bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages
Authors: Peters Paul J. , Bhattacharya Jayanta , Hibbitts Samantha , Dittmar Matthias T. , Simmons Graham , Bell Jeanne , Simmonds Peter , Clapham Paul R.
Published: June 2004

Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4+CCR5+cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.
Identification of an Antigenic Determinant on the S2 Domain of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Capable of Inducing Neutralizing Antibodies
Authors: Zhang Hong , Wang Guangwen , Li Jian , Nie Yuchun , Shi Xuanling , Lian Gewei , Wang Wei , Yin Xiaolei , Zhao Yang , Qu Xiuxia , Ding Mingxiao , Deng Hongkui
Published: June 2004

Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.
Selection, Transmission, and Reversion of an Antigen-Processing Cytotoxic T-Lymphocyte Escape Mutation in Human Immunodeficiency Virus Type 1 Infection
Authors: Allen Todd M. , Altfeld Marcus , Yu Xu G. , O'Sullivan Kristin M. , Lichterfeld Mathias , Le Gall Sylvie , John Mina , Mothe Bianca R. , Lee Paul K. , Kalife Elizabeth T. , Cohen Daniel E. , Freedberg Kenneth A. , Strick Daryld A. , Johnston Mary N. , Sette Alessandro , Rosenberg Eric S. , Mallal Simon A. , Goulder Philip J. R. , Brander Christian , Walker Bruce D.
Published: June 2004

Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8
+
T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes.
Selection Pressure-Driven Evolution of the Epstein-Barr Virus-Encoded Oncogene LMP1 in Virus Isolates from Southeast Asia
Authors: Burrows Jacqueline M. , Bromham Lindell , Woolfit Megan , Piganeau Gwenaël , Tellam Judy , Connolly Geoff , Webb Natasha , Poulsen Leith , Cooper Leanne , Burrows Scott R. , Moss Denis J. , Haryana Sofia M. , Ng Mun , Nicholls John M. , Khanna Rajiv
Published: June 2004

The geographically constrained distribution of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in southeast Asian populations suggests that both viral and host genetics may influence disease risk. Although susceptibility loci have been mapped within the human genome, the role of viral genetics in the focal distribution of NPC remains an enigma. Here we report a molecular phylogenetic analysis of an NPC-associated viral oncogene,
LMP1
, in a large panel of EBV isolates from southeast Asia and from Papua New Guinea, Africa, and Australia, regions of the world where NPC is and is not endemic, respectively. This analysis revealed that
LMP1
sequences show a distinct geographic structure, indicating that the southeast Asian isolates have evolved as a lineage distinct from those of Papua New Guinea, African, and Australian isolates. Furthermore, a likelihood ratio test revealed that the C termini of the LMP1 sequences of the southeast Asian lineage are under significant positive selection pressure, particularly at some sites within the C-terminal activator regions. We also present evidence that although the N terminus and transmembrane region of LMP1 have undergone recombination, the C-terminal region of the gene has evolved without any history of recombination. Based on these observations, we speculate that selection pressure may be driving the LMP1 sequences in virus isolates from southeast Asia towards a more malignant phenotype, thereby influencing the endemic distribution of NPC in this region.
Nuclear Sequestration of Cellular Chaperone and Proteasomal Machinery during Herpes Simplex Virus Type 1 Infection
Authors: Burch April D. , Weller Sandra K.
Published: June 2004

Herpes simplex virus type 1 (HSV-1) encodes a portal protein that forms a large oligomeric structure believed to provide the conduit for DNA entry and exit from the capsid. Chaperone proteins often facilitate the folding and multimerization of such complex structures. In this report, we show that cellular chaperone proteins, components of the 26S proteasome, and ubiquitin-conjugated proteins are sequestered in discrete foci in the nucleus of the infected cell. The immediate-early viral protein ICP0 was shown to be necessary to establish these foci at early times during infection and sufficient to redistribute chaperone molecules in transfected cells. Furthermore, we found that not only is the portal protein, UL6, localized to these sites during infection, but it is also a substrate for ubiquitin modification. Our results suggest that HSV-1 has evolved an elegant mechanism for facilitating protein quality control at specialized foci within the nucleus.
Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection
Authors: Radhakrishnan Sujatha , Gordon Jennifer , Del Valle Luis , Cui Jianqi , Khalili Kamel
Published: June 2004

The human polyomavirus, JC virus (JCV), encodes two regulatory proteins at the early (T antigen) and the late (agnoprotein) phases of viral infection whose activities are important for the production of the viral capsid proteins and the dysregulation of several host factors and their functions. For this study, we designed and utilized an RNA interference strategy via small interfering RNAs (siRNAs) that targeted the expression of T antigen and agnoprotein in human astrocytic cells. The treatment of cells with specific siRNA oligonucleotides targeting a conserved region of T antigen, nucleotides (nt) 4256 to 4276 (Mad-1 strain), caused a >50% decline in the level of T antigen and in its transcriptional activity upon the viral capsid genes as well as a significant reduction in viral DNA replication in infected cells. Similarly, a single siRNA that aimed at nt 324 to 342 of agnoprotein noticeably reduced early and late viral protein production. A combined treatment of the infected cells with both T-antigen and agnoprotein siRNAs completely abolished viral capsid protein production, indicative of the ability of the siRNAs to effectively halt multiplication of the virus in infected cells. These observations provide a new avenue for possible treatments of patients with the JCV-induced demyelinating disease progressive multifocal leukoencephalopathy.
“Sleeping Beauty”: Quiescence inSaccharomyces cerevisiae
Authors: Gray Joseph V. , Petsko Gregory A. , Johnston Gerald C. , Ringe Dagmar , Singer Richard A. , Werner-Washburne Margaret
Published: June 2004

The cells of organisms as diverse as bacteria and humans can enter stable, nonproliferating quiescent states. Quiescent cells of eukaryotic and prokaryotic microorganisms can survive for long periods without nutrients. This alternative state of cells is still poorly understood, yet much benefit is to be gained by understanding it both scientifically and with reference to human health. Here, we review our knowledge of one “model” quiescent cell population, in cultures of yeast grown to stationary phase in rich media. We outline the importance of understanding quiescence, summarize the properties of quiescent yeast cells, and clarify some definitions of the state. We propose that the processes by which a cell enters into, maintains viability in, and exits from quiescence are best viewed as an environmentally triggered cycle: the cell quiescence cycle. We synthesize what is known about the mechanisms by which yeast cells enter into quiescence, including the possible roles of the protein kinase A, TOR, protein kinase C, and Snf1p pathways. We also discuss selected mechanisms by which quiescent cells maintain viability, including metabolism, protein modification, and redox homeostasis. Finally, we outline what is known about the process by which cells exit from quiescence when nutrients again become available.
LAGRANGIAN AND SYMMETRY STRUCTURE OF THE DIVERGENCE CLEANING MODEL BASED ON GENERALIZED LAGRANGE MULTIPLIERS
Authors: LEE Y. J. , MUNZ C.-D. , SCHNEIDER R.
Published: June 2004

A field theoretical method for the treatment of the often violated charge conservation laws in computational electrodynamics is presented. This approach explores the basic symmetry features of Maxwell theory and the analogy between the gauge field anomalies of quantum field theory and the violation of charge conservation law on the lattice, in Lorentz covariant Lagrangian formalism. A mathematical construction of the counter terms to the anomalous charge conservation law is proposed, and thereby a consistent theory for the Generalized Lagrange Multiplier [Formula: see text] method is presented, which has so far lacked a concrete theoretical framework. Based on the established theoretical framework, the [Formula: see text] method has been further extended and the question regarding whether [Formula: see text] method solves "right" equations is answered. This extended [Formula: see text] method with new insight is then applied to magnetohydrodynamics [Formula: see text] and recently proposed "shallow water" [Formula: see text]. In particular, a [Formula: see text]-based Godunov-type finite-volume solver for the "shallow water" [Formula: see text] system on the Cartesian grid has been developed, and the introduced theoretical framework for [Formula: see text] model is validated. In addition, associated new analytic features of the "shallow water" [Formula: see text] system is also presented.
EVIDENCE OF "ESSENTIAL UNCERTAINTY" IN EMERGENCY-WARD LENGTH OF STAY
Authors: PHILIPPE PIERRE , GARCIA MARIA R. , WEST BRUCE J.
Published: June 2004

Scaling in random time series is a novel way of gaining insight into mechanisms of complex systems. Scaling parameters characterize searches for the presence of "essential" uncertainty in outcomes of complex systems. The presence of this type of uncertainty in the emergency system (ES) can point to unusual ways of relieving the financial burden to the health system and improve the public health. The objective of this paper is to test for the presence of "essential" uncertainty in an outcome variable of the ES, i.e. emergency-ward length of stay (EWLS). An inverse power law (IPL) function fit to data can assess "essential" uncertainty. The study of EWLS has been undertaken in ten large Quebec hospitals. We find that all hospital EWLS are well fit by an IPL, as determined by an aggregated allometric relation. The presence of "essential" uncertainty is further confirmed by stratifying the EWLS according to proxies of disease complexity and severity at entry in emergency ward. Results point out that the various hospital dynamic systems embed "essential" uncertainty to various degrees. We conclude that intervention to reduce hospital health care costs must be centered on the interaction and feedback characterizing the ES processing of the patients.
Modulation of chloride secretory responses and barrier function of intestinal epithelial cells by the Salmonella effector protein SigD
Authors: Bertelsen Lone S. , Paesold Günther , Marcus Sandra L. , Finlay Brett B. , Eckmann Lars , Barrett Kim E.
Published: June 2004

The Salmonella effector protein SigD is an inositol phosphate phosphatase that inhibits phosphatidylinositol 3-kinase-dependent signaling. Because epidermal growth factor (EGF) inhibits chloride secretion via phosphatidylinositol 3-kinase, we explored whether Salmonella infection might modify the inhibitory effect of EGF. As expected, EGF inhibited chloride secretion induced by carbachol in T84 epithelial cells. Infection with wild-type (WT) but not sigD− mutant S. typhimurium SL1344 decreased CCh-stimulated chloride secretion. Moreover, WT but not sigD− Salmonella reduced the inhibitory effect of EGF on carbachol-stimulated chloride secretion. Complementation of sigD restored the ability of mutant Salmonella to reverse the inhibitory effect of EGF. EGF-induced EGF receptor phosphorylation was similar in cells infected with either WT or mutant Salmonella, and neither WT nor sigD − Salmonella altered recruitment of the p85 subunit of phosphatidylinositol 3-kinase to EGF receptor, implying that SigD acts downstream of these signaling events. Furthermore, transepithelial resistance fell more rapidly in cells infected with WT vs. sigD − Salmonella, indicating an early role for SigD in reducing barrier function, perhaps via activation of protein kinase C. We conclude that the Salmonella bacterial effector protein SigD may play critical roles in the pathogenesis of disease caused by this microorganism.
Nonnutritive swallowing and respiration relationships in preterm lambs
Authors: Reix Philippe , Arsenault Julie , Langlois Carole , Niyonsenga Théophile , Praud Jean-Paul
Published: June 2004

The aim of the present study was to assess the effects of the different states of alertness on 1) nonnutritive swallowing (NNS) frequency, 2) the relationship between NNS and the respiratory cycle, and 3) the association of NNS with spontaneous apneas. Recordings of sleep states, diaphragm and laryngeal constrictor electrical activity, nasal flow, electrocardiogram, respiratory inductance plethysmography, and pulse oximetry were obtained from six preterm lambs without sedation. Analysis of 2,468 NNS showed that 1) NNS frequency was higher during quiet wakefulness and active sleep (AS) than in quiet sleep; 2) in all states of alertness, a greater number of NNS (38%) were preceded and followed by an inspiration; 3) although NNS and central apneas were rarely coincidental, AS appeared to favor their association; and 4) most obstructive apneas occurred in AS and were coincidental with bursts of NNS. Compared with results in full-term lambs, premature birth does not modify the NNS-respiratory coordination. However, AS in preterm lambs is characterized by a higher association of NNS bursts with obstructive apneas.
Endothelial cells as early sensors of pulmonary interstitial edema
Authors: Daffara Rossella , Botto Laura , Beretta Egidio , Conforti Elena , Faini Andrea , Palestini Paola , Miserocchi Giuseppe
Published: June 2004

We studied responses of endothelial and epithelial cells in the thin portion of the air-blood barrier to a rise in interstitial pressure caused by an increase in extravascular water (interstitial edema) obtained in anesthetized rabbits receiving saline infusion (0.5 ml·kg−1·min−1 for 3 h). We obtained morphometric analyses of the cells and of their microenvironment (electron microscopy); furthermore, we also studied in lung tissue extracts the biochemical alterations of proteins responsible for signal transduction (PKC, caveolin-1) and cell-cell adhesion (CD31) and of proteins involved in membrane-to-cytoskeleton linkage (α-tubulin and β-tubulin). In endothelial cells, we observed a folding of the plasma membrane with an increase in cell surface area, a doubling of plasmalemma vesicular density, and an increase in cell volume. Minor morphological changes were observed in epithelial cells. Edema did not affect the total plasmalemma amount of PKC, β-tubulin, and caveolin-1, but α-tubulin and CD-31 increased. In edema, the distribution of these proteins changed between the detergent-resistant fraction of the plasma membrane (DRF, lipid microdomains) and the rest of the plasma membrane [high-density fractions (HDFs)]. PKC and tubulin isoforms shifted from the DRF to HDFs in edema, whereas caveolin-1 increased in DRF at the expense of a decrease in phosphorylated caveolin-1. The changes in cellular morphology and in plasma membrane composition suggest an early endothelial response to mechanical stimuli arising at the interstitial level subsequently to a modest (∼5%) increase in extravascular water.
Genetic dissection of systemic autoimmune disease in Nrf2-deficient mice
Authors: Li Jiang , Stein Thor D. , Johnson Jeffrey A.
Published: June 2004

Systemic lupus erythematosus (SLE) is an autoimmune disorder with immune-complex deposition that affects multiple organs. Previous studies have suggested the involvement of oxidative stress and apoptosis in SLE, but no clear link to etiology has been established. Here we show that mice deficient in a transcription factor responsible for controlling the expression of numerous detoxification and antioxidant genes develop an autoimmune disease with multiple organ pathologies that closely resembles human SLE. Aged female mice with a knockout of nuclear factor, erythroid-derived 2, like 2 (nrf2) are prone to develop antibodies against double-stranded DNA and the Smith antigen as well as IgG, IgM, and C3 deposition in kidney, liver, heart, and brain. Prior to the development of autoimmune antibodies and organ pathology, oxidative damage occurs in the liver and kidney as indicated by the increased levels of the DNA oxidation marker 8-hydroxydeoxyguanosine and the later increase in the lipid peroxidation product malondialdehyde. Gene expression profiles demonstrate an early decrease in numerous antioxidant and detoxification genes in the livers and altered levels of cytokines and T and B cell-specific genes in the spleens of nrf2 knockout mice. These data strongly suggest that a deficiency in detoxification and increased oxidative stress can result in the development of a systemic autoimmune disease.
Composition of pigments of Santorini frescoes: The Rietveld method as an aid in qualitative phase analysis
Authors: Rasmussen Svend Erik , Grundvig Sidsel , Friedrich Walter L.
Published: June 2004

Ten fragments of bronze age frescoes from the Greek group of volcanic islands known as Santorini have been examined by powder X-ray diffraction. A qualitative phase analysis based on line positions only was supplemented by the Rietveld method which uses complete diffraction profiles to increase the credibility of the phase analysis.
X-ray powder diffraction analysis of three 4-tert-butylcalix(4)arenes
Authors: Zhang Ming-Tao , Qiao Yuan-Yuan , Lin Shao-Fan , Yao Xin-Kan
Published: June 2004

The X-ray powder diffraction patterns for three 4-tert-butylcalix(4)arenes were determined. The similarity and differences between them were compared and discussed.
Subphysiologic Apolipoprotein E (ApoE) Plasma Levels Inhibit Neointimal Formation After Arterial Injury in ApoE-Deficient Mice
Authors: Wientgen Hilke , Thorngate Fayanne E. , Omerhodzic Sabina , Rolnitzky Linda , Fallon John T. , Williams David L. , Fisher Edward A.
Published: June 2004

Objective—Apolipoprotein E (apoE) reduces mouse atherosclerosis progression independent of plasma cholesterol level effects. A mouse artery injury model was used to examine whether apoE exhibits beneficial lipid-independent effects on neointimal formation.

Methods and Results—ApoE-deficient (apoE−/−), wild-type (WT), and transgenic apoE−/− mice (secreting apoE at different levels from adrenal glands) underwent femoral artery injury. Mice with low expression of plasma apoE (0.1% of WT) had cholesterol levels approximately half those of apoE−/− littermates (but still ≈6× >WT). Mice with higher expression (HE; 2% to 3% of WT) of plasma apoE had cholesterol levels approximately twice those of WT. Injured WT mouse (versus apoE−/−) arteries had a smaller mean intima-to-media (I/M) ratio (0.87 versus 1.96;P<0.05). HE mice tended to have lower mean I/M ratios (1.3;P>0.05 versus apoE−/− mice). Multiple regression analysis indicated that apoE levels were significantly associated with reduced I/M ratios, but plasma cholesterol levels were not, before or after adjusting for apoE. In addition, foam cell content of the neointima and media of injured arteries, a negative prognostic indicator in postangioplasty human lesions, was inversely related to plasma apoE levels.

Conclusions—Similar to its effects on atherosclerosis progression, in a mouse model of restenosis, a subphysiological level of apoE was associated with beneficial effects on lesion size/composition.
Lysosomal Cysteine Proteases in Atherosclerosis
Authors: Liu Jian , Sukhova Galina K. , Sun Jiu-Song , Xu Wei-Hua , Libby Peter , Shi Guo-Ping
Published: June 2004

Atherosclerosis is an inflammatory disease characterized by extensive remodeling of the extracellular matrix architecture of the arterial wall. Although matrix metalloproteinases and serine proteases participate in these pathologic events, recent data from atherosclerotic patients and animals suggest the participation of lysosomal cysteine proteases in atherogenesis. Atherosclerotic lesions in humans overexpress the elastolytic and collagenolytic cathepsins S, K, and L but show relatively reduced expression of cystatin C, their endogenous inhibitor, suggesting a shift in the balance between cysteine proteases and their inhibitor that favors remodeling of the vascular wall. Extracts of human atheromatous tissue show greater elastolytic activity in vitro than do those from healthy donors. The cysteinyl protease inhibitor E64d limits this increased elastolysis, indicating involvement of cysteine proteases in elastin degradation during atherogenesis. Furthermore, inflammatory cytokines augment expression and secretion of active cysteine proteases from cultured monocyte-derived macrophages, vascular smooth muscle cells, and endothelial cells and increase degradation of extracellular elastin and collagen. Cathepsin S–deficient cells or those treated with E64d show significantly impaired elastolytic or collagenolytic activity. Additionally, recent in vivo studies of atherosclerosis-prone, LDL receptor–null mice lacking cathepsin S show participation of this enzyme in the initial infiltration of leukocytes, medial elastic lamina degradation, endothelial cell invasion, and neovascularization, illustrating an important role for cysteine proteases in arterial remodeling and atherogenesis.
Nomogram to Diagnose Familial Combined Hyperlipidemia on the Basis of Results of a 5-Year Follow-Up Study
Authors: Veerkamp Mario J. , de Graaf Jacqueline , Hendriks Jan C.M. , Demacker Pierre N.M. , Stalenhoef Anton F.H.
Published: June 2004

Background—

Familial combined hyperlipidemia (FCH) is traditionally diagnosed by total plasma cholesterol and/or triglyceride levels above the 90th percentile adjusted for age and gender. In a recent study, we showed that the diagnosis of FCH on the basis of these diagnostic criteria was inconsistent in 26% of the subjects over a 5-year period. This result emphasizes the need for reevaluation of the diagnostic criteria for FCH.

Methods and Results—

A total of 32 families (299 subjects) were studied in 1994 and 1999. A subject was defined “truly” FCH when diagnosed FCH in 1994 and/or 1999 on the basis of traditional plasma lipid criteria. Additional lipid and lipoprotein parameters, including apolipoprotein B (apoB) and small, dense LDL, were measured at both time points. In total, 121 subjects (40%) were defined as truly FCH. Multivariate analysis revealed that absolute apoB values combined with triglyceride and total cholesterol levels adjusted for age and gender best predicted truly FCH. A nomogram including these parameters is provided to simply and accurately calculate the probability to be affected by FCH. Furthermore, it is shown that when percentiles of triglyceride and total cholesterol adjusted for age and gender are not available in a population, the definition of FCH can be established on the basis of hypertriglyceridemia (>1.5 mmol/L) and hyper-apoB (>1200 mg/L).

Conclusions—

The diagnosis of FCH is best predicted by absolute apoB levels combined with triglyceride and total cholesterol levels adjusted for age and gender and can accurately be calculated by a nomogram. This definition is also a good predictor of cardiovascular risk in FCH.
Dietary Sodium Restriction Rapidly Improves Large Elastic Artery Compliance in Older Adults With Systolic Hypertension
Authors: Gates Phillip E. , Tanaka Hirofumi , Hiatt William R. , Seals Douglas R.
Published: June 2004

We determined the temporal effects of dietary sodium restriction on large elastic artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64±2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54±11 mmol/d,
P
<0.01) versus baseline (135±14). Compared with baseline (0.11±0.01 mm/mm Hg), carotid artery compliance was increased by 27% (to 0.14±0.02,
P
<0.05) at the end of week 1 of sodium restriction, attaining peak levels by week 2 (+46%, to 0.16±0.02,
P
<0.01). Similarly, supine resting brachial artery SBP was reduced by >5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (−12 mm Hg,
P
<0.01 versus baseline). The 24-hour ambulatory SBP was ≈3 mm Hg lower at week 1 of sodium restriction and ≈6 mm Hg lower by week 2 (
P
<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of sodium restriction were strongly related to the corresponding increases in carotid compliance (
r
=0.80,
P
<0.01). Urinary sodium excretion, carotid artery compliance, and SBP were not different during normal sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium restriction rapidly improves large elastic artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by sodium restriction in these patients.
Origins of Serum Semicarbazide-Sensitive Amine Oxidase
Authors: Stolen Craig M. , Yegutkin Gennady G. , Kurkijärvi Riikka , Bono Petri , Alitalo Kari , Jalkanen Sirpa
Published: June 2004

Semicarbazide-sensitive amine oxidases (SSAO) are enzymes that are capable of deaminating primary amines to produce aldehyde, ammonia, and hydrogen peroxide. This activity has been associated with vascular adhesion protein-1 (VAP-1) and is found in the serum, endothelium, adipose, and smooth muscle of mammals. Circulating SSAO activity is increased in congestive heart failure, diabetes, and inflammatory liver diseases. To investigate the origin of circulating SSAO activity, two transgenic mouse models were created with full-length human VAP-1 (hVAP-1) expressed on either endothelial (mTIEhVAP-1) or adipose tissues (aP2hVAP-1), with tie-1 and adipocyte P2 promoters, respectively. Under normal conditions a circulating form of hVAP-1 was found at high levels in the serum of mice with endothelium-specific expression and at low levels in the serum of mice with adipose specific expression. The level of circulating hVAP-1 in the transgenic mice varied with gender, transgene zygosity, diabetes, and fasting. Serum SSAO activity was absent from VAP-1 knockout mice and endothelial cell–specific expression of human VAP-1 restored SSAO activity to the serum of VAP-1 knockout mice. Together, these experiments show that in the mouse VAP-1 is the only source of serum SSAO, that under physiological conditions vascular endothelial cells can be a major source of circulating VAP-1 protein and SSAO, and that serum VAP-1 can originate from both endothelial cells and adipocytes during experimental diabetes. An increased endothelial cell capacity for lymphocyte binding and altered expression of redox-sensitive proteins was also associated with the mTIEhVAP-1 transgene.
A2 Alelle of GpIIIa Gene Is a Risk Factor for Stroke Caused by Large-Vessel Disease in Males
Authors: Slowik Agnieszka , Dziedzic Tomasz , Turaj Wojciech , Pera Joanna , Glodzik-Sobanska Lidia , Szermer Pawel , Malecki Maciej T. , Figlewicz Denise A. , Szczudlik Andrzej
Published: June 2004

Background and Purpose—

Glycoprotein IIIa (GpIIIa) is a platelet membrane receptor for fibrinogen and von Willebrand factor. It plays a key role in platelet aggregation. Previous studies in stroke patients, without analysis based on specific subtypes of stroke cause, have not shown any link between GpIIIa A1/A2 polymorphism and stroke risk. We studied the significance of the GpIIIa gene A1/A2 polymorphism in stroke patients with different stroke causes.

Methods—

We genotyped 92 patients with stroke caused by large-vessel disease (LVD stroke) and 184 matched controls; 103 patients with stroke caused by small-vessel disease (SVD stroke) and 206 controls; and 182 patients with cardioembolic stroke (CE stroke) and 182 controls (TOAST criteria). The GpIIIa A1/A2 polymorphism was analyzed by polymerase chain reaction followed by restriction enzyme digestion and electrophoresis.

Results—

The genotype distribution of the GpIIIa gene in patients with LVD stroke (A1/A1, 63%; A1/A2, 34.8%; A2/A2, 2.2%) differed significantly from their controls (A1A1, 79.3%; A1/A2, 20.1%; A2/A2, 0.6%). The distribution of the GpIIIa A1/A2 polymorphism in patients with SVD stroke and CE stroke was similar to that of their controls. In contrast to females with LVD stroke, we found that males with LVD stroke presented with an overrepresentation of at least 1 A2 allele of the GpIIIa gene when compared with their controls (39.7% versus 23.0%;
P
=0.003). Conditional logistic regression analysis showed that possession of at least 1 A2 allele of the GpIIIa gene was an independent risk factor for LVD stroke in males (OR, 2.51; 95% CI, 1.21 to 5.20).

Conclusion—

A2 allele of the GpIIIa gene is an independent risk factor for LVD stroke in males.
A Coarse-to-Fine Disparity Energy Model with Both Phase-Shift and Position-Shift Receptive Field Mechanisms
Authors: Chen Yuzhi , Qian Ning
Published: June 2004

Numerous studies suggest that the visual system uses both phase-and position-shift receptive field (RF) mechanisms for the processing of binocular disparity. Although the difference between these two mechanisms has been analyzed before, previous work mainly focused on disparity tuning curves instead of population responses. However, tuning curve and population response can exhibit different characteristics, and it is the latter that determines disparity estimation. Here we demonstrate, in the framework of the disparity energy model, that for relatively small disparities, the population response generated by the phase-shift mechanism is more reliable than that generated by the position-shift mechanism. This is true over a wide range of parameters, including the RF orientation. Since the phase model has its own drawbacks of underestimating large stimulus disparity and covering only a restricted range of disparity at a given scale, we propose a coarse-to-fine algorithm for disparity computation with a hybrid of phase-shift and position-shift components. In this algorithm, disparity at each scale is always estimated by the phase-shift mechanism to take advantage of its higher reliability. Since the phase-based estimation is most accurate at the smallest scale when the disparity is correspondingly small, the algorithm iteratively reduces the input disparity from coarse to fine scales by introducing a constant position-shift component to all cells for a given location in order to offset the stimulus disparity at that location. The model also incorporates orientation pooling and spatial pooling to further enhance reliability. We have tested the algorithm on both synthetic and natural stereo images and found that it often performs better than a simple scale-averaging procedure.
Learning Classification in the Olfactory System of Insects
Authors: Huerta Ramón , Nowotny Thomas , García-Sanchez Marta , Abarbanel H. D. I. , Rabinovich M. I.
Published: June 2004

We propose a theoretical framework for odor classification in the olfactory system of insects. The classification task is accomplished in two steps. The first is a transformation from the antennal lobe to the intrinsic Kenyon cells in the mushroom body. This transformation into a higher-dimensional space is an injective function and can be implemented without any type of learning at the synaptic connections. In the second step, the encoded odors in the intrinsic Kenyon cells are linearly classified in the mushroom body lobes. The neurons that perform this linear classification are equivalent to hyperplanes whose connections are tuned by local Hebbian learning and by competition due to mutual inhibition. We calculate the range of values of activity and size fo the network required to achieve efficient classification within this scheme in insect olfaction. We are able to demonstrate that biologically plausible control mechanisms can accomplish efficient classification of odors.
The Co-option of the University and the Privileging of Annihilation
Authors: McKinley Michael
Published: June 2004

It is a popular belief in modern democratic societies that the universities are unique as sites of teaching, inquiry, research, and writing which, above all, are marked by their independence from the various forces which influence so much of the life outside of the academy. Unfortunately, the popular belief is wrong; and is particularly wrong where the universities in question are defined, as most are wont to define themselves, as ‘research universities’, and where the disciplines are those most in demand by military/industrial interests, or most given to pretences of prediction and control, and sought after by those policy communities of the state which seek power in, and over, human affairs, both at home and abroad. In plain terms, if independent inquiry in the ‘relevant’ areas of the mainstream American research universities, and under the conditions outlined, is predicated upon the independence of the individual university, then, on an everyday basis, those universities have been, and remain, hopelessly compromised.
Re-Reading Rick Turner in the New South Africa
Authors: Fluxman Tony , Vale Peter
Published: June 2004

Using the writings of the assassinated South African political philosopher Rick Turner, this article provides a critique of South Africa ten years after the end of apartheid. Influenced by both Western Marxism and utopian thinking, Turner developed a model of democratic socialism which offered a vision of a ‘new South Africa’. This was countered by the ideology of the market and, later, by the force of the ‘end of history’ thesis. The article argues that inequalities continue in South Africa because the promise of Western Marxism was squeezed out by the convergence of communist political ideology and capitalist modernization.
Reconstituting ‘Common-sense’ Knowledge: Representations of Globalization Protests
Authors: Adler Glenn , Mittelman James H.
Published: June 2004

Common sense about globalization protests is embodied in media representations, aided by public intellectuals, and imported into the classroom. Survey research demonstrates that the template of representations is partially accurate and partly misleading. The protesters’ perspectives show considerable complexity, and indicate a selective rejection of neoliberal policies and core institutions but not an overall ‘antiglobalization’ stance. Even if not totally coherent, these bundles are not just random collections of beliefs, attitudes, goals, and strategies. They raise doubts about authoritative imagery and pose questions about transformative possibilities. It is well to recall that for Gramsci, critical thinking should not merely oppose but become part of people’s understanding of their own conditions, bringing about a new common sense.
Education, International Relations and the Net
Authors: Luke Timothy W.
Published: June 2004

This analysis examines new forms of collective action made possible by Internetmediated communication. In particular, it reconsiders the operations of online higher education in network-based environments. It argues that the critics, like David Noble, and supporters, like Peter Drucker, of such undertakings need to be much more cautious about the potential of these technologies. However, the ways in which such online systems of education work also provide useful ‘denationalizing’ or ‘globalizing’ experiences that can serve as new social models for individuals engaged in cyberactivist movements, both intranationally and transnationally. Yet the workings of online education per se also constitute a new political environment by creating opportunities to study and teach at new flexible transnational sites that are less constrained by historically rooted territorial domains, cultural traditions, and social practices. These opportunities, in turn, create an unstable mix of negative and positive implications, but they are not absolutely either all positive or wholly negative.
Disrupting the ‘Student as Consumer’ Model: the New Emancipatory Project
Authors: Newson Janice A.
Published: June 2004

This article first outlines political, economic and cultural changes that underlie the prevailing conception of college and university students as consumers of educational services. It describes several implications of this conception for classroom teaching, particularly for the practices of critical pedagogues. It argues that while the consumerist orientations of students help to anchor the model of student as consumer, the model itself also provides students with a basis for critiquing the services that they receive from educational institutions. It then raises the question of how this model of student can be disrupted. Drawing from the author’s own teaching experiences, it describes ways that faculty members can encourage critical reflection among their students about their consumerist orientations and awaken and nourish their sense of political entitlement based on their membership in an intellectual community.
Critical Pedagogy and International Studies: Reconstructing Knowledge Through Dialogue with the Subaltern
Authors: Hovey Rebecca
Published: June 2004

The emerging trend and pressure for higher education to internationalize the curriculum, meet the challenges of globalization and prepare students for global citizenship is identified as the ‘global turn’ in education. The notion of knowledge production in a global context raises epistemological questions regarding the community of knowing subjects and institutions who participate in and structure such knowledge systems. Critical pedagogy offers a theoretical framework in which we can imagine students and teachers engaging in dialogue with knowing subjects of other cultures and locations with the aim of creating a global community of knowledge production. Challenges to such dialogue as articulated by subaltern studies are viewed as critical in considering the politics of knowledge claims and imagining the possibility of democratic practices and discourse in global and international knowledge construction.
Political Theory, the University and Globalization: toward a Comparative Dialogics
Authors: Rosow Stephen J.
Published: June 2004

As culture becomes more central to the teaching of international relations, political theory is likewise more a part of international relations. In light of globalization and the increasing salience of global cultural politics, the way political theory is taught and practiced must be revisited as well. This article investigates one such investigation, the idea of a comparative political theory. Comparative political theory seeks to introduce non-Western thought into political theory. This article probes the pedagogical difficulties this poses for a liberal democratic higher education.
Seasonal Fractional Integration in the Spanish Tourism Quarterly Time Series
Authors: Gil-Alana Luis A. , De Gracia Fernando Perez , CuÑado Juncal
Published: June 2004

Seasonal fractional models are shown in this article to be alternative credible ways of modeling the seasonal component in the Spanish tourism time series. The authors use a testing procedure, due to Robinson, that permits them to consider unit and fractional orders of integration in raw time series. This method is applied to the number of foreigners and the number of foreign guest nights in Spain, the results showing that the orders of integration in both series are higher than 0 but smaller than 1, implying seasonal long memory behavior.
Influence of Household Origin and Social Class on Choice of Rural Vacation Destinations
Authors: Zamora Jorge , Valenzuela Fredy , Vasquez-Parraga Arturo Z.
Published: June 2004

This research examines the effect of origin (rural and urban) and social class (upper and middle classes) of heads of households on their choice of rural vacation destinations. A quota survey was conducted with equal samples of households residing in rural areas and households residing in urban areas. The results show that households of rural origin favor rural (grassroots) destinations over urban destinations even though some currently reside in an urban area.
A Ranking of International Tourism and Hospitality Journals
Authors: Pechlaner Harald , Zehrer Anita , Matzler Kurt , Abfalter Dagmar
Published: June 2004

Attempts to assess the quality of academic publications have been increasing lately. Due to the number of existing journals, it is hard to make a representative selection and to find criteria for determining quality. Hence, questions arise, including what sort of journals are more important in terms of reputation, readership frequency, and relevance to scientific research and practice. Recent studies on journal rankings have been carried out on the basis of both objective data (citation counts) and the quality perceptions of experts. This study attempts a rating of tourism and hospitality journals among the scientific community according to the journals’ readership frequency, scientific and practical relevance, overall reputation, and the importance of being published in the journals to the academic career of the respondents.
Classification of Adventure Travelers: Behavior, Decision Making, and Target Markets
Authors: Sung Heidi H.
Published: June 2004

Focusing on consumer and travel behavior of adventure travelers, this study proposes a classification of adventure travelers for segmenting the U.S. adventure travel market. A survey of adventure travelers (N = 892) examined traveler characteristics, trip-related factors in the decision-making process, and perception of adventure travel. Cluster analysis identified six distinct adventure traveler subgroups as (1) general enthusiasts, (2) budget youngsters, (3) soft moderates, (4) upper high naturalists, (5) family vacationers, and (6) active soloists. Implications of the classified adventure traveler subgroup characteristics in conjunction with their perception of adventure travel and the involvement with adventure tourism establishments are discussed. The study findings will help adventure travel providers and marketers better understand adventure travelers and formulate strategies to cater to target segments effectively.
Destination Positioning Analysis through a Comparison of Cognitive, Affective, and Conative Perceptions
Authors: Pike Steven , Ryan Chris
Published: June 2004

There has been exponential growth in the number of studies of destination image appearing in the tourism literature. However, few have addressed the issues of destination positioning analysis and the role of affective perceptions. This article analyzes the market positions held by a competitive set of destinations through a comparison of cognitive, affective, and conative perceptions. Cognition was identified by trialing a factor analytic adaptation of importanceperformance analysis. Affect was measured using an affective response grid, while conation was gauged by stated intent to visit. The alignment of the results from these techniques identified leadership positions held by two quite different destinations on two quite different dimensions of destination attractiveness. It is suggested that this method of positioning analysis offers a practical means for destination marketers faced with the challenge of identifying the one or few features from their diverse and multiattributed product range that could be developed to differentiate their destination in a meaningful way to consumers.