bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Mycophenolate Mofetil and Lisinopril on Collagen Deposition in Unilateral Ureteral Obstruction in Rats
Authors: Gonçalves Rômulo G. , Biato Marco A. , Colosimo Ricardo D.G. , Martinusso Cesônia A. , Pecly Inah D. , Farias Eliene K. , Cardoso Lúcio R. , Takiya Christina M. , Ornellas José F.R. , Leite  Jr Maurilo
Published: October 2004

Background/Aims: Unilateral ureteral obstruction (UUO) in rats has been used as a model of renal interstitial fibrosis, in which therapeutic trials can be of important clinical relevance. In this study, we investigated the effects of mycophenolate mofetil (MMF), the angiotensin-converting enzyme (ACE) inhibitor lisinopril (L), and the combination of both drugs, given daily for 14 days to UUO rats, on the renal fibrogenic process triggered by UUO. Methods: Rats underwent surgical UUO, followed by treatment with daily doses of either MMF, lisinopril, or both, and were then sacrificed after 14 days. Kidney fragments were fixed for histopathological examination (hematoxylin-eosin and periodic acid-Schiff reactive) and immunohistochemistry for myofibroblasts (α-smooth muscle actin; α-SMA) and macrophages (ED-1). Histomorphometrical analysis of collagen was performed with Sirius red staining, and collagen content was assessed by the amount of hydroxyproline. Cortex and medulla were analyzed separately. Results: MMF, lisinopril and MMF+L reduced the density of α-SMA- and ED-1-positive cells (p < 0.05), interstitial volume (p < 0.05) and decreased Sirius-red-stained areas by 54.6, 35.6 and 58.0%, and hydroxyproline content by 60.1, 49.7 and 62.7%, respectively. No differences were observed among treated groups. Conclusion: MMF and the ACE inhibitor lisinopril attenuated the progression of the fibrogenic process of UUO in an equivalent manner. The combination of both drugs did not add any further improvement in the collagen content.
Hepatocyte Growth Factor Suppresses Vascular Medial Hyperplasia and Matrix Accumulation in Advanced Pulmonary Hypertension of Rats
Authors: Ono Masamichi , Sawa Yoshiki , Mizuno Shinya , Fukushima Norihida , Ichikawa Hajime , Bessho Kazuhiko , Nakamura Toshikazu , Matsuda Hikaru
Published: October 2004

Background—Pulmonary hypertension (PH) is a progressive disease characterized by raised pulmonary vascular resistance, thought to be curable only through lung transplantation. Pathophysiologically, proliferation of pulmonary artery smooth muscle cells triggers pulmonary arterial stenosis and/or regurgitation, especially in advanced PH.

Methods and Results—Using a rat model of advanced pulmonary vascular disease produced by injecting monocrotaline, we show that hepatocyte growth factor (HGF) targets pulmonary arterioles and blocks the progression of PH. In these rats, endogenous HGF production was dramatically downregulated during developing experimental PH, but c-Met/HGF receptor was abundant in the medial layers of pulmonary arterioles. HGF gene transfection 2 weeks after the monocrotaline injection resulted in milder medial hyperplasia in lung arterioles and inhibited overgrowth of pulmonary artery smooth muscle cells. Notably, exogenous HGF reduced lung expression levels of endothelin-1 and transforming growth factor-β, which are critically involved in PH-linked fibrogenic events. Overall, medial wall thickening of pulmonary arteries was almost completely prevented by HGF, and the total collagen deposition in the lung decreased; both effects contributed to the suppression of pulmonary artery hypertension.

Conclusions—Our results suggest that the loss of endogenous HGF may be a feature of the pathogenesis of PH and that HGF supplementation may minimize pathological lung conditions, even advanced PH.
Stromal Cell–Derived Factor-1 and CXCR4 Interaction Is Critical for Development of Transplant Arteriosclerosis
Authors: Sakihama Hideyasu , Masunaga Taro , Yamashita Kenichiro , Hashimoto Taku , Inobe Manabu , Todo Satoru , Uede Toshimitsu
Published: October 2004

Background—

Posttransplant chronic allograft deterioration associated with development of transplant arteriosclerosis (TA) remains an unresolved problem. Recent studies suggest that the smooth muscle cells (SMCs) constituting the neointima are derived from recipient hematopoietic stem cells (HSCs). However, the underlying mechanisms of the process are not yet fully elucidated.

Methods and Results—

We examined the genes expressed in allografts at different stages of TA development using a mice aortic transplantation model. Genes were analyzed by a differential mRNA display technique. We show that stromal cell–derived factor-1α (SDF-1α) is a critical molecular target for the treatment of TA. During the course of TA, intragraft SDF-1α expression was upregulated with time, and the circulating HSCs expressing its counterreceptor CXCR4 increased in the recipients receiving allografts. CXCR4-positive HSCs, derived from transplant recipients, migrated into allografts via microvessels in the adventitia and then toward the luminal side. The HSCs differentiated into SMC-like cells, contributing to the in situ formation of the neointima. In support of a functional role for these molecules, in vivo neutralization of SDF-1α inhibited HSC mobilization and significantly attenuated neointimal formation.

Conclusions—

Interaction between SDF-1α and CXCR4 plays a key role in TA development. Blockade of SDF-1α may become a new therapeutic modality for TA.
Balanced Regulation of mRNA Production for Fas and Fas Ligand in Lymphocytes From Centenarians
Authors: Pinti Marcello , Troiano Leonarda , Nasi Milena , Bellodi Cristian , Ferraresi Roberta , Mussi Chiara , Salvioli Gianfranco , Cossarizza Andrea
Published: October 2004

Background—

The functionality of the immune system during aging is crucial for protection against the most common age-related diseases. Apoptosis plays a central role in the senescence of the immune system, as evidenced by the increased plasma membrane expression of a key molecule like Fas protein. We analyzed the mRNA levels of different forms of Fas (total [tFas] and membrane [mFas]) and of its ligand (FasL) in peripheral blood lymphocytes from centenarians, the best example of successful aging, who were compared with young and middle-aged donors.

Methods and Results—

Using real-time polymerase chain reaction, we quantified mRNA for different forms of Fas and for FasL. In resting lymphocytes, mRNA for tFas, but not for mFas, significantly increases with age, whereas FasL mRNA significantly decreases. In vitro production of Fas/FasL mRNA after different stimuli was similar in cells from the 3 groups. Even if the percentage of Fas
+
cells was higher than in the other groups, peripheral blood lymphocytes from centenarians had normal Fas-induced apoptosis, as revealed by flow cytometry. By ELISA, we observed that cells from centenarians showed normal in vitro production of the soluble form of Fas (sFas) and that plasma levels of such molecule were significantly higher in centenarians than in the other groups.

Conclusions—

Lymphocytes from centenarians are able to balance the production of proapoptotic (mFas and FasL) and antiapoptotic (sFas) molecules, whose proportions are likely crucial for the well-preserved immune functionality at the extreme limits of human life.
Analysis of Catheter-Tip (8-mm) and Actual Tissue Temperatures Achieved During Radiofrequency Ablation at the Orifice of the Pulmonary Vein
Authors: Bunch T. Jared , Bruce G. Keith , Johnson Susan B. , Sarabanda Alvaro , Milton Mark A. , Packer Douglas L.
Published: October 2004

Background—

Many ablative approaches in or near the orifice of the pulmonary vein (PV) have demonstrated success in eliminating atrial fibrillation. Despite current practice, there are no data regarding the in vivo efficacy and safety of an 8-mm catheter tip for ablation at the PV orifice.

Methods and Results—

Ten mongrel dogs were studied. Thermocouples were implanted in the atrial muscle of the PV orifice. Intracardiac echocardiography monitored catheter position, tip/tissue orientation, and microbubble formation. Ninety-four ablations were performed for 120 seconds. A temperature discrepancy >10°C between the catheter tip and tissue occurred during 47 (50%) of the ablations. Despite termination of energy delivery, the average tissue temperature remained within 1°C of the achieved steady state for 9 seconds. A temperature discrepancy >10°C was more common in the right superior PV, with oblique catheter positioning, when tissue temperatures were >60°C or 80°C, and with type 1 or type 2 microbubble formation. However, microbubbles were not present in 7 (13%, type 1) and 10 (40%, type 2) ablations with tissue temperatures >80°C. The maximum tissue temperature achieved with non–full-thickness lesions was 47.3±7.4°C vs 75.9±11.7°C (
P
<0.0001) for full-thickness lesions.

Conclusions—

Marked discrepancies between catheter-tip and tissue temperatures occurred with higher temperatures, prolonged ablation times, and unfavorable catheter thermistor–tissue contact. Also, these data suggest a conservative approach to atrial ablation, because full-thickness lesions were obtained when tissue temperatures reached 50°C to 60°C and the tissue retained high heat levels despite termination of radiofrequency energy. Finally, microbubbles are inconsistent markers of tissue overheating.
Radiation Exposure During Catheter Ablation of Atrial Fibrillation
Authors: Lickfett Lars , Mahesh Mahadevappa , Vasamreddy Chandra , Bradley David , Jayam Vinod , Eldadah Zayd , Dickfeld Timm , Kearney Deborah , Dalal Darshan , Lüderitz Berndt , Berger Ronald , Calkins Hugh
Published: October 2004

Background—

The purpose of this study was to determine the radiation exposure during catheter ablation of atrial fibrillation (AF) using the pulmonary vein (PV) approach.

Methods and Results—

The study included 15 patients with AF and 5 patients each with atrial flutter and atrioventricular nodal reentrant tachycardia (AVNRT) who underwent fluoroscopically guided procedures on a biplane x-ray system operated at a low-frame pulsed fluoroscopy (7.5 frames per second). Radiation exposure was measured directly with 50 to 60 thermoluminescent dosimeters (TLDs). Peak skin doses (PSDs), effective radiation doses, and risk of fatal malignancies were all computed. Mean fluoroscopy durations for AF procedures were 67.8±21 minutes in the right anterior oblique (RAO) and 61.9±16.6 minutes in the left anterior oblique (LAO) projection, significantly different from that required for atrial flutter and AVNRT. The mean PSDs measured with the TLDs were 1.0±0.5 Gy in the RAO and 1.5±0.4 Gy in the LAO projection. The lifetime risk of excess fatal malignancies normalized to 60 minutes of fluoroscopy was 0.07% for women and 0.1% for men.

Conclusions—

The relatively small amounts of the patient’s radiation exposure in this study, despite the prolonged fluoroscopy durations, can be attributed to the use of very-low-frame pulsed fluoroscopy, the avoidance of magnification, and optimal adjustments of the fluoroscopy exposure rates. The resulting lifetime risk of fatal malignancy is within the range previously reported for standard supraventricular arrhythmias.
Inhibitory G Protein Overexpression Provides Physiologically Relevant Heart Rate Control in Persistent Atrial Fibrillation
Authors: Bauer Alexander , McDonald Amy D. , Nasir Khurram , Peller Leah , Rade Jeffrey J. , Miller Julie M. , Heldman Alan W. , Donahue J. Kevin
Published: October 2004

Background—

The need for new treatment strategies for cardiac arrhythmias has motivated our continuing development of gene therapeutic options. Previously, we reported a decreased heart rate in an acute model of atrial fibrillation after atrioventricular nodal gene transfer. Here, we expand those observations to persistent atrial fibrillation and severe heart failure.

Methods and Results—

After 3 weeks of atrial fibrillation, domestic swine received atrioventricular nodal gene transfer with adenoviruses encoding β-galactosidase (β-gal), wild-type Gα
i2
(wtGi), or constitutively active mutant (cGi). Heart rates in awake, alert animals were not altered by β-gal or wtGi. cGi caused a sustained 15% to 25% decrease in heart rate. The wtGi effect became evident with sedation. A tachycardia-induced cardiomyopathy was present before gene transfer. In the β-gal group, cardiomyopathy worsened over time. In the wtGi group, the condition improved slightly, and in the cGi group, ejection fraction was near normal at the end of the study. TUNEL staining results corroborated this finding.

Conclusions—

cGi overexpression in the porcine atrioventricular node causes physiologically relevant heart rate control in persistent atrial fibrillation. These data advance the development of gene therapy as a potential treatment for common cardiac arrhythmias.
Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults
Authors: Juonala Markus , Viikari Jorma S.A. , Laitinen Tomi , Marniemi Jukka , Helenius Hans , Rönnemaa Tapani , Raitakari Olli T.
Published: October 2004

Background—

Endothelial vasodilator dysfunction and carotid intima-media thickening (IMT) are 2 indicators of subclinical cardiovascular disease. We examined their correlation and interaction with risk factors in a large, community-based cohort of young adults.

Methods and Results—

As part of the longitudinal Cardiovascular Risk in Young Finns Study, we measured endothelium-dependent brachial artery flow–mediated dilatation (FMD) and carotid artery IMT by ultrasound in 2109 healthy adults aged 24 to 39 years. FMD was inversely associated with IMT (
P
≤0.001) in a multivariate model adjusted for age, sex, brachial vessel size, and several risk variables. The subjects with age- and sex-specific FMD values in the extreme deciles were classified into groups of impaired (n=204, FMD=1.1±1.4%, mean±SD) and enhanced (n=204, FMD=16.3±2.9%) FMD response. The number of risk factors was correlated with increased IMT in subjects with an impaired FMD response (
P
<0.05) but not in subjects with an enhanced FMD response (
P
>0.2).

Conclusions—

Brachial FMD is inversely associated with carotid IMT. The number of risk factors in young adults is correlated with increased IMT in subjects with evidence of endothelial dysfunction, but not in subjects with preserved endothelial function. These observations suggest that endothelial dysfunction is an early event in atherosclerosis and that the status of systemic endothelial function may modify the association between risk factors and atherosclerosis.
Deletion of p66
shc
Gene Protects Against Age-Related Endothelial Dysfunction
Authors: Francia Pietro , delli Gatti Chiara , Bachschmid Markus , Martin-Padura Ines , Savoia Carmine , Migliaccio Enrica , Pelicci Pier Giuseppe , Schiavoni Marzia , Lüscher Thomas Felix , Volpe Massimo , Cosentino Francesco
Published: October 2004

Background—

Enhanced production of reactive oxygen species (ROS) has been recognized as the major determinant of age-related endothelial dysfunction. The p66
shc
protein controls cellular responses to oxidative stress. Mice lacking p66
shc
(p66
shc−/−
) have increased resistance to ROS and a 30% prolonged life span. The present study investigates age-dependent changes of endothelial function in this model.

Methods and Results—

Aortic rings from young and old p66
shc−/−
or wild-type (WT) mice were suspended for isometric tension recording. Nitric oxide (NO) release was measured by a porphyrinic microsensor. Expression of endothelial NO synthase (eNOS), inducible NOS (iNOS), superoxide dismutase, and nitrotyrosine-containing proteins was assessed by Western blotting. Nitrotyrosine residues were also identified by immunohistochemistry. Superoxide (O
2
−
) production was determined by coelenterazine-enhanced chemiluminescence. Endothelium-dependent relaxation in response to acetylcholine was age-dependently impaired in WT mice but not in p66
shc−/−
mice. Accordingly, an age-related decline of NO release was found in WT but not in p66
shc−/−
mice. The expression of eNOS and manganese superoxide dismutase was not affected by aging either in WT or in p66
shc−/−
mice, whereas iNOS was upregulated only in old WT mice. It is interesting that old WT mice displayed a significant increase of O
2
−
production as well as of nitrotyrosine expression compared with young animals. Such age-dependent changes were not found in p66
shc−/−
mice.

Conclusions—

We report that inactivation of the p66
shc
gene protects against age-dependent, ROS-mediated endothelial dysfunction. These findings suggest that the p66
shc
is part of a signal transduction pathway also relevant to endothelial integrity and may represent a novel target to prevent vascular aging.
Effects of NOS3 Glu298Asp Polymorphism on Hemodynamic Reactivity to Stress: Influences of Ethnicity and Obesity
Authors: Malhotra Surender , Poole Joseph , Davis Harry , Dong Yanbin , Pollock Jennifer , Snieder Harold , Treiber Frank
Published: October 2004

Studies on the associations between the nitric oxide synthase gene (NOS3) Glu298Asp polymorphism and hypertension status or blood pressure (BP) levels have had inconsistent results. Potential moderating influences of ethnicity, sex, and obesity on the effects of the NOS3 polymorphism have not been examined. We evaluated the influence of these factors on associations between the NOS3 polymorphism, nitric oxide metabolites (NOx), and hemodynamics at rest and during stress. Subjects were 235 African American (AA) and 262 European American (EA) young adults (18.5±2.6 years). Hemodynamic measurements and blood samples for NOx assays were taken before and after a competitive video game challenge. Glu298Asp polymorphism was detected by polymerase chain reaction–restriction enzyme digestion assay. A regression model was built using genotypes, ethnicity, sex, and obesity (body mass index >85th percentile) and their interactions controlling for age; 20.1% of AAs and 49.8% of EAs were carriers of the Asp allele. AAs, regardless of obesity status, exhibited high diastolic blood pressure (DBP) reactivity unless they were nonobese and noncarriers of the Asp allele. EAs exhibited lower DBP reactivity unless they were obese Asp allele carriers. AA nonobese carriers exhibited the greatest total peripheral resistance reactivity. Obese Asp allele carriers exhibited the greatest increases in cardiac output and the greatest decrease in NOx to the stressor. Results indicate the importance of examining impact of BP control-related genetic polymorphisms within the context of moderating factors such as adiposity and ethnicity.
cGMP-Dependent Protein Kinase Mediates NO- but not Acetylcholine-Induced Dilations in Resistance Vessels In Vivo
Authors: Koeppen Michael , Feil Robert , Siegl Daniel , Feil Susanne , Hofmann Franz , Pohl Ulrich , de Wit Cor
Published: October 2004

cGMP and cGMP-dependent protein kinase type I (cGKI) mediate the dilation of large vessels in response to NO and acetylcholine (ACh). However, the physiological significance of the NO/cGMP/cGKI pathway in resistance vessels is controversial. Here, we analyzed NO- and ACh-induced dilations of arterioles in cGKI-deficient (cGKI
−/−
) or endothelial NO synthase–deficient (eNOS
−/−
) mice. Mean arterial pressure was similar in cGKI
−/−
and wild-type mice (≈105 mm Hg). Pressure drops in response to intracarotid bolus application of the NO donor sodium nitroprusside (SNP) were almost abolished in cGKI
−/−
mice, whereas ACh-induced pressure decreases remained intact in cGKI
−/−
and eNOS
−/−
mice. The direct observation of arterioles in the cremaster muscle by intravital microscopy showed impaired SNP-induced dilations in cGKI
−/−
mice (by ≈80%) and normal ACh-induced dilations in cGKI
−/−
and eNOS
−/−
mice. ACh-induced dilations in eNOS
−/−
mice were attenuated by iberiotoxin (by ≈50%), indicating that they were mediated in part by Ca
2+
-activated K
+
channels, but not by inhibitors of cyclooxygenase or p450-monooxygenases. We conclude that cGMP and cGKI are the major effectors of NO to induce acute dilations of murine resistance vessels. However, the NO/cGMP/cGKI pathway is not essential for ACh-induced dilation of arterioles and for basal blood pressure regulation in mice.
Endothelin-1 Gene and Progression of Blood Pressure and Left Ventricular Mass
Authors: Dong Yanbin , Wang Xiaoling , Zhu Haidong , Treiber Frank A. , Snieder Harold
Published: October 2004

Endothelin-1 (ET-1) is a powerful vasconstrictor peptide implicated in development of essential hypertension and left ventricular hypertrophy. To evaluate the impact of genetic variability of the ET-1 gene on progression of blood pressure (BP) and left ventricular mass (LVM), we conducted individual growth curve modeling for 537 European American and black youths with 12 assessments during a 15-year period. Four common single-nucleotide polymorphisms (SNPs) including T-1370G, +138/ex1 del/ins, T-37/in2C, and Lys198Asn were included in this study. Single SNP analyses showed that individuals with the +138/ex1 ins allele had a borderline significant lower systolic BP (SBP;
P
=0.072). Furthermore, the −37/in2C allele showed an SBP-lowering effect in males, accounting for 1.6% between-subject variation of SBP (
P
=0.016). Haplotype analyses in males confirmed the BP-lowering effect of the −37/in2C allele. SBP in individuals homozygous for the del (+138/ex1) −C (−37/in2) haplotype was 3.3 mm Hg lower than those homozygous for the del (+138/ex1) −T (−37/in2) haplotype (
P
=0.038). For LVM, we observed a significant gene–environment interaction. LVM levels were 20 g higher in carriers versus noncarriers of the −1370G allele in the low socioeconomic status (SES) group only (
P
=0.004). In summary, our results uncover a sex-specific protective effect of variation in the ET-1 gene on the progression of hypertension risk, and a SES-specific effect on risk of developing left ventricular hypertrophy in multiethnic youth.
Canonical Correlation Analysis: An Overview with Application to Learning Methods
Authors: Hardoon David R. , Szedmak Sandor , Shawe-Taylor John
Published: October 2004

We present a general method using kernel canonical correlation analysis to learn a semantic representation to web images and their associated text. The semantic space provides a common representation and enables a comparison between the text and images. In the experiments, we look at two approaches of retrieving images based on only their content from a text query. We compare orthogonalization approaches against a standard cross-representation retrieval technique known as the generalized vector space model.
Modeling of Synchronized Bursting Events: The Importance of Inhomogeneity
Authors: Persi Erez , Horn David , Volman Vladislav , Segev Ronen , Ben-Jacob Eshel
Published: October 2004

Cultured in vitro neuronal networks are known to exhibit synchronized bursting events (SBE), during which most of the neurons in the system spike within a time window of approximately 100 msec. Such phenomena can be obtained in model networks based on Markram-Tsodyks frequency-dependent synapses. In order to account correctly for the detailed behavior of SBEs, several modifications have to be implemented in such models. Random input currents have to be introduced to account for the rising profile of SBEs. Dynamic thresholds and inhomogeneity in the distribution of neuronal resistances enable us to describe the profile of activity within the SBE and the heavy-tailed distributions of interspike intervals and interevent intervals. Thus, we can account for the interesting appearance of Lévy distributions in the data.
The Acquisition of Bulimia: Childhood Experience
Authors: Day Merrie
Published: October 2004

This article is concerned with the childhood experience that seems to be preparatory for the onset of bulimia. Three women's serial experiences of bulimia (reported in 4 interviews describing specific binge-purge episodes) were investigated and one pattern of experiencing that led to bulimia emerged. As the interview process deepened (interview 1 to interview 4), the data moved from symptom-related to life-related. The general structure that captured the essence of the lived experience of bulimia remained the same but the individual experiences varied as these women live out their unique lives. In understanding the totality of the phenomenon of bulimia, it is important to remember that although each of the six key constituents is described separately, in the life-world all the constituents merge together as they interact with each other and with the whole of the experience. These bulimic women reported having family backgrounds in which they experienced a sense of diminished self and dissatisfaction in interactions with significant others and self. They found themselves pressured to maintain a less than integrated life, and in rapid transition from 'awareful' behaving to automatic and anonymous functioning. A psychological hunger seems to possess them and this is lived out during the anonymous phase of their existence. Their need for the mastery and control ordinarily lacking in their lives becomes a symptomatic expression that has relevance for them in respect to the deep psychological pain that is only partially expressed. The phenomenal body and self are given priority over objective reality, resulting in distorted perceptions of "fatness" and feelings of terror of "fat."
The Self-Overcoming Subject: Freud's Challenge to the Cartesian Ontology
Authors: Fowler Steven
Published: October 2004

Two strands of enlightenment rationality—the mechanistic/deterministic and the self-overcoming—are distinguished, and the presence of the later in the work of Sigmund Freud is delineated. Beginning with Freud's investigations of hysteria, Freud's view of the person as a self-overcoming entity is spelled out in his theory of the unconscious and his theory of sexuality. It is argued that Freud provides, in the realm of empirical science, evidence that converges with the ontological conception of the person as a "being-in-the-world" developed by Heidegger in the philosophical classic, Being and Time.
For the Sake of ‘Peace and Security’?
Authors: Higashino Atsuko
Published: October 2004

The need to achieve stability and security in Europe has been a core motivation for European Union actors in their decision in favour of enlargement, calling for new measures to advance the enlargement process. EU leaders have often justified changes to the existing enlargement strategy by making reference to threats to security in Europe and by claiming that eastern enlargement could be the way to attain peace and security in Europe. Never has EU enlargement been so frequently connected with security debates. The overall effect of security concerns on the enlargement process, however, has not been adequately analysed in previous studies of EU enlargement; enlargement policy has largely been explained from economic and commercial viewpoints. This article explores the role of security concerns in EU enlargement — ‘security’ that does not necessarily come in the military form, but in what I refer to as a ‘speech act’, drawing on insights from the Copenhagen School of security studies. The article comprises (1) a conceptual framework to consider how ‘security’ as ‘speech act’ (or the ‘securitization’ approach) can explain the enlargement process, (2) three case studies of security influences in the context of EU enlargement, and (3) conclusions on when and how security has mattered in the EU enlargement process.
Europeanization of Nordic Security
Authors: Rieker Pernille
Published: October 2004

During the Cold War period, the security policies of the Nordic states were referred to as the ‘Nordic balance’ — a combination of policies aimed at preserving a balance between the two superpowers. While the end of the Cold War paved the way for a different and more complex security approach, it took some time before the Nordic states responded to this new security context. The article argues that, rather than adapting to the changing conditions created by the end of the Cold War, the Nordic states changed their security approaches in response to the European integration process. It attempts to show how different phases in the post-Cold War European integration process have influenced the national security approaches of Sweden, Finland, Denmark and Norway. While all four security approaches have been Europeanized, the speed and the character of these changes seem to vary due to a combination of differing ties to the European Union and differing security policy traditions.
Conceptualizing organizational discourse as situated symbolic action
Authors: Heracleous Loizos , Marshak Robert J.
Published: October 2004

This article presents a conceptualization of organizational discourse as situated symbolic action, drawing from the fields of speech act theory, rhetoric, ethnography of communication and social constructionism. This conceptualization is illustrated through analysis of an episode of negotiated order accessed through an organization development intervention; a meeting of senior managers of Systech, a major IT organization, to decide on a new business model. This perspective helps to respond to some of the key challenges facing the organizational discourse field in terms of developing more clearly specified conceptualizations of discourse suited to the organizational level of analysis, achieving a more holistic and discourse-sensitive understanding of empirical contexts by organizational researchers, and illustrating that organizational discourse analysis is not simply an intellectual luxury but can have pragmatic, relevant implications.
Paradox as invitation to act in problematic change situations
Authors: Beech Nic , Burns Harry , de Caestecker Linda , MacIntosh Robert , MacLean Donald
Published: October 2004

It has been argued that organizational life typically contains paradoxical situations such as efforts to manage change which nonetheless seem to reinforce inertia. Four logical options for coping with paradox have been explicated, three of which seek resolution and one of which ‘keeps the paradox open’. The purpose of this article is to explore the potential for managerial action where the paradox is held open through the use of theory on ‘serious playfulness’. Our argument is that paradoxes, as intrinsic features in organizational life, cannot always be resolved through cognitive processes. What may be possible, however, is that such paradoxes are transformed, or ‘moved on’ through action and as a result the overall change effort need not be stalled by the existence of embedded paradoxes.
‘Hottentots’ and the evolution of European racism
Authors: Hudson Nicholas
Published: October 2004

Springing from the argument in recent scholarship that ‘race’ is a doctrine that emerged only in the post-Enlightenment, this essay develops a theory concerning the ideological history of ‘racism’, understood in its modern Western sense. While it is impossible to examine all forms of Western racism, the author focuses on evolving reactions in European travel accounts, belles-lettres and anthropology to the Khoikhoi, popularly known as ‘Hottentots’, a people that became proverbial as the most wretched and degraded of all ‘savages’. The question posed is why the Khoikhoi, a relatively peripheral and cooperative people, attracted this virulent hatred.

Challenging the assumption of the small body of modern scholarship on the Khoikhoi, I maintain that this spite derived not simply from a sense of the Hottentots’ ‘Otherness’, but more accurately from the awareness that this people upset models of ethnicity that supported the Western vision of the non-European world. Europeans needed to neutralize the ideological threat represented by the Khoikhoi, a programme that culminated in the development of the modern science of ‘race’. ‘Race’, and its corresponding ideology of ‘racism’, I conclude, involves not merely the exclusion, but an approximation and appropriation of the ‘Other’ into Western systems of thought: the ultimate and fatal destiny of this highly distinct and independent culture.
Effect of Post-mold Curing on Package Reliability
Authors: Mengel Manfred , Mahler Joachim , Schober Wolfgang
Published: October 2004

Silica filled epoxy resins as encapsulation in chip packages reveal a major influence on the reliability and functionality of microelectronic devices. In this study, the resulting effects of postmold curing (PMC) on the thermomechanical and chemical properties of different mold compounds were observed. Polymer systems of the investigated mold compounds were based on two orthocresol novolacs (OCN), one biphenyl and one multifunctional resin (MFR). It could be shown, that longer thermal treatment after curing leads in general to further cross-linking of the polymer chains and increases the glass transition temperature Tg. Therefore, the temperature resistance of the mold for following process steps after package assembling, like soldering, can be improved as well as the reliability during temperature cycle tests. However, PMC treatment also increases the moisture absorption. Here, MFR mold exhibit the highest moisture absorption. Also the high Tg of the MFR mold is not much influenced by PMC. Hence, further thermal treatment after curing of the MFR mold is not necessary. In case of OCN and biphenyl mold types, the advantages of PMC are predominating.
An Evaluation of the Effects of Type and Temperature of Aqueous Media on the Compressive Strength of Glass-Epoxy Composites
Authors: Kishore  , Ravi Kumar N. L.
Published: October 2004

Epoxy systems reinforced with E-glass fibers, exposed to 100 h in three separate media were subjected to compressive mode of deformation. The difference in weight, i.e., before and after exposure to 100 h, following immersion in media was noted. Compared to the data obtained at room temperature in plain water (i.e., PR), the absorption levels in plain water containing a small proportion of dilute HCl at room temperature (i.e., PAR) were lower while samples in plain water at elevated (50 C) temperature (i.e., PH) show higher absorption. The compression strength and fractographic features, noted on the compression failed samples, are reported in this work. The experiment reveals that the media exposed samples generally exhibit lower strengths compared to the dry (i.e., unexposed) samples. Among the media exposed samples, the PAR set shows a small rise in strength while the PR and PH sets display a lowering of values. These changes have been attributed to various factors like medium ingress into samples inducing an alteration in the response of the interface regions, presence of either lengthy or fragmented fibers and resin smear on the fibers. In PAR case, the lower diffusion helps first in lowering the extent of its recording a decrement in strength vis-à-vis the dry case and this trend may be countered by the size of the Cl being different and in the end a small rise in strength is recorded. The fractographic features reveal interface separation, either scattered debris or a cleaner surface of fibers or adherence of resin on fibers region as well as appearance or otherwise of long or short fibers depending on whether the tests were done on unexposed samples or on the ones subjected to immersion in a specific aqueous medium.
Glass Fiber-reinforced Polymer Composites of High Compressive Strength
Authors: Zheng Yaping , Ning Rongchang , Zheng Ying
Published: October 2004

Glass-reinforced composites with high compressive strength were prepared using two different epoxy resins and various curing agents such as matrix and S-glass fibers (S-GF) as glass reinforcement. The mechanical properties of various composites were examined and the free volumes were also investigated by the Positron annihilation lifetime spectroscopy measurements (PALS). Results for tensile, compression, bending, impact, hardness, distortion temperature, glass transition temperature and their association with free volume were reported for the composites, with the matrix of high material density and low free volume displaying distinct superior mechanical properties. The curing agents also have a significant effect on the compressive strength of composites, with the composite TDE-85/MPD/S-GF consistently showing the highest compression resistance.
Manufacturing and Cure Kinetics Modeling for Macro Fiber Composite Actuators
Authors: Williams R. Brett , Grimsley Brian W. , Inman Daniel J. , Wilkie W. Keats
Published: October 2004

The use of piezoelectric ceramic materials for structural actuation is a fairly welldeveloped practice that has found use in a wide variety of applications. However, just as advanced composites offer many benefits over traditional engineering materials for structural design, actuators that utilize the active properties of piezoelectric fibers can improve upon many of the limitations encountered with monolithic piezoceramic devices used to control structural dynamics. This paper discusses the Macro Fiber Composite (MFC) actuator, which utilizes piezoceramic fibers, for example, lead zirconate titanate (PZT), embedded in an epoxy matrix for structural actuation. An overview of the MFC assembly process is presented, followed by a cure kinetics model that describes the behavior of the thermosetting epoxy matrix. This empirical model is seen to agree closely with the experimental data.
The OECD Jobs Strategy and the European Employment Strategy: Two Views of the Labour Market and the Welfare State
Authors: Casey Bernard H.
Published: October 2004

High unemployment in the 1990s prompted policy responses at supranational as well as national levels, notably the OECD Jobs Strategy and the European Employment Strategy. Both strategies reflect a supply-side orientation, but the European strategy pays more attention to the role of ‘social partners’, the potential negative consequences of certain policy responses, and the interconnections between employment and social protection policies. Each strategy was subject to evaluation by its sponsor and, regardless of evidence, was judged a success. Thus, even if there is ‘one view of the labour market’ and there are, perhaps, ‘two views of the welfare state’, there is also a shared approach to evaluation.
Reconstructing the deconstructed - hypertext and literary education
Authors: Ensslin Astrid
Published: October 2004

In this article I endeavour to connect two major achievements of postmodernism which, at first glance, may appear incompatible: deconstruction in literature and literary criticism on the one hand and constructivism in educational theory and practice on the other. Subverting traditional literary values such as authorial integrity and power, linearity and logic of plot, consistency of character, the distance between the reader and printed text as well as, above all, the death of the author, poststructuralism has long been recognized as a rather embattled concept. This is due to its evasiveness and hence relative inapplicability to literary criticism and pedagogy. Venturing to overcome this dilemma, the article will investigate the implications of educational constructivism. The chief aim is to link some of its concepts with postmodern literature in such a way as to facilitate didactic methodology in the field of poststructuralist literature. Literary hypertext- the so-called incarnation of postmodern literary theory - will be used as a stereotypical example of poststructuralist evasiveness. The article proposes that literary hypertext has considerable educational potential. Not only does the genre invite subjectcentred pedagogy, which allows students to learn according to their own interests and prior knowledge, but, paradoxically, it also defies the unviability of poststructuralist literature by resurrecting the dead author in collectiveness. The proposal will be illustrated by a case study report, describing the implementation of literary hypertext in an undergraduate German creative writing classroom.
Software Project Management and Quality Engineering Practices for Complex, Coupled Multiphysics, Massively Parallel Computational Simulations: Lessons Learned From ASCI
Authors: Post D. E. , Kendall R. P.
Published: October 2004

Many institutions are now developing large-scale, complex, coupled multiphysics computational simulations for massively parallel platforms for the simulation of the performance of nuclear weapons and certification of the stockpile, and for research in climate and weather prediction, magnetic and inertial fusion energy, environmental systems, astrophysics, aerodynamic design, combustion, biological and biochemical systems, and other areas. The successful development of these simulations is aided by attention to sound software project management and software engineering. We have developed “lessons learned” from a set of code projects that the Department of Energy National Nuclear Security Agency has sponsored to develop nuclear weapons simulations over the last 50 years. We find that some, but not all, of the software project management and development practices (rather than processes) commonly employed for non-technical software add value to the development of scientific software and we identify those that we judge add value. Another key finding, consistent with general software industry experience, is that the optimal project schedule and resource level are solely determined by the requirements once the requirements are fixed.
Productivity Metrics and Models for High Performance Computing
Authors: Sterling Thomas
Published: October 2004

Historically, high performance computing has been measured in terms of peak or delivered performance, and to a lesser extent to performance to cost. Such metrics fail to capture the impact on the usefulness and ease of use of such systems. Productivity has been identified as a new parameter for high end computing systems that include both delivered system performance and the programmability of the system. System productivity is directly affected by many factors contributing to the achieved performance, the speed with which users construct application programs, and the availability of the system to perform user applications. This paper explores the concept of productivity as a quantifiable; parameter through a series of analytical models and considers the factors that contribute to it.
Defining and Measuring the Productivity of Programming Languages
Authors: Kennedy Ken , Koelbel Charles , Schreiber Robert
Published: October 2004

The goal of programming support systems is to make it possible for application developers to produce software faster, without any degradation in software quality. However, it is essential that this goal must not be achieved at the cost of performance: programs written in a high-level language and intended to solve large problems on highly parallel machines must not be egregiously less efficient than the same applications written in a lower-level language. Because this has been a traditional stumbling block for high-level languages, metrics for productivity analysis must explore the trade-off between programming effort and performance.

To that end, we propose the use of two dimensionless ratios, relative power and relative efficiency, to measure the productivity of programming interfaces. In this paper we define these concepts, describe their application, and explore various ways for measuring them, including both empirical strategies and expert opinion. Rather than combine these metrics into a single number representing a universal productivity, we propose that they be represented graphically in at least two dimensions so that the trade-offs between abstraction and performance are clearly depicted. However, we also introduce a single problem-dependent parameter that allows us to reason about the relative productivity of two languages for a given problem.
Performance Metrics Based on Computational Action
Authors: Numrich Robert W.
Published: October 2004

We propose a new performance metric based on computational action. We examine work as it evolves in time and compute computational action as the integral of the work function over time. We compare the action generated at less than full power with the action that could have been generated at full power. We claim that the goal of performance optimization is to minimize lost, or wasted, action. We calculate our metric for some computers in the Top500 list (http://www.top500.org) and propose a new ranking based on least action wasted. When work is a function of the resources applied, we use the classical techniques of the calculus of variations to minimize wasted action. From the result of this exercise, we calculate productivity as the ratio of work produced to resources used.
High Performance Computing Productivity Model Synthesis
Authors: Kepner Jeremy
Published: October 2004

The Defense Advanced Research Projects Agency (DARPA) High Productivity Computing System (HPCS) program is developing systems that deliver increased value to users at a rate commensurate with the rate of improvement in the underlying technologies. For example, if the relevant technology was silicon, the goal of such a system would be to double in productivity (or value) every 18 months, following Moore's law. The key questions are how we define and measure productivity, and what the underlying technologies that affect productivity are. The goal of this paper is to synthesize from several different productivity models a single model that captures the main features of all the models. In addition we will start the process of putting the model on an empirical foundation by incorporating selected results from the software engineering and high performance computing (HPC) communities. An asymptotic analysis of the model is conducted to check that it makes sense in certain special cases. The model is extrapolated to a HPC context and several examples are explored, including HPC centers, HPC users, and interactive grid computing. Finally, the model hints at a profoundly different way of viewing HPC systems, where the user must be included in the equation, and innovative hardware is a key aspect to lowering the very high costs of HPC software.
A Garment in the Dock; or, How the FBI Illuminated the Prehistory of A Pair of Denim Jeans (Winner of the Journal of Material Culture Alfred Gell essay competition 2004)
Authors: Hauser Kitty
Published: October 2004

This article looks at research carried out at the FBI Laboratory’s Special Photographic Unit in the identification of denim trousers from bank surveillance film. This research, which was published in 1998, showed that despite the ubiquity of jeans, each pair has individual identifying characteristics caused by the manufacturing process and by wear, and that these might be used as evidence in the identification of criminal suspects. What the FBI research also inadvertently illuminated was an otherwise hidden relationship between garment, maker and wearer, in an effective - if accidental - reversal of commodity fetishism.
Social research on the under-16s: a consideration of the issues from a UK perspective
Authors: Piercy Hilary , Hargate Maria
Published: October 2004

This article aims to consider the current situation with regard to the issue of consent in relation to health-based research on the under-16s. It considers the legal situation with regard to the issues of consent, assent and dissent, and their application to research. Although under-16s can consent to treatment if deemed competent according to the ‘Fraser guidelines’, application of this principle in relation to research appears to be less clear with variability in published guidance and the approach taken by ethics committees. Recent policy changes including Research Governance have increased the scrutiny of consent to research, and current changes appear likely to increase the requirement for parental consent for those aged below 18 years. The impact of these ambiguities and changes upon young people as service users are considered with particular reference to sexual health, where they often access the service as autonomous individuals.