bluuebunny/crossref_metadata_2025 huggingface dataset:
From the editor
Authors: Stafford Tom , Chau Patrick Y.K.
Published: April 2009

Greetings! Welcome to another fine issue of Data Base for Advances in Information Systems.

In this issue we feature a fine paper by Warkentin, Moore, Bekkering and Johnston on the nature of risk in systems development work. The interesting aspect of this work is the notion that risk factors which may hinder development projects, while frequently viewed by development professionals as existing in discrete categories, may well be more holistic and arise from unique organizational culture aspects idiosyncratic to individual firms. This is a break from traditional views of risk issues in systems development, and is likely to give us much food for thought as we consider development practices in the modern and emergent organizational forms of the information age.

Also in this issue, we provide the last of a sequence of special articles brought from the Chinese chapter of AIS for your consideration. The annual meeting of the Chinese Association produced a number of fine papers, many with a decidedly technical flavor, and we wished to showcase some more of those here, following our last issue, which was dedicated to some of the more managerial papers that evolved from that Chinese Association conference. Herein, you will find some interesting work on emerging algorithms for the exploration of data streams (Wang et al.), the use of sequenced algorithms for applying AI approaches to the selection of virtual firm partners (Zhong et al.) and for the use of innovative algorithms to mine Web site data for purposes of fueling recommendation and personalization systems (Wei et al.). These are quite technical approaches, but very important for the effective management and control of the burgeoning online world of information that we are now inhabiting.

We are grateful to guest editors Guoqing Chen, Yu Chen and Kang Xie for bringing this interesting collection of scholarship from our Chinese Association colleagues to our pages. As part of the Editorial vision that Patrick and I have espoused, we anticipate Data Base will continue to lead in the development and publication of leading edge research, the world over.

To that end, we continue to welcome leading edge research from the four corners of the world at our online submission and review portal, found at http://the-database.org. We look forward to seeing some of your best work in these pages soon!
Analysis of systems development project risks
Authors: Warkentin Merrill , Moore Robert S. , Bekkering Ernst , Johnston Allen C.
Published: April 2009

Information systems development projects are a significant expenditure of time, effort and money for many enterprises. Historically it has been estimated that 50-80% of projects fail to achieve their objectives for a variety of reasons. Researchers have identified numerous factors associated with system development failure. In this paper, we first synthesize the vast research regarding systems development risk factors and provide a framework that illustrates interactions between risk factors. The framework was used to develop an open-ended questionnaire that was answered by an inter-industry group of experienced systems development engineers and project managers. Analysis of their reports indicates that experienced professionals perceive that all risk factors (technical, resource, etc.) ultimately derive from organizationally-oriented factors, to be solved with organizational responses. This holistic viewpoint of risk assessment is counter to that of systems professionals more involved in day-to-day development decision making. For these developers, risks are more likely to be characterized as fitting into traditional discrete categories. This apparent dichotomy of risk importance was further investigated through an intra-organizational study which directly assessed how professionals recognize and treat risks in the development process. Results illustrate that a successful project environment may be characterised as one in which all systems professionals maintain a holistic view of organizational risk and that organizational culture, as opposed to experience, may predicate such an environment. Implications and future research directions are discussed.
Special issue series for information systems research in China
Authors: Chen Guoqing , Chen Yu , Xie Kang
Published: April 2009

The past decades have witnessed enormous changes in China on economic, social, and cultural aspects, which have brought far-reaching impacts on global business and technology development. Since the early 1990s, IT has been transforming Chinese business and society, but the country still faces formidable challenges in developing and using the technology to further modernize itself. IT applications in China were introduced relatively late in technology evolution compared to those in the developed countries, forcing business managers to contend with a lack of experience, know-how, and infrastructure. On the other hand, this late start has also meant that Chinese companies could be able to choose from more advanced technologies, learn from the experience of others, and be less bothered by the problems associated with legacy systems.

Along with the development of IT/IS application and management, information systems research in China has also been accelerating and fusing with global academic streams. Notably, research efforts on both managerial and technical perspectives are flourishing in recent years. In 2005, the China Association for Information Systems (CNAIS) was established as a chapter of AIS serving China, aimed at promoting the exchange of ideas, experiences, and knowledge among scholars and professionals engaged in the development, management, and use of information systems and technology. With the support of CNAIS, this series of special issue papers presents some recent progress in IS research from Chinese scholars.

The papers included in this special issue series, which spans volume 40(1) and 40(2), presents extended versions of work selected, via a standard review process, from the 2007 CNAIS Congress (CNAIS2007) held in November 8-10, 2007, in Kunming, China. CNAIS2007 accepted over 170 refereed papers and featured plenary talks by distinguished scholars such as Michael Myers from the University of Auckland and Dennis Galletta from the University of Pittsburgh. Among the papers selected for this special issue series, four them focus on the management aspect of information systems while three concentrate on technical research, giving rise to two natural groups, respectively.

As the guest editors of this special issue series, we would like to thank all the authors for the contributions and all referees for their kind cooperation and help. We heartily thank Professor Patrick Y.K. Chau, Global Co-Editor of The DATA BASE for Advances in Information Systems, for providing us with the opportunity to edit and publish this issue, as well as for his valuable guidance in the editorial process.
An integrated optimization algorithm of GA and ACA-based approaches for modeling virtual enterprise partner selection
Authors: Zhong Yao , Jian Liu , Zijun Wu
Published: April 2009

In the emerging information age, traditional enterprises have been increasingly replaced by virtual enterprises because they are incompatible with new business environments. The virtual enterprise, also called the dynamic alliance, gradually becomes a new organization pattern. In the process of establishing virtual enterprises, the appropriate method of partner selection is one of key problems. After reviewing the virtual enterprise concept, characteristics, and constitution, this paper proposes a hybrid algorithm in which it fuses the Genetic Algorithm (GA) into an Ant Colony Optimization Algorithm (ACA) for optimizing the problem of partner selection. The paper briefly analyzes some flaws and merits in both ACA and GA methods and proposes the benefits and necessity of applying the integration of GA into ACA to resolve partner selection problems. A hybrid algorithm is then presented for optimizing the problem of virtual enterprise partner selection. Finally, the result of an illustrative numerical case demonstrates the integrated algorithm, showing better performance in both efficiency and effectiveness than the GA and ACA methods in partner selection. The conclusions in this paper can be useful for guiding problem solving in similar virtual enterprise scenarios.
Automatic assessment and adaptation to real world pointing performance
Authors: Hurst Amy
Published: April 2009

There is a growing population of individuals who are motivated to use a computer but find it physically difficult to do so, particularly when using a pointing device such as a mouse. Common pointing problems include inability to select small targets, difficulty moving a pointing device in a straight line, or difficulty controlling the pointer's buttons. There are many software adaptations that can improve pointing performance, however the key to these solutions is identifying when to deploy them. In my thesis, I am working to build software that can automatically assess pointing problems and their severity during real world computer use, and deploy appropriate assistive adaptations. In order to evaluate real world interaction with GUIs, I am developing both data capture and analysis tools that are application independent. This software-based approach to improving computer access is powerful because it will be able to adapt to an individual's changing needs and work across applications.
Improving computer interaction for older adults
Authors: Hollinworth Nic
Published: April 2009

A point and click interface can present difficulties for older adults (particularly those with physical impairments) who may not easily be able to operate a standard input device such as a mouse or trackball. The use of gestural commands, via a multitouch touchscreen device, is an alternative and direct method of interacting with an application. This research investigates whether gestural commands on a multitouch touchscreen device can make interfaces easier to use, learn and remember for older adults.
Critically analyzing workplace discourse to inform AAC device design
Authors: Bruce Carrie
Published: April 2009

The purpose of this paper is to introduce a study on workplace discourse that will be conducted to inform design of AAC vocabulary to better support workers' communication needs. Although some work has been done by AAC researchers and mainstream discourse researchers, there is limited evidence that can be used in AAC device prediction systems that is related to workplace and, more specifically, task-oriented discourse. The limitations in our understanding of workers' conversational needs warrant investigation into their discourse and the associated physical, temporal, and social environment factors. This study will collect and critically analyze spoken workplace conversation from 20 workers using discourse analysis and corpus linguistic techniques.
Generation of accessible diagrams by semantics preserving adaptation
Authors: Goncu Cagatay
Published: April 2009

Diagrams are important components of educational materials. They can be found in various media. Printed media, such as text books, have traditionally been the most commonly used media for educational material, however online electronic resources, such as web pages and e-books, are becoming increasingly popular sources of educational content. Online materials include static diagrams, like text books, but may also include dynamic content such as animations and components that can interact with the user.
Good visual aesthetics equals good web accessibility
Authors: Mbipom Grace
Published: April 2009

This paper summarises a doctoral research project titled Empirical Investigation of Visual Aesthetics and Accessibility (EIVAA). The project proposes to investigate the relationship between visual aesthetics and Web accessibility, with the aim of building a framework to guide the development of aesthetic accessible Web content. As a first step, a formative study was conducted to examine the relationship between visual aesthetics and Web accessibility from a technical perspective. Thirty Web pages that had previously been rated on various aspects of their visual appearance in a study by Michailidou et al. [20] were investigated. The visual aesthetic dimensions considered in their study were "clean", "clear", "organised", "beautiful", and "interesting". In our study, all thirty Web pages were tested for accessibility using an automatic evaluation tool, "Cynthia Says". Initial results show that Web pages which were previously agreed by participants to be visually clean, clear, and organised had lesser numbers of Web Content Accessibility Guidelines (WCAG) 1.0 failures. This suggests that visually pleasing pages along these design dimensions may not pose a barrier to accessibility. The implications of our study and future research directions are discussed.
Automatic readability assessment for people with intellectual disabilities
Authors: Feng Lijun
Published: April 2009

My research goal is to advance our understanding of, and quantify, what makes a text easy or difficult to read, in particular for readers with intellectual disabilities. Previous research in automatic readability assessment has looked at a limited class of lexi-cal and syntactic properties of texts. Moreover, these models are usually not targeted towards any particular group of readers. In my own work, by contrast, I have used sophisticated computational tools to build an automatic readability metric that exploits global semantic (discourse level) properties of a text, in addition to well-studied lexical and syntactic features. Our preliminary results (Feng et al., 2009) confirm the value of discourse attributes. My research is targeted towards understanding the particular difficulties faced by readers with intellectual disabilities. The ultimate goal is not simply to model and understand readability issues, but also to aide in the development of automatic language processing tools that can rewrite texts to be more readable.
Menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women
Authors: Carter Jason R. , Lawrence Johnathan E. , Klein Jenna C.
Published: April 2009

Sympathetic baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) responses during early follicular (EF) and midluteal (ML) phases of the menstrual cycle are controversial. We hypothesize an augmented sympathetic BRS and MSNA response to orthostatic stress during the ML phase of the menstrual cycle. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP) (−5, −10, −15, −20, −30, and −40 mmHg; 3 min/stage) in 13 healthy, eumenorrheic women (age 21 ± 1 yr). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA at rest and during progressive LBNP. Plasma estradiol (42 ± 6 vs. 112 ± 12 pg/ml; P < 0.01) and progesterone (2 ± 0 vs. 10 ± 2 ng/ml; P < 0.04) were elevated during the ML phase. Resting MSNA (8 ± 1 vs. 11 ± 1 bursts/min), MAP (79 ± 2 vs. 78 ± 2 mmHg), and HR (58 ± 2 vs. 60 ± 2 beats/min) were not different during EF and ML phases. MSNA and HR increased during progressive LBNP ( P < 0.001), and the increases in MSNA burst frequency (bursts/min) and HR were similar during both phases. In contrast, increases in total MSNA (arbitrary units) during progressive LBNP were augmented during the ML phase ( P < 0.04), but this response does not appear to be linked to differences in sympathetic BRS. Progressive LBNP did not change MAP during either phase. Our results demonstrate an augmentation of the MSNA response to progressive LBNP during the ML phase of the menstrual cycle. These findings suggest that hormonal fluctuations of eumenorrheic women may influence sympathoexcitation during an orthostatic challenge, but not through sympathetic baroreflex-mediated pathways.
PGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice
Authors: Leick Lotte , Hellsten Ylva , Fentz Joachim , Lyngby Stine S. , Wojtaszewski Jørgen F. P. , Hidalgo Juan , Pilegaard Henriette
Published: April 2009

The aim of the present study was to test the hypothesis that PGC-1α is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1α-dependent mechanism. Whole body PGC-1α knockout (KO) and littermate wild-type (WT) mice were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13 mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4) 4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC-1α KO mice, VEGF protein expression was ∼60–80% lower and the capillary-to-fiber ratio ∼20% lower than in WT. Basal VEGF mRNA expression was similar in WT and PGC-1α KO mice, but acute exercise and AICAR treatment increased the VEGF mRNA content in WT mice only. Exercise training of young mice increased skeletal muscle VEGF protein expression ∼50% in WT mice but with no effect in PGC-1α KO mice. Furthermore, a training-induced prevention of an age-associated decline in VEGF protein content was observed in WT but not in PGC-1α KO muscles. In addition, repeated AICAR treatments increased skeletal muscle VEGF protein expression ∼15% in WT but not in PGC-1α KO mice. This study shows that PGC-1α is essential for exercise-induced upregulation of skeletal muscle VEGF expression and for a training-induced prevention of an age-associated decline in VEGF protein content. Furthermore, the findings suggest an AMPK-mediated regulation of VEGF expression through PGC-1α.
Leucine restriction inhibits chondrocyte proliferation and differentiation through mechanisms both dependent and independent of mTOR signaling
Authors: Kim Mimi S. , Wu Ke Ying , Auyeung Valerie , Chen Qian , Gruppuso Philip A. , Phornphutkul Chanika
Published: April 2009

Linear growth in children is sensitive to nutritional status. Amino acids, in particular leucine, have been shown to regulate cell growth, proliferation, and differentiation through the mammalian target of rapamycin (mTOR), a nutrient-sensing protein kinase. Having recently demonstrated a role for mTOR in chondrogenesis, we hypothesized that leucine restriction, acting through mTOR, would inhibit growth plate chondrocyte proliferation and differentiation. The effect of leucine restriction was compared with that of the specific mTOR inhibitor, rapamycin. Leucine restriction produced a dose-dependent inhibition of fetal rat metatarsal explant growth. This was accounted by reduced cell proliferation and hypertrophy but not apoptosis. mTOR activity, as reflected by ribosomal protein S6 phosphorylation, was only partially inhibited by leucine restriction, whereas rapamycin abolished S6 phosphorylation. In chondrogenic ATDC5 cells, leucine restriction inhibited cell number, proteoglycan accumulation, and collagen X expression despite minimal inhibition of mTOR. Microarray analysis demonstrated that the effect of leucine restriction on ATDC5 cell gene expression differed from that of rapamycin. Out of 1,571 genes affected by leucine restriction and 535 genes affected by rapamycin, only 176 genes were affected by both. These findings indicate that the decreased chondrocyte growth and differentiation associated with leucine restriction is only partly attributable to inhibition of mTOR signaling. Thus nutrient restriction appears to directly modulate bone growth through unidentified mTOR-independent mechanisms in addition to the well-characterized mTOR nutrient-sensing pathway.
Individual molecular response to elevated intraocular pressure in perfused postmortem human eyes
Authors: Comes Núria , Borrás Teresa
Published: April 2009

Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. In the clinic, the response to elevated pressure and thus the risk for development of glaucoma differs among individuals. We took advantage of our ability to subject postmortem human eyes from the same individual to physiological and elevated pressure in a perfused outflow model and compared individual patterns of gene expression under pressure. The architecture of the trabecular meshwork, tissue responsible for the maintenance of IOP, was conserved. We performed two sets of experiments. The first set ( n = 5, 10 eyes) used Affymetrix GeneChips, identified the 20 most pressure-altered genes in each individual, and compared their pressure response in the other four. The second set ( n = 5, 10 eyes) selected 21 relevant trabecular meshwork genes and examined, by real-time TaqMan-PCR, the rank of their abundance and of their pressure differential expression in each individual. The majority of the up- and downregulated top-changers of each individual showed an individual response trend. Few genes were general responders. Individual responders included STATH, FBN2, TF, OGN, IL6, IGF1, CRYAB, and ELAM1 (marker for glaucoma). General responders included MMP1, MMP10, CXCL2, and PDPN. In addition, we found that although the relative abundance of selected genes was very similar among nonstressed individuals, the response to pressure of those same genes had a marked individual component. Our results offer the first molecular insight on the variation of the individual response to IOP observed in the clinical setting.
Acute Kidney Injury Is Associated With Increased Long-Term Mortality After Cardiothoracic Surgery
Authors: Hobson Charles E. , Yavas Sinan , Segal Mark S. , Schold Jesse D. , Tribble Curtis G. , Layon A. Joseph , Bihorac Azra
Published: April 2009

Background—

Long-term survival after acute kidney injury (AKI) is poorly studied. We report the relationship between long-term mortality and AKI with small changes in serum creatinine during hospitalization after various cardiothoracic surgery procedures.

Methods and Results—

This was a retrospective study of 2973 patients with no history of chronic kidney disease who were discharged from the hospital after cardiothoracic surgery between 1992 and 2002. AKI was defined by the RIFLE classification (Risk, Injury, Failure, Loss, and End stage), which requires at least a 50% increase in serum creatinine and stratifies patients into 3 grades of AKI: Risk, injury, and failure. Patient survival was determined through the National Social Security Death Index. Long-term survival was analyzed with a risk-adjusted Cox proportional hazards regression model. Survival was worse among patients with AKI and was proportional to its severity, with an adjusted hazard ratio of 1.23 (95% CI 1.06 to 1.42) for the least severe RIFLE risk class and 2.14 (95% CI 1.73 to 2.66) for the RIFLE failure class compared with patients without AKI. Survival was worse among all subgroups of cardiothoracic surgery with AKI except for valve surgery. Patients with complete renal recovery after AKI still had an increased adjusted hazard ratio for death of 1.28 (95% CI 1.11 to 1.48) compared with patients without AKI.

Conclusions—

The risk of death associated with AKI after cardiothoracic surgery remains high for 10 years regardless of other risk factors, even for those patients with complete renal recovery. Improved renal protection and closer postdischarge follow-up of renal function may be warranted.
Differences in Specialist Consultations for Cardiovascular Disease by Race, Ethnicity, Gender, Insurance Status, and Site of Primary Care
Authors: Cook Nakela L. , Ayanian John Z. , Orav E. John , Hicks LeRoi S.
Published: April 2009

Background—

Consultation with cardiologists may improve the quality of ambulatory care and reduce disparities for patients with heart disease. We assessed the use of cardiology consultations and the associated quality by race/ethnicity, gender, insurance status, and site of care.

Methods and Results—

In a retrospective cohort, we examined electronic records of 9761 adults with coronary artery disease or congestive heart failure (CHF) receiving primary care at practices affiliated with 2 academic medical centers during 2000 to 2005. During this period, 79.6% of patients with coronary artery disease and 90.3% of patients with CHF had a cardiology consultation. In multivariate analyses, women were less likely to receive a consultation than men for both conditions (coronary artery disease: hazard ratio, 0.89; 95% CI, 0.85 to 0.93; CHF: hazard ratio, 0.93; 95% CI, 0.87 to 0.99). Women also had 15% fewer follow-up consultations than men (
P
<0.001). Similarly, patients at community health centers were less likely to receive a consultation (coronary artery disease: hazard ratio, 0.79; 95% CI, 0.74 to 0.84; CHF: hazard ratio, 0.77; 95% CI: 0.71 to 0.84) and had 20% fewer follow-up consultations (
P
<0.001) relative to those at hospital-based practices. Black and Hispanic patients with CHF had 13% fewer follow-up consultations than white patients (
P
=0.01 and
P
=0.04, respectively). In adjusted analyses, consultation was associated with better processes of care compared with no consultation (
P
<0.001), particularly for women (
P
<0.001 for interaction between consultation and gender).

Conclusions—

Among ambulatory patients with coronary artery disease or CHF, women and those at community health centers have less access to cardiologists. Consultation is associated with better quality of care and narrows the gender gap in quality.
Incidence and Prognostic Significance of Thrombocytopenia Developed During Acute Coronary Syndrome in Contemporary Clinical Practice
Authors: Wang Tracy Y. , Ou Fang-Shu , Roe Matthew T. , Harrington Robert A. , Ohman E. Magnus , Gibler W. Brian , Peterson Eric D.
Published: April 2009

Background—

Prior studies examining thrombocytopenia among patients with acute coronary syndromes (ACS) evaluated highly selected patients in a clinical trial setting using varying definitions of thrombocytopenia. The incidence, severity, and prognostic significance of acquired thrombocytopenia during ACS in community practice have not been well defined.

Methods and Results—

We examined 36 182 patients with non–ST-segment elevation ACS enrolled at 379 US hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) quality improvement initiative between June 2004 and December 2006. Patients with baseline platelet counts <150×10
9
/L were excluded. Overall, 4697 patients (13%) developed new thrombocytopenia, defined as nadir platelet count <150×10
9
/L (referenced lower limit of normal), during their ACS hospitalization. Risks of in-hospital mortality and bleeding correlated directly with severity of thrombocytopenia; even mild thrombocytopenia (nadir 100 to 149×10
9
/L) was associated with increased risks of mortality (adjusted odds ratio [OR], 2.01; 95% CI, 1.69 to 2.38) and bleeding (adjusted OR, 3.76; 95% CI, 3.43 to 4.12). Each 10% drop in platelet count was associated with increased mortality and bleeding risks (adjusted ORs, 1.39 [95% CI, 1.33 to 1.46] and 1.89 [95% CI, 1.83 to 1.95], respectively). A ≥50% drop in platelet count was associated with higher risk of adverse outcomes regardless of the nadir count. A novel combined definition of acquired thrombocytopenia—nadir <150×10
9
/L or platelet count drop ≥50%—identifies a population of ACS patients at higher risk of mortality and major bleeding (adjusted ORs, 2.58 [95% CI, 2.23 to 2.98] and 4.32 [95% CI, 3.97 to 4.70], respectively).

Conclusions—

Thrombocytopenia, a common complication of ACS, is associated with increased mortality and bleeding risks. Even mild thrombocytopenia or a platelet count drop ≥50% in the setting of normal nadir values is clinically significant. Application of a combined definition for thrombocytopenia using both absolute and relative thresholds permits increased sensitivity for patients at high risk of adverse outcomes.
Regulation of the Human Cardiac Mitochondrial Ca2+Uptake by 2 Different Voltage-Gated Ca2+Channels
Authors: Michels Guido , Khan Ismail F. , Endres-Becker Jeannette , Rottlaender Dennis , Herzig Stefan , Ruhparwar Arjang , Wahlers Thorsten , Hoppe Uta C.
Published: April 2009

Background—Impairment of intracellular Ca2+homeostasis and mitochondrial function has been implicated in the development of cardiomyopathy. Mitochondrial Ca2+uptake is thought to be mediated by the Ca2+uniporter (MCU) and a thus far speculative non-MCU pathway. However, the identity and properties of these pathways are a matter of intense debate, and possible functional alterations in diseased states have remained elusive.

Methods and Results—By patch clamping the inner membrane of mitochondria from nonfailing and failing human hearts, we have identified 2 previously unknown Ca2+-selective channels, referred to as mCa1 and mCa2. Both channels are voltage dependent but differ significantly in gating parameters. Compared with mCa2 channels, mCa1 channels exhibit a higher single-channel amplitude, shorter openings, a lower open probability, and 3 to 5 subconductance states. Similar to the MCU, mCa1 is inhibited by 200 nmol/L ruthenium 360, whereas mCa2 is insensitive to 200 nmol/L ruthenium 360 and reduced only by very high concentrations (10 μmol/L). Both mitochondrial Ca2+channels are unaffected by blockers of other possibly Ca2+-conducting mitochondrial pores but were activated by spermine (1 mmol/L). Notably, activity of mCa1 and mCa2 channels is decreased in failing compared with nonfailing heart conditions, making them less effective for Ca2+uptake and likely Ca2+-induced metabolism.

Conclusions—Thus, we conclude that the human mitochondrial Ca2+uptake is mediated by these 2 distinct Ca2+channels, which are functionally impaired in heart failure. Current properties reveal that the mCa1 channel underlies the human MCU and that the mCa2 channel is responsible for the ruthenium red–insensitive/low-sensitivity non-MCU–type mitochondrial Ca2+uptake.
Matrix Metalloproteinase-7 and ADAM-12 (a Disintegrin and Metalloproteinase-12) Define a Signaling Axis in Agonist-Induced Hypertension and Cardiac Hypertrophy
Authors: Wang Xiang , Chow Fung Lan , Oka Tatsujiro , Hao Li , Lopez-Campistrous Ana , Kelly Sandra , Cooper Stephan , Odenbach Jeffrey , Finegan Barry A. , Schulz Richard , Kassiri Zamaneh , Lopaschuk Gary D. , Fernandez-Patron Carlos
Published: April 2009

Background—Excessive stimulation of Gq protein–coupled receptors by cognate vasoconstrictor agonists induces a variety of cardiovascular processes, including hypertension and hypertrophy. Here, we report that matrix metalloproteinase-7 (MMP-7) and a disintegrin and metalloproteinase-12 (ADAM-12) form a novel signaling axis in these processes.

Methods and Results—In functional studies, we targeted MMP-7 in rodent models of acute, long-term, and spontaneous hypertension by 3 complementary approaches: (1) Pharmacological inhibition of activity, (2) expression knockdown (by antisense oligodeoxynucleotides and RNA interference), and (3) gene knockout. We observed that induction of acute hypertension by vasoconstrictors (ie, catecholamines, angiotensin II, and the nitric oxide synthase inhibitorNG-nitro-l-arginine methyl ester) required the posttranscriptional activation of vascular MMP-7. In spontaneously hypertensive rats, knockdown of MMP-7 (by RNA interference) resulted in attenuation of hypertension and stopped development of cardiac hypertrophy. Quantitative reverse-transcription polymerase chain reaction studies in mouse models of MMP-7 knockdown (by RNA interference) and gene knockout revealed that MMP-7 controlled the transcription of ADAM-12, the major metalloproteinase implicated in cardiac hypertrophy. In mice with angiotensin II–induced hypertension and cardiac hypertrophy, myocardial ADAM-12 and downstream hypertrophy marker genes were overexpressed. Knockdown of MMP-7 attenuated hypertension, inhibited ADAM-12 overexpression, and prevented cardiac hypertrophy.

Conclusions—Agonist signaling of both hypertension and hypertrophy depends on posttranscriptional and transcriptional mechanisms that involve MMP-7, which is transcriptionally connected with ADAM-12. Approaches targeting this novel MMP-7/ADAM-12 signaling axis could have generic therapeutic potential in hypertensive disorders caused by multiple or unknown agonists.
Cardiac Mast Cells Mediate Left Ventricular Fibrosis in the Hypertensive Rat Heart
Authors: Levick Scott P. , McLarty Jennifer L. , Murray David B. , Freeman Rebecca M. , Carver Wayne E. , Brower Gregory L.
Published: April 2009

Correlative data suggest that cardiac mast cells are a component of the inflammatory response that is important to hypertension-induced adverse myocardial remodeling. However, a causal relationship has not been established. We hypothesized that adverse myocardial remodeling would be inhibited by preventing the release of mast cell products that may interact with fibroblasts and other inflammatory cells. Eight-week-old male spontaneously hypertensive rats were treated for 12 weeks with the mast cell stabilizing compound nedocromil (30 mg/kg per day). Age-matched Wistar-Kyoto rats served as controls. Nedocromil prevented left ventricular fibrosis in the spontaneously hypertensive rat independent of hypertrophy and blood pressure, despite cardiac mast cell density being elevated. The mast cell protease tryptase was elevated in the spontaneously hypertensive rat myocardium and was normalized by nedocromil. Treatment of isolated adult spontaneously hypertensive rat cardiac fibroblasts with tryptase induced collagen synthesis and proliferation, suggesting this as a possible mechanism of mast cell-mediated fibrosis. In addition, nedocromil prevented macrophage infiltration into the ventricle. The inflammatory cytokines interferon-γ and interleukin (IL)-4 were increased in the spontaneously hypertensive rat and normalized by nedocromil, whereas IL-6 and IL-10 were decreased in the spontaneously hypertensive rat, with nedocromil treatment normalizing IL-6 and increasing IL-10 above the control. These results demonstrate for the first time a causal relationship between mast cell activation and fibrosis in the hypertensive heart. Furthermore, these results identify several mechanisms, including tryptase, inflammatory cell recruitment, and cytokine regulation, by which mast cells may mediate hypertension-induced left ventricular fibrosis.
Free Leptin Is Associated With Masked Hypertension in Nonobese Subjects
Authors: Thomopoulos Costas , Papadopoulos Dimitris P. , Papazachou Ourania , Bratsas Athanassios , Massias Spiros , Anastasiadis Georgios , Perrea Despina , Makris Thomas
Published: April 2009

The aim of the study was to investigate whether diverse clinical blood pressure phenotypes are associated with free leptin surrogates, as reflected by plasma leptin, human soluble leptin receptor, and their ratio (ie, free leptin index) in nonobese normoglycemic subjects. Three separate clinic blood pressure measurements and ambulatory blood pressure monitoring were implemented to divide 494 subjects (aged 44±5 years; 272 men; body mass index: <30 kg/m
2
) into hypertensives (n=166), white-coat hypertensives (n=82), masked hypertensives (n=66), and normotensives (n=180). Participants underwent echocardiography, while, from fasting venous blood samples, metabolic profile, plasma leptin, and its receptor levels were assessed. Hypertensives and masked hypertensives demonstrated higher levels of log (10)(leptin) and log (10)(free leptin index), as well as lower levels of log (10)(human soluble leptin receptor) with respect to normotensives. White-coat hypertensives had similar free leptin surrogates compared with normotensives. Younger age, 24-hour systolic and diastolic blood pressures, 24-hour heart rate, and left ventricle mass index were common correlates of free leptin surrogates. After adjustment for confounders, masked hypertensive and hypertensive with respect to normotensive phenotype were associated with log (10)(leptin) with odds ratios (95% CIs) of 1.31 (1.12 to 3.80) and 1.26 (1.09 to 2.24), respectively, log (10)(human soluble leptin receptor) with 0.65 (0.53 to 0.78) and 0.69 (0.57 to 0.84), respectively, and log (10)(free leptin index) with 2.46 (1.32 to 7.23) and 1.84 (1.26 to 3.73), respectively (
P
<0.05 for all of the cases). Free leptin surrogates are associated with masked hypertension in nonobese normoglycemic subjects. Free leptin is almost equally increased in masked and sustained hypertension, suggesting a similar leptin-related vascular impairment.
High Dietary Taurine Reduces Apoptosis and Atherosclerosis in the Left Main Coronary Artery
Authors: Zulli Anthony , Lau Eza , Wijaya Bagus P.P. , Jin Xin , Sutarga Komang , Schwartz Grace D. , Learmont Jonathon , Wookey Peter J. , Zinellu Angelo , Carru Ciriaco , Hare David L.
Published: April 2009

We sought to determine whether taurine could specifically protect against coronary artery disease during an atherogenic diet and whether taurine affects the lipid profile, metabolites of methionine, and endothelial atherogenic systems. Rabbits were fed one of the following diets for 4 weeks: (1) control diet; (2) 0.5% cholesterol+1.0% methionine; or (3) 0.5% cholesterol+1.0% methionine+2.5% taurine. Endothelial function was examined, and the left main coronary artery atherosclerosis was quantified by stereology and semiquantitative immunohistochemistry to determine the endothelial expression of proteins related to the NO, renin-angiotensin, endoplasmic reticulum, and oxidative stress systems, as well as apoptosis. Taurine normalized hyperhomocysteinemia (
P
<0.05) and significantly reduced hypermethioninemia (
P
<0.05) but not lipidemia. The intima:media ratio was reduced by 28% (
P
=0.034), and atherosclerosis was reduced by 64% (
P
=0.012) and endothelial cell apoptosis by 30% (
P
<0.01). Endothelial cell CCAAT/enhancer binding protein homologous protein was normalized (
P
<0.05). Taurine failed to improve hyperlipidemia, endothelial function, or endothelial proteins related to the NO, renin-angiotensin, and oxidative stress systems. Taurine reduces left main coronary artery wall pathology associated with decreased plasma total homocysteine, methionine, apoptosis, and normalization of CCAAT/enhancer binding protein homologous protein. These results elucidate the antiapoptotic and antiatherogenic properties of taurine, possibly via normalization of endoplasmic reticulum stress.
Blood Pressure Lowering Effects of a New Long-Acting Inhibitor of Phosphodiesterase 5 in Patients With Mild to Moderate Hypertension
Authors: Wolk Robert , Smith William B. , Neutel Joel M. , Rubino John , Xuan Dawei , Mancuso James , Gilbert James , Pressler Milton L.
Published: April 2009

Inhibition of phosphodiesterase 5 is an attractive candidate mechanism for blood pressure (BP) lowering. In this study, a novel long-acting phosphodiesterase 5 inhibitor, PF-00489791, was evaluated in 133 patients with mild to moderate hypertension, randomized into 1 of 4 groups: placebo, 4 mg, 10 mg, and 20 mg titrated after 14 days of dosing to 40 mg. Study medication was administered once daily for 28 days. Ambulatory BP monitoring was used. There was a statistically significant decrease (compared with placebo) in mean daytime systolic BP on day 28 at the 10 and 20/40 mg doses (by ≈5 and ≈7 mm Hg, respectively). Changes in mean daytime diastolic BP corresponded with those in systolic BP. The magnitude of BP lowering was greater on day 1 than on days 14 and 28, but the response was sustained between days 14 and 28. PF-00489791 also exerted BP lowering effects on mean 24-hour ambulatory BP. There was a dose-related increase in plasma cGMP concentration (statistically significant at the 20/40 mg dose). There was an increased incidence of headaches at the 10 and 20/40 mg doses (22% and 21%, respectively, compared with 12% with placebo) and an increased incidence of dyspepsia/gastroesophageal reflux disease and musculoskeletal adverse events at the 20/40 mg dose. In conclusion, PF-00489791 causes a clinically meaningful and sustained BP lowering in patients with hypertension. It is generally safe and well tolerated at the clinically efficacious doses.
The Neural Bases of Distraction and Reappraisal
Authors: McRae Kateri , Hughes Brent , Chopra Sita , Gabrieli John D. E. , Gross James J. , Ochsner Kevin N.
Published: April 2009

Distraction and reappraisal are two commonly used forms of cognitive emotion regulation. Functional neuroimaging studies have shown that each one depends upon interactions between pFC, interpreted as implementing cognitive control, and limbic regions, interpreted as mediating emotional responses. However, no study has directly compared distraction with reappraisal, and it remains unclear whether they draw upon different neural mechanisms and have different emotional consequences. The present fMRI study compared distraction and reappraisal and found both similarities and differences between the two forms of emotion regulation. Both resulted in decreased negative affect, decreased activation in the amygdala, and increased activation in prefrontal and cingulate regions. Relative to distraction, reappraisal led to greater decreases in negative affect and to greater increases in a network of regions associated with processing affective meaning (medial prefrontal and anterior temporal cortices). Relative to reappraisal, distraction led to greater decreases in amygdala activation and to greater increases in activation in prefrontal and parietal regions. Taken together, these data suggest that distraction and reappraisal differentially engage neural systems involved in attentional deployment and cognitive reframing and have different emotional consequences.
Detection of a Weak Somatosensory Stimulus: Role of the Prestimulus Mu Rhythm and Its Top–Down Modulation
Authors: Zhang Yan , Ding Mingzhou
Published: April 2009

The ongoing neural activity in human primary somatosensory cortex (SI) is characterized by field potential oscillations in the 7–13 Hz range known as the mu rhythm. Recent work has shown that the magnitude of the mu oscillation immediately preceding the onset of a weak stimulus has a significant impact on its detection. The neural mechanisms mediating this impact remain not well understood. In particular, whether and how somatosensory mu rhythm is modulated by executive areas prior to stimulus onset for improved behavioral performance has not been investigated. We addressed these issues by recording 128-channel scalp electroencephalogram from normal volunteers performing a somatosensory perception experiment in which they reported the detection of a near-threshold electrical stimulus (∼50% detection rate) delivered to the right index finger. Three results were found. First, consistent with numerous previous reports, the N1 component (∼140 msec) of the somatosensory-evoked potential was significantly enhanced for perceived stimulus compared to unperceived stimulus. Second, the prestimulus mu power and the evoked N1 amplitude exhibited an inverted-U relationship, suggesting that an intermediate level of prestimulus mu oscillatory activity is conducive to stimulus processing and perception. Third, a Granger causality analysis revealed that the prestimulus causal influence in the mu band from prefrontal cortex to SI was significantly higher for perceived stimulus than for unperceived stimulus, indicating that frontal executive structures, via ongoing mu oscillations, exert cognitive control over posterior sensory cortices to facilitate somatosensory processing.
Specific and Nonspecific Neural Activity during Selective Processing of Visual Representations in Working Memory
Authors: Oh Hwamee , Leung Hoi-Chung
Published: April 2009

In this fMRI study, we investigated prefrontal cortex (PFC) and visual association regions during selective information processing. We recorded behavioral responses and neural activity during a delayed recognition task with a cue presented during the delay period. A specific cue (“Face” or “Scene”) was used to indicate which one of the two initially viewed pictures of a face and a scene would be tested at the end of a trial, whereas a nonspecific cue (“Both”) was used as control. As expected, the specific cues facilitated behavioral performance (faster response times) compared to the nonspecific cue. A postexperiment memory test showed that the items cued to remember were better recognized than those not cued. The fMRI results showed largely overlapped activations across the three cue conditions in dorsolateral and ventrolateral PFC, dorsomedial PFC, posterior parietal cortex, ventral occipito-temporal cortex, dorsal striatum, and pulvinar nucleus. Among those regions, dorsomedial PFC and inferior occipital gyrus remained active during the entire postcue delay period. Differential activity was mainly found in the association cortices. In particular, the parahippocampal area and posterior superior parietal lobe showed significantly enhanced activity during the postcue period of the scene condition relative to the Face and Both conditions. No regions showed differentially greater responses to the face cue. Our findings suggest that a better representation of visual information in working memory may depend on enhancing the more specialized visual association areas or their interaction with PFC.
Neural Dynamics Associated with Semantic and Episodic Memory for Faces: Evidence from Multiple Frequency Bands
Authors: Zion-Golumbic Elana , Kutas Marta , Bentin Shlomo
Published: April 2009

Prior semantic knowledge facilitates episodic recognition memory for faces. To examine the neural manifestation of the interplay between semantic and episodic memory, we investigated neuroelectric dynamics during the creation (study) and the retrieval (test) of episodic memories for famous and nonfamous faces. Episodic memory effects were evident in several EEG frequency bands: theta (4–8 Hz), alpha (9–13 Hz), and gamma (40–100 Hz). Activity in these bands was differentially modulated by preexisting semantic knowledge and by episodic memory, implicating their different functional roles in memory. More specifically, theta activity and alpha suppression were larger for old compared to new faces at test regardless of fame, but were both larger for famous faces during study. This pattern of selective semantic effects suggests that the theta and alpha responses, which are primarily associated with episodic memory, reflect utilization of semantic information only when it is beneficial for task performance. In contrast, gamma activity decreased between the first (study) and second (test) presentation of a face, but overall was larger for famous than nonfamous faces. Hence, the gamma rhythm seems to be primarily related to activation of preexisting neural representations that may contribute to the formation of new episodic traces. Taken together, these data provide new insights into the complex interaction between semantic and episodic memory for faces and the neural dynamics associated with mnemonic processes.
Two Comments on the Surface Quasigeostrophic Model for the Atmospheric Energy Spectrum
Authors: Lindborg Erik
Published: April 2009

The horizontal wavenumber spectra of wind and temperature in the upper troposphere and lower stratosphere display a narrow k−3 range at scales on the order of 1000 km and a broad k−5/3 range at mesoscales on the order of 1 to 500 km. Recently, Tulloch and Smith suggested that a surface quasigeostrophic (SQG) turbulence model can explain the observed spectra. Here, it is first argued that the mesoscale spectra are not likely to be explained by any quasigeostrophic model because the Rossby number corresponding to the mesoscale dynamics is on the order of unity or larger. Then it is argued that the SQG model in particular cannot explain the observations because its mesoscale spectrum displays a k−5/3 dependence only in a very thin layer just below the tropopause. The thickness of this layer can be estimated to be of the order of 10 m, whereas aircraft measurements are typically performed several hundred meters away from the tropopause.