bluuebunny/crossref_metadata_2025 huggingface dataset:
SCHEDULING TWO-MACHINE FLOW SHOPS WITH EXACT DELAYS
Authors: LEUNG JOSEPH Y.-T. , LI HAIBING , ZHAO HAIRONG
Published: April 2007

We consider two-machine flow shop problems with exact delays. In this model, there are two machines, the upstream machine and the downstream machine. Each job j has two operations: the first operation has to be processed on the upstream machine and the second operation has to be processed on the downstream machine, subject to the constraint that the time interval between the completion time of the first operation and the start time of the second operation is exactly [Formula: see text]. We concentrate on the objectives of makespan and total completion time. For the makespan objective, we first show that the problem is strongly NP-hard even if there are only two possible delay values. We then show that some special cases of the problem are solvable in polynomial time. Finally, we design efficient approximation algorithms for the general case and some special cases. For the total completion time objective, we give optimal polynomial-time algorithm for a special case and an efficient approximation algorithm for another one.
SHRINKING RESTARTING AUTOMATA
Authors: JURDZIŃSKI TOMASZ , OTTO FRIEDRICH
Published: April 2007

Restarting automata were introduced by Jančar et al. to model the so-called analysis by reduction. A computation of a restarting automaton consists of a sequence of cycles such that in each cycle the automaton performs exactly one rewrite step, which replaces a small part of the tape content by another, even shorter word. Here we consider a natural generalization of this model, called shrinking restarting automaton, where we only require that there exists a weight function such that each rewrite step decreases the weight of the tape content with respect to that function. While it is still unknown whether the two most general types of one-way restarting automata, the RWW-automaton and the RRWW-automaton, differ in their expressive power, we will see that the classes of languages accepted by the shrinking RWW-automaton and the shrinking RRWW-automaton coincide. As a consequence of our proof, it turns out that there exists a reduction by morphisms from the language class [Formula: see text] to the class [Formula: see text]. Further, we will see that the shrinking restarting automaton is a rather robust model of computation. Finally, we will relate shrinking RRWW-automata to finite-change automata. This will lead to some new insights into the relationships between the classes of languages characterized by (shrinking) restarting automata and some well-known time and space complexity classes.
ONLINE AND DYNAMIC RECOGNITION OF SQUAREFREE STRINGS
Authors: JANSSON JESPER , PENG ZESHAN
Published: April 2007

The online squarefree recognition problem is to detect the first occurrence of a square in a string whose characters are provided as input one at a time. We present an efficient algorithm to solve this problem for strings over arbitrarily ordered alphabets in O(n log n) time, where n is the ending position of the first square. We also note that the same technique yields an O(n·(|Σn|+ log n))-time algorithm for general alphabets, where |Σn| is the number of different symbols in the first n positions of the input string. (This is faster than the previously fastest method for general alphabets when |Σn| = o( log 2 n).) Finally, we present a simple algorithm for a dynamic version of the problem over general alphabets in which we are initially given a squarefree string, followed by a series of updates, and the objective is to determine after each update if the resulting string is still squarefree.
ON THE POWER OF DETERMINISTIC AND SEQUENTIAL COMMUNICATING P SYSTEMS
Authors: CIENCIALA LUDĚK , CIENCIALOVÁ LUCIE , FRISCO PIERLUIGI , SOSÍK PETR
Published: April 2007

We characterize the computational power of several restricted variants of communicating P systems. We show that 2-deterministic communicating P systems with 2 membranes, working in either minimally or maximally parallel mode, are computationally universal. Considering the sequential mode, 2 membranes are shown to characterize the power of partially blind multicounter machines. Next, a characterization of the power of 1-deterministic communicating P systems is given. Finally, we show that the nondeterministic variant in maximally parallel mode is universal already with 1 membrane. These results demonstrate differences in computational power between nondeterminism, 2-determinism and 1-determinism, on one hand, and between sequential, minimally and maximally parallel modes, on the other hand.
ADAPTIVE INFORMATION ACCESS: PERSONALIZATION AND PRIVACY
Authors: SMYTH BARRY
Published: April 2007

As online information continues to grow at an exponential rate our ability to access this information effectively does not, and users are often frustrated by how difficult it is to locate the right information quickly and easily. So-called personalization technology is a potential solution to this information overload problem: by automatically learning about the needs and preferences of users, personalized information access solutions have the potential to offer users a more proactive and intelligent form of information access that is sensitive to their long-term preferences and current needs. In this paper, we document two case-studies of the use of personalization techniques to support information browsing and search. In addition, we consider the inevitable privacy issues that go hand-in-hand with profiling and personalization techniques and highlight the importance of striking the right balance between privacy and personalization when it comes to the development and deployment of practical systems.
AVATAR: ENHANCING THE PERSONALIZED TELEVISION BY SEMANTIC INFERENCE
Authors: FERNÁNDEZ YOLANDA BLANCO , ARIAS JOSÉ J. PAZOS , SOLLA ALBERTO GIL , CABRER MANUEL RAMOS , NORES MARTÍN LÓPEZ , DUQUE JORGE GARCÍA , VILAS ANA FERNÁNDEZ , REDONDO REBECA P. DÍAZ , MUŃOZ JESÚS BERMEJO
Published: April 2007

The generalized arrival of Digital TV will lead to a significant increase in the amount of channels and programs available to end users, making it difficult to find interesting programs among a myriad of irrelevant contents. Thus, in this field, automatic content recommenders should receive special attention in the following years to improve assistance to users. Current approaches of content recommenders have significant well-known deficiencies that hamper their wide acceptance. In this paper, a new approach for automatic content recommendation is presented that considerably reduces those deficiencies. This approach, based on the so-called Semantic Web technologies, has been implemented in the AVATAR tool, a hybrid content recommender that makes extensive use of well-known standards, such as TV-Anytime and OWL. Our proposal has been evaluated experimentally with real users, showing significant increases in the recommendation accuracy with respect to other existing approaches.
SUBSUMPTION DEGREES BETWEEN ENTITY TYPES AND NAMES FOR APPROXIMATE KNOWLEDGE RETRIEVAL
Authors: CAO TRU H. , HUYNH DAT T.
Published: April 2007

The Web has become a huge and indispensable source of information to be used and shared globally, where knowledge is commonly represented and stored in RDF, or alternatively, in conceptual graphs. Managing and searching for web information have gone beyond the relational database model, as the data are semi-structured and inexact answers are often the case. Usually, approximate searching results are due to mismatching between entity types and names in a query and an answer. Firstly, this research work focuses on partial subsumption of a query graph to an answer graph, which is an unsymmetric measure in contrast to similarity. Secondly, it proposes a population-based method for defining subsumption degrees between entity types, one to another, and a class-sensitive soft TF-IDF method for entity names. Lastly, on the one hand, for a user-friendly interface and easily readable query expressions, conceptual graphs are employed at the front-end. On the other hand, in order to take the advantage of the existing platform of SeRQL, an exact RDF query language, the query modification tactic is used to retrieve the knowledge graphs that are close to a query graph, before the subsumption degrees of the query graph to those answer graphs are calculated.
MONITORING EVENT FLOWS AND MODELLING SCENARIOS FOR CRISIS PREDICTION: APPLICATION TO ETHNIC CONFLICTS FORECASTING
Authors: DELAVALLADE THOMAS , MOUILLET LAURE , BOUCHON-MEUNIER BERNADETTE , COLLAIN EMMANUEL
Published: April 2007

We have developed an early warning prototype, based on a knowledge management approach, so as to carry out the online detection of crises. Experts, with the help of automatic tools, design an ontology describing domain-specific crisis eruption processes. Then a recognition engine performs model-based inference, in order to identify among the events feeding the system, typical sequences that might trigger a crisis. Crises are described in the ontology through the template technique which provides also mechanisms to assess the similarity between stored scenarios and event flows related to the monitored process. This technique takes into account imperfect knowledge and uncertainties: for instance, imprecise temporal constraints between events are represented by fuzzy sets.
Rational Speculative Bubbles in the Thai Stock Market: Econometric Tests and Implications
Authors: Watanapalachaikul Sethapong , Islam Sardar M. N.
Published: April 2007

Understanding of factors like economic fundamentals or bubbles that normally determine the returns of stock in any emerging market such as the Thai stock market is essential for academic, investment planning and public policy reasons. An empirical study of the existence of rational speculative bubbles in the Thai stock market is undertaken by using the Weibull Hazard model. The conventional Weibull Hazard model is used as a benchmark model for other speculative bubble models. Empirical results suggest the presence of rational speculative bubbles in the Thai stock market, especially during the pre-crisis period. While rational speculative bubbles were not present immediately after the post-crisis period, some were observed a few years after the crisis. A possible explanation for such a result concerning rational speculative behaviour and bubbles in the emerging stock markets could be attributed to the presence of market imperfections in emerging stock markets, requiring institutional and policy developments to ensure efficient operation of the stock market.
Do Asian Stock Markets Follow a Random Walk? Evidence from LM Unit Root Tests with One and Two Structural Breaks
Authors: Lean Hooi Hooi , Smyth Russell
Published: April 2007

This paper applies univariate and panel Lagrange Multiplier (LM) unit root tests with one and two structural breaks to examine the random walk hypothesis for stock prices in eight Asian countries. The results from the univariate LM unit root tests and panel LM unit root test with one structural break suggest that stock prices in each country is characterized by a random walk, but the findings from the panel LM unit root test with two structural breaks suggest that stock prices in the eight countries are mean reverting.
The Effects of Foreign Bank Entry on the Thai Banking Market: Empirical Analysis from 1990 to 2002
Authors: Okuda Hidenobu , Rungsomboon Suvadee
Published: April 2007

This paper investigates the impact of foreign bank entry on Thai domestic banks by using panel data on 17 domestic commercial banks from 1990 to 2002. The study examines different factors affecting bank performance, including changes in the foreign ownership of banks, financial regulations, and market structure. The results show that an increase in the presence of foreign banks has led to a rise in overhead expenses, a decline in profits, and an increase in the interest spreads of domestic banks. In the short run, increased competition from foreign banks seems to have negative effects on domestic banks.
Explaining the Risk/Return Mismatch of the MSCI China Index: A Systematic Risk Analysis
Authors: Liang Priscilla
Published: April 2007

This study examines a risk/return mismatch of the MSCI China Index, which has offered investors low returns and high volatility, yet remains a favorite within the global investors' portfolio. The paper suggests several insights, both from behavioral and traditional finance perspectives, to explain this mismatch. An international risk decomposition model is applied to separate the total risk of China's index return into global systematic risks, regional systematic risks and country specific risks. It suggests the index's lower than average systematic risk might be one of the explanations for its risk/return mismatch. The study also finds that the China Index's systematic risks, both global and regional, have been increasing, but more so at the global level.
ORGANISATIONAL SUSTAINABILITY: A CASE FOR FORMULATING A TAILOR-MADE DEFINITION
Authors: KIEWIET DERK JAN , VOS JANITA F. J.
Published: April 2007

Making sustainability operational within organisational practice requires dealing with three interrelated questions: A "what-question", an "attribute-question" and a "who-question". The complexity of these questions needs a tailor-made interpretation of sustainability. This paper provides a framework that can be used for obtaining such a tailor-made interpretation of sustainability. This framework is based on the notion that staff members somehow need to make sense of sustainability. By taking a cognitive mapping approach, a multidimensional space of sustainability can be deduced. The interpretation of the dimensions of this space can then provide a definition of sustainability. We illustrate the framework by obtaining an image of sustainability for a firm of consulting engineers.
WATER SUPPLY VULNERABILITY ASSESSMENT FOR SUSTAINABLE LIVELIHOODS
Authors: HADIPURO WIJANTO
Published: April 2007

All the United Nations' members have already committed to achieve the Millennium Development Goals (MDGs) to reduce by half the proportion of 1.1 billion people without sustainable access to safe drinking water by 2015. The problem is that with all the limiting capacities, which half should be prioritized and what kind of policy intervention can be used to achieve the goal.

This paper proposes a methodology on water supply vulnerability assessment, specifically for meeting basic human needs. Based on the impacts to the five assets owned by a certain household and the causes of the lack of access, the policy intervention can be tailored made as to what problems the community faces. Hopefully the method can be used by multilateral donors or agencies and all levels of government to focus on a certain community or area that should be prioritized to meet the MDG target.
HYPER-SPECTRAL DATA CLUSTERING METHOD BASED UPON THE SENSITIVE SUBSPACE
Authors: ZHAO WENCANG , WANG WEI
Published: April 2007

We put forward a quick clustering method for large numbers of data, with high dimensions, which is based on sensitive subspace consisting of the data set's sensitive dimensions. We first estimate the probability density of each dimension by the parzen window algorithm, enhance its optional ability through extracting zeroes and smoothness processing, then through the recognition of the number of the rallying points and the gain of the sensitive dimensions in order to compose the sensitive subspace, and lastly, we perform the Rival Penalized Competitive Learning (RPCL) clustering in the subspace. Moreover, we detected the red tide of hyper-spectral data using this method. Furthermore, the overall improvement in terms of the computational speed is about nine times faster.
MONTE CARLO METHODS IN FUZZY GAME THEORY
Authors: ABDALLA AREEG , BUCKLEY JAMES
Published: April 2007

In this paper, we consider a two-person zero-sum game with fuzzy payoffs and fuzzy mixed strategies for both players. We define the fuzzy value of the game for both players [Formula: see text] and also define an optimal fuzzy mixed strategy for both players. We then employ our fuzzy Monte Carlo method to produce approximate solutions, to an example fuzzy game, for the fuzzy values [Formula: see text] for Player I and [Formula: see text] for Player II; and also approximate solutions for the optimal fuzzy mixed strategies for both players. We then look at [Formula: see text] and [Formula: see text] to see if there is a Minimax theorem [Formula: see text] for this fuzzy game.
Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy
Authors: Shi Haifei , Strader April D. , Woods Stephen C. , Seeley Randy J.
Published: April 2007

White adipose tissue is the principal site for lipid accumulation. Males and females maintain distinctive white adipose tissue distribution patterns. Specifically, males tend to accumulate relatively more visceral fat, whereas females accumulate relatively more subcutaneous fat. The phenomenon of maintaining typical sex-specific fat distributions suggests sex-specific mechanisms that regulate energy balance and adiposity. We used two distinct approaches to reduce fat mass, caloric restriction (CR), and surgical fat removal (termed lipectomy) and assessed parameters involved in the regulation of energy balance. We found that male and female mice responded differentially to CR- and to lipectomy-induced fat loss. Females decreased energy expenditure during CR or after lipectomy. In contrast, males responded by eating more food during food return after CR or after lipectomy. Female CR mice conserved subcutaneous fat, whereas male CR mice lost adiposity equally in the subcutaneous and visceral depots. In addition, female mice had a reduced capability to restore visceral fat after fat loss. After CR, plasma leptin levels decreased in male but not in female mice. The failure to increase food intake after returning to ad libitum intake in females could be due to the relatively stable levels of leptin. In summary, we have found sexual dimorphisms in the response to fat loss that point to important underlying differences in the strategies by which male and female mice regulate body weight.
Targeted Imaging of Colonic Tumors in Smad3−/− Mice Discriminates Cancer and Inflammation
Authors: Deane Natasha G. , Manning H. Charles , Foutch A. Coe , Washington M. Kay , Aronow Bruce A. , Bornhop Darryl J. , Coffey Robert J.
Published: April 2007

The peripheral benzodiazepine receptor (PBR) is a trans-mitochondrial membrane protein that modulates steroid biosynthesis. Recently, up-regulation and nuclear localization of PBR has been shown to be associated with colon, prostate, and breast cancer. PBR has been targeted by the exogenous synthetic ligand, PK11195, for various purposes including imaging. To capitalize on these observations, we developed a high-throughput, noninvasive, in vivo imaging approach to detect spontaneously arising colonic tumors in mice using a novel PBR-targeted molecular imaging agent (NIR-conPK11195). NIR-conPK11195 localized and was retained in colonic adenomas and carcinomas in Smad3−/− mice but not in non-neoplastic hamartomas or chronically inflamed colonic tissue. Using a fluorescence signal-to-noise ratio of ≥4-fold 13 h after injection of the agent, we detected colonic tumors with a sensitivity of 67% and a specificity of 86% in a cohort of 37 Smad3−/− mice and control littermates. Furthermore, using oral administration of dextran sulfate to induce colonic inflammation, we showed that the clearance profile of NIR-conPK11195 distinguished transient uptake in inflammatory tissue from longer term retention in tumors. Taken together, these results indicate that NIR-conPK11195 is a promising optical molecular imaging tool to rapidly screen for colonic tumors in mice and to discriminate inflammation from cancer. (Mol Cancer Res 2007;5(4):341–9)
Loss of p53 Expression Correlates with Metastatic Phenotype and Transcriptional Profile in a New Mouse Model of Head and Neck Cancer
Authors: Ku Tony K.S. , Nguyen Dan C. , Karaman Mazen , Gill Parkash , Hacia Joseph G. , Crowe David L.
Published: April 2007

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most frequent cancer worldwide. Because HNSCC is largely acquired by environmental carcinogen exposure rather than through germ line mutations, there are no known familial forms of the disease in humans nor are there inbred rodent strains prone to spontaneous head and neck tumors. Transgenic animals with inactivation of tumor suppressor genes commonly mutated in human cases of HNSCC provide attractive models for studying the pathogenesis of head and neck cancer. p53 is the most frequently inactivated tumor suppressor gene in HNSCC. We used a chemical induction protocol in mice heterozygous for the p53 gene to evaluate how p53 inactivation contributed to head and neck carcinogenesis the mouse model. Metastatic squamous cell carcinomas developed in 100% of animals. Histopathologically, the tumors ranged from well to poorly differentiated and showed many molecular features of human HNSCC. Mice carrying only one p53 allele developed tumors with significantly reduced latency compared with wild-type controls (average, 18 versus 22 weeks). Metastatic cancer cells showed complete loss of p53 expression when compared with primary tumors. Transcriptional profiling showed not only distinct genetic differences between primary and metastatic tumors, but also when cancers from heterozygous null and wild-type animals were compared. Our results provide novel insights into the molecular genetics of tumor progression in head and neck cancer. (Mol Cancer Res 2007;5(4):351–62)
HMGA2 Regulates Transcription of the Imp2 Gene via an Intronic Regulatory Element in Cooperation with Nuclear Factor-κB
Authors: Cleynen Isabelle , Brants Jan R. , Peeters Kristel , Deckers Rob , Debiec-Rychter Maria , Sciot Raf , Van de Ven Wim J.M. , Petit Marleen M.R.
Published: April 2007

IMP2 (insulin-like growth factor-II mRNA binding protein 2) is an oncofetal protein that is aberrantly expressed in several types of cancer. We recently identified the Imp2 gene as a target gene of the architectural transcription factor HMGA2 (high mobility group A2) and its tumor-specific truncated form HMGA2Tr. In this study, we investigated the mechanism via which HMGA2 regulates Imp2 gene expression. We show that HMGA2 and HMGA2Tr directly regulate transcription of the Imp2 gene by binding to an AT-rich regulatory region located in the first intron. In reporter experiments, we show that this AT-rich regulatory region mimics the response of the endogenous Imp2 gene to HMGA2 and HMGA2Tr. Furthermore, we show that a consensus nuclear factor-κB (NF-κB) binding site located immediately adjacent to the AT-rich regulatory region binds NF-κB and that NF-κB and HMGA2 cooperate to regulate Imp2 gene expression. Finally, we provide evidence that there is a strong and statistically significant correlation between HMGA2 and IMP2 gene expression in human liposarcomas. (Mol Cancer Res 2007;5(4):363–72)
Randomized Trial Comparing Same-Day Discharge With Overnight Hospital Stay After Percutaneous Coronary Intervention
Authors: Heyde Gerlind S. , Koch Karel T. , de Winter Robbert J. , Dijkgraaf Marcel G.W. , Klees Margriet I. , Dijksman Lea M. , Piek Jan J. , Tijssen Jan G.P.
Published: April 2007

Background—

Percutaneous coronary intervention (PCI) in a day-case setting might reduce logistic constraints on hospital resources, but data on safety are limited. We evaluated the safety and feasibility of same-day discharge after PCI.

Methods and Results—

Eight hundred consecutive patients scheduled for elective PCI by femoral approach were randomized to same-day discharge or overnight hospital stay. Four hours after PCI, patients were triaged as suitable for early discharge or not. Suitable patients were discharged immediately or kept overnight, according to randomization. Patients with an indication for extended hospital stay were not discharged regardless of randomization. Primary end points were death, myocardial infarction, coronary artery bypass graft surgery, repeat PCI, or puncture-related complications occurring within 24 hours after PCI. A total of 403 patients were assigned to same-day discharge, of whom 77 (19%) were identified for extended observation; 397 patients were assigned to overnight stay, of whom 85 (21%) were identified for extended observation. Among all patients, the composite primary end point occurred in 9 (2.2%) same-day discharge patients and in 17 (4.2%) overnight stay patients (risk difference, −0.020; 95% CI, −0.045 to −0.004;
P
for noninferiority <0.0001). Among patients deemed suitable for early discharge, the composite end point occurred in 1 of 326 (0.3%) same-day discharge patients and 2 of 312 (0.6%) overnight-stay patients (risk difference, −0.003; 95% CI, −0.014 to 0.007;
P
for noninferiority <0.0001). The last 3 events were related to puncture site.

Conclusions—

Same-day discharge after elective PCI is feasible and safe in the majority (80%) of patients selected for day-case PCI. Same-day discharge does not lead to additional complications compared with overnight stay.
Defining Obesity Cut Points in a Multiethnic Population
Authors: Razak Fahad , Anand Sonia S. , Shannon Harry , Vuksan Vladimir , Davis Bonnie , Jacobs Ruby , Teo Koon K. , McQueen Matthew , Yusuf Salim
Published: April 2007

Background—

Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI >30 kg/m
2
) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans.

Methods and Results—

We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207 Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or “hidden” factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure–related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by ≈6 kg/m
2
among non-European groups compared with Europeans.

Conclusions—

Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.
Compartmentalization of Cardiac β-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5
Authors: Takimoto Eiki , Belardi Diego , Tocchetti Carlo G. , Vahebi Susan , Cormaci Gianfrancesco , Ketner Elizabeth A. , Moens An L. , Champion Hunter C. , Kass David A.
Published: April 2007

Background—

Recent cell-based studies have found that cGMP synthesis and hydrolysis by phosphodiesterase (PDE) appear compartmentalized, with nitric oxide synthase–derived and/or PDE type 5 (PDE-5)–hydrolyzable cGMP undetected at the sarcolemmal membrane in contrast to cGMP stimulated by natriuretic peptide. In the present study, we determine the functional significance of such compartments with a comparison of β-adrenergic modulation by PDE-5 inhibition to that of natriuretic peptide stimulation in both cardiomyocytes and intact hearts. The potential role of differential cGMP and protein kinase G stimulation by these 2 modulators was also studied.

Methods and Results—

Intact C57/BL6 mouse hearts were studied with pressure-volume analysis, and adult isolated myocytes were studied with fluorescence microscopy. PDE-5 inhibition with 0.1 to 1 μmol/L sildenafil (SIL) suppressed isoproterenol (ISO)-stimulated contractility, whereas 10 μmol/L atrial natriuretic peptide (ANP) had no effect. ISO suppression by SIL was prevented in cells pretreated with a protein kinase G inhibitor. Surprisingly, myocardial cGMP changed little with SIL+ISO yet rose nearly 5-fold with ANP, whereas protein kinase G activation (vasodilator-stimulated protein phosphorylation; ELISA assay) displayed the opposite: increased with SIL+ISO but unaltered by ANP+ISO. PDE-5 and ANP compartments were functionally separated, as inhibition of nitric oxide synthase by N
w
-nitro-L-arginine methyl ester eliminated antiadrenergic effects of SIL, yet this was not restorable by co-stimulation with ANP.

Conclusions—

Regulation of cardiac β-adrenergic response by cGMP is specifically linked to a nitric oxide–synthesis/PDE-5–hydrolyzed pool signaling via protein kinase G. Natriuretic peptide stimulation achieves greater detectable increases in cGMP but not protein kinase G activity and does not modulate β-adrenergic response. Such disparities likely contribute to differential cardiac regulation by drugs that modulate cGMP synthesis and hydrolysis.
Predictors of Outcome in Chronic Thromboembolic Pulmonary Hypertension
Authors: Bonderman Diana , Skoro-Sajer Nika , Jakowitsch Johannes , Adlbrecht Christopher , Dunkler Daniela , Taghavi Sharokh , Klepetko Walter , Kneussl Meinhard , Lang Irene M.
Published: April 2007

Background—

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intraluminal thrombus organization and fibrous obliteration of pulmonary arteries. Recently, associated medical conditions such as splenectomy, ventriculoatrial shunt for the treatment of hydrocephalus, permanent central intravenous lines, inflammatory bowel disease, and osteomyelitis were found to be associated with the development of CTEPH. The study aim was to define the impact of these novel risk factors on survival.

Methods and Results—

Between January 1992 and December 2006, 181 patients diagnosed with CTEPH were tracked with the use of our center’s customized computer database. A Cox regression model was used to examine relations between survival and associated medical conditions, age, sex, hemodynamic parameters, modified New York Heart Association functional class at diagnosis, CTEPH type, pulmonary endarterectomy, and anti-cardiolipin antibodies/lupus anticoagulant. During a median observation time of 22.1 (range, 0.03 to 152) months, the clinical end point of cardiovascular death or lung transplantation occurred in 48 cases (27%). Pulmonary endarterectomy (hazard ratio, 0.14; 95% CI, 0.05 to 0.41;
P
=0.0003), associated medical conditions (hazard ratio, 3.17; 95% CI, 1.70 to 5.92;
P
=0.0003), and pulmonary vascular resistance (hazard ratio, 1.02; 95% CI, 1.00 to 1.04;
P
=0.04) were predictors of survival. Thirty-day postoperative mortality (24% versus 9%) and the incidence of postoperative pulmonary hypertension (92% versus 20%) were substantially higher in patients with associated medical conditions.

Conclusions—

CTEPH-predisposing medical conditions, such as splenectomy, permanent central intravenous lines, and certain inflammatory disorders, predict poor survival in CTEPH.
Diagnostic Thresholds for Ambulatory Blood Pressure Monitoring Based on 10-Year Cardiovascular Risk
Authors: Kikuya Masahiro , Hansen Tine W. , Thijs Lutgarde , Björklund-Bodegård Kristina , Kuznetsova Tatiana , Ohkubo Takayoshi , Richart Tom , Torp-Pedersen Christian , Lind Lars , Ibsen Hans , Imai Yutaka , Staessen Jan A.
Published: April 2007

Background—

Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement.

Methods and Results—

We performed 24-hour ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mm Hg), normal (130/85 mm Hg), and high (140/90 mm Hg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 116.8/74.2 mm Hg for 24 hours, 121.6/78.9 mm Hg for daytime, and 100.9/65.3 mm Hg for nighttime. Corresponding thresholds for normal ABP were 123.9/76.8, 129.9/82.6, and 110.2/68.1 mm Hg, respectively, and those for ambulatory hypertension were 131.0/79.4, 138.2/86.4, and 119.5/70.8 mm Hg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mm Hg.

Conclusions—

Population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.
Lack of the Antioxidant Enzyme Glutathione Peroxidase-1 Accelerates Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice
Authors: Lewis Paul , Stefanovic Nada , Pete Josefa , Calkin Anna C. , Giunti Sara , Thallas-Bonke Vicki , Jandeleit-Dahm Karin A. , Allen Terri J. , Kola Ismail , Cooper Mark E. , de Haan Judy B.
Published: April 2007

Background—

Recent clinical studies have suggested a major protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx1) in diabetes-associated atherosclerosis. We induced diabetes in mice deficient for both GPx1 and apolipoprotein E (ApoE) to determine whether this is merely an association or whether GPx1 has a direct effect on diabetes-associated atherosclerosis.

Methods and Results—

ApoE-deficient (ApoE
−/−
) and ApoE/GPx1 double-knockout (ApoE
−/−
GPx1
−/−
) mice were made diabetic with streptozotocin and aortic lesion formation, and atherogenic pathways were assessed after 10 and 20 weeks of diabetes. Aortic proinflammatory and profibrotic markers were determined by both quantitative reverse-transcription polymerase chain reaction analysis after 10 weeks of diabetes and immunohistochemical analysis after 10 and 20 weeks of diabetes. Sham-injected nondiabetic counterparts served as controls. Atherosclerotic lesions within the aortic sinus region, as well as arch, thoracic, and abdominal lesions, were significantly increased in diabetic ApoE
−/−
GPx1
−/−
aortas compared with diabetic ApoE
−/−
aortas. This increase was accompanied by increased macrophages, α-smooth muscle actin, receptors for advanced glycation end products, and various proinflammatory (vascular cell adhesion molecule-1) and profibrotic (vascular endothelial growth factor and connective tissue growth factor) markers. Quantitative reverse-transcription polymerase chain reaction analysis showed increased expression of receptors for advanced glycation end products (RAGE), vascular cell adhesion molecule-1, vascular endothelial growth factor, and connective tissue growth factor. Nitrotyrosine levels were significantly increased in diabetic ApoE
−/−
GPx1
−/−
mouse aortas. These findings were observed despite upregulation of other antioxidants.

Conclusions—

Lack of functional GPx1 accelerates diabetes-associated atherosclerosis via upregulation of proinflammatory and profibrotic pathways in ApoE
−/−
mice. Our study provides evidence of a protective role for GPx1 and establishes GPx1 as an important antiatherogenic therapeutic target in patients with or at risk of diabetic macrovascular disease.
Global Improvement of Vascular Function and Redox State With Low-Dose Folic Acid
Authors: Shirodaria Cheerag , Antoniades Charalambos , Lee Justin , Jackson Clare E. , Robson Matthew D. , Francis Jane M. , Moat Stuart J. , Ratnatunga Chandi , Pillai Ravi , Refsum Helga , Neubauer Stefan , Channon Keith M.
Published: April 2007

Background—

Although dietary folate fortification lowers plasma homocysteine and may reduce cardiovascular risk, high-dose folic acid therapy appears to not alter clinical outcome. Folic acid and its principal circulating metabolite, 5-methyltetrahydrofolate, improve vascular function, but mechanisms relating folate dose to vascular function remain unclear. We compared the effects of folic acid on human vessels using pharmacological high-dose versus low-dose treatment, equivalent to dietary folate fortification.

Methods and Results—

Fifty-six non–folate-fortified patients with coronary artery disease were randomized to receive low-dose (400 μg/d) or high-dose (5 mg/d) folic acid or placebo for 7 weeks before coronary artery bypass grafting. Vascular function was quantified by magnetic resonance imaging before and after treatment. Vascular superoxide and nitric oxide bioavailability were determined in segments of saphenous vein and internal mammary artery. Low-dose folic acid increased nitric oxide–mediated endothelium-dependent vasomotor responses, reduced vascular superoxide production, and improved enzymatic coupling of endothelial nitric oxide synthase through availability of the cofactor tetrahydrobiopterin. No further improvement in these parameters occurred with high-dose compared with low-dose treatment. Whereas plasma 5-methyltetrahydrofolate increased proportionately with treatment dose of folic acid, vascular tissue 5-methyltetrahydrofolate showed no further increment with high-dose compared with low-dose folic acid.

Conclusions—

Low-dose folic acid treatment, comparable to daily intake and dietary fortification, improves vascular function through effects on endothelial nitric oxide synthase and vascular oxidative stress. High-dose folic acid treatment provides no additional benefit. These direct vascular effects are related to vascular tissue levels of 5-methyltetrahydrofolate rather than plasma levels. High-dose folic acid treatment likely confers no further benefit in subjects already receiving folate supplementation.
Adiponectin Level and Left Ventricular Hypertrophy in Japanese Men
Authors: Mitsuhashi Hirotsugu , Yatsuya Hiroshi , Tamakoshi Koji , Matsushita Kunihiro , Otsuka Rei , Wada Keiko , Sugiura Kaichiro , Takefuji Seiko , Hotta Yo , Kondo Takahisa , Murohara Toyoaki , Toyoshima Hideaki
Published: April 2007

A recent study has demonstrated that adiponectin inhibited hypertrophic signaling in the myocardium of mice, implying that a decrease in the blood adiponectin level could cause cardiac muscle hypertrophy. We hypothesized that a relationship might exist between the serum adiponectin level and electrocardiographically diagnosed left ventricular hypertrophy (ECG-LVH), and we examined this hypothesis by epidemiological study of 2839 Japanese male workers who were not taking medications for hypertension. ECG-LVH was defined as meeting Sokolow–Lyon voltage criteria and/or Cornell voltage-duration product. The subjects were categorized by tertiles of serum adiponectin level, and a multivariate logistic regression analysis was conducted relating left ventricular hypertrophy to adiponectin tertiles adjusting for potential confounding factors. Prevalence of ECG-LVH in the studied sample was 16.7%. Adiponectin ranged from 1.0 to 5.0 μg/mL in the lowest category and from 7.4 to 30.6 μg/mL in the highest. Compared with subjects in the highest adiponectin category, those in the lowest one had a significantly higher prevalence of ECG-LVH independent of age, body mass index, and systolic blood pressure with an odds ratio of 1.50 and a 95% CI of 1.16 to 1.94. Further adjustment for high-density lipoprotein cholesterol, triglyceride, and insulin resistance did not change the association (odds ratio: 1.68; 95% CI: 1.28 to 2.21;
P
<0.001). Similar results were obtained when different criteria for ECG-LVH were used or when subjects were stratified by blood pressure or body mass index. Adiponectin concentration was inversely and independently associated with ECG-LVH in Japanese men.
Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats
Authors: Waki Hidefumi , Liu Beihui , Miyake Masao , Katahira Kiyoaki , Murphy David , Kasparov Sergey , Paton Julian F.R.
Published: April 2007

Junctional adhesion molecule-1 (JAM-1) forms part of the tight junction between adjacent endothelial cells. Using microarray technology, we showed previously that JAM-1 was differentially expressed in the brain stem of spontaneously hypertensive rats compared with normotensive Wistar–Kyoto (WKY) rats. In this study, we quantified the expression of JAM-1 in the brain stem of spontaneously hypertensive rats and WKY rats and established whether any differential expression was confined to this region of the brain or was ubiquitous throughout the central nervous system and, indeed, the whole body. Because the nucleus tractus solitarii plays a pivotal role in arterial pressure regulation, we assessed whether JAM-1 in this region affects the chronic regulation of arterial pressure. Real time RT-PCR revealed that JAM-1 mRNA was upregulated in multiple regions of the brain and all of the peripheral vascular beds studied. In the nucleus tractus solitarii, the level of JAM-1 mRNA was significantly higher in both young (3-week–old, prehypertensive) and adult male spontaneously hypertensive rats (15 to 18 weeks old) than that of age-matched WKY rats (fold differences; prehypertensives: 1.01±0.06 versus 1.59±0.13; n=10;
P
<0.01; adult: 1.08±0.14 versus 2.86±0.57; n=10;
P
<0.01). After adenoviral-mediated expression of JAM-1 in the nucleus tractus solitarii of adult WKY rats (15 weeks old; n=6), systolic pressure was increased from 120±4 to 132±4 mm Hg (
P
<0.01). Our data suggest that JAM-1 expression in the spontaneously hypertensive rat is upregulated throughout the body compared with the WKY rat and that this is not secondary to the hypertension. When JAM-1 is expressed in the nucleus tractus solitarii, it raises arterial pressure, suggesting a novel prohypertensive role for this protein within the brain stem.
Difference in Neutrophil Superoxide Generation During Pregnancy Between Preeclampsia and Essential Hypertension
Authors: Tsukimori Kiyomi , Nakano Hitoo , Wake Norio
Published: April 2007

This study investigated whether production of reactive oxygen species by neutrophils differs between women with preeclampsia and those with essential hypertension. First, we assessed superoxide production by neutrophils during pregnancy and 4 weeks after delivery in 15 healthy pregnant women, 12 women with preeclampsia, and 7 pregnant women with essential hypertension. We then examined effects of serum from each subject on superoxide production by neutrophils obtained from healthy nonpregnant women. Neutrophil superoxide production was measured by cytochrome C reduction. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide production was significantly increased in neutrophils from women with preeclampsia and women with essential hypertension compared with normal pregnant women. Four weeks postpartum, the level of superoxide production was significantly decreased in women with preeclampsia but not in women with either normal pregnancy or essential hypertension. When neutrophils obtained from nonpregnant women were preincubated with predelivery sera from each group, sera from women with preeclampsia significantly enhanced superoxide production compared with sera from the other 2 groups. When postpartum serum was used, enhancement of neutrophil superoxide production by serum from women with preeclampsia was significantly decreased compared with that by predelivery serum. In conclusion, increased neutrophil superoxide production resolved after delivery in preeclampsia, whereas activation persisted postpartum in women with essential hypertension. The different transition of neutrophil superoxide production in response to pregnancy appears to be that preeclampsia is characterized by the presence of serum factors that enhance neutrophil superoxide production. Thus, in preeclampsia, serum factors bear a more essential role producing superoxide than a behavior of neutrophils.
Inversion Variability in the Hawaiian Trade Wind Regime
Authors: Cao Guangxia , Giambelluca Thomas W. , Stevens Duane E. , Schroeder Thomas A.
Published: April 2007

Using 1979–2003 radiosonde data at Hilo and Līhu‘e, Hawaii, the trade wind inversion (TWI) is found to occur approximately 82% of the time at each station, with average base heights of 2225 m (781.9 hPa) for Hilo and 2076 m (798.8 hPa) for Līhu‘e. A diurnal pattern in base height of nighttime high and afternoon low is consistently found during summer at Hilo. Inversion base height has a September maximum and a secondary maximum in April. Frequency of inversion occurrence was found to be higher during winters and lower during summers of El Niño years than non–El Niño years. Significant upward trends were found for inversion frequency at Hilo for March–May (MAM), June–August (JJA), and September–November (SON) seasons, and at Līhu‘e for all seasons and for annual values.
The Spatial and Temporal Distribution of Lightning Strikes and Their Relationship with Vegetation Type, Elevation, and Fire Scars in the Northern Territory
Authors: Kilinc Musa , Beringer Jason
Published: April 2007

In this paper the authors explore the spatial and temporal patterns of lightning strikes in northern Australia for the first time. In particular, the possible relationships between lightning strikes and elevation, vegetation type, and fire scars (burned areas) are examined. Lightning data provided by the Bureau of Meteorology were analyzed for a 6-yr period (1998–2003) over the northern, southern, and coastal regions of the Northern Territory (NT) through the use of Geographical Information Systems (GIS) to determine the spatial and temporal characteristics of lightning strikes. It was determined that the highest densities of lightning strikes occurred during the monsoon transitional period (dry to wet) and during the active monsoon periods, when atmospheric moisture is highest. For the period of this study, lightning was far more prevalent over the northern region (1.21 strikes per km2 yr−1) than over the southern (0.58 strikes per km2 yr−1) and coastal regions (0.71 strikes per km2 yr−1). Differences in vegetation cover were suggested to influence the lightning distribution over the northern region of the NT, but no relationship was found in the southern region. Lightning strikes in the southern region showed a positive relationship with elevations above 800 m, but no relationship was found in the northern region, which could be due to the low-lying topography of the area. A comparison of lightning densities between burned and unburned areas showed high variability; however, the authors suggest that, under ideal atmospheric conditions, large-scale fire scars (>500 m) could produce lightning strikes triggered by either enhanced free convection or mesoscale circulations.