bluuebunny/crossref_metadata_2025 huggingface dataset:
GENERATING MULTISCROLL CHAOTIC ATTRACTORS: THEORIES, METHODS AND APPLICATIONS
Authors: LÜ JINHU , CHEN GUANRONG
Published: June 2006

Over the last two decades, theoretical design and circuit implementation of various chaos generators have been a focal subject of increasing interest due to their promising applications in various real-world chaos-based technologies and information systems. In particular, generating complex multiscroll chaotic attractors via simple electronic circuits has seen rapid development. This article offers an overview of the subject on multiscroll chaotic attractors generation, including some fundamental theories, design methodologies, circuit implementations and practical applications. More precisely, the article first describes some effective design methods using piecewise-linear functions, cellular neural networks, nonlinear modulating functions, circuit component design, switching manifolds, multifolded tori formation, and so on. Based on different approaches, computer simulation and circuit implementation of various multiscroll chaotic attractors are then discussed in detail, with some theoretical proofs and laboratory experiments presented for verification and demonstration. It is then followed by some discussion on potential applications of multiscroll chaotic attractors, including secure and digital communications, synchronous prediction, random bit generation, and so on. The article is finally concluded with some future research outlooks, putting the important subject into engineering perspective.
A SYSTEM OF REACTION–DIFFUSION EQUATIONS IN THE UNSTIRRED CHEMOSTAT WITH AN INHIBITOR
Authors: NIE HUA , WU JIANHUA
Published: June 2006

A system of reaction–diffusion equations is considered in the unstirred chemostat with an inhibitor. Global structure of the coexistence solutions and their local stability are established. The asymptotic behavior of the system is given as a function of the parameters, and it is determined when neither, one, or both competing populations survive. Finally, the results of some numerical simulations indicate that the global stability of the steady-state solutions is possible. The main tools for our investigations are the maximum principle, monotone method and global bifurcation theory.
A COMMENT ON A NONIDEAL CENTRIFUGAL VIBRATOR MACHINE BEHAVIOR WITH SOFT AND HARD SPRINGS
Authors: DANTAS MÁRCIO JOSÉ HORTA , BALTHAZAR JOSÉ MANOEL
Published: June 2006

This paper concerns a type of rotating machine (centrifugal vibrator), which is supported on a nonlinear spring. This is a nonideal kind of mechanical system. The goal of the present work is to show the striking differences between the cases where we take into account soft and hard spring types. For soft spring, we prove the existence of homoclinic chaos. By using the Melnikov's Method, we show the existence of an interval with the following property: if a certain parameter belongs to this interval, then we have chaotic behavior; otherwise, this does not happen. Furthermore, if we use an appropriate damping coefficient, the chaotic behavior can be avoided. For hard spring, we prove the existence of Hopf's Bifurcation, by using reduction to Center Manifolds and the Bezout Theorem (a classical result about algebraic plane curves).
Mitochondrial Retrograde Signaling
Authors: Liu Zhengchang , Butow Ronald A.
Published: June 2006

Mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus under normal and pathophysiological conditions. The best understood of such pathways is retrograde signaling in the budding yeast Saccharomyces cerevisiae. It involves multiple factors that sense and transmit mitochondrial signals to effect changes in nuclear gene expression; these changes lead to a reconfiguration of metabolism to accommodate cells to defects in mitochondria. Analysis of regulatory factors has provided us with a mechanistic view of regulation of retrograde signaling. Here we review advances in the yeast retrograde signaling pathway and highlight its regulatory factors and regulatory mechanisms, its physiological functions, and its connection to nutrient sensing, TOR signaling, and aging.
Induction of Competence Regulons as a General Response to Stress in Gram-Positive Bacteria
Authors: Claverys Jean-Pierre , Prudhomme Marc , Martin Bernard
Published: June 2006

Bacterial transformation, a programmed mechanism for genetic exchange originally discovered in Streptococcus pneumoniae, is widespread in bacteria. It is based on the uptake and integration of exogenous DNA into the recipient genome. This review examines whether induction of competence for genetic transformation is a general response to stress in gram-positive bacteria. It compares data obtained with bacteria chosen for their different lifestyles, the soil-dweller Bacillus subtilis and the major human pathogen S. pneumoniae. The review focuses on the relationship between competence and other global responses in B. subtilis, as well as on recent evidence for competence induction in response to DNA damage or antibiotics and for the ability of S. pneumoniae to use competence as a substitute for SOS. This comparison reveals that the two species use different fitness-enhancing strategies in response to stress conditions. Whereas B. subtilis combines competence and SOS induction, S. pneumoniae relies only on competence to generate genetic diversity through transformation.
Transcription factor FOXF1 regulates growth hormone variant gene expression
Authors: Lomenick Jefferson P. , Hubert Michael A. , Handwerger Stuart
Published: June 2006

Deletion analysis of the human growth hormone variant (GHV) promoter in transient transfection studies in BeWo choriocarcinoma and HepG2 cells indicated that the region extending from nt −158/+57 retained full transcriptional activity. DNase I footprint analysis of the fragment revealed a protected region at nt −82/−77, which is in a putative FOXF1/FOXF2 binding site. Supershift assays using an antiserum to human FOXF1 demonstrated that the protected region binds FOXF1. Overexpression of FOXF1 in BeWo and HepG2 cells induced the GHV promoter, whereas overexpression of FOXF2 was without effect. Mutagenesis of the FOXF1/FOXF2 site reduced basal promoter activity by 50–60% and markedly attenuated transactivation of the promoter by FOXF1. These studies indicate that FOXF1 induces GHV expression by interaction with a FOXF1/FOXF2 cis-element in the proximal promoter.
Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion
Authors: Christopher Michael , Rantzau Christian , Chen Zhi-Ping , Snow Rodney , Kemp Bruce , Alford Frank P.
Published: June 2006

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-β-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FAOX) blockade by methylpalmoxirate (MP; 5 × 12 hourly 10 mg/kg doses). During the basal equilibrium period (0–150 min), fasting dogs ( n = 8) were infused with [3-3H]glucose followed by either 2-h saline or AICAR (1.5–2.0 mg·kg−1·min−1) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FAOX blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (Rd tissue), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCRg) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC∼pSer221) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and Rd tissue responses were markedly attenuated, but MCRg and GF increased significantly. SkM substrates were unchanged, but ACC∼pSer221 rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FAox blockade.
Filopodia formation via a specific Eph family member and PI3K in immortalized cholangiocytes
Authors: Fukushima Koji , Ueno Yoshiyuki , Inoue Jun , Kanno Noriatsu , Shimosegawa Tooru
Published: June 2006

Biliary ducts are lined with epithelial cells, which consist of at least two types of cholangiocytes, small and large. In contrast to large cholangiocytes, which are involved in secretion, the role of small cholangiocytes has not been elucidated. To address this question, we analyzed the migration-based characteristics of these cells that may help to understand their functions in vivo. Interestingly, dibutyryl cAMP induced marked filopodia formation and cdc42 activation in the normal mouse cholangiocyte (NMC)-small cell line compared with the NMC-large cell line. Analysis of members of the ephrin (Eph)A family of guidance molecules revealed a distinct subcellular distribution of EphA5 and EphA8 members: EphA8 was equally expressed by both cell types and localized subcellularly in peripheral cell membranes, whereas EphA5 was expressed predominantly in NMC-S and localized to filopodia. Moreover, cAMP-inducible filopodia formation in these cells was abrogated using EphA5 short interfering RNA. Finally, we found that the Rho family GTPase cdc42 was activated in a manner dependent on EphA5. Wortmannin, a specific inhibitor of phosphotidylinositol 3-kinase (PI3K), abolished the activation of cdc42 dependent on EphA5, suggesting the involvement of PI3K in the EphA5-cdc42 pathway. Together, our findings suggest a cAMP-EphA5-cdc42-dependent regulation of small cholangiocyte migration, which are anticipated to facilitate the understanding of the nature of cholangiocytes and to explain certain general aspects of cAMP-cdc42 activation signaling with regard to cell morphogenesis.
Hyperoxia enhances metaboreflex sensitivity during static exercise in humans
Authors: Houssière Anne , Najem Boutaina , Cuylits Nicolas , Cuypers Sophie , Naeije Robert , van de Borne Philippe
Published: June 2006

Peripheral chemoreflex inhibition with hyperoxia decreases sympathetic nerve traffic to muscle circulation [muscle sympathetic nerve activity (MSNA)]. Hyperoxia also decreases lactate production during exercise. However, hyperoxia markedly increases the activation of sensory endings in skeletal muscle in animal studies. We tested the hypothesis that hyperoxia increases the MSNA and mean blood pressure (MBP) responses to isometric exercise. The effects of breathing 21% and 100% oxygen at rest and during isometric handgrip at 30% of maximal voluntary contraction on MSNA, heart rate (HR), MBP, blood lactate (BL), and arterial O2saturation (SaO2) were determined in 12 healthy men. The isometric handgrips were followed by 3 min of postexercise circulatory arrest (PE-CA) to allow metaboreflex activation in the absence of other reflex mechanisms. Hyperoxia lowered resting MSNA, HR, MBP, and BL but increased SaO2compared with normoxia (all P < 0.05). MSNA and MBP increased more when exercise was performed in hyperoxia than in normoxia (MSNA: hyperoxic exercise, 255 ± 100% vs. normoxic exercise, 211 ± 80%, P = 0.04; and MBP: hyperoxic exercise, 33 ± 9 mmHg vs. normoxic exercise, 26 ± 10 mmHg, P = 0.03). During PE-CA, MSNA and MBP remained elevated (both P < 0.05) and to a larger extent during hyperoxia than normoxia ( P < 0.05). Hyperoxia enhances the sympathetic and blood pressure (BP) reactivity to metaboreflex activation. This is due to an increase in metaboreflex sensitivity by hyperoxia that overrules the sympathoinhibitory and BP lowering effects of chemoreflex inhibition. This occurs despite a reduced lactic acid production.
Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury
Authors: Simon Brett A. , Easley R. Blaine , Grigoryev Dmitry N. , Ma Shwu-Fan , Ye Shui Q. , Lavoie Tera , Tuder Rubin M. , Garcia Joe G. N.
Published: June 2006

Human acute lung injury is characterized by heterogeneous tissue involvement, leading to the potential for extremes of mechanical stress and tissue injury when mechanical ventilation, required to support critically ill patients, is employed. Our goal was to establish whether regional cellular responses to these disparate local mechanical conditions could be determined as a novel approach toward understanding the mechanism of development of ventilator-associated lung injury. We utilized cross-species genomic microarrays in a unilateral model of ventilator-associated lung injury in anesthetized dogs to assess regional cellular responses to local mechanical conditions that potentially contribute pathogenic mechanisms of injury. Highly significant regional differences in gene expression were observed between lung apex/base regions as well as between gravitationally dependent/nondependent regions of the base, with 367 and 1,544 genes differentially regulated between these regions, respectively. Major functional groupings of differentially regulated genes included inflammation and immune responses, cell proliferation, adhesion, signaling, and apoptosis. Expression of genes encoding both acute lung injury-associated inflammatory cytokines and protective acute response genes were markedly different in the nondependent compared with the dependent regions of the lung base. We conclude that there are significant differences in the local responses to stress within the lung, and consequently, insights into the cellular responses that contribute to ventilator-associated lung injury development must be sought in the context of the mechanical heterogeneity that characterizes this syndrome.
Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs
Authors: Cardinal René , Pagé Pierre , Vermeulen Michel , Bouchard Caroline , Ardell Jeffrey L. , Foreman Robert D. , Armour J. Andrew
Published: June 2006

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.
Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats
Authors: Wangensteen Rosemary , Rodríguez-Gómez Isabel , Moreno Juan Manuel , Álvarez-Guerra Miriam , Osuna Antonio , Vargas Félix
Published: June 2006

This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the hemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7-NI), an inhibitor of nNOS, were studied. Six groups of male Wistar rats were used: control, 7-NI (30 mg·kg−1·day−1by gavage), T450, T475 (50 or 75 μg thyroxine·rat−1·day−1, respectively), T450+7-NI, and T475+7-NI. All treatments were maintained for 4 wk. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, pulse pressure (PP), and HR were measured in conscious rats, and morphological, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T475 and control rats was analyzed by Western blot analysis. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg iv) was used to evaluate the sympathetic contribution to BP in T475 and T475+7-NI rats. T4produced an increased hypothalamic nNOS expression and dose-related increases in blood pressure (BP), HR, and PP vs. control rats. 7-NI did not modify BP or any other hemodynamic variable in normal rats. However, 7-NI produced a marked reduction in BP, HR, PP, and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T475 group. Pentolinium produced a greater MAP decrease in the T475+7-NI than in the T475 group. In conclusion, administration of 7-NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.
Continued divergence in V̇o2 maxof rats artificially selected for running endurance is mediated by greater convective blood O2delivery
Authors: Gonzalez Norberto C. , Kirkton Scott D. , Howlett Richard A. , Britton Steven L. , Koch Lauren G. , Wagner Harrieth E. , Wagner Peter D.
Published: June 2006

We previously showed that after seven generations of artificial selection of rats for running capacity, maximal O2uptake (V̇o2 max) was 12% greater in high-capacity (HCR) than in low-capacity runners (LCR). This difference was due exclusively to a greater O2uptake and utilization by skeletal muscle of HCR, without differences between lines in convective O2delivery to muscle by the cardiopulmonary system (Q̇o2 max). The present study in generation 15 (G15) female rats tested the hypothesis that continuing improvement in skeletal muscle O2transfer must be accompanied by augmentation in Q̇o2 maxto support V̇o2 maxof HCR. Systemic O2transport was studied during maximal normoxic and hypoxic exercise (inspired Po2∼70 Torr). V̇o2 maxdivergence between lines increased because of both improvement in HCR and deterioration in LCR: normoxic V̇o2 maxwas 50% higher in HCR than LCR. The greater V̇o2 maxin HCR was accompanied by a 41% increase in Q̇o2 max: 96.1 ± 4.0 in HCR vs. 68.1 ± 2.5 ml stpd O2·min−1·kg−1in LCR ( P < 0.01) during normoxia. The greater G15 Q̇o2 maxof HCR was due to a 48% greater stroke volume than LCR. Although tissue O2diffusive conductance continued to increase in HCR, tissue O2extraction was not significantly different from LCR at G15, because of the offsetting effect of greater HCR blood flow on tissue O2extraction. These results indicate that continuing divergence in V̇o2 maxbetween lines occurs largely as a consequence of changes in the capacity to deliver O2to the exercising muscle.
Effects of Spatial Attention on Contrast Response Functions in Macaque Area V4
Authors: Williford Tori , Maunsell John H. R.
Published: June 2006

Previous single-unit studies of visual cortex have reported that spatial attention modulates responses to different orientations and directions proportionally, such that it does not change the width of tuning functions for these properties. Other studies have suggested that spatial attention causes a leftward shift in contrast response functions, such that its effects on responses to stimuli of different contrasts are not proportional. We have further explored the effects of attention on stimulus-response functions by measuring the responses of 131 individual V4 neurons in two monkeys while they did a task that controlled their spatial attention. Each neuron was tested with a set of stimuli that spanned complete ranges of orientation and contrast during different states of attention. Consistent with earlier reports, attention scaled responses to preferred and nonpreferred orientations proportionally. However, we did not find compelling evidence that the effects were best described by a leftward shift of the contrast response function. The modulation of neuronal responses by attention was well described by either a leftward shift or proportional scaling of the contrast response function. Consideration of differences in experimental design and analysis that may have contributed to this discrepancy suggests that it was premature to exclude a proportional scaling of responses to different contrasts by attention in favor of a leftward shift of contrast response functions. The current results reopen the possibility that the effects of attention on stimulus-response functions are well described by a single proportional increase in a neuron's response to all stimuli.
Naltrexone Implants – Duration, Tolerability and Clinical Usefulness
Authors: Waal Helge , Frogopsahl Grethe , Olsen Linda , Christophersen Asbjørg S. , Mørland Jørg
Published: June 2006

Naltrexone blocks opioid effects effectively, but poor compliance limits the clinical usefulness in the treatment of opioid dependence. Long-acting implanted formulations might increase the clinical feasibility. Several implants have been produced, but few clinical reports have been published. This paper describes an open trial with an Australian implant. This implant is claimed to have duration of up to six months with double implants and acceptable levels of side effects. This was explored in the present pilot study with 13 opioid-dependent patients. By single implant of 1.8 g naltrexone the duration judged by naltrexone plasma levels above 1 ng/ml naltrexone was between 2 and 4 months. Double implants maintained such plasma levels for 5–6.5 months. Clinically, the implants appeared promising. Side effects were minimal. During the period with adequate plasma levels of naltrexone, use of opioids was absent and use of other psychoactive drugs reduced. At 1-year follow-up, the patients rated the implants highly positively.
Hepatitis C Virus Infection among Injecting Drug Users in the Czech Republic – Prevalence and Associated Factors
Authors: Zabransky Tomas , Mravcik Viktor , Korcisova Blanka , Rehak Vratislav
Published: June 2006

Aim: To determine the prevalence of, and factors associated with, hepatitis C virus (HCV) infection in the population of Czech injecting drug users (IDUs). Design: Multicentric cross-sectional study. Setting: A convenience sample of injecting drug users was recruited using the snowball sampling method. Participants: Sample of 760 IDUs from 9 different Czech regions. Measurement: We used one-drop instant blood tests to determine the anti-HCV antibodies status; a structured questionnaire was completed during the interview with the researcher. We calculated the ratio of positive findings and performed univariate analyses of correlations between predictors and independent variables. Finally, we created a logistic regression model that controlled for age, region of residence, reported sharing of injection paraphernalia, and length of injection drug use and for the interaction between length of injection use and imprisonmentin order to assess the predictive value of imprisonment in an individual’s history. Findings: 226 participants (29.74% of the tested sample) were found to be anti-HCV positive. After adjusting for the sensitivity of the test, the ‘true proportion’ was 34.97% (95% CI: 31.56–38.35). Many correlated independent variables were found in the univariate analyses. In our logistic regression model, we have found that imprisonment increases the odds of being anti-HCV positive by a factor of 4.3. Conclusion: Anti-HCV seroprevalence remains relatively low in the Czech IDUs population compared to similar populations in the developed countries. Regional differences exist in anti-HCV prevalence within the Czech Republic. The strong association of anti-HCV prevalence with imprisonment history when controlled for other potentially clinically important factors suggests the need for more effective preventive measures in Czech prisons.
Posttransplant Kaposi’s Sarcoma Restricted to the Site of a Previous Deep Venous Thrombosis: Abrupt Onset after Withdrawal of Sirolimus
Authors: González-López Marcos A. , Rodrigo Emilio , González-Vela M. Carmen , Fernández-Llaca Héctor , Arias-Rodríguez Manuel A. , Val-Bernal J. Fernando
Published: June 2006

Kaposi’s sarcoma (KS) is an angioproliferative neoplasia associated with human herpesvirus 8 (HHV-8) infection. HHV-8 generates KS by means of the secretion of vascular endothelial growth factor (VEGF) andup-regulation of VEGF receptor, KDR, in endothelial cells. We report a case of KS in a 72-year-old male with a renal transplant who had received immunosuppressant drugs including sirolimus, mycophenolate mofetil, tacrolimus and steroids. KS developed 11 months after transplantation, in relation to deep venous thrombosis and withdrawal of sirolimus due to toxicity. Multiple purple papules and nodules were observed exclusively in the limb affected by thrombosis. Diagnosis of KS was confirmed by biopsy. Progressive withdrawal of prednisone was accompanied by full remission of the tumour. The thrombosis and withdrawal of sirolimus may have acted as cofactors in the development of KS, favouring the activation of the VEGF/KDR autocrine loop. Our experience contributes to further evidence that sirolimus may protect against KS.
Dysregulation of the Ubiquitin-Proteasome System in Human Carotid Atherosclerosis
Authors: Versari Daniele , Herrmann Joerg , Gössl Mario , Mannheim Dallit , Sattler Katherine , Meyer Fredric B. , Lerman Lilach O. , Lerman Amir
Published: June 2006

Objective—The ubiquitin-proteasome system is the principal degradation route of intracellular and oxidized proteins, thus regulating many cellular processes conceivably important for atherosclerosis. The aim of this study was to evaluate the activity of ubiquitin-proteasome system in human carotid artery plaques in relation to oxidative stress and clinical manifestation.

Methods and Results—In carotid endarterectomy specimens from 83 asymptomatic and 94 symptomatic patients, content of ubiquitin, ubiquitin conjugates, matrix metalloproteases, and NADPH-oxidase-p67 was evaluated by immunoblotting; proteolytic proteasome activity by fluorometric assay; single and double immunostaining for ubiquitin conjugates, 3-nitrotyrosine, apoptosis, smooth muscle α-actin, and macrophage CD-68, as well as Sirius Red staining for collagen were performed. Compared with asymptomatic patients, symptomatic patients showed a more unstable plaque phenotype, an increased degree of apoptosis, a significantly higher ubiquitin conjugates content (17.72±1.36 versus 10.99±1.04;P<0.001), and lower proteasome activity (5.01±0.70 versus 9.41±1.19 nmol AMC/mg protein/min;P<0.01). Ubiquitin conjugates content was directly correlated to NADPH-p67 and degree of apoptosis. Immunostaining revealed colocalization of ubiquitin conjugates and 3-nitrotyrosine, and accumulation of ubiquitin conjugates in smooth muscle cells and macrophages.

Conclusions—In human carotid plaques increased oxidative stress is associated with inhibition of the proteasome activity and accumulation of ubiquitin conjugates, particularly in symptomatic patients. These results suggest a possible role of the ubiquitin-proteasome system in influencing plaque stability.
IL-20 Is Expressed in Atherosclerosis Plaques and Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Chen Wei-Yu , Cheng Bor-Chih , Jiang Meei-Jyh , Hsieh Mei-Yi , Chang Ming-Shi
Published: June 2006

Objective—

Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro- or antiatherogenic factors. Interleukin-20 (IL-20) belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis. However, the association between IL-20 and atherosclerosis is undetermined. Therefore, we sought to investigate whether IL-20 is associated with atherosclerosis.

Methods and Results—

We examined the expression of IL-20 and its receptor complex IL-20R1/IL-20R2 in atherosclerotic lesions of humans and mice using immunohistochemical staining. IL-20 was expressed in macrophage-rich areas. Both IL-20 and IL-20R1/IL-20R2 were expressed by endothelial cells lining the intimal microvessels, vasa vasorum, but rarely in nonatherosclerotic arteries. We used reverse-transcription polymerase chain reaction to analyze gene expression. IL-20 transcripts increased in hypoxic monocytes and monocytes treated with oxidized low-density lipoprotein. The expression of IL-20R1 and IL-20R2 was also upregulated by human umbilical vein endothelial cells in response to hypoxic treatment. Incubating IL-20 with human umbilical vein endothelial cells upregulated CXCL9 and CXCL11 transcripts. Furthermore, in vivo administration of IL-20 expression vector using intramuscular electroporation promoted atherosclerosis in apolipoprotein E-deficient mice.

Conclusions—

Our data suggest that IL-20 is a proatherogenic cytokine that contributes to the progression of atherosclerosis.
Integrin–Matrix Interactions in the Cerebral Microvasculature
Authors: del Zoppo Gregory J. , Milner Richard
Published: June 2006

The integrity of all organ systems requires faithful interaction between its component cells and the extracellular matrix (ECM). In the central nervous system (CNS), matrix adhesion receptors are uniquely expressed by the cells comprising the microvascular compartment, and by neurons and their supporting glial cells. Cells within the cerebral microvasculature express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Capillaries of the cerebral microvasculature consist of the luminal endothelium, which is separated from circumferential astrocyte end-feet by the intervening ECM of the basal lamina. Endothelial cells and astrocytes cooperate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells, and oligodendroglia. Significant alterations in both cellular adhesion receptors and their ligands occur under the conditions of focal cerebral ischemia, multiple sclerosis (MS) and the modeled condition experimental autoimmune encephalomyelitis (EAE), certain tumors of the CNS, and arteriovenous malformations (AVMs). The changes in matrix adhesion receptor expression in these conditions support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood–brain permeability barrier, and that modulation of these receptors contribute to alterations in the barrier during brain injury. This review examines current information about cell adhesion receptor expression within the cerebral microvasculature and surrounding tissue, and their potential roles during the vascular responses to local injury.
Changes in Metabolic Syndrome Variables Since Childhood in Prehypertensive and Hypertensive Subjects
Authors: Srinivasan Sathanur R. , Myers Leann , Berenson Gerald S.
Published: June 2006

That essential hypertension is associated with metabolic syndrome is known. However, information is scant regarding the course of development of adverse levels of blood pressure and other risk variables of metabolic syndrome in youth at risk for developing hypertension. This aspect was studied, retrospectively, in a community-based cohort of normotensive (n=2206), prehypertensive (n=721), and hypertensive (n=328) subjects examined serially during childhood (4 to 11 years), adolescence (12 to 18 years), and adulthood (19 to 42 years). Prehypertensive subjects versus normotensive subjects had significantly higher body mass index and subscapular skinfold, systolic (SBP) and diastolic (DBP) blood pressures, and triglycerides beginning in childhood; higher glucose in adolescence; and higher low-density lipoprotein cholesterol, fasting insulin, and insulin resistance index in adulthood. Hypertensive subjects versus normotensive subjects had higher adiposity measures, SBP and DBP, glucose, and triglycerides beginning in childhood; higher insulin and insulin resistant index in childhood and adulthood; and lower high-density lipoprotein, cholesterol in adulthood. Most of these variables progressed adversely at an increased rate in prehypertensive and hypertensive subjects. In a multivariate analysis, adverse changes in adiposity, SBP, and DBP were independently associated with prehypertensive status; and adverse changes in adiposity, SBP and DBP, insulin resistant index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides with hypertension status. As young adults, prehypertensive and hypertensive subjects showed significantly higher prevalence of obesity, hyperinsulinemia, hyperglycemia, and dyslipidemias. Thus, excess adiposity and blood pressure beginning in childhood and accelerated adverse longitudinal changes in risk variables of metabolic syndrome through young adulthood characterize the early natural history of hypertension.
Angiotensin II Type-2 Receptor Stimulation Prevents Neural Damage by Transcriptional Activation of Methyl Methanesulfonate Sensitive 2
Authors: Mogi Masaki , Li Jian-Mei , Iwanami Jun , Min Li-Juan , Tsukuda Kana , Iwai Masaru , Horiuchi Masatsugu
Published: June 2006

The molecular mechanisms of the contribution of angiotensin II type-1 receptor blockers to neuronal protection are still unclear. Here, we investigated the effect of angiotensin II type-2 (AT2) receptor stimulation on neurons and cognitive function involving a new neuroprotective factor, methyl methanesulfonate sensitive 2 (MMS2). Angiotensin II treatment of neurospheres enhanced their differentiation and increased MMS2 expression. Knockdown of the MMS2 gene by small interference RNA (siRNA) significantly reduced the number of neurospheres, with loss of sphere formation. An angiotensin II type-1 receptor blocker, valsartan, enhanced such neurosphere differentiation and MMS2 induction, whereas an AT2receptor antagonist, PD123319, inhibited them. After mice underwent permanent middle cerebral artery occlusion, AT2receptor mRNA expression was significantly increased in the ischemic side of the brain. Passive avoidance rate to evaluate cognitive function was significantly impaired in AT2receptor null (Agtr2−) mice compared with wild-type mice. Treatment with valsartan prevented the cognitive decline in wild-type mice, but this effect was weaker inAgtr2−mice. In ischemic brain regions, MMS2 was increased in wild-type mice, but not inAgtr2−mice. Valsartan also enhanced MMS2 expression to a greater degree in wild-type mice. Finally, intracerebroventricular administration of MMS2 siRNA showed more impaired avoidance rate after middle cerebral artery occlusion compared with that in control siRNA–transfected mice. These findings experimentally support the clinical evidence and indicate a unique mechanism of the AT2receptor in brain protection.
Dual-Chamber Versus Single-Chamber Detection Enhancements for Implantable Defibrillator Rhythm Diagnosis
Authors: Friedman Paul A. , McClelland Robyn L. , Bamlet William R. , Acosta Helbert , Kessler David , Munger Thomas M. , Kavesh Neal G. , Wood Mark , Daoud Emile , Massumi Ali , Schuger Claudio , Shorofsky Stephen , Wilkoff Bruce , Glikson Michael
Published: June 2006

Background—

Delivery of inappropriate shocks caused by misdetection of supraventricular tachycardia (SVT) remains a substantial complication of implanted cardioverter/defibrillator (ICD) therapy. Whether use of optimally programmed dual-chamber ICDs lowers this risk compared with that in single-chamber ICDs is not clear.

Methods and Results—

Subjects with a clinical indication for ICD (n=400) at 27 participating centers received dual-chamber ICDs and were randomly assigned to strictly defined optimal single- or dual-chamber detection in a single-blind manner. Programming minimized ventricular pacing. The primary end point was the proportion of SVT episodes inappropriately detected from the time of programming until crossover or end of study. On a per-episode basis, 42% of the episodes in the single-chamber arm and 69% of the episodes in the dual-chamber arm were due to SVT. Mortality (3.5% in both groups) and early study withdrawal (14% single-chamber, 11% dual-chamber) were similar in both groups. The rate of inappropriate detection of SVT was 39.5% in the single-chamber detection arm compared with 30.9% in the dual-chamber arm. The odds of inappropriate detection were decreased by almost half with the use of the dual-chamber detection enhancements (odds ratio, 0.53; 95% confidence interval, 0.30 to 0.94;
P
=0.03).

Conclusions—

Dual-chamber ICDs, programmed to optimize detection enhancements and to minimize ventricular pacing, significantly decrease inappropriate detection.
Evidence for Cardiovascular Autonomic Dysfunction in Neonates With Coarctation of the Aorta
Authors: Polson Jaimie W. , McCallion Naomi , Waki Hidefumi , Thorne Gareth , Tooley Mark A. , Paton Julian F.R. , Wolf Andrew R.
Published: June 2006

Background—

Coarctation of the aorta (CoA) is associated with hypertension and abnormalities of blood pressure control, which persist after late repair. Assumptions that neonatal repair would prevent development of blood pressure abnormalities have not been supported by recent data. We hypothesized that early pathological adjustment of autonomic cardiovascular function may already be established in the neonate with coarctation.

Methods and Results—

We studied 8 otherwise well neonates with simple CoA and compared measures of spontaneous baroreflex sensitivity, heart rate variability, and blood pressure variability with 13 healthy newborn babies. Spontaneous baroreflex sensitivity was calculated with sequence methodology from an ECG, and noninvasive blood pressure was recorded with a Portapres. Heart rate variability was determined with time- and frequency-domain measures. Blood pressure variability was measured in the frequency domain. In comparison with normal controls, neonates with CoA had raised blood pressure (78.9±3.8 versus 67.1±2.1 mm Hg), depressed baroreflex sensitivity (8.7±1.5 versus 13.8±1.1 ms/mm Hg), reduced heart rate variability (total power 16.5±3.1 versus 31.5±2.2 ms
2
), and an increase in the high-frequency component of blood pressure variability (3.1±0.3 versus 2.2±0. 2 mm Hg
2
). This is not the pattern expected if neonates with CoA simply had subclinical cardiac failure.

Conclusions—

These data suggest that infants with CoA already show signs of pathological adjustment of autonomic cardiovascular homeostasis. Further longitudinal studies are required to determine whether these alterations play a role in the increased risk of late hypertension in these patients.
Babes in Bondage? Debt Shifting by German Immigrants in Early America
Authors: Grubb Farley
Published: June 2006

Data from ship manifests and servant auctions can clarify the extent to which German immigrant families in early America resorted to intra-family debt shifting by selling their children into bondage. This evidence is at odds with the standard descriptions presented in literary sources, which exaggerate and stigmatize the practice. Market competition provided German immigrant parents with a financial opportunity that colonial welfare law constrained them to take. This debt shifting, however, affected only children within a particular, and narrow, age range, and German immigrant parents were not callously treating their children as salable assets by taking advantage of it.
Rocking the Cradle: Downsizing the New England Family
Authors: Main Gloria L.
Published: June 2006

Between 1790 and 1840, median completed family size in New England genealogies fell by half. Age at marriage rose only moderately during this period, but the rate of premarital pregnancy plummeted, intervals between births lengthened, and mothers' age at last birth fell to thirty-seven. Analysis of the number of children born to a subset of mothers younger than thirty in various Connecticut and New Hampshire towns c. 1818 suggests that couples' motives for postponing births appear to have been as much cultural as economic.
Transportation Convictions during the Great Irish Famine
Authors: Woodward Nicholas
Published: June 2006

Periods of famine would seem to entail not only increased criminal activity but also a greater range of people willing to commit crimes to avoid starvation. Transportation data from Ireland during the Great Famine of the 1840s confirms an increase in criminal activity, revealing that the locus of crime shifted significantly toward the areas most seriously affected by famine conditions. The characteristics of the criminals, however, did not change dramatically. Young men continued to be the main perpetrators, as they had been before the Famine, although those convicted during the Famine often received lighter sentences.
Multivariate Information Bottleneck
Authors: Slonim Noam , Friedman Nir , Tishby Naftali
Published: June 2006

The information bottleneck (IB) method is an unsupervised model independent data organization technique. Given a joint distribution, p(X, Y), this method constructs a new variable, T, that extracts partitions, or clusters, over the values of X that are informative about Y. Algorithms that are motivated by the IB method have already been applied to text classification, gene expression, neural code, and spectral analysis. Here, we introduce a general principled framework for multivariate extensions of the IB method. This allows us to consider multiple systems of data partitions that are interrelated. Our approach utilizes Bayesian networks for specifying the systems of clusters and which information terms should be maintained. We show that this construction provides insights about bottleneck variations and enables us to characterize the solutions of these variations. We also present four different algorithmic approaches that allow us to construct solutions in practice and apply them to several real-world problems.
Variational Bayesian Multinomial Probit Regression with Gaussian Process Priors
Authors: Girolami Mark , Rogers Simon
Published: June 2006

It is well known in the statistics literature that augmenting binary and polychotomous response models with gaussian latent variables enables exact Bayesian analysis via Gibbs sampling from the parameter posterior. By adopting such a data augmentation strategy, dispensing with priors over regression coefficients in favor of gaussian process (GP) priors over functions, and employing variational approximations to the full posterior, we obtain efficient computational methods for GP classification in the multiclass setting.1 The model augmentation with additional latent variables ensures full a posteriori class coupling while retaining the simple a priori independent GP covariance structure from which sparse approximations, such as multiclass informative vector machines (IVM), emerge in a natural and straightforward manner. This is the first time that a fully variational Bayesian treatment for multiclass GP classification has been developed without having to resort to additional explicit approximations to the nongaussian likelihood term. Empirical comparisons with exact analysis use Markov Chain Monte Carlo (MCMC) and Laplace approximations illustrate the utility of the variational approximation as a computationally economic alternative to full MCMC and it is shown to be more accurate than the Laplace approximation.
A Novel Neural Network for a Class of Convex Quadratic Minimax Problems
Authors: Gao Xing-Bao , Liao Li-Zhi
Published: June 2006

Based on the inherent properties of convex quadratic minimax problems, this article presents a new neural network model for a class of convex quadratic minimax problems. We show that the new model is stable in the sense of Lyapunov and will converge to an exact saddle point in finite time by defining a proper convex energy function. Furthermore, global exponential stability of the new model is shown under mild conditions. Compared with the existing neural networks for the convex quadratic minimax problem, the proposed neural network has finite-time convergence, a simpler structure, and lower complexity. Thus, the proposed neural network is more suitable for parallel implementation by using simple hardware units. The validity and transient behavior of the proposed neural network are illustrated by some simulation results.
Kernel Projection Classifiers with Suppressing Features of Other Classes
Authors: Washizawa Yoshikazu , Yamashita Yukihiko
Published: June 2006

We propose a new classification method based on a kernel technique called suppressed kernel sample space projection classifier (SKSP), which is extended from kernel sample space projection classifier (KSP).

In kernel methods, samples are classified after they are mapped from an input space to a high-dimensional space called a feature space. The space that is spanned by samples of a class in a feature space is defined as a kernel sample space. In KSP, an unknown input vector is classified to the class of which projection norm onto the kernel sample space is maximized. KSP can be interpreted as a special type of kernel principal component analysis (KPCA). KPCA is also used in classification problems. However, KSP has more useful properties compared with KPCA, and its accuracy is almost the same as or better than that of KPCA classifier.

Since KSP is a single-class classifier, it uses only self-class samples for learning. Thus, for a multiclass classification problem, even though there are very many classes, the computational cost does not change for each class. However, we expect that more useful features can be obtained for classification if samples from other classes are used. By extending KSP to SKSP, the effects of other classes are suppressed, and useful features can be extracted with an oblique projection.

Experiments on two-class classification problems, indicate that SKSP shows high accuracy in many classification problems.
A Neighborhood-Based Enhancement of the Gauss-Newton Bayesian Regularization Training Method
Authors: Pinzolas Miguel , Toledo Ana , Pedreño Juan Luís
Published: June 2006

This work develops and tests a neighborhood-based approach to the Gauss-Newton Bayesian regularization training method for feedforward backpropagation networks. The proposed method improves the training efficiency, significantly reducing requirements on memory and computational time while maintaining the good generalization feature of the original algorithm. This version of the Gauss-Newton Bayesian regularization greatly expands the scope of application of the original method, as it allows training networks up to 100 times larger without losing performance.