MARSILI M. , PIETRONERO L.
Published: July 2003

Irreversible dynamics in media with quenched disorder seems to be the essential mechanism for a variety of phenomena like fracture propagation or displacement of immiscible fluids in disordered porous media. This problem does not seem to be treatable along the standard theoretical schemes. Recently a new approach has been introduced that allows mapping of a deterministic dynamics with quenched disorder like that of Invasion Percolation into a stochastic dynamics with memory. This memory consists essentially in a cognitive process that modifies the probability distribution of quenched variables conditionally to all previous events. This approach, together with the FST and the corresponding analysis of the scale invariant dynamics, provides a new framework to understand the self organization and to compute the critical exponents of problems like Invasion Percolation and Bak and Sneppen.
SCALING PROPERTIES OF THE KURAMOTO-SIVASHINSKY EQUATION
Authors: LI JI , SANDER LEONARD M.
Published: July 2003

The Kuramoto-Sivishinsky model describes the dynamics of a cellular flame front. It has been known for some time that on scales large compared with the size of a cell the front appears to be a self-affine fractal which has noisy dynamics in 1+1 dimensions. We use the inverse method of Lam and Sander (Phys. Rev. Lett.71, 561 (1993)) to show explicitly how the scaling occurs and how deterministic chaos at small scales develops into noisy dynamics at large scales, and how a small scale pattern becomes a large scale disordered fractal via an intermediate scaling regime.
ON THE RIEMANN-LIOUVILLE FRACTIONAL CALCULUS AND SOME RECENT APPLICATIONS
Authors: NONNENMACHER THEO F. , METZLER RALF
Published: July 2003

When Benoit Mandelbrot discussed the problem of fractional Brownian motion in his classic book The Fractal Geometry of Nature, he already pointed out some strong relations to the Riemann-Liouville fractional integral and differential calculus. Over the last decade several papers have appeared in which integer-order, standard differential equations modeling processes of relaxation, oscillation, diffusion and wave propagation are generalized to fractional order differential equations. The basic idea behind all that is that the order of differentiation need not be an integer but a fractional number (i.e. dq/dtq with 0<q<1). Applications to slow relaxation processes in complex systems like polymers or even biological tissue and to self-similar protein dynamics will be discussed. In addition, we investigate a fractional diffusion equation and we present the corresponding probability density function for the location of a random walker on a fractal object. Fox-functions play a dominant part.
Netted matrices
Authors: Stănică Pantelimon
Published: July 2003

We prove that powers of 4‐netted matrices (the entries satisfy a four‐term recurrence δai,j = αai−1,j + βai−1,j + γai,j−1) preserve the property of nettedness: the entries of the eth power satisfy , where the coefficients are all instances of the same sequence xe+1 = (β + δ)xe − (βδ + αγ)xe−1. Also, we find a matrix Qn(a, b) and a vector v such that Qn(a, b) e · v acts as a shifting on the general second‐order recurrence sequence with parameters a, b. The shifting action of Qn(a, b) generalizes the known property . Finally, we prove some results about congruences satisfied by the matrix Qn(a, b).
An optimal order yielding discrepancy principle for simplified regularization of ill‐posed problems in Hilbert scales
Authors: George Santhosh , Nair M. Thamban
Published: July 2003

Recently, Tautenhahn and Hämarik (1999) have considered a monotone rule as a parameter choice strategy for choosing the regularization parameter while considering approximate solution of an ill‐posed operator equation Tx = y, where T is a bounded linear operator between Hilbert spaces. Motivated by this, we propose a new discrepancy principle for the simplified regularization, in the setting of Hilbert scales, when T is a positive and selfadjoint operator. When the data y is known only approximately, our method provides optimal order under certain natural assumptions on the ill‐posedness of the equation and smoothness of the solution. The result, in fact, improves an earlier work of the authors (1997).
On fuzzy subbundles of vector bundles
Authors: Murali V. , Lubczonok G.
Published: July 2003

This paper considers fuzzy subbundles of a vector bundle. We
define the operations sum, product, tensor product, Hom, and intersection of fuzzy subbundles and in each case, we characterize the corresponding flag of vector subbundles. We then propose two alternative definitions of integrability on fuzzy subbundles of a given type and discuss their naturality, merits, and shortcomings. We do these here with a view to introduce and study integrable fuzzy subbundles of tangent bundles on manifolds and foliations in further papers.
On common fixed points, periodic points, and recurrent points of continuous functions
Authors: Alikhani-Koopaei Aliasghar
Published: July 2003

It is known that two commuting continuous functions on an interval need not have a common fixed point. However, it is not known if such two functions have a common periodic point. we had conjectured that two commuting continuous functions on an interval will typically have disjoint sets of periodic points. In this paper, we first prove that S is a nowhere dense subset of [0, 1] if and only if is a nowhere dense subset of C([0, 1]). We also give some results about the common fixed, periodic, and recurrent points of
functions. We consider the class of functions f with continuous ωf studied by Bruckner and Ceder and show that the set of recurrent points of such functions are closed intervals.
Two‐machine flowshop scheduling problem to minimize makespan ortotal completion time with random and bounded setup times
Authors: Allahverdi Ali , Aldowaisan Tariq , Sotskov Yuri N.
Published: July 2003

This paper addresses the two‐machine flowshop scheduling problem with separate setup times to minimize makespan or total completion time (TCT). Setup times are relaxed to be random variables rather than deterministic as commonly used in the OR literature. Moreover, distribution‐free setup times are used where only the lower and upper bounds are given. Global and local dominance relations are developed for the considered flowshops and an illustrative numerical example is given.
Real Gel′fand‐Mazur division algebras
Authors: Abel Mati , Panova Olga
Published: July 2003

We show that the complexification of a real locally pseudoconvex (locally absorbingly pseudoconvex, locally multiplicatively pseudoconvex, and exponentially galbed) algebra (A, τ) is a complex locally pseudoconvex (resp., locally absorbingly pseudoconvex, locally multiplicatively pseudoconvex, and exponentially galbed) algebra and all elements in the complexification of a commutative real exponentially galbed algebra (A, τ) with bounded elements are bounded if the multiplication in (A, τ) is jointly continuous. We give conditions for a commutative strictly real topological division algebra to be a commutative real Gel′fand‐Mazur division algebra.
A necessary and sufficient condition for the existence of a unique solution of a discrete boundary value problem
Authors: Abu-Saris Raghib , Ahmad Wajdi
Published: July 2003

A kth‐order linear difference equation with constant coefficients subject to boundary conditions is considered. A necessary and sufficient condition for the existence of a unique solution for such a boundary value problem is established. The condition established answers a fundamental
question for well‐posedness and can be easily applied using a simple and computationally tractable algorithm that does not require finding the roots of the associated characteristic equation.
Proximinal subspaces of A(K) of finite codimension
Authors: Rao T. S. S. R. K.
Published: July 2003

We study an analogue of Garkavi′s result on proximinal subspaces of C(X) of finite codimension in the context of the space A(K) of affine continuous functions on a compact convex set K. We give an example to show that a simple‐minded analogue of Garkavi′s result fails for these spaces. When K is a metrizable Choquet simplex, we give a necessary and sufficient condition for a boundary measure to attain its norm on A(K). We also exhibit proximinal subspaces of finite codimension of A(K) when the measures are supported on a compact subset of the extreme boundary.
Induction of Tissue Factor in the Arterial Wall During Recurrent Thrombus Formation
Authors: D’Andrea Davide , Ravera Marta , Golino Paolo , Rosica Annamaria , De Felice Mario , Ragni Massimo , Cirillo Plinio , Vigorito Francesco , Corcione Nicola , Tommasini Paola , Gargiulo Annarita , Piro Orlando , Calabró Paolo , Chiariello Massimo
Published: July 2003

Objective—

Tissue factor (TF) is normally expressed at low levels in the media of blood vessels, but it is readily induced after vessel injury. It is not known whether vascular damage per se or thrombus formation is responsible for this phenomenon.

Methods and Results—

Cyclic flow variations (CFVs), attributable to recurrent thrombus formation, were induced in stenotic rabbit carotid arteries with endothelial injury. CFVs were observed for 30 minutes and 2, 4, and 8 hours in different groups of animals. Another group of rabbits pretreated with hirudin before inducing arterial damage to inhibit thrombus formation was observed for 8 hours. Arterial sections were immunostained for TF. Undamaged arteries served as controls. In additional rabbits, in situ hybridization experiments were performed. No TF expression was observed in the media of control vessels, whereas a progressive increase in TF mRNA and protein expression was observed in carotid arteries as CFVs progressed. No increase in TF expression was observed in animals pretreated with hirudin. In vitro experiments demonstrated that TF mRNA is induced in smooth muscle cells stimulated with activated platelets as well as with some platelet-derived mediators.

Conclusions—

This phenomenon may contribute to sustain intravascular thrombus formation after the initial thrombogenic stimulus.
Strikingly Low Circulating CRP Concentrations in Ultramarathon Runners Independent of Markers of Adiposity
Authors: Tomaszewski Maciej , Charchar Fadi J. , Przybycin Malgorzata , Crawford Lynne , Wallace A. Michael , Gosek Katarzyna , Lowe Gordon D. , Zukowska-Szczechowska Ewa , Grzeszczak Wladyslaw , Sattar Naveed , Dominiczak Anna F.
Published: July 2003

Objective—

This study was undertaken to evaluate to what extent C-reactive protein (CRP) can be reduced by exercise by examining its circulating concentrations in male ultramarathon runners and to determine if low leptin as a robust circulating marker of fat mass could account for low CRP in such men.

Methods and Results—

Sixty-seven male ultramarathon runners and 63 sedentary male controls of similar age and body mass index were recruited. CRP and leptin were measured by ELISA and radioimmunoassay, respectively. Median CRP concentration in lean (body mass index <25 kg/m
2
) marathon runners was less than half control median (0.4 [0.2 to 0.9] mg/L versus 0.9 [0.5 to 2.7] mg/L,
P
=0.0013) and, more strikingly, in nonlean runners was approximately 26% of control median (0.4 [0.3 to 0.8] mg/L versus 1.5 [0.9 to 2.5] mg/L,
P
=0.0002). Circulating leptin levels were also substantially lower in lean (45% less) and nonlean (63% less, both
P
<0.0001) ultramarathon runners. However, interleukin-6 levels were not different. Furthermore, leptin adjustment only minimally attenuated the case-control difference in CRP, suggesting that mechanisms other than fat mass reduction contribute to low concentrations of CRP in marathon runners.

Conclusions—

This study suggests that circulating CRP concentrations can be markedly suppressed, independently of total adiposity or indeed fat mass, by intense regular physical exercise.
Randomized Comparison of Distal Protection With a Filter-Based Catheter and a Balloon Occlusion and Aspiration System During Percutaneous Intervention of Diseased Saphenous Vein Aorto-Coronary Bypass Grafts
Authors: Stone Gregg W. , Rogers Campbell , Hermiller James , Feldman Robert , Hall Patrick , Haber Robert , Masud A. , Cambier Patrick , Caputo Ron P. , Turco Mark , Kovach Richard , Brodie Bruce , Herrmann Howard C. , Kuntz Richard E. , Popma Jeffrey J. , Ramee Steve , Cox David A.
Published: July 2003

Background—

The high rate of periprocedural complications resulting from atherothrombotic embolization after percutaneous intervention in diseased saphenous vein grafts is reduced by distal microcirculatory protection using a balloon occlusion and aspiration system. Whether filter-based catheters, which offer the inherent advantages of maintained perfusion and ease of use, are as effective for this purpose has not been established.

Methods and Results—

A total of 651 patients undergoing percutaneous intervention of 682 saphenous vein graft lesions were prospectively randomized to distal protection with the filter-based FilterWire EX versus the GuardWire balloon occlusion and aspiration system. Device success was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (
P
=0.25). Postprocedural measures of epicardial flow and angiographic complications were similar between the 2 groups, although bailout IIb/IIIa inhibitors were required slightly less frequently in the FilterWire EX group (0% versus 1.5%,
P
=0.03). The primary end point, the composite incidence of death, myocardial infarction, or target vessel revascularization at 30 days, occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% CI]=−1.7% [−6.4%, 3.1%];
P
for superiority=0.53,
P
for noninferiority=0.0008).

Conclusions—

Distal protection with the FilterWire EX may be safely used as an adjunct to percutaneous intervention of diseased saphenous vein grafts and, compared with distal protection with the GuardWire balloon occlusion and aspiration system, results in similar rates of major adverse cardiac events at 30 days.
Activation and Functional Significance of the Renin-Angiotensin System in Mice With Cardiac Restricted Overexpression of Tumor Necrosis Factor
Authors: Flesch Markus , Höper Anje , Dell’Italia Louis , Evans Kenda , Bond Richard , Peshock Ronald , Diwan Abhinav , Brinsa Theresa A. , Wei Chih-Chang , Sivasubramanian Natarajan , Spinale Francis G. , Mann Douglas L.
Published: July 2003

Background—

The functional significance of cross-regulation between the renin-angiotensin system (RAS) and tumor necrosis factor (TNF) has been established in nonmyocyte cell types; however, the degree and functional significance of the interaction between RAS and TNF has not been characterized in the heart.

Methods and Results—

We examined the expression of components of the RAS in a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF. When examined at 4, 8, and 12 weeks of age, the MHCsTNF mice had increased activation of myocardial RAS, as shown by an increase in ACE mRNA level and ACE activity and increased angiotensin II peptide levels. Furthermore, myocardial angiotensin receptor mRNA and protein levels were reduced in the MHCsTNF mice, consistent with homologous desensitization of the receptors. However, expression of renin and angiotensinogen was not increased in MHCsTNF mice compared with littermate controls. To determine the functional significance of RAS activation in the MHCsTNF mice, we treated the mice with an angiotensin type I receptor antagonist, losartan (30 mg/kg), or diluent from 4 to 8 weeks of age. Analysis of cardiac structure with MRI showed that treatment with losartan normalized left ventricular mass and wall thickness. Furthermore, treatment with losartan reduced myocardial collagen content and reduced the incidence of myocyte apoptosis.

Conclusions—

Taken together, these results show that there are functionally significant interactions between RAS and TNF in the heart and that these interactions play an important role in the development and progression of left ventricular remodeling.
Functional and Biochemical Evaluation of Platelet Aspirin Resistance After Coronary Artery Bypass Surgery
Authors: Zimmermann N. , Wenk A. , Kim U. , Kienzle P. , Weber A.-A. , Gams E. , Schrör K. , Hohlfeld T.
Published: July 2003

Background—

Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown.

Methods and Results—

Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and α-granule secretion were effectively inhibited by 30 or 100 μmol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG.

Conclusions—

Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.
Increased Thrombosis After Arterial Injury in Human C-Reactive Protein–Transgenic Mice
Authors: Danenberg Haim D. , Szalai Alexander J. , Swaminathan Rajesh V. , Peng Lin , Chen Zhiping , Seifert Philip , Fay William P. , Simon Daniel I. , Edelman Elazer R.
Published: July 2003

Background—

C-reactive protein (CRP), an acute-phase reactant long considered merely an innocent bystander in the inflammatory process, is now recognized as a powerful predictor of cardiovascular events. Emerging in vitro evidence suggests that CRP may have direct proinflammatory and prothrombotic effects on monocytes and endothelial cells. To determine whether CRP directly modulates vascular cell function in vivo, we subjected wild-type mice, which do not express CRP, and human CRP–transgenic (CRPtg) mice to 2 models of arterial injury.

Methods and Results—

Baseline serum CRP levels in CRPtg mice were 18±6 mg/L. CRP levels were undetectable in wild-type mice. Transluminal wire injury led to complete thrombotic occlusion of the femoral artery at 28 days in 75% of CRPtg arteries (6 of 8) compared with 17% (2 of 12) in wild-type mice (
P
<0.05). In a model of arterial photochemical injury, clot formation time was shortened in CRPtg mice; mean time to occlusion was 33±19 minutes compared with 59±19 minutes in wild-type mice (n=10;
P
<0.05).

Conclusions—

Arterial injury in CRPtg mice results in an expedited and higher rate of thrombotic occlusion. This is the first report of a prothrombotic phenotype directly attributable to the presence of human CRP in vivo. Investigation of the inflammatory-thrombotic axis in CRPtg mice may elucidate the prothrombotic actions of CRP in unstable arterial diseases and may pave the way for novel therapeutic interventions for preventing cardiovascular events.
Role of Reactive Oxygen Species in Endothelin-Induced Hypertension
Authors: Sedeek Mona H. , Llinas Maria T. , Drummond Heather , Fortepiani Lourdes , Abram Sean R. , Alexander Barbara T. , Reckelhoff Jane F. , Granger Joey P.
Published: July 2003

Recent reports have indicated that endothelin-induced vasoconstriction in isolated aortic vascular rings may be mediated by the production of superoxide anion. The purpose of this study was to determine the role of superoxide anion in mediating the chronic renal and hypertensive actions of endothelin. Endothelin-1 (5 pmol/kg per minute) was chronically infused into the jugular vein by use of mini-osmotic pump for 9 days in male Sprague-Dawley rats and in rats treated with the superoxide anion scavenger tempol (30 mg/kg per day). Mean arterial pressure in the endothelin-1–treated rats was 141±3 mm Hg, compared with 125±2 mm Hg in control rats. Endothelin-1 increased renal vascular resistance (15.3±2.5 versus 10±1.3 mm Hg/mL per minute) and decreased renal plasma flow (6.5±0.9 versus 8.7±0.7 mL/min) in control rats. Endothelin-1 also significantly increased TBARS in the kidney and urinary 8-isoprostaglandin F
2α
excretion. The increase in arterial pressure in response to endothelin-1 was completely abolished by tempol (127±4 versus 127±4 mm Hg). Tempol also markedly attenuated the renal plasma flow and renal vascular resistance response to endothelin-1. Tempol also significantly decreased the level of 8-isoprostaglandin F
2α
in the endothelin-1–treated rats. Tempol had no effect on arterial pressure or renal hemodynamics in control rats. These data indicate that formation of reactive oxygen species may play an important role in mediating hypertension induced by chronic elevations in endothelin.
Eicosapentaenoic Acid Protects Endothelial Cells Against Anoikis Through Restoration of cFLIP
Authors: Suzuki Takashi , Fukuo Keisuke , Suhara Toshimitsu , Yasuda Osamu , Sato Naoyuki , Takemura Yukihiro , Tsubakimoto Maki , Ogihara Toshio
Published: July 2003

Dietary supplementation with eicosapentaenoic acid (EPA) improves the prognosis of chronic inflammatory diseases, including atherosclerosis. The mechanism underlying these beneficial effects, however, remains to be elucidated. Here we show that EPA protects endothelial cells from anoikis through upregulation of the cellular FLICE (Fas-associating protein with death domain-like interleukin-1–converting enzyme)-inhibitory protein (cFLIP), an endogenous inhibitor of caspase-8. EPA-induced upregulation of cFLIP expression was partially suppressed by the phosphatidylinositol-3-kinase inhibitor wortmannin. Conversely, treatment with insulinlike growth factor-1 (IGF-1), an activator of phosphatidylinositol-3-kinase/Akt signaling, or infection with an adenoviral construct expressing the constitutively active
Akt
gene induced upregulation of cFLIP expression. In addition, pretreatment of endothelial cells with either EPA or IGF-1 protected them from anoikis, suggesting that EPA-induced protection against anoikis is partially mediated through activation of Akt. On the other hand, when endothelial cells were already detached, treatment of these cells with EPA but not with IGF-1 protected them against anoikis. Importantly, EPA restored cFLIP expression without activating Akt signaling in detached endothelial cells, whereas IGF-1 had no effect. Additionally, exogenously restored expression of cFLIP by the tetracycline-regulated adenovirus system protected endothelial cells against anoikis. Furthermore, EPA was protective against the loss of endothelium in an organ culture of rat aortas. These findings suggest that EPA protects against endothelial cell anoikis through restoration of cFLIP expression, which might contribute to the mechanism underlying the beneficial effects of EPA in patients with hypertension.
Contribution of Genetic Factors to Renal Lesions in the Stroke-Prone Spontaneously Hypertensive Rat
Authors: Gigante Bruna , Rubattu Speranza , Stanzione Rosita , Lombardi Alessia , Baldi Alfonso , Baldi Feliciano , Volpe Massimo
Published: July 2003

Stroke-prone spontaneously hypertensive rats (SHRSP) develop renal lesions more frequently than the closely related control strain, the stroke-resistant SHR. The aim of this study was to investigate the contribution of genetic factors to the enhanced susceptibility to renal damage of SHRSP in an SHRSP/SHR F2 intercross by means of a genotype/phenotype cosegregation analysis. For this purpose, 154 6-week-old F2-SHRSP/SHR rats (79 male, 75 female) were fed a stroke-permissive Japanese diet for 4 weeks. Systolic blood pressure (SBP) was recorded at the end of the dietary period. Renal damage was scored from 0 to 3, and 274 genetic markers polymorphic between SHR and SHRSP were genotyped. Linkage of genotype markers to the degree of renal disease was determined by χ
2
test. Experimental threshold level to declare linkage was calculated by QTL cartographer. SBP was not correlated to renal damage (ρ coefficient, 0.201;
P
=NS). Grade 2 and grade 3 lesions were more frequent in male than in female rats (
P
=0.01). Two loci, D1Rat238, on chromosome 1 and the IGF receptor-binding protein 4 (Rbp4g) on chromosome 10, were significantly linked to the degree of renal damage, with SHRSP allele being aggressive at D1Rat238 locus and protective at Rbp4g locus. In male rats only, the SHRSP allele at one locus on chromosome 16, D16Mit2, was associated with a more severe degree of renal disease. Our results demonstrate that in this intercross, susceptibility to renal damage is influenced by several genetic loci acting independently from high blood pressure levels and also shows a sexual dimorphism.
Reduced Endothelial Vascular Relaxation in Growth-Restricted Offspring of Pregnant Rats With Reduced Uterine Perfusion
Authors: Payne Jason A. , Alexander Barbara T. , Khalil Raouf A.
Published: July 2003

Low birth weight as the result of placental insufficiency increases the risk of hypertension in young adults; however, the vascular mechanisms involved are unclear. We tested the hypothesis that intrauterine fetal growth restriction caused by placental insufficiency results in low-birth-weight offspring with impaired endothelium-dependent vascular relaxation, enhanced vasoconstriction, and hypertension. The body weight and arterial pressure were measured in young (4 weeks), adolescent (8 weeks), and adult (12 weeks) male offspring of normal pregnant rats and pregnant rats with reduced uteroplacental perfusion (intrauterine growth-restricted, IUGR), and aortic strips were isolated for measurement of isometric contraction. The body weight was lower whereas the arterial pressure was higher in IUGR than normal rats at 4 weeks (113±3 versus 98±2), 8 weeks (133±3 versus 121±6), and 12 weeks (144±4 versus 131±3 mm Hg). Phe (10
−5
mol/L) caused an increase in active stress that was greater in IUGR than in normal rats at 4 weeks (12.4 versus 7.8), 8 weeks (13.3 versus 8.4), and 12 weeks (14.6 versus 9.0×10
4
N/m
2
). Removal of the endothelium enhanced Phe-induced stress in normal but not IUGR rats. In endothelium-intact strips, acetylcholine (ACh) caused relaxation of Phe contraction and induced nitrite/nitrate production that were smaller in IUGR than normal rats. L-NAME (10
−4
mol/L), which inhibits NO synthase, or ODQ (10
−5
mol/L), which inhibits cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe contraction in normal but not IUGR rats. Thus endothelium-dependent NO-mediated vascular relaxation is inhibited in IUGR offspring of pregnant rats with reduced uteroplacental perfusion, and this may explain the increased vascular constriction and arterial pressure in young adults with low birth weight.
Estrogen or the AT1 Antagonist Olmesartan Reverses the Development of Profound Hypertension in the Congenic mRen2.Lewis Rat
Authors: Chappell Mark C. , Gallagher Patricia E. , Averill David B. , Ferrario Carlos M. , Brosnihan K. Bridget
Published: July 2003

The influence of estrogen on the regulation of cardiovascular function remains a controversial and complex area of investigation. We assessed the effects of estrogen depletion in the congenic mRen(2).Lewis rat, established from the back-cross of the original (mRen2)-27 transgenic onto the Lewis inbred strain. Ovariectomy of heterozygous mRen(2).Lewis at 4 to 5 weeks resulted in a progressive increase in blood pressure compared with the sham surgery congenics at weeks 6 to 11. At 11 weeks, the ovariectomized mRen(2).Lewis (OVX) systolic blood pressure averaged 195±3.7 mm Hg versus 141±4.0 mm Hg for sham. Plasma Angiotensin (Ang) II, serum ACE activity, plasma renin concentration, as well as urinary excretion of Ang II, 8-isoprostane F
2α
, and endothelin-1 were elevated; however, renal mRNA levels of eNOS were suppressed after ovariectomy. Estrogen replacement reduced blood pressure below both the sham and OVX by 11 weeks (125±2.9 mm Hg, n=7,
P
<0.01 versus OVX and sham). Moreover, the AT
1
receptor antagonist olmesartan (CS866; week 12 to 16) essentially normalized blood pressure to 113±5.4 mm Hg (n=6,
P
<0.01 versus OVX and sham). The attenuation of the hypertension was still evident 7 weeks after complete withdrawal of treatment (124±4.1 mm Hg at week 23). In summary, the OVX mRen.2.Lewis exhibited a rapid and sustained increase in blood pressure. Estrogen or olmesartan lowered pressure by a similar extent. We conclude that the ovary exerts considerable influence on the regulation of the blood pressure in the mRen2.Lewis strain, possibly by limiting activation of the renin-angiotensin system.
ATP-Dependent Mechanism for Coordination of Intercellular Ca
2+
Signaling and Renin Secretion in Rat Juxtaglomerular Cells
Authors: Yao Jian , Suwa Michihiro , Li Bing , Kawamura Kazuko , Morioka Tetsuo , Oite Takashi
Published: July 2003

A change in intracellular Ca
2+
is considered to be the common final signaling pathway through which renin secretion is governed. Therefore, information relating to the generation, control, and processing of Ca
2+
signaling in juxtaglomerular cells (JG) will be critical for understanding JG cell behavior. In this study, we investigated the means by which JG cells harmonize their intracellular Ca
2+
signals and explored the potential role of these mechanisms in renin secretion. Mechanical stimulation of a single JG cell initiated propagation of an intercellular Ca
2+
wave to up to 11.9±4.1 surrounding cells, and this was prevented in the presence of the ATP-degrading enzyme, apyrase (1.7±0.7 cells), or by desensitization of purinergic receptors via pretreatment of cells with ATP (1.8±0.9 cells), thus implicating ATP as a mediator responsible for the propagation of intercellular Ca
2+
signaling. Consistent with this, JG cells were demonstrated not to express the gap junction protein connexin43, and neither did they possess functional gap junction communication. Furthermore, massive mechanical stretching of JG cells elicited a 3-fold increase in ATP release. Administration of ATP into isolated perfused rat kidneys induced a rapid, potent, and persistent inhibition of renin secretion, together with a transient elevation of renal vascular resistance. ATP (1 mmol/L) caused up to 79% reduction of the renin secretion activated by lowering the renal perfusion flow (
P
<0.01). Taken together, our results indicate that under mechanical stimulation, ATP functions as a paracellular mediator to regulate renin secretion, possibly through modulating intra- and intercellular Ca
2+
signals.
Pressure-Induced Vascular Activation of Nuclear Factor-κB
Authors: Lemarié Catherine A. , Esposito Bruno , Tedgui Alain , Lehoux Stéphanie
Published: July 2003

The effects of mechanical factors on nuclear factor (NF)-κB activation and its potential functional roles have been very little explored in the intact vessel. Thus, we chose to study the regulation of NF-κB by intraluminal pressure using an organ culture model of mouse carotid arteries maintained at 80 or 150 mm Hg during 24 hours. Gel shift analysis revealed an increase in the DNA-binding capacity of NF-κB in vessels at high pressure compared with vessels at normal pressure (304±49%;
P
<0.001). This coincided with reduced levels of the endogenous NF-κB inhibitor IκBα in arteries at 150 mm Hg (52±7%;
P
<0.001), as detected by Western blot. To study the functional role of the pressure-induced activation of NF-κB, we evaluated the rate of apoptosis (TUNEL method) in carotid arteries cultured with or without an inhibitor peptide blocking nuclear translocation of NF-κB. No apoptosis was detected in control arteries either at 80 or 150 mm Hg. However, in the presence of the NF-κB inhibitor peptide, we observed apoptosis in vessels at 80 mm Hg (5±1%;
P
<0.001 versus untreated controls), which was markedly increased in vessels at 150 mm Hg (14±2%;
P
<0.001). These results were corroborated by immunohistochemical analysis showing positive staining for cleaved caspase 3 in vessels at 80 mm Hg treated with the NF-κB inhibitor peptide, which was additionally enhanced in treated vessels at 150 mm Hg. Our findings demonstrate that high intraluminal pressure activates NF-κB in arteries. Moreover, the activation of NF-κB seems to play a key role in preventing apoptosis in vascular cells, especially when vessels are exposed to high intraluminal pressure.
Type 5 Adenylyl Cyclase Disruption Alters Not Only Sympathetic But Also Parasympathetic and Calcium-Mediated Cardiac Regulation
Authors: Okumura Satoshi , Kawabe Jun-ichi , Yatani Atsuko , Takagi Gen , Lee Ming-Chih , Hong Chull , Liu Jing , Takagi Ikuyo , Sadoshima Junichi , Vatner Dorothy E. , Vatner Stephen F. , Ishikawa Yoshihiro
Published: July 2003

In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (
AC5
−/−
), a major cardiac isoform, there was no compensatory increase in other isoforms of AC in the heart. Both basal and isoproterenol (ISO)-stimulated AC activities were decreased by 30% to 40% in cardiac membranes. The reduced AC activity did not affect cardiac function (left ventricular ejection fraction [LVEF]) at baseline. However, increases in LVEF after ISO were significantly attenuated in
AC5
−/−
(
P
<0.05, n=11). Paradoxically, conscious
AC5
−/−
mice had a higher heart rate compared with wild-type (WT) mice (613±8 versus 523±11 bpm,
P
<0.01, n=14 to 15). Muscarinic agonists decreased AC activity, LVEF, and heart rate more in WT than in
AC5
−/−
. In addition, baroreflex-mediated, ie, neuronally regulated, bradycardia after phenylephrine was also attenuated in
AC5
−/−
. The carbachol-activated outward potassium current (at −40 mV) normalized to cell capacitance in
AC5
−/−
(2.6±0.4 pA/pF, n=16) was similar to WT (2.9±0.3 pA/pF, n=27), but calcium (Ca
2+
)-mediated inhibition of AC activity and Ca
2+
channel function were diminished in
AC5
−/−
. Thus,
AC5
−/−
attenuates sympathetic responsiveness and also impairs parasympathetic and Ca
2+
-mediated regulation of the heart, indicating that those actions are not only regulated at the level of the receptor and G-protein but also at the level of type 5 AC.
Matrix and Bioabsorbable Polymeric Coils Accelerate Healing of Intracranial Aneurysms
Authors: Murayama Yuichi , Tateshima Satoshi , Gonzalez Nestor R. , Vinuela Fernando
Published: July 2003

Background and Purpose—

Acceleration of intra-aneurysmal clot organization and fibrosis may be a solution to preventing aneurysm recanalization after endovascular treatment. The purpose of this study was to evaluate the short-term efficacy and long-term safety of the new Matrix coil system.

Methods—

Matrix coils consist of thin platinum coils covered with a bioabsorbable, polymeric material (polyglycolic acid/lactide). Fifty-two experimental aneurysms were created in 26 swine. All of the aneurysms were tightly packed with Matrix or Guglielmi detachable coils (GDC). Comparative angiographic and histopathologic data were analyzed at 2 weeks (n=14), 3 months (n=6), and 6 months (n=6) after embolization.

Results—

Three aneurysms treated with GDC ruptured despite tight packing. No recanalization or rupturing was observed in the aneurysms embolized with Matrix coils. At 14 days after embolization, the aneurysms treated with Matrix coils exhibited a more extensive area of organized thrombus when compared with the aneurysms treated with GDC (87% versus 75%,
P
=0.008, n=11). At 3 months, both Matrix and GDC-treated aneurysms demonstrated complete clot organization. Neck tissue thickness was higher in Matrix-treated aneurysms at 14 days and 3 months, but not at 6 months. No untoward parent artery stenosis was observed in aneurysms treated with Matrix during follow-up. The angiographic cross-sectional area of the Matrix-treated aneurysms was smaller than those treated with GDC at the 3 months.

Conclusion—

Matrix accelerated aneurysm fibrosis and neointima formation without parent artery stenosis. The Matrix system might prevent aneurysmal recanalization after endovascular treatment of cerebral aneurysms.
The Development of Communicative Gestures in Japanese Infants
Authors: Blake Joanna , Osborne Patricia , Cabral Marlene , Gluck Pamela
Published: July 2003

Twelve Japanese infant-mother dyads were video-recorded at home in naturalistic interaction approximately every two weeks at varying ages between 9 and 14 months. Changes in their gestural repertoire that were similar to other groups studied previously were: an increase over sessions in Comment gestures, namely pointing but not showing, and a decrease in overall Request gestures, particularly reaching. Request gestures involving cognizance of agency increased, however. Increases in Object exchange gestures and decreases in Protest/Rejection and Emotive gestures found in previous studies were not replicated in this group. Agency gestures after 12 months were related to number of words understood, as reported on the JCDI. There was good agreement on the whole between gestures reported by mothers on the JCDI and the same gestures observed directly. These results provide some support for the universality of key gestural changes considered important for language acquisition.
The Acquisition of Temporal Event Sequencing: A Cross-Linguistic Study Using an Elicited Imitation Task
Authors: Winskel Heather
Published: July 2003

Forty children aged between 3;6 and 7;6 years from each of three languages, English, Thai and Lisu, were asked to repeat sentences containing the bi-referential relations signalled by then, before, after, when, while, at the same time, until and since. Performance on this elicited imitation task revealed that, across languages, then has a relatively early acquisition and since has a relatively late acquisition. Language specific effects were also found, namely a relatively early acquisition of until in Lisu, and a relatively early acquisition of before and late acquisition of after in Thai. Analysis of substitution errors revealed common substitutions across languages for and and when, and of mono- for bi-referential responses. There was qualified support for the predictions that sequentiality ( then, before, after) occurs prior to simultaneity ( while, at the same time), and for a relatively late acquisition of `sequence and duration' ( since, until).
Psychiatry Beyond the Asylum: The Origins of German Military Psychiatry Before World War I
Authors: Lengwiler Martin
Published: July 2003

This study examines the co-operation between psychiatry and the army in Germany between 1870 and 1914, leading to the establishment of military psychiatry as an independent discipline. Arguing that military psychiatry played a key role in the history of modern clinical psychiatry, the paper points out how the first generation of military psychiatrists developed innovative diagnostic technologies, such as the intelligence test, and established crucial institutional alliances between psychiatric clinics, military authorities, and local and national administrations. The early history of military psychiatry marks the transition of psychiatry from a medical sub-discipline to a more generally applicable `social technology' assessing the borderline between normality and abnormality in multiple social contexts.
Two Registers of Madness in Enlightenment Britain. Part 2
Authors: Laffey Paul
Published: July 2003

In Part 1 of this essay, I argued that in Augustan and Georgian England it was widely understood that madness could have two more-or-less distinct meanings. `Moral' madness was the subject's own fault, and he/she remained accountable for actions commissioned under its effects. The `morally' mad individual's thoughts and actions were understood to be self-directed; at base, in moral madness, delusional ideas arose in the mind, and by definition remained within the moral province of the individual. By contrast, in `real' madness, the sufferer was the passive recipient of body-based sickness. Correspondingly, he/she was understood to be innocent, but paid for this exculpation of moral accountability by surrendering full personhood. In Part 2, I shall examine various ways in which eighteenth-century Britons approached and assessed insanity's two meanings. I shall then remark on the late eighteenth-century attempt to develop a psychological (i.e., moral) rendering of insanity's characteristics and its treatment.
Georg Groddeck: Originality and Exclusion
Authors: Avila Lazslo Antonio , Winston Mark
Published: July 2003

This paper reviews Georg Groddeck's contribution to medicine and the other human sciences. His creative and original thinking, which was both radical and provocative, deserves a fresh appraisal. I present some of the ideas he developed in his seminal `Psychic Conditioning and the Psychoanalytic Treatment of Organic Disorders', published in German in 1917, which may be considered as the foundation of modern psychosomatic medicine. In this text, Groddeck proposed that all diseases contain symbolic meanings which need to be unveiled in order to bring about mental and physical transformation. He held that unconscious processes determine how susceptible we are to diseases, the nature of these diseases, and the conditions for our recovery.

Groddeck's work has been neglected, and I suggest that his radical ideas about the connection between the mind and the body make his work simultaneously difficult to assimilate and essential for expanding this frontier of knowledge.
The Airborne Transmission of Infection in Hospital Buildings: Fact or Fiction?
Authors: Beggs C. B.
Published: July 2003

Airborne transmission is known to be the route of infection for diseases such as tuberculosis and aspergillosis. It has also been implicated in nosocomial outbreaks of MRSA, Acinetobacter spp. and Pseudomonas spp. Despite this there is much scepticism about the role that airborne transmission plays in nosocomial outbreaks. This paper investigates the airborne spread of infection in hospital buildings, and evaluates the extent to which it is a problem. It is concluded that although contact-spread is the principle route of transmission for most infections, the contribution of airborne micro-organisms to the spread of infection is likely to be greater than is currently recognised. This is partly because many airborne micro-organisms remain viable while being non-culturable, with the result that they are not detected, and also because some infections arising from contact transmission involve the airborne transportation of micro-organisms onto inanimate surfaces.
The Hospital Tap Water System as a Source of Nosocomial Legionella Infections for Staff Members and Patients
Authors: Pancer Katarzyna , Stypułkowska Hanna , Krogulska Bozena , Matuszewska Renata
Published: July 2003

The number of nosocomial infections due to Legionella pneumophila is probably underestimated in many countries. The aim of the present study was to estimate the risk of legionellosis due to L. pneumophila sg 1 and sg 2-14 for patients and hospitals staff members from the water system in a Polish hospital. Samples were taken from hospital tap water systems before and after thermal disinfection (80°C) when a reduction in Legionella positive samples of 91-40% was found. L. pneumophila sg 1 was only detected in water samples taken before disinfection. Simultaneously, serum samples from staff members were collected and examined by micro-agglutination tests using antigens prepared from type strains of L. pneumophila 10 serogroups and four strains of L. pneumophila sg 2-14 isolated from the hospital water system. The level of antibodies to L. pneumophila sg 1 was insignificant. However a high (≥256) titre of antibodies was found to some type L. pneumophila as well as to environmental L. pneumophila strains. The results of this study show a possible risk to hospital staff members' from infection by Legionella other than L. pneumophila sg 1. It was demonstrated that the high number of legionellae in water distribution systems can be successfully reduced by heat treatment.
Risks Caused by Airborne Microbes in Hospitals - Source Control is Important
Authors: Kalliokoski Pentti
Published: July 2003

Effective source control is the key issue in all matters concerning hygiene and hospitals are by no means an exception. Besides taking steps to provide good isolation, this means that local ventilation exhausts and isolating enclosures should be used if there are obvious or even probable sources. Quick repair of moisture damage from whatever source is important. The control of microbes dispersed by the personnel in a hospital is also controlled most effectively by wearing special protective clothing and restricting it to the environment where it is needed. Even though it is generally admitted by the medical professionals that prevention is highly cost-effective, this is, nevertheless, commonly forgotten in hospitals.