bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperglycemia prevents the suppressive effect of hyperinsulinemia on plasma adiponectin levels in healthy humans
Authors: Blümer Regje M. E. , van der Crabben Saskia N. , Stegenga Michiel E. , Tanck Michael W. , Ackermans Mariette T. , Endert Erik , van der Poll Tom , Sauerwein Hans P.
Published: June 2008

Adiponectin is a fat-derived hormone with insulin-sensitizing properties. In patients with type 2 diabetes plasma adiponectin levels are decreased. Since these patients are characterized by high plasma insulin and glucose concentrations, hyperinsulinemia and hyperglycemia could be responsible for the downregulation of adiponectin. Insulin decreases adiponectin levels in humans. The effect of hyperglycemia is unknown. To determine the selective effects of insulin, glucose, or their combination on plasma adiponectin, clamps were performed in six healthy males on four occasions in a crossover design: 1) lower insulinemic-euglycemic clamp (100 pmol/l insulin, 5 mmol/l glucose) (reference clamp); 2) hyperinsulinemic-euglycemic clamp (400 pmol/l insulin, 5 mmol/l glucose); 3) lower insulinemic-hyperglycemic clamp (100 pmol/l insulin, 12 mmol/l glucose); and 4) hyperinsulinemic-hyperglycemic clamp (400 pmol/l insulin, 12 mmol/l glucose). Adiponectin concentrations and high-molecular-weight (HMW)-to-total adiponectin ratio were measured at the start and end of the 6-h clamps. After the 6-h study period, total plasma adiponectin levels were significantly ( P = 0.045) decreased by 0.63 μg/ml in the lower insulinemic-euglycemic clamp ( clamp 1). In both euglycemic groups ( clamps 1 and 2) adiponectin concentrations significantly declined ( P = 0.016) over time by 0.56 μg/ml, whereas there was no change in both hyperglycemic groups ( clamps 3 and 4) ( P = 0.420). In none of the clamps did the ratio of HMW to total adiponectin change. We conclude that insulin suppresses plasma adiponectin levels already at a plasma insulin concentration of 100 pmol/l. Hyperglycemia prevents the suppressive effect of insulin. This suggests that, in contrast to glucose, insulin could be involved in the downregulation of plasma adiponectin in insulin-resistant patients.
Estrous cycle variation of TRPV1-mediated cross-organ sensitization between uterus and NMDA-dependent pelvic-urethra reflex activity
Authors: Peng Hsien-Yu , Huang Pei-Chen , Liao Jiuan-Miaw , Tung Kwong-Chung , Lee Shin-Da , Cheng Chen-Li , Shyu Jyh-Cherng , Lai Cheng-Yuan , Chen Gin-Den , Lin Tzer-Bin
Published: June 2008

Cross-organ sensitization between the uterus and the lower urinary tract (LUT) underlies the high concurrence of pelvic pain syndrome and LUT dysfunctions, and yet the role of gonadal steroids is still unknown. We tested the hypothesis that cross-organ sensitization on pelvic-urethra reflex activity caused by uterine capsaicin instillation is estrous cycle dependent. When compared with the baseline reflex activity (1.00 ± 0.00 spikes/stimulation), uterine capsaicin instillation significantly increased reflex activity (45.42 ± 9.13 spikes/stimulation, P < 0.01, n = 7) that was corroborated by an increase in phosphorylated NMDA NR2B ( P < 0.05, n = 4) but not NR2A subunit ( P > 0.05, n = 4) expression. Both intrauterine pretreatment with capsazepine (5.02 ± 2.11 spikes/stimulation, P < 0.01, n = 7) and an intrathecal injection of AP5 (3.21 ± 0.83 spikes/stimulation, P < 0.01, n = 7) abolished the capsaicin-induced cross-organ sensitization and the increment in the phosphorylated NR2B level ( P < 0.05, n = 4). The degrees of the cross-organ sensitization increased in a dose-dependent manner with the concentration of instilled capsaicin from 100 to 300 μM in both the proestrus and metestrus stages, whereas they weakened when the concentrations were higher than 1,000 μM. Moreover, the cross-organ sensitization caused by the uterine capsaicin instillation increased significantly in the rats during the proestrus stage when compared with the metestrus stage ( P < 0.01, n = 7). These results suggest that estrogen levels might modulate the cross-organ sensitization between the uterus and the urethra and underlie the high concurrence of pelvic pain syndrome and LUT dysfunctions.
Increased Responsiveness to Toll‐Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis
Authors: Kowalski M. L. , Wolska A. , Grzegorczyk J. , Hilt J. , Jarzebska M. , Drobniewski M. , Synder M. , Kurowski M.
Published: June 2008

Background. Cell signaling via Toll‐like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent‐onset RA, osteoarthrosis (OA), and healthy control (HC).
Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll‐like receptors mRNA in leukocytes was analyzed using real‐time qPCR.
Results. PBMCs from RA patients spontaneously produced less IL‐6 and TNFα than cells from OA and HC subjects.
LPS increased cytokines′ production in all groups. In RA patients increase was dramatic (30 to 48‐fold and 17 to 31‐fold, for respective cytokines) compared to moderate (2 to 8‐fold) in other groups. LPS induced 15‐HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients.
Conclusion. PBMCs from recent‐onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide.
TLR expression is differentially regulated in healthy and arthritic subjects.
Feasibility Study and Design of a Wearable System-on-a-Chip Pulse Radar for Contactless Cardiopulmonary Monitoring
Authors: Zito Domenico , Pepe Domenico , Neri Bruno , Zito Fabio , De Rossi Danilo , Lanatà Antonio
Published: June 2008

A new system-on-a-chip radar sensor for next-generation wearable wireless interface applied to the human health care and safeguard is presented. The system overview is provided and the feasibility study of the radar sensor is presented. In detail, the overall system consists of a radar sensor for detecting the heart and breath rates and a low-power IEEE 802.15.4 ZigBee radio interface, which provides a wireless data link with remote data acquisition and control units. In particular, the pulse radar exploits 3.1–10.6 GHz ultra-wideband signals which allow a significant reduction of the transceiver complexity and then of its power consumption. The operating principle of the radar for the cardiopulmonary monitoring is highlighted and the results of the system analysis are reported. Moreover, the results obtained from the building-blocks design, the channel measurement, and the ultra-wideband antenna realization are reported.
Influence of Uncertainties on the Dynamic Buckling Loads of Structures Liable to Asymmetric Postbuckling Behavior
Authors: Gonçalves Paulo B. , Santee Donald Mark
Published: June 2008

Structural systems liable to asymmetric bifurcation usually become unstable at static load levels lower than the linear buckling load of the perfect structure. This is mainly due to the imperfections present in real structures. The imperfection sensitivity of structures under static loading is well studied in literature, but little is know on the sensitivity of these structures under dynamic loads. The aim of the present work is to study the behavior of an archetypal model of a harmonically forced structure, which exhibits, under increasing static load, asymmetric bifurcation. First, the integrity of the system under static load is investigated in terms of the evolution of the safe basin of attraction. Then, the stability boundaries of the harmonically excited structure are obtained, considering different loading processes. The bifurcations connected with these boundaries are identified and their influence on the evolution of safe basins is investigated. Then, a parametric analysis is conducted to investigate the influence of uncertainties in system parameters and random perturbations of the forcing on the dynamic buckling load. Finally, a safe lower bound for the buckling load, obtained by the application of the Melnikov criterion, is proposed which compare well with the scatter of buckling loads obtained numerically.
Probabilistic and Fuzzy Arithmetic Approaches for the Treatment of Uncertainties in the Installation of Torpedo Piles
Authors: Kunitaki Denise Margareth Kazue Nishimura , de Lima Beatriz Souza Leite Pires , Evsukoff Alexandre Gonçalves , Jacob Breno Pinheiro
Published: June 2008

The “torpedo” pile is a foundation system that has been recently considered to anchor mooring lines and risers of floating production systems for offshore oil exploitation. The pile is installed in a free fall operation from a vessel. However, the soil parameters involved in the penetration model of the torpedo pile contain uncertainties that can affect the precision of analysis methods to evaluate its final penetration depth. Therefore, this paper deals with methodologies for the assessment of the sensitivity of the response to the variation of the uncertain parameters and mainly to incorporate into the analysis method techniques for the formal treatment of the uncertainties. Probabilistic and “possibilistic” approaches are considered, involving, respectively, the Monte Carlo method (MC) and concepts of fuzzy arithmetic (FA). The results and performance of both approaches are compared, stressing the ability of the latter approach to efficiently deal with the uncertainties of the model, with outstanding computational efficiency, and therefore, to comprise an effective design tool.
Serum Concentration of Interleukin‐6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgaris
Authors: Narbutt Joanna , Lukamowicz Jolanta , Bogaczewicz Jarosław , Sysa-Jedrzejowska Anna , Torzecka Jolanta Dorota , Lesiak Aleksandra
Published: June 2008

As most studies on pemphigus vulgaris (PV) pathogenesis concern its active stage, we aimed to evaluate the serum concentration of TNF‐α, IL‐1, and IL‐6 in PV patients in clinical remission. The study group consisted of sera from 19 PV patients in active stage and from 24 patients in clinical remission. 19 sera taken from healthy subjects served as the controls. Serum IL‐6 concentrations in PV active and PV remission group were significantly higher when compared to the controls (P < .05). In patients in active stage of PV, a significant correlation between serum IL‐1 and IL‐6 concentrations was found (rP = 0.46; P < .05). We also found a negative correlation between TNF‐α level and pemphigus antibodies titer in the patients from the remission group (rS = −0.47303; P < .02). Our data suggest that IL‐6 and TNF‐α may be involved in maintaining immunological disturbances in remission stage of PV.
Pleiotropic Effects and Cholesterol-Lowering Therapy
Authors: Shaw Steven M. , Fildes James E. , Yonan Nizar , Williams Simon G.
Published: June 2008

HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors, or ‘statins’, have revolutionized the management of patients with atherosclerotic vascular disease. Following 2 large acute coronary syndrome trials, additional clinical benefit outside their effect of low-density lipoprotein (LDL) lowering was proposed. This concept was introduced following the observation of cardiovascular event rate reduction, only weeks after initiation of treatment and supposedly before the effect of LDL lowering could have influenced atheroma volume burden. Furthermore, there has been a substantial compilation of experimental data demonstrating beneficial effects of statins on inflammation, thrombosis, platelet aggregation, immunomodulation and endothelial function. These are hypothesized to occur via the interruption of the mevalonate pathway. However, the absolute benefit of these non-lipid-lowering effects, often referred to as ‘pleiotropic effects’, has been challenged by meta-analysis data. Anti-inflammatory actions have also been proposed to occur by the process of LDL lowering alone rather than due to a unique property of statins. Furthermore, some experimental data reports have shown evidence of pleiotropic effects in non-statin lipid-modifying agents. In this review article, we consolidate what is known so far and critically analyse the literature in order to highlight the outstanding issues.
Myocardial Bridging in Absence of Coronary Artery Disease: Proposal of a New Classification Based on Clinical-Angiographic Data and Long-Term Follow-Up
Authors: Schwarz Ernst R. , Gupta Rajiv , Haager Philipp K. , vom Dahl Juergen , Klues Heinrich G. , Minartz Juergen , Uretsky Barry F.
Published: June 2008

Background: There is no widely accepted classification to guide therapy in patients with symptomatic myocardial bridging (MB). Methods: A retrospective analysis of 157 patients with chest pain, angiographic MB of the left anterior descending artery without obstructive coronary artery disease (CAD) was performed. Patients were evaluated for clinical symptoms, objective signs of ischemia by stress test, intracoronary Doppler flow measurement and coronary flow reserve. 100 patients without CAD or MB served as controls. Results: There was no difference in clinical symptoms and objective signs of ischemia between controls and patients with MB. The length of MB was 22.6 ± 7.8 mm, maximal systolic luminal diameter reduction 71 ± 16%, and maximal mid-diastolic luminal reduction 34.7 ± 13% as demonstrated by quantitative coronary angiography (QCA). Intracoronary Doppler showed significantly increased average peak flow velocity (APV), average systolic peak velocity (ASPV), average diastolic peak flow velocity (ADPV), and maximal peak velocity (MPV) in MB versus proximal and distal segments at rest and after maximal vasodilatation (p < 0.001 for all parameters). Coronary flow reserve was significantly higher proximally (2.9 ± 0.9) compared with segments distal to the MB (2.0 ± 0.6, p < 0.01). We propose a new MB classification for symptomatic patients with MB:Type A:incidental finding on angiography, no objective signs of ischemia; Type B: objective signs of ischemia, and Type C: with or without objective signs of ischemia and altered intracoronary hemodynamics (by QCA/CFR/intracoronary Doppler). 5-Year follow-up data based on this classification showed that types B and C responded well to β-blockers or calcium channel antagonists. Patients with type C refractory to medical therapy were treated with stenting of the MB. Conclusion: Patients with MB without CAD did not have a higher prevalence of chest pain or abnormal non-invasive stress tests compared to patients without CAD or MB. Intracoronary hemodynamic measurement is a novel approach that may be valuable in defining the functional significance of MB. We propose a classification of symptomatic patients with MB without CAD using non-invasive and invasive parameters to guide therapeutic choices.
Transcatheter Closure of a Ventricular Septal Defect following Myectomy for Hypertrophic Obstructive Cardiomyopathy
Authors: Spies Christian , Ujivari Franz , Schraeder Rainer
Published: June 2008

Post-operative ventricular septal defect (VSD) following septal myectomy in patients with hypertrophic obstructive cardiomyopathy (HOCM) is a rare complication which may warrant closure. Repeat early sternotomy for surgical closure of the VSD seems undesirable and transcatheter VSD closure may be a valid alternative. We report the case of successful closure of a 10-mm VSD following surgical therapy for HOCM using an Amplatzer Muscular VSD Occluder.
Efficacy of Prokinetic Agents in Improving Bowel Preparation for Colonoscopy
Authors: Mishima Yuko , Amano Yuji , Okita Koichi , Takahashi Yoshiko , Moriyama Nobuyuki , Ishimura Norihisa , Furuta Kenji , Ishihara Shunji , Adachi Kyoichi , Kinoshita Yoshikazu
Published: June 2008

Background and Aim: Colonoscopy plays an important role in the diagnosis and treatment of gastrointestinal illness in both Western countries and Japan. However, preparative bowel cleansing for colonoscopy is frequently troublesome for elderly and/or constipated patients, since they must drink larger volumes of lavage solution for adequate cleansing. We investigated the use of prokinetic agents for improving the efficacy and tolerability of bowel cleansing prior to colonoscopy. Methods: 613 patients were divided into two groups according to oral lavage solution used (polyethylene glycol or magnesium citrate), and were further randomized to receive either vehicle (100 ml water) alone, vehicle with 5 mg mosapride citrate, or vehicle with 50 mg itopride hydrochloride 30 min before administration of lavage solution. Experimental parameters included bowel cleansing quality, times to first defecation and completion of bowel cleansing, and incidence of uncomfortable abdominal symptoms during colonoscopy preparation. Results: Administration of mosapride citrate or itopride hydrochloride prior to oral lavage solution did not significantly improve bowel cleansing quality. However, statistically significantly fewer uncomfortable abdominal symptoms were found in patients who received mosapride citrate or itopride hydrochloride versus vehicle alone. Conclusion: Prokinetic agents effectively decreased the incidence of uncomfortable abdominal symptoms experienced during colonoscopy preparation.
Upper Gastrointestinal Bleeding in Patients with Aspirin and Clopidogrel Co-Therapy
Authors: Ng Fook-Hong , Lam Kwok-Fai , Wong Siu-Yin , Chang Chee-My , Lau Yuk-Kong , Yuen Wai-Cheung , Chu Wai-Ming , Wong Benjamin C.Y.
Published: June 2008

Introduction: The major complication of aspirin and clopidogrel (A+C) co-therapy is upper gastrointestinal bleeding (UGIB). However, data are unavailable for real-life situations. Furthermore, the treatment effect of antisecretory agents is unknown. Aim: This cohort study aimed to determine the occurrence of UGIB. The treatment effect of H2-receptor antagonist (H2RA) and proton pump inhibitor (PPI) was also analyzed. Method: The records of 987 consecutive patients on A+C co-therapy between January 2001 and September 2006 were analyzed. The follow-up ended on the dates of a first occurrence of UGIB, stopping A+C co-therapy, a change in the antisecretory class, death, or March 2007. Results: After a follow-up of 5.8 ± 6.5 months, UGIB occurred in 39 (4.0%) patients. PPI, H2RA and control were prescribed in 213, 287 and 487 patients respectively. After adjustment for age, dose of aspirin, previous UGIB and duration of treatment, the risk was marginally reduced by H2RA (OR = 0.43, 95% CI 0.18–0.91, p = 0.04) and significantly reduced by PPI (OR = 0.04, 95% CI 0.002–0.21, p = 0.002), as compared to control. Conclusion: The occurrence of UGIB associated with A+C co-therapy for a median of 5.8 months was 4.0%. Co-prescription with PPI was associated with a lower risk.
Resistin Is Closely Related to Systemic Inflammation in Obstructive Sleep Apnea
Authors: Yamamoto Yasushi , Fujiuchi Satoru , Hiramatsu Mie , Nishigaki Yutaka , Takeda Akinori , Fujita Yuka , Yamazaki Yasuhiro
Published: June 2008

Background: Obstructive sleep apnea (OSA) is closely related to systemic inflammation. Resistin is an adipocyte-derived cytokine (adipokine) that may link obesity with inflammation. Objective: We aimed to investigate whether incremental changes in OSA severity, from normal to severe, primarily affect the levels of resistin and other adipokines. Methods: Serum levels of resistin, interleukin-6 (IL-6) and leptin were examined in 31 men with OSA and 10 men without OSA, matched for age, body mass index (BMI) and several metabolic profiles. In 11 of the 31 men with OSA, these mediators were reexamined after 3 months of nasal continuous airway pressure (nCPAP) therapy. Results: Levels of resistin and IL-6 were simultaneously elevated in men with OSA compared with those in men without OSA (p < 0.05), while levels of leptin did not differ. The resistin and IL-6 levels tended to increase with increasing disease severity (p < 0.05), which was based on the apnea-hypopnea index (AHI). The average oxyhemoglobin saturation during sleep (p < 0.01) and IL-6 (p < 0.05) emerged as significant determinants of resistin, even after adjustments for age, BMI, leptin levels and metabolic risk factors. After nCPAP therapy, the elevated levels of resistin and IL-6 decreased, reaching almost baseline levels of controls. Before treatment, AHI correlated positively with the reduction rate in resistin (p < 0.05). Conclusion: In OSA patients, resistin production can be enhanced by hypoxic stress during sleep, possibly mediating systemic inflammatory processes. nCPAP therapy may play a beneficial role in the control of resistin production.
Atrial Fibrillation Begets Atrial Fibrillation
Authors: Lu Zhibing , Scherlag Benjamin J. , Lin Jiaxiong , Niu Guodong , Fung Kar-Ming , Zhao Lichao , Ghias Muhammad , Jackman Warren M. , Lazzara Ralph , Jiang Hong , Po Sunny S.
Published: June 2008

Background—

The mechanism(s) for acute changes in electrophysiological properties of the atria during rapid pacing induced atrial fibrillation (AF) is not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in acute atrial electrical remodeling and AF induced by 6-hour rapid atrial pacing.

Methods and Results—

Continuous rapid pacing (1200 bpm, 2� threshold [TH]) was performed at the left atrial appendage. Group 1 (n=7) underwent 6-hour pacing immediately followed by ganglionated plexi (GP) ablation; group 2 (n=7) underwent GP ablation immediately followed by 6-hour pacing; and group 3 (n=4) underwent administration of autonomic blockers, atropine (1 mg/kg), and propranolol (0.6 mg/kg) immediately followed by 6-hour pacing. The effective refractory period (ERP) and window of vulnerability (WOV, in milliseconds), ie, the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF, were measured at 2�TH and 10�TH at the left atrium, right atrium, and pulmonary veins every hour before and after GP ablation or autonomic blockade. In group 1, ERP was markedly shortened in the first 2 hours and then stabilized both at 2�TH and 10�TH; however, WOV was progressively widened throughout the 6-hour period. After GP ablation, ERP was significantly longer than before ablation and AF could not be induced (WOV=0) at either 2�TH or 10�TH. In groups 2 and 3, rapid atrial pacing failed to shorten the ERP. AF could not be induced in 6 of 7 dogs in group 2 and all 4 dogs in group 3 during the 6-hour pacing period.

Conclusion—

The intrinsic cardiac autonomic nervous system plays a crucial role in the acute stages of atrial electrical remodeling induced by rapid atrial pacing.
In Vivo Monitoring of Inflammation After Cardiac and Cerebral Ischemia by Fluorine Magnetic Resonance Imaging
Authors: Flögel Ulrich , Ding Zhaoping , Hardung Hendrik , Jander Sebastian , Reichmann Gaby , Jacoby Christoph , Schubert Rolf , Schrader Jürgen
Published: June 2008

Background—

In this study, we developed and validated a new approach for in vivo visualization of inflammatory processes by magnetic resonance imaging using biochemically inert nanoemulsions of perfluorocarbons (PFCs).

Methods and Results—

Local inflammation was provoked in 2 separate murine models of acute cardiac and cerebral ischemia, followed by intravenous injection of PFCs. Simultaneous acquisition of morphologically matching proton (
1
H) and fluorine (
19
F) images enabled an exact anatomic localization of PFCs after application. Repetitive
1
H/
19
F magnetic resonance imaging at 9.4 T revealed a time-dependent infiltration of injected PFCs into the border zone of infarcted areas in both injury models, and histology demonstrated a colocalization of PFCs with cells of the monocyte/macrophage system. We regularly found the accumulation of PFCs in lymph nodes. Using rhodamine-labeled PFCs, we identified circulating monocytes/macrophages as the main cell fraction taking up injected nanoparticles.

Conclusions—

PFCs can serve as a “positive” contrast agent for the detection of inflammation by magnetic resonance imaging, permitting a spatial resolution close to the anatomic
1
H image and an excellent degree of specificity resulting from the lack of any
19
F background. Because PFCs are nontoxic, this approach may have a broad application in the imaging and diagnosis of numerous inflammatory disease states.
Angiotensin II–Triggered p44/42 Mitogen-Activated Protein Kinase Mediates Sympathetic Excitation in Heart Failure Rats
Authors: Wei Shun-Guang , Yu Yang , Zhang Zhi-Hua , Weiss Robert M. , Felder Robert B.
Published: June 2008

Angiotensin II (Ang II), acting via angiotensin type 1 receptors in the brain, activates the sympathetic nervous system in heart failure (HF). We reported recently that Ang II stimulates mitogen-activated protein kinase (MAPK) to upregulate brain angiotensin type 1 receptors in HF rats. In this study we tested the hypothesis that Ang II–activated MAPK signaling pathways contribute to sympathetic excitation in HF. Intracerebroventricular administration of PD98059 and UO126, 2 selective p44/42 MAPK inhibitors, induced significant decreases in mean arterial pressure, heart rate, and renal sympathetic nerve activity in HF rats, but had no effect on these variables in sham-operated rats. Pretreatment with losartan attenuated the effects of PD98059. Intracerebroventricular administration of the p38 MAPK inhibitor SB203580 and the c-Jun N-terminal kinase inhibitor SP600125 had no effect on mean arterial pressure, heart rate, or renal sympathetic nerve activity in HF. The phosphatidylinositol 3-kinase inhibitor LY294002 induced a small decrease in mean arterial pressure and heart rate but no change in renal sympathetic nerve activity. Immunofluorescent staining demonstrated increased p44/42 MAPK activity in neurons of the paraventricular nucleus of the hypothalamus of HF rats, colocalized with Fra-like activity (indicating chronic neuronal excitation). Intracerebroventricular PD98059 and UO126 reduced Fra-like activity in the paraventricular nucleus of the hypothalamus neurons in HF rats. In confirmatory acute studies, intracerebroventricular Ang II increased mean arterial pressure, heart rate, and renal sympathetic nerve activity in baroreceptor-denervated rats and Fra-like immunoreactivity in the paraventricular nucleus of the hypothalamus of neurally intact rats. Central administration of PD98059 markedly reduced these responses. These data demonstrate that intracellular p44/42 MAPK activity contributes to Ang II–induced neuronal excitation in the paraventricular nucleus of the hypothalamus and augmented sympathetic nerve activity in rats with HF.
Tissue-Type Plasminogen Activator Release in Healthy Subjects and Hypertensive Patients
Authors: Giannarelli Chiara , Virdis Agostino , De Negri Ferdinando , Duranti Emiliano , Magagna Armando , Ghiadoni Lorenzo , Salvetti Antonio , Taddei Stefano
Published: June 2008

The relationship between adrenergic stimuli and NO in modulating tissue-type plasminogen activator (t-PA) release from endothelial cells was investigated in normotensive subjects and essential hypertensive patients. Sympathetic activation, a well-known stimulus for endogenous fibrinolysis, is also involved in the determination of cardiovascular risk in essential hypertension. However, the existence of cross-talk between adrenergic stimuli and NO availability in modulating t-PA release is not well established yet. We assessed the release of t-PA in the forearm microcirculation of 58 normotensive subjects (mean age: 47±9 years) and 44 essential hypertensive patients (mean age: 48±11 years) under specific intra-arterial adrenergic stimuli. Intrabrachial infusion of epinephrine (0.1 to 0.3 μg/100 mL per minute) induced greater t-PA release in normotensive subjects as compared with essential hypertensive patients (P<0.05). However, inhibition of NO synthase with NG-monomethyl-l-arginine (100 μg/100 mL per minute) infusion blunted epinephrine-induced t-PA release in normotensive subjects (P<0.05) but not in essential hypertensive patients. In normotensive subjects, t-PA release by epinephrine was not affected by phentolamine (8 μg/100 mL per minute) coinfusion and was abolished in the presence of propanolol (10 μg/100 mL per minute). Intrabrachial isoproterenol (0.03 μg/100 mL per minute) induced a significant increase in t-PA release (P<0.01), an effect blunted by NG-monomethyl-l-arginine (P<0.05). In essential hypertensive patients, the response to isoproterenol was impaired as compared with normotensive subjects and was unaffected by NG-monomethyl-l-arginine coinfusion. In conclusion, the results of the present study demonstrate that adrenergic-induced t-PA release is mediated by β-adrenoreceptors via a mechanism involving the NO pathway. Our results show an impaired adrenergic-stimulated t-PA release among essential hypertensive patients, probably mediated via a reduced NO availability. This impaired fibrinolytic activity might contribute to the increased cardiovascular risk associated with hypertension.
Prognostic Value of Ambulatory Heart Rate Revisited in 6928 Subjects From 6 Populations
Authors: Hansen Tine W. , Thijs Lutgarde , Boggia José , Li Yan , Kikuya Masahiro , Björklund-Bodegård Kristina , Richart Tom , Ohkubo Takayoshi , Jeppesen Jørgen , Torp-Pedersen Christian , Lind Lars , Sandoya Edgardo , Imai Yutaka , Wang Jiguang , Ibsen Hans , O'Brien Eoin , Staessen Jan A.
Published: June 2008

The evidence relating mortality and morbidity to heart rate remains inconsistent. We performed 24-hour ambulatory blood pressure monitoring in 6928 subjects (not on β-blockers; mean age: 56.2 years; 46.5% women) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We computed standardized hazard ratios for heart rate, while stratifying for cohort, and adjusting for blood pressure and other cardiovascular risk factors. Over 9.6 years (median), 850, 325, and 493 deaths accrued for total, cardiovascular, and noncardiovascular mortality, respectively. The incidence of fatal combined with nonfatal end points was 805, 363, 439, and 324 for cardiovascular, stroke, cardiac, and coronary events, respectively. Twenty-four-hour heart rate predicted total (hazard ratio: 1.15) and noncardiovascular (hazard ratio: 1.18) mortality but not cardiovascular mortality (hazard ratio: 1.11) or any of the fatal combined with nonfatal events (hazard ratio: ≤1.02). Daytime heart rate did not predict mortality (hazard ratio: ≤1.11) or any fatal combined with nonfatal event (hazard ratio: ≤0.96). Nighttime heart rate predicted all of the mortality outcomes (hazard ratio: ≥1.15) but none of the fatal combined with nonfatal events (hazard ratio: ≤1.11). The night:day heart rate ratio predicted total (hazard ratio: 1.14) and noncardiovascular mortality (hazard ratio: 1.12) and all of the fatal combined with nonfatal events (hazard ratio: ≥1.15) with the exception of stroke (hazard ratio: 1.06). Sensitivity analyses, in which we stratified by risk factors or from which we excluded 1 cohort at a time or the events occurring within 2 years of enrollment, showed consistent results. In the general population, heart rate predicts total and noncardiovascular mortality. With the exception of the night:day heart rate ratio, heart rate did not add to the risk stratification for fatal combined with nonfatal cardiovascular events. Thus, heart rate adds little to the prediction of cardiovascular risk.
Identifying Semitic Roots: Machine Learning with Linguistic Constraints
Authors: Daya Ezra , Roth Dan , Wintner Shuly
Published: June 2008

Words in Semitic languages are formed by combining two morphemes: a root and a pattern. The root consists of consonants only, by default three, and the pattern is a combination of vowels and consonants, with non-consecutive “slots” into which the root consonants are inserted. Identifying the root of a given word is an important task, considered to be an essential part of the morphological analysis of Semitic languages, and information on roots is important for linguistics research as well as for practical applications. We present a machine learning approach, augmented by limited linguistic knowledge, to the problem of identifying the roots of Semitic words. Although programs exist which can extract the root of words in Arabic and Hebrew, they are all dependent on labor-intensive construction of large-scale lexicons which are components of full-scale morphological analyzers. The advantage of our method is an automation of this process, avoiding the bottleneck of having to laboriously list the root and pattern of each lexeme in the language. To the best of our knowledge, this is the first application of machine learning to this problem, and one of the few attempts to directly address non-concatenative morphology using machine learning. More generally, our results shed light on the problem of combining classifiers under (linguistically motivated) constraints.
Dependency Parsing of Turkish
Authors: Eryiğit Gülşen , Nivre Joakim , Oflazer Kemal
Published: June 2008

The suitability of different parsing methods for different languages is an important topic in syntactic parsing. Especially lesser-studied languages, typologically different from the languages for which methods have originally been developed, pose interesting challenges in this respect. This article presents an investigation of data-driven dependency parsing of Turkish, an agglutinative, free constituent order language that can be seen as the representative of a wider class of languages of similar type. Our investigations show that morphological structure plays an essential role in finding syntactic relations in such a language. In particular, we show that employing sublexical units called inflectional groups, rather than word forms, as the basic parsing units improves parsing accuracy. We test our claim on two different parsing methods, one based on a probabilistic model with beam search and the other based on discriminative classifiers and a deterministic parsing strategy, and show that the usefulness of sublexical units holds regardless of the parsing method. We examine the impact of morphological and lexical information in detail and show that, properly used, this kind of information can improve parsing accuracy substantially. Applying the techniques presented in this article, we achieve the highest reported accuracy for parsing the Turkish Treebank.
Training Tree Transducers
Authors: Graehl Jonathan , Knight Kevin , May Jonathan
Published: June 2008

Many probabilistic models for natural language are now written in terms of hierarchical tree structure. Tree-based modeling still lacks many of the standard tools taken for granted in (finite-state) string-based modeling. The theory of tree transducer automata provides a possible framework to draw on, as it has been worked out in an extensive literature. We motivate the use of tree transducers for natural language and address the training problem for probabilistic tree-to-tree and tree-to-string transducers.
Lagrangian Transport through an Ocean Front in the Northwestern Mediterranean Sea
Authors: Mancho Ana M. , Hernández-García Emilio , Small Des , Wiggins Stephen , Fernández Vicente
Published: June 2008

With the tools of lobe dynamics, the authors analyze the structures present in the velocity field obtained from a numerical simulation of the surface circulation in the northwestern Mediterranean Sea. In particular, focus is placed on the North Balearic Front, the westernmost part of the transition zone between saltier and fresher waters in the western Mediterranean, which is here interpreted in terms of the presence of a semipermanent “Lagrangian barrier,” across which little transport occurs. Identified are relevant hyperbolic trajectories and their manifolds, and it is shown that the transport mechanism known as the turnstile, previously identified in abstract dynamical systems and simplified model flows, is also at work in this complex and realistic ocean flow. In addition, nonlinear dynamics techniques are shown to be powerful enough to identify the key geometric structures in this part of the Mediterranean. The construction also reveals the spatiotemporal routes along which this transport happens. Topological changes in that picture, which are associated with the crossing by eddies and may be interpreted as the breakdown of the front, are also observed during the simulation.
Boundary Mixing Associated with Tidal and Near-Inertial Internal Waves
Authors: Aucan Jerome , Merrifield Mark
Published: June 2008

Moorings deployed on the south (August–November 2002) and north (November 2002–June 2003) flanks of the Kaena Ridge, Hawaii, are used to document the flow variability associated with mixing within 200 m from the boundary, deep along the ridge, as part of the Hawaii Ocean Mixing Experiment (HOME). At both sites, strong temperature inversions are detected with vertical scales of ∼100 m. A Thorpe-scale analysis of the overturns yields a time-averaged dissipation near the bottom at the south site (1.2 × 10−8 W kg−1) that is 10 times higher than the north site (1.9 × 10−9 W kg−1), with both higher than the dissipation at similar depths 30 km from the ridge. On the south flank, observed horizontal currents and vertical displacements are dominated by the semidiurnal internal tide. On the north flank, the semidiurnal tide is less energetic than on the south, with a different vertical structure as tidal amplitudes decrease toward the boundary. These differences are attributed to greater separation from the bottom of downward-propagating internal tides at the north site compared to the south site, resulting in higher mixing at the south site. Near the boundary, near-inertial to diurnal oscillations are more energetic at the north than the south site. This asymmetry is attributed to near-inertial internal waves that are generated north of the ridge by winter storms; the ridge shadows the equatorward-propagating near-inertial internal waves leading to negligible amplitudes on the southern lee side. The near-inertial waves combine with internal tidal motions to create high strain conditions that lead to mixing at the north site.
The Mechanical Energy Input to the Ocean Induced by Tropical Cyclones
Authors: Liu Ling Ling , Wang Wei , Huang Rui Xin
Published: June 2008

Wind stress and tidal dissipation are the most important sources of mechanical energy for maintaining the oceanic general circulation. The contribution of mechanical energy due to tropical cyclones can be a vitally important factor in regulating the oceanic general circulation and its variability. However, previous estimates of wind stress energy input were based on low-resolution wind stress data in which strong nonlinear events, such as tropical cyclones, were smoothed out.

Using a hurricane–ocean coupled model constructed from an axisymmetric hurricane model and a three-layer ocean model, the rate of energy input to the world’s oceans induced by tropical cyclones over the period from 1984 to 2003 was estimated. The energy input is estimated as follows: 1.62 TW to the surface waves and 0.10 TW to the surface currents (including 0.03 TW to the near-inertial motions). The rate of gravitational potential energy increase due to tropical cyclones is 0.05 TW. Both the energy input from tropical cyclones and the increase of gravitational potential energy of the ocean show strong interannual and decadal variability with an increasing rate of 16% over the past 20 years. The annual mean diapycnal upwelling induced by tropical cyclones over the past 20 years is estimated as 39 Sv (Sv ≡ 106 m3 s−1). Owing to tropical cyclones, diapycnal mixing in the upper ocean (below the mixed layer) is greatly enhanced. Within the regimes of strong activity of tropical cyclones, the increase of diapycnal diffusivity is on the order of (1 − 6) × 10−4 m2 s−1. The tropical cyclone–related energy input and diapycnal mixing may play an important role in climate variability, ecology, fishery, and environments.
Parameterization of Mixed Layer Eddies. Part II: Prognosis and Impact
Authors: Fox-Kemper Baylor , Ferrari Raffaele
Published: June 2008

The authors propose a parameterization for restratification by mixed layer eddies that develop from baroclinic instabilities of ocean fronts. The parameterization is cast as an overturning streamfunction that is proportional to the product of horizontal buoyancy gradient, mixed layer depth, and inertial period. The parameterization has remarkable skill for an extremely wide range of mixed layer depths, rotation rates, and vertical and horizontal stratifications. In this paper a coarse resolution prognostic model of the parameterization is compared with submesoscale mixed layer eddy resolving simulations. The parameterization proves accurate in predicting changes to the buoyancy. The climate implications of the proposed parameterization are estimated by applying the restratification scaling to observations: the mixed layer depth is estimated from climatology, and the buoyancy gradients are from satellite altimetry. The vertical fluxes are comparable to monthly mean air–sea fluxes in large areas of the ocean and suggest that restratification by mixed layer eddies is a leading order process in the upper ocean. Critical regions for ocean–atmosphere interaction, such as deep, intermediate, and mode water formation sites, are particularly affected.
Parameterization of Mixed Layer Eddies. Part I: Theory and Diagnosis
Authors: Fox-Kemper Baylor , Ferrari Raffaele , Hallberg Robert
Published: June 2008

Ageostrophic baroclinic instabilities develop within the surface mixed layer of the ocean at horizontal fronts and efficiently restratify the upper ocean. In this paper a parameterization for the restratification driven by finite-amplitude baroclinic instabilities of the mixed layer is proposed in terms of an overturning streamfunction that tilts isopycnals from the vertical to the horizontal. The streamfunction is proportional to the product of the horizontal density gradient, the mixed layer depth squared, and the inertial period. Hence restratification proceeds faster at strong fronts in deep mixed layers with a weak latitude dependence. In this paper the parameterization is theoretically motivated, confirmed to perform well for a wide range of mixed layer depths, rotation rates, and vertical and horizontal stratifications. It is shown to be superior to alternative extant parameterizations of baroclinic instability for the problem of mixed layer restratification. Two companion papers discuss the numerical implementation and the climate impacts of this parameterization.
On the Weakly Nonlinear Ekman Layer: Thickness and Flux
Authors: Pedlosky Joseph
Published: June 2008

The first-order effects of nonlinearity on the thickness and frictionally driven flux in the Ekman layer are described for the case of an Ekman layer on a solid, flat plate driven by an overlying geostrophic flow as well as the Ekman layer on a free surface driven by a wind stress in the presence of a deep geostrophic current. In both examples, the fluid is homogeneous. Particular attention is paid to the effect of nonlinearity in determining the thickness of the Ekman layer in both cases. An analytical expression for the Ekman layer thickness as a function of Rossby number is given when the Rossby number is small. The result is obtained by insisting that the perturbation expansion of the Ekman problem in powers of the Rossby number remains uniformly valid. There are two competing physical effects. The relative vorticity of the geostrophic currents tends to reduce the width of the layer, but the vertical velocity induced in the layer can fatten or thin the layer depending on the sign of the vertical velocity. The regularized expansion is shown to give, to lowest order, expressions for the flux in agreement with earlier calculations.
Gyres and Jets: Inversion of Tracer Data for Ocean Circulation Structure
Authors: Herbei Radu , McKeague Ian W. , Speer Kevin G.
Published: June 2008

This paper describes a quasi-3D Bayesian inversion of oceanographic tracer data from the South Atlantic Ocean. Initially, one active neutral-density layer is considered with an upper and lower boundary. The available hydrographic data are linked to model parameters (water velocities, diffusion coefficients) via a 3D advection–diffusion equation. A robust solution to the inverse problem can be obtained by introducing prior information about parameters and modeling the observation error. This approach estimates both horizontal and vertical flow as well as diffusion coefficients. A system of alternating zonal jets is found at the depths of the North Atlantic Deep Water, consistent with direct measurements of flow and concentration maps. A uniqueness analysis of the model is performed in terms of the oxygen consumption rate. The vertical mixing coefficient bears some relation to the bottom topography even though the authors do not incorporate topography into their model. The method is extended to a multilayer model, using thermal wind relations weakly in a local fashion (as opposed to integrating the entire water column) to connect layers vertically. Results suggest that the estimated deep zonal jets extend vertically, with a clear depth-dependent structure. The vertical structure of the flow field is modified by the tracer fields relative to the a priori flow field defined by thermal wind. The velocity estimates are consistent with independent observed flow at the depths of the Antarctic Intermediate Water; at still shallower depths, above the layers considered here, the subtropical gyre is a significant feature of the horizontal flow.
Dissecting Aortic Aneurysm in Childhood and Adolescence
Authors: Fikar Charles R. , Amrhein James A. , Harris J. Peter , Lewis Evelyn R.
Published: June 2008

A 15-year-old adolescent male with dissecting aortic aneurysm is presented. His young age, lack of predisposing factors, and fulminant course with rapid progression to death precluded a correct antemortem diagnosis. Review of the literature reveals that most instances of dissecting aortic aneurysm in childhood and adolescence are associated with predisposing conditions, es pecially congenital cardiovascular anomalies. The clinical picture is generally characteristic. Prompt evaluation and therapy may be lifesaving.
Refractory Hypertension in an Otherwise Healthy Adolescent
Authors: Davis Charles A. , Kallen Ronald J. , Goldberg Alan D.
Published: June 2008

Severe hypertension, for which no cause could be found, developed in an adolescent female. The patient's blood pressure was refractory to intensive pharmacologtc intervention. After 1½ years of medical management, the patient's intra-arterial blood pressures were found to be in the normotensive range. Individuals with labile hypertension may be refractory to pharmacologic control and may require continuous pressure monitoring in order to establish a proper diagnosis.
The Thoracic Outlet Syndrome Produced by Costochondritis
Authors: Pasquariello P.S. , Sherk Henry H. , Miller James E.
Published: June 2008

Thoracic outlet syndrome (TOS) is a rare condition in children. Compression of the neurvascular bundle as it passes from the neck through the thorax into the arm may be produced by numerous anatomic and structural abnormalities. This case represents compression produced by spasm of the pectoralis minor muscle originating from costochondritis.