bluuebunny/crossref_metadata_2025 huggingface dataset:
The Establishment, Inheritance, and Function of Silenced Chromatin inSaccharomyces cerevisiae
Authors: Rusche Laura N. , Kirchmaier Ann L. , Rine Jasper
Published: April 2003

▪ Abstract  Genomes are organized into active regions known as euchromatin and inactive regions known as heterochromatin, or silenced chromatin. This review describes contemporary knowledge and models for how silenced chromatin in Saccharomyces cerevisiae forms, functions, and is inherited. In S. cerevisiae, Sir proteins are the key structural components of silenced chromatin. Sir proteins interact first with silencers, which dictate which regions are silenced, and then with histone tails in nucleosomes as the Sir proteins spread from silencers along chromosomes. Importantly, the spreading of silenced chromatin requires the histone deacetylase activity of Sir2p. This requirement leads to a general model for the spreading and inheritance of silenced chromatin or other special chromatin states. Such chromatin domains are marked by modifications of the nucleosomes or DNA, and this mark is able to recruit an enzyme that makes further marks. Thus, among different organisms, multiple forms of repressive chromatin can be formed using similar strategies but completely different proteins. We also describe emerging evidence that mutations that cause global changes in the modification of histones can alter the balance between euchromatin and silenced chromatin within a cell.
The RNA Polymerase II Elongation Complex
Authors: Shilatifard Ali , Conaway Ronald C. , Conaway Joan Weliky
Published: April 2003

▪ Abstract  Synthesis of eukaryotic mRNA by RNA polymerase II is an elaborate biochemical process that requires the concerted action of a large set of transcription factors. RNA polymerase II transcription proceeds through multiple stages designated preinitiation, initiation, and elongation. Historically, studies of the elongation stage of eukaryotic mRNA synthesis have lagged behind studies of the preinitiation and initiation stages; however, in recent years, efforts to elucidate the mechanisms governing elongation have led to the discovery of a diverse collection of transcription factors that directly regulate the activity of elongating RNA polymerase II. Moreover, these studies have revealed unanticipated roles for the RNA polymerase II elongation complex in such processes as DNA repair and recombination and the proper processing and nucleocytoplasmic transport of mRNA. Below we describe these recent advances, which highlight the important role of the RNA polymerase II elongation complex in regulation of eukaryotic gene expression.
Trk Receptors: Roles in Neuronal Signal Transduction
Authors: Huang Eric J. , Reichardt Louis F.
Published: April 2003

▪ Abstract  Trk receptors are a family of three receptor tyrosine kinases, each of which can be activated by one or more of four neurotrophins—nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3 and NT4). Neurotrophin signaling through these receptors regulates cell survival, proliferation, the fate of neural precursors, axon and dendrite growth and patterning, and the expression and activity of functionally important proteins, such as ion channels and neurotransmitter receptors. In the adult nervous system, the Trk receptors regulate synaptic strength and plasticity. The cytoplasmic domains of Trk receptors contain several sites of tyrosine phosphorylation that recruit intermediates in intracellular signaling cascades. As a result, Trk receptor signaling activates several small G proteins, including Ras, Rap-1, and the Cdc-42-Rac-Rho family, as well as pathways regulated by MAP kinase, PI 3-kinase and phospholipase-C-γ (PLC-γ). Trk receptor activation has different consequences in different cells, and the specificity of downstream Trk receptor-mediated signaling is controlled through expression of intermediates in these signaling pathways and membrane trafficking that regulates localization of different signaling constituents. Perhaps the most fascinating aspect of Trk receptor-mediated signaling is its interplay with signaling promoted by the pan-neurotrophin receptor p75NTR. p75NTR activates a distinct set of signaling pathways within cells that are in some instances synergistic and in other instances antagonistic to those activated by Trk receptors. Several of these are proapoptotic but are suppressed by Trk receptor-initiated signaling. p75NTR also influences the conformations of Trk receptors; this modifies ligand-binding specificity and affinity with important developmental consequences.
Biology of the p21-Activated Kinases
Authors: Bokoch Gary M.
Published: April 2003

▪ Abstract  The p21-activated kinases (PAKs) 1–3 are serine/threonine protein kinases whose activity is stimulated by the binding of active Rac and Cdc42 GTPases. Our understanding of the regulation and biology of these important signaling proteins has increased tremendously since their discovery in the mid-1990s. PAKs 1–3 are activated by a variety of GTPase-dependent and -independent mechanisms. This complexity reflects the contributions of PAK function in many cellular signaling pathways and the need to carefully control PAK action in a highly localized manner. PAKs serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signaling, and cell-cycle progression. Consequently, PAKs have also been implicated in a number of pathological conditions and in cell transformation. We propose here a key role for PAK action in coordinating the dynamics of the actin and microtubule cytoskeletons during directional motility of cells, as well as in other functions requiring cytoskeletal polarization.
A Genetic Approach to Mammalian Glycan Function
Authors: Lowe John B. , Marth Jamey D.
Published: April 2003

▪ Abstract  The four essential building blocks of cells are proteins, nucleic acids, lipids, and glycans. Also referred to as carbohydrates, glycans are composed of saccharides that are typically linked to lipids and proteins in the secretory pathway. Glycans are highly abundant and diverse biopolymers, yet their functions have remained relatively obscure. This is changing with the advent of genetic reagents and techniques that in the past decade have uncovered many essential roles of specific glycan linkages in living organisms. Glycans appear to modulate biological processes in the development and function of multiple physiologic systems, in part by regulating protein-protein and cell-cell interactions. Moreover, dysregulation of glycan synthesis represents the etiology for a growing number of human genetic diseases. The study of glycans, known as glycobiology, has entered an era of renaissance that coincides with the acquisition of complete genome sequences for multiple organisms and an increased focus upon how posttranslational modifications to protein contribute to the complexity of events mediating normal and disease physiology. Glycan production and modification comprise an estimated 1% of genes in the mammalian genome. Many of these genes encode enzymes termed glycosyltransferases and glycosidases that reside in the Golgi apparatus where they play the major role in constructing the glycan repertoire that is found at the cell surface and among extracellular compartments. We present a review of the recently established functions of glycan structures in the context of mammalian genetic studies focused upon the mouse and human species.

Nothing tends so much to the advancement of knowledge as the application of a new instrument. The native intellectual powers of men in different times are not so much the causes of the different success of their labours, as the peculiar nature of the means and artificial resources in their possession.

T. Hager: Force of Nature ( 1 )
SIGNALING AT THE GROWTH CONE: Ligand-Receptor Complexes and the Control of Axon Growth and Guidance
Authors: Huber Andrea B. , Kolodkin Alex L. , Ginty David D. , Cloutier Jean-François
Published: April 2003

▪ Abstract  The guidance of axons during the establishment of the nervous system is mediated by a variety of extracellular cues that govern cytoskeletal dynamics in axonal growth cones. A large number of these guidance cues and their cell-surface receptors have now been identified, and the intracellular signaling pathways by which these cues induce cytoskeletal rearrangements are becoming defined. This review summarizes our current understanding of the major families of axon guidance cues and their receptors, with a particular emphasis on receptor signaling mechanisms. We also discuss recent advances in understanding receptor cross talk and how the activities of guidance cues and their receptors are modulated during neural development.
Implications of the Tobacco Industry Documents for Public Health and Policy
Authors: Bero Lisa
Published: March 2003

▪ Abstract  The release of previously secret internal tobacco industry documents has given the public health community unprecedented insight into the industry's motives, strategies, tactics, and data. The documents provide information that is not available from any other source and describe the history of industry activities over the past 50 years. The documents show that the tobacco industry has been engaged in deceiving policy makers and the public for decades. This paper begins with a brief history of the tobacco industry documents and describes the methodological challenges related to locating and analyzing an enormous number of poorly indexed documents. It provides an overview of selected important findings of document research conducted to date, including analyses of industry documents on nicotine and addiction, product design, marketing and promotion, passive smoke, and internal activities. The paper concludes with a discussion of the implications of tobacco document research for public health and the application of such research to fields other than tobacco control.
Methodologic Advances and Ongoing Challenges in Designing Community-Based Health Promotion Programs
Authors: Thompson Beti , Coronado Gloria , Snipes Shedra A. , Puschel Klaus
Published: March 2003

▪ Abstract  Community intervention trials continue to attract researchers as potential ways to achieve widespread, long-term change in health behaviors. The first generations of community studies were somewhat unsophisticated in design and analysis, and their promise may have been overstated. As design and analysis issues were better defined, as secular trends caught up with the behaviors that researchers were trying to change, or as other unknown variables affected community studies, small effects of interventions were observed in community trials. Discussions were held in professional meetings and reported in the literature: Should community trials be discontinued? In general, the answer was a qualified no. In this paper, we briefly review some of the many advances made in community intervention trials, and address in more detail the challenges ahead.
Geographic Information Systems and Public Health
Authors: Ricketts Thomas C.
Published: March 2003

▪ Abstract  Geographic information systems (GIS) and analyses based on GIS have become widespread and well accepted. GIS is not the complete solution to understanding the distribution of disease and the problems of public health but is an important way in which to better illuminate how humans interact with their environment to create or deter health.
Supporting Informed Consumer Health Care Decisions: Data Presentation Approaches that Facilitate the Use of Information in Choice
Authors: Hibbard Judith H. , Peters Ellen
Published: March 2003

▪ Abstract  To make informed choices and navigate within a complex health care system, consumers must have easily available, accurate, and timely information, and they must use it. Contrary to the consumer-driven approach, however, the evidence demonstrates that having an abundance of information does not always translate into its being used to inform choices. The challenge is not merely to communicate accurate information to consumers, but to understand how to present and target that information so that it is actually used in decision-making. This paper reviews what is known from studies of human judgment and decision-making and discusses their implications for supporting informed consumer choice. We delineate the types of decisions that consumers and patients are making, the barriers to using information effectively in choice, and draw upon the evidence for the efficacy of different presentation strategies to propose an initial framework for evaluating and choosing comparative information presentation approaches.
What's Behind the Health Expenditure Trends?
Authors: Mehrotra Ateev , Dudley R. Adams , Luft Harold S.
Published: March 2003

▪ Abstract  In this paper, we review the literature on a number of the potential explanations for the rise in health care expenditures in the United States: the aging population, the costs of dying, technology, physician incomes, administrative costs, prescription drugs, managed care, and the underfunding of public health. Our goal is not to pass definitive judgment on the force(s) driving health care costs, but rather to make the reader a more educated consumer of these widely cited data. We place special emphasis on how health expenditures are measured and the inherent weaknesses in the methodology. We find that frequently it is difficult to accurately estimate how individual forces influence total health care expenditures. Moreover, we conclude that interpreting the causes of the rise in expenditures goes beyond simple observations of trends and depends on how we value various segments and aspects of health and health care.
Will a Healthy Lifestyle Help Prevent Alzheimer's Disease?
Authors: Pope Sandra K. , Shue Valorie M. , Beck Cornelia
Published: March 2003

▪ Abstract  Alzheimer's disease (AD) appears to resemble other chronic diseases, whereby a myriad of interconnected factors, including those associated with lifestyle, are involved in disease development. In this paper, we examine accepted and proposed risk factors for AD and explore health behaviors, including diet, exercise, prevention of injury, and cognitive stimulation, that may help prevent AD. Adherence to a healthy lifestyle may directly protect against AD or may prevent diseases associated with AD, such as vascular disease and diabetes. A healthy lifestyle to prevent AD may be important throughout life rather than after disease manifestation and may be particularly relevant if other factors, such as genetic predisposition, also increase risk of AD. If changes in lifestyle can help prevent AD by reducing modifiable risk factors, this knowledge can aid individuals who wish to take action to protect themselves and their families from the disease.
Management of Chronic Disease by Patients
Authors: Clark Noreen M.
Published: March 2003

▪ Abstract  Chronic conditions dominate health care in most parts of the world, including the United States. Management of a disease by the patient is central to control of its effects. A wide range of influences in the person's social and physical environments enhance or impede management efforts. Interventions to improve management by patients can produce positive outcomes including better monitoring of a condition, fewer symptoms, enhanced physical and psychosocial functioning, and reduced health care use. Successful programs have been theory based. Self-regulation is a promising framework for the development of interventions. Nonetheless, serious gaps in understanding and improving disease management by patients remain because of an emphasis on clinical settings for program delivery, neglect of the factors beyond patient behavior that enable or deter effective management, limitations of study designs in much work to date, reliance on short-term rather than long-term assessments, and failure to evaluate the independent contribution of various program components.
c-Src Induces Phosphorylation and Translocation of p47phox
Authors: Touyz R.M. , Yao G. , Schiffrin E.L.
Published: April 2003

Objectives—

The aim of this study was to determine molecular mechanisms whereby c-Src regulates angiotensin II (Ang II)-mediated NAD(P)H oxidase-derived ·O
2
−
in human vascular smooth muscle cells (VSMCs).

Methods and Results—

VSMCs from human small arteries were studied. Ang II increased NAD(P)H oxidase-mediated generation of ·O
2
−
and H
2
O
2
(
P
<0.01). PP2, c-Src inhibitor, attenuated these effects by 70% to 80%. Immunoprecipitation of p47phox, followed by immunoblotting with antiphosphoserine antibody, demonstrated a rapid increase (1.5- to 2-fold) in p47phox phosphorylation in Ang II-stimulated cells. This was associated with p47phox translocation from cytosol to membrane, as assessed by immunoblotting and immunofluorescence. PP2 abrogated these effects. Long-term Ang II stimulation (6 to 24 hours) increased NAD(P)H oxidase subunit expression. c-Src inhibition decreased abundance of gp91phox, p22phox, and p47phox. Confirmation of c-Src-dependent regulation of NAD(P)H oxidase was tested in VSMCs from c-Src
−/−
mice. Ang II-induced ·O
2
−
generation was lower in c-Src
−/−
than c-Src
+/+
counterparts. This was associated with decreased p47phox phosphorylation, blunted Ang II-stimulated NAD(P)H oxidase activation, and failure of Ang II to increase subunit expression.

Conclusions—

c-Src regulates NAD(P)H oxidase-derived ·O
2
−
generation acutely by stimulating p47phox phosphorylation and translocation and chronically by increasing protein content of gp91phox, p22phox, and p47phox in Ang II-stimulated cells. These novel findings identify NAD(P)H oxidase subunits, particularly p47phox, as downstream targets of c-Src.
Increased Low-Density Lipoprotein Oxidation and Impaired High-Density Lipoprotein Antioxidant Defense Are Associated With Increased Macrophage Homing and Atherosclerosis in Dyslipidemic Obese Mice
Authors: Mertens Ann , Verhamme Peter , Bielicki John K. , Phillips Michael C. , Quarck Rozenn , Verreth Wim , Stengel Dominique , Ninio Ewa , Navab Mohamad , Mackness Bharti , Mackness Mike , Holvoet Paul
Published: March 2003

Background—

Obesity-associated dyslipidemia in humans is associated with increased low-density lipoprotein (LDL) oxidation. Mice with combined leptin and LDL receptor deficiency are obese and show severe dyslipidemia and insulin resistance. We investigated the association between oxidation of apolipoprotein B–containing lipoproteins, high-density lipoprotein (HDL) antioxidant defense, and atherosclerosis in these mice.

Methods and Results—

LDL receptor knockout (LDLR
−/−
), leptin-deficient (ob/ob), double-mutant (LDLR
−/−
;ob/ob), and C57BL6 mice were fed standard chow. Double-mutant mice had higher levels of non-HDL (
P
<0.001) and HDL (
P
<0.01) cholesterol and of triglycerides (
P
<0.001). They also had higher oxidative stress, evidenced by higher titers of autoantibodies against malondialdehyde-modified LDL (
P
<0.001). C57BL6 and ob/ob mice had no detectable lesions. Lesions covered 20% of total area of the thoracic abdominal aorta in double-mutant mice compared with 3.5% in LDLR
−/−
mice (
P
<0.01). Higher macrophage homing and accumulation of oxidized apolipoprotein B-100–containing lipoproteins were associated with larger plaque volumes in the aortic root of double-mutant mice (
P
<0.01). The activity of the HDL-associated antioxidant enzymes paraoxonase and lecithin:cholesterol acyltransferase (LCAT) (ANOVA;
P
<0.0001 for both) was lower in double-mutant mice. Adenovirus-mediated LCAT gene transfer in double-mutant mice increased plasma LCAT activity by 64% (
P
<0.01) and reduced the titer of autoantibodies by 40% (
P
<0.01) and plaque volume in the aortic root by 42% (
P
<0.05) at 6 weeks.

Conclusions—

Dyslipidemia and insulin resistance in obese LDL receptor–deficient mice are associated with increased oxidative stress and impaired HDL-associated antioxidant defense, evidenced by decreased paraoxonase and LCAT activity. Transient LCAT overexpression was associated with a reduction of oxidative stress and atherosclerosis.
Peripheral Adiposity Exhibits an Independent Dominant Antiatherogenic Effect in Elderly Women
Authors: Tankó László B. , Bagger Yu Z. , Alexandersen Peter , Larsen Philip J. , Christiansen Claus
Published: March 2003

Background—

Although several lines of evidence point to an atherogenic role of central fat mass (CFM), few data are available to address the specific role played by peripheral fat mass (PFM).

Methods and Results—

This study was a cross-sectional analysis of 1356 women aged 60 to 85 years. Study variables were physical measures, CFM and PFM measured by DEXA, aortic calcification (AC) graded on lateral radiographs, lipid and glucose metabolites, blood pressure, and information on lifestyle factors and coronary disease. Peripheral fat mass showed independent negative correlation with both atherogenic metabolic risk factors and AC (
P
<0.001). The most severe insulin resistance-dyslipidemic syndrome and AC (score 5.10±0.76) was found in women with high central fat percentage (CF%, 21.7±0.2%) and low peripheral fat percentage (PF%, 18.3±0.2%, n=48). The least severe AC (score 2.45±0.31) was found in obese women with high CF% (21.6±0.1%) and high PF% (27.3±0.14%, n=112). The insulin resistance-dyslipidemic syndrome was also less severe compared with those with the same CF% but low PF%. The most favorable metabolic profile characterized women with low CF% (11.56±0.16%) and high PF% (26.86±0.33%, n=44). In women with a history of myocardial infarct (18.41±0.55%, n=45), CF% was significantly higher compared with women with no manifest coronary disease (16.48±0.12%, n=1210) without differences in PF%.

Conclusions—

In elderly women, localization of fat mass is apparently more important for atherosclerosis than obesity per se; although CFM is associated with atherogenic tendencies, PFM seems to exhibit an independent dominant antiatherogenic effect.
Rapamycin Attenuates Load-Induced Cardiac Hypertrophy in Mice
Authors: Shioi Tetsuo , McMullen Julie R. , Tarnavski Oleg , Converso Kimber , Sherwood Megan C. , Manning Warren J. , Izumo Seigo
Published: March 2003

Background—

Cardiac hypertrophy, or an increase in heart size, is an important risk factor for cardiac morbidity and mortality. The mammalian target of rapamycin (mTOR) is a component of the insulin-phosphoinositide 3-kinase pathway, which is known to play a critical role in the determination of cell, organ, and body size.

Methods and Results—

To examine the role of mTOR in load-induced cardiac hypertrophy, we administered rapamycin, a specific inhibitor of mTOR, to mice with ascending aortic constriction. Activity of p70 ribosomal S6 kinase 1 (S6K1), an effector of mTOR, was increased by 3.8-fold in the aortic-constricted heart. Pretreatment of mice with 2 mg · kg
−1
· d
−1
of rapamycin completely suppressed S6K1 activation and S6 phosphorylation in response to pressure overload. The heart weight/tibial length ratio of vehicle-treated aortic-banded mice was increased by 34.4±3.6% compared with vehicle-treated sham-operated mice. Rapamycin suppressed the load-induced increase in heart weight by 67%. Attenuation of cardiac hypertrophy by rapamycin was associated with attenuation of the increase in myocyte cell size induced by aortic constriction. Rapamycin did not cause loss of body weight, lethality, or left ventricular dysfunction.

Conclusions—

mTOR or its target(s) seems to play an important role in load-induced cardiac hypertrophy. Because systemic administration of rapamycin has been used successfully for the treatment of transplant rejection in clinical practice, it may be a useful therapeutic modality to suppress cardiac hypertrophy in patients.
Atrial High Rate Episodes Detected by Pacemaker Diagnostics Predict Death and Stroke
Authors: Glotzer Taya V. , Hellkamp Anne S. , Zimmerman John , Sweeney Michael O. , Yee Raymond , Marinchak Roger , Cook James , Paraschos Alexander , Love John , Radoslovich Glauco , Lee Kerry L. , Lamas Gervasio A.
Published: March 2003

Background—

Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic. We prospectively studied a 312-patient (pt) subgroup of MOST (MOde Selection Trial), a 2010-patient, 6-year randomized trial of DDDR versus VVIR pacing in sinus node dysfunction (SND). The purpose of the study was to correlate atrial high rate events (AHREs) detected by pacemaker diagnostics with clinical outcomes.

Methods and Results—

Pacemakers were programmed to log an AHRE when the atrial rate was >220 bpm for 10 consecutive beats. Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes. The 312 patients were median age 74 years, 55% female, and 60% had a history of SVT. 160 of 312 (51.3%) patients enrolled had at least 1 AHRE >5 minutes duration over median follow-up of 27 months. Cox proportional hazards analysis assessed the relationship of AHREs with clinical events, adjusting for prognostic variables and baseline covariates. The presence of any AHRE was an independent predictor of the following: total mortality (hazard ratio AHRE versus no AHRE and 95% confidence intervals=2.48 [1.25, 4.91],
P
=0.0092); death or nonfatal stroke (2.79 [1.51, 5.15],
P
=0.0011); and atrial fibrillation (5.93 [2.88, 12.2],
P
=0.0001). There was no significant effect of pacing mode on the presence or absence of AHREs.

Conclusions—

AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke, and 6 times as likely to develop atrial fibrillation as similar patients without AHRE.
Decreased Reendothelialization and Increased Neointima Formation With Endostatin Overexpression in a Mouse Model of Arterial Injury
Authors: Hutter Randolph , Sauter Bernhard V. , Reis Ernane D. , Roque Merce , Vorchheimer David , Carrick Francine E. , Fallon John T. , Fuster Valentin , Badimon Juan J.
Published: March 2003

Background—

Impaired endothelial regeneration contributes to arterial lesion formation. Endostatin is a specific inhibitor of endothelial cell growth and induces endothelial cell apoptosis. We examined the effect of endostatin overexpression on reendothelialization and neointima formation in a mouse model of arterial injury.

Methods and Results—

Mice underwent femoral arterial denudation and received recombinant adenovirus, expressing either murine endostatin (n=19) or control adenoviral vector (n=12), by jugular vein injection. Endostatin gene transfer resulted in high serum levels of endostatin. Strong adenoviral gene expression of β-galactosidase–expressing control vector was detected in liver tissue and was absent in the injured arterial wall at 1 week. Deposits of endostatin protein were detected along the denuded arterial wall and were not seen in the noninjured contralateral artery at 1 week. Endostatin deposits were also absent in the injured artery of control vector–treated animals. Overexpression of endostatin led to decreased reendothelialization and increased apoptosis of luminal endothelial cells 2 and 4 weeks after arterial injury (
P
<0.05). In addition, endostatin overexpression resulted in increased neointima formation (
P
<0.05). Endothelial apoptosis and neointima area correlated positively with endostatin serum levels, whereas the degree of reendothelialization correlated negatively with endostatin serum levels (
P
<0.05). Furthermore, poor reendothelialization correlated with increased neointima formation (
P
<0.05).

Conclusions—

In summary, decreased reendothelialization and enhanced endothelial apoptosis, in response to endostatin overexpression, were associated with increased neointima formation. These findings demonstrate that high serum levels of endostatin are capable of inhibiting endothelial regeneration and promoting arterial lesion growth in conditions of endothelial injury.
Noninvasive Assessment of Left Ventricular Force-Frequency Relationships Using Tissue Doppler–Derived Isovolumic Acceleration
Authors: Vogel Michael , Cheung Michael M.H. , Li Jia , Kristiansen Steen B. , Schmidt Michael R. , White Paul A. , Sorensen Keld , Redington Andrew N.
Published: March 2003

Background—

We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of right ventricular contractile function. In this study, we assessed the usefulness of IVA to measure left ventricular (LV) contractile function and force-frequency relationships in an experimental preparation.

Methods and Results—

In study 1, we examined 6 pigs by use of tissue Doppler imaging of LV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (E
max
), and dP/dt
max
by conductance catheterization. Animals were paced via the right atrium at a rate of 130 bpm. IVA was compared with elastance during contractility modulation by esmolol and dobutamine and assessed during preload reduction and afterload increase. In study 2, in 6 more pigs, force-frequency data were obtained during incremental atrial pacing from 120 to 180 bpm. Study 1: Esmolol led to a decrease in IVA and E
max
(
P
<0.03 and <0.02, respectively), both of which increased during dobutamine infusion (
P
<0.02 and <0.03, respectively). IVA was unaffected by significant (
P
<0.001) acute reduction of LV volume and a significantly increased LV afterload (systolic pressure increase,
P
<0.001). Study 2: There was a positive correlation between IVA and dP/dt
max
(
r
2
=0.92,
P
<0.05). As heart rate was increased from 120 to 160 bpm, there were significant increases in both IVA and dP/dt
max
(
P
<0.0004 and
P
=0.02, respectively). Over the same range of heart rates, there was no significant change in E
max
(
P
=0.22).

Conclusions—

IVA is a measurement of LV contractile function that is unaffected by preload and afterload changes within a physiological range and can be used noninvasively to measure LV force-frequency relationships.
Plasma Concentrations and Genetic Variation of Matrix Metalloproteinase 9 and Prognosis of Patients With Cardiovascular Disease
Authors: Blankenberg Stefan , Rupprecht Hans J. , Poirier Odette , Bickel Christoph , Smieja Marek , Hafner Gerd , Meyer Jürgen , Cambien François , Tiret Laurence
Published: March 2003

Background—

Matrix metalloproteinase (MMP)-9 secretion by macrophages and other inflammatory cells accelerates atherosclerotic progression and destabilizes vulnerable plaque in animal models. However, epidemiological data evaluating the prognostic impact of circulating concentrations and functional genetic variations of MMP-9 are lacking.

Methods and Results—

In a prospective study of 1127 patients with documented coronary artery disease, we measured baseline plasma MMP-9 levels and determined the MMP-9/C-1562T and MMP-9/R279Q genotypes. During the follow-up period (mean of 4.1 years), 97 patients died from cardiovascular (CV) causes. Median concentrations of MMP-9 were significantly higher among patients who experienced a fatal CV event than among those who did not (62.2 versus 47.8 ng/mL;
P
<0.0001). The crude hazard risk ratio of CV death associated with increasing quartiles of MMP-9 was 1.4 (95% CI, 1.2 to 1.8;
P
<0.0001), and after adjustment for clinical and therapeutic confounders, it was 1.3 (95% CI, 1.1 to 1.6;
P
=0.005). Additional adjustment for highly sensitive CRP, interleukin-6, fibrinogen, and interleukin-18 revealed a hazard risk ratio to 1.2 (95% CI, 0.9 to 1.6;
P
=0.15). The T allele of the C-1562T polymorphism was associated with increased MMP-9 levels in a fairly codominant fashion (
P
=0.004). Although none of the polymorphisms was significantly related with future CV death, there was a significant association (
P
=0.02) between the R279Q polymorphism and CV events in patients with stable angina.

Conclusions—

Plasma MMP-9 concentration was identified as a novel predictor of CV mortality in patients with coronary artery disease. Whether it provides independent prognostic information compared with other inflammatory markers will have to be additionally assessed.
Effect of the Asp
298
Variant of Endothelial Nitric Oxide Synthase on Survival for Patients With Congestive Heart Failure
Authors: McNamara Dennis M. , Holubkov Richard , Postava Lisa , Ramani Ravi , Janosko Karen , Mathier Michael , MacGowan Guy A. , Murali Srinivas , Feldman Arthur M. , London Barry
Published: March 2003

Background—

Significant variation exists within the endothelial nitric oxide synthase (NOS3) gene that may influence cardiovascular risk. The Asp
298
variant of NOS3 has a shorter half-life in endothelial cells. Given the importance of nitric oxide in the heart failure syndrome, we evaluated the effect of this variant on event-free survival in a population with systolic dysfunction.

Methods and Results—

Four hundred sixty-nine patients (72% male, 49% ischemic; mean age, 56±12 years) with systolic dysfunction (left ventricular ejection fraction ≤0.45) were enrolled in a study of Genetic Risk Assessment of Cardiac Events (GRACE). The polymorphism in exon 7 of NOS3, a G-T transition at position 894 that results in a Glu to Asp amino acid substitution for codon 298, was genotyped and subjects were followed prospectively to the end point of death or heart transplantation. Event-free survival was compared on the basis of the presence (group 1, n=266) or absence (group 2, n=203) of the Asp
298
variant. Event-free survival was significantly poorer in patients with the Asp
298
variant (percent event-free survival group 1 at 1/2/3 years=78/65/54; group 2=82/72/64,
P
=0.03). In subset analysis, the adverse impact of the Asp
298
variant was primarily in patients with nonischemic cardiomyopathy (group 1=82/73/63; group 2=87/79/71,
P
=0.03) and was not apparent among patients with ischemic heart disease (group 1=75/59/47; group 2=74/62/54,
P
=0.71).

Conclusions—

For patients with heart failure caused by systolic function, the Asp
298
variant of NOS3 is associated with poorer event-free survival, particularly in patients with nonischemic cardiomyopathy.
Low Pro-Brain Natriuretic Peptide Levels Predict Benign Clinical Outcome in Acute Pulmonary Embolism
Authors: Kucher Nils , Printzen Gert , Doernhoefer Tanja , Windecker Stephan , Meier Bernhard , Hess Otto Martin
Published: March 2003

Background—

The role of pro-brain natriuretic peptide (proBNP) for the prediction of clinical outcome has not been examined in patients with acute pulmonary embolism (PE).

Methods and Results—

ProBNP levels were measured in 73 patients with acute PE within 4 hours of admission. Adverse clinical outcome was defined as in-hospital death or the need for at least 1 of the following: cardiopulmonary resuscitation, mechanical ventilation, pressors, thrombolysis, catheter fragmentation, or surgical embolectomy. In the 53 patients with a benign clinical outcome, proBNP (median 121, range 16 to 34 802 pg/mL) was lower than in 20 patients with adverse clinical outcome (median 4250, range 92 to 49 607 pg/mL;
P
<0.0001). The negative predictive value of proBNP levels <500 pg/mL to predict adverse clinical outcome was 97% (95% confidence interval 84 to 99). ProBNP remained an independent predictor for adverse clinical outcome (odds ratio 14.6; 95% confidence interval 1.5 to 139.0;
P
=0.02) after adjusting for severity of PE (submassive/massive), troponin T levels >0.01ng/mL, age >70 years, gender, and history of congestive heart failure.

Conclusions—

Low proBNP levels predict an uneventful hospital course in patients with acute PE. A proBNP level <500 pg/mL identifies patients who will be potential candidates for an abbreviated hospital length of stay or care on a completely outpatient basis.
Kodak Moments, Flashbulb Memories: Reflections on 9/11
Authors: Kirshenblatt-Gimblett Barbara
Published: March 2003

The catastrophe of 9/11 transformed life in New York City. Grassroots responses were spontaneous, improvised, and ubiquitous. Every surface was blanketed with candles, flowers, flags, and missing persons' posters that became the focal point of shrines memorializing the missing and presumed deceased. The catastrophe produced a series of equivocal situations: Kodak moment or surrogate body? Crime scene or tourist attraction? Missing person notice or obituary? Cheap souvenir or involuntary memento? Voyeurism or mourning? Above all, the question of documentation: When, where, and how should documentation of memorials be exhibited?
A Day in the Life of a Prison Theatre Program
Authors: Moller Lorraine
Published: March 2003

The artistic director of Rehabilitation through the Arts recounts making Voices from Within with and for inmates of Sing Sing, a high-security prison north of New York City. The play, a collaboration developed in a workshop with playwright Barbara Quintero, portrays the strategies prisoners consciously or unconsciously use to survive the experience of incarceration.
What's New-and Renewed-Onstage in China
Authors: Conceison Claire
Published: March 2003

This new feature of TDR presents reports on various performances and artists. In this issue we offer an account of the 2002 Chinese theatre season, a performance rumination on the atomic bomb and 9/11, the experience of groupies at a parodic “cock-rock” concert, and a selection of performative haikus composed by a San Francisco performance artist.
Painting As Performance Charlotte Salomon's Life? or Theatre?
Authors: Barnett Claudia
Published: March 2003

Charlotte Salomon's 1942 series of paintings, Life? or Theatre?, into which she incorporates elements of music and drama, wonders whether life and theatre are polar opposites or an engaged dialectic. Salomon anticipated the advent of performance theory by insisting on the performative qualities of her paintings. Her art exists in the unstable, ever-changing space between past and future, fact and fiction, life and death.
Not in Between Lyric Painting, Visual History, and the Postcolonial Future
Authors: Moten Fred
Published: March 2003

The lyrical radio speeches of Patrice Lumumba are recaptured in the art of Tshibumba Kanda. But in order to understand this spirit of the postcolonial future as a revolutionary, intellectual force, we must make a detour through the work of C.L.R. James and Cedric Robinson. The theory and practice of revolution is bound to the way the individual emerges as a theoretical possibility and phenomenological actuality in and out of the revolutionary ensemble.
Saint Sebastian and the Blue-Eyed Blacks Corpus Christi in Cusco, Peru
Authors: Harris Max
Published: March 2003

The early summer festival of Corpus Christi has been for many centuries the occasion for vibrant street theatre throughout the Roman Catholic world. The pageantry thrives in Cusco, Peru, where the week of Corpus Christi festivities runs concurrently with the massive civic parades that precede the reconstructed Inca solstice festival of Inti Raymi. This miscegenation of festive traditions befits the celebration's multiple ethnic referents, invoking the heritages of Spain, the Incas, the rural Indians of the Amazon and the Andes, and urban mestizos.
At Home in the World? The Bharatanatyam Dancer As Transnational Interpreter
Authors: O'Shea Janet
Published: March 2003

Bharatanatyam dancers often explain what they are about to perform, offering an introduction to the dance and to the particular narrative to be enacted. This kind of preperformance synopsis brings into play an English verbal framework and a South Indian choreographic one. The explanation interprets the “Eastern” choreography through the “Western” linguistic system. This spoken interlocution risks representing bharatanatyam more as a means of entry into a cultural field of reference than as a set of choreographic choices and compositional devices.
DIVERSE: A Framework for Building Extensible and Reconfigurable Device-Independent Virtual Environments and Distributed Asynchronous Simulations
Authors: Kelso John , Satterfield Steven G. , Arsenault Lance E. , Ketchan Peter M. , Kriz Ronald D.
Published: March 2003

We present DIVERSE, a highly modular collection of complimentary software packages designed to facilitate the creation of device-independent virtual environments and distributed asynchronous simulations. DIVERSE is free/open source software, containing both end-user programs and C++ application programming interfaces (APIs).

DPF is the DIVERSE graphics interface to OpenGL Performer. A program using the DPF API can run without modification on platforms ranging from fully immersive systems such as CAVEs to generic desktop workstations.

The DIVERSE toolkit (DTK) contains all the nongraphical components of DIVERSE, such as networking utilities, hardware device access, and navigational techniques. It introduces a software implementation of networks of replicated noncoherent shared memory. It also introduces a method that seamlessly extends hardware drivers into interprocess and Internet hardware services.

We will describe the design of DIVERSE and present a specific example of how it is being used to aid researchers.
Handling Heterogeneity in Networked Virtual Environments
Authors: Trefftz Helmuth , Marsic Ivan , Zyda Michael
Published: March 2003

The availability of inexpensive and powerful graphics cards as well as fast Internet connections make networked virtual environments viable for millions of users and many new applications. It is therefore necessary to cope with the growing heterogeneity that arises from differences in computing power, network speed, and users' preferences. This paper describes an architecture that accommodates the heterogeneity while allowing a manager to define systemwide policies. One of the main objectives of our scheme is to allow slower nodes to participate in the session by preventing fast nodes from flooding slow nodes with too many messages. Policies and users' preferences can be expressed as simple linear equations forming a model that describes the system as a whole as well as its individual components. When solutions to this model are mapped back to the problem domain, viable solutions that accommodate heterogeneity and system policies are obtained. For example, slower nodes may receive less frequent updates than faster ones for one or several information streams. The results of our experiments with a proof-of-concept system are described.
Distributed Applications for Collaborative Three-Dimensional Workspaces
Authors: Schmalstieg Dieter , Reitmayr Gerhard , Hesina Gerd
Published: March 2003

This paper focuses on the distributed architecture of the collaborative threedimensional user interface management system, Studierstube. The system allows multiple users to experience a shared 3D workspace populated by multiple applications using see-through head-mounted displays or other presentation media such as projection systems. Building large, ubiquitous, or mobile workspaces requires distribution of applications over several hosts in varying and dynamic configurations. The system design is based on a distributed shared scene graph that alleviates the application programmer from explicitly considering distribution and that avoids a separation of graphical and application data. The idea of unifying all system data in the scene graph is taken to its logical consequence by implementing application instances as nodes in the scene graph. Through the distributed shared scene graph mechanism, consistency of scene graph replicas and the contained application nodes is assured. Dynamic configuration management is based on application migration between participating hosts and a spatial model of locales allowing dynamic workgroup management. We describe a number of experimental workspaces that demonstrate the use of these configuration management techniques.
An Extensible Event-Based Infrastructure for Networked Virtual Worlds
Authors: Purbrick Jim , Greenhalgh Chris
Published: March 2003

Many VR platforms emphasize extensibility to support as wide a range of applications as possible. The current trend is to move this extensibility to lower levels of the system to support extensibility of infrastructure mechanisms such as networking protocols. This kind of extensibility allows the runtime of the virtual environment system to evolve even while the system is running. This paper presents a new virtual environment platform that allows multiple infrastructure mechanisms to be added to and coexist within the running system, with different elements of the virtual world using different mechanisms. This allows the virtual environment system to efficiently support a wider range of applications by, for example, having only certain virtual objects use conservative consistency and persistence. It can also optimize the performance of the CVE by tailoring the infrastructure mechanisms according to the different roles played by different objects in the virtual environment.
Immersive and Interactive Exploration of Billion-Atom Systems
Authors: Sharma Ashish , Nakano Aiichiro , Kalia Rajiv K. , Vashishta Priya , Kodiyalam Sanjay , Miller Paul , Zhao Wei , Liu Xinlian , Campbell Timothy J. , Haas Andy
Published: March 2003

We have developed a visualization system, namedAtomsviewer, to render a billion atoms from the results of a molecular dynamics simulation. This system uses a hierarchical view frustum culling algorithm based on the octree data structure to efficiently remove atoms that are outside of the field of view. A novel occlusion culling algorithm, using a probability function, then selects atoms with a high probability of being visible. These selected atoms are further tested with a traditional occlusion culling algorithm before being rendered as spheres at varying levels of detail. To achieve scalability, Atomsviewer is distributed over a cluster of PCs that execute a parallelized version of the hierarchical view frustum culling and the probabilistic occlusion culling, and a graphics workstation that renders the atoms. We have used Atomsviewer to render a billion-atom data set on a dual processor SGI Onyx2 with an InfiniteReality2 graphics pipeline connected to a four-node PC cluster.
Cluster Overlap Distribution Map: Visualization for Gene Expression Analysis Using Immersive Projection Technology
Authors: Kano Makoto , Nishimura Kunihiro , Tsutsumi Shuichi , Aburatani Hiroyuki , Hirota Koichi , Hirose Michitaka
Published: March 2003

In this paper, we discuss possible applications of virtual reality technologies, such as immersive projection technology (IPT), in the field of genome science, and propose cluster-oriented visualization that attaches importance to data separation of large gene data sets with multiple variables. Based on these strategies, we developed the cluster overlap distribution map (CDCM), which is a visualization methodology using IPT for pairwise comparison between cluster sets generated from different gene expression data sets. This methodology effectively provides the user with indications of gene clusters that are worth a close examination. In addition, by using the plate window manager system, which enables the user to manipulate existing 2D GUI applications in the virtual 3D space, we developed the virtual environment for the comprehensive analysis from providing the indications to further examination by referring to the database on Web sites. Our system was applied in the comparison between the gene expression data sets of hepatocellular carcinomas and hepatoblastomas, and the effectiveness of the system was confirmed.
Real-Time Haptic and Visual Simulation of Bone Dissection
Authors: Agus Marco , Giachetti Andrea , Gobbetti Enrico , Zanetti Gianluigi , Zorcolo Antonio
Published: March 2003

Bone dissection is an important component of many surgical procedures. In this paper, we discuss a haptic and visual simulation of a bone-cutting burr that is being developed as a component of a training system for temporal bone surgery. We use a physically motivated model to describe the burr-bone interaction, which includes haptic forces evaluation, the bone erosion process, and the resulting debris. The current implementation, directly operating on a voxel discretization of patient-specific 3D CT and MR imaging data, is efficient enough to provide real-time feedback on a low-end multiprocessing PC platform.