bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability Analysis of Open-loop Stiffness Control to Suppress Self-excited Vibrations
Authors: Makihara Kanjuro , Ecker Horst , Dohnal Fadi
Published: April 2005

We present stability investigations on vibration cancelling employing three different types of variable-stiffness actuators. A two-mass system is considered, with a base mass attached to the ground and a top mass connected to the base mass. The top mass is subject to self-excitation forces. The stiffness of an actuator connecting the base mass and the ground may change with time, according to a predetermined control frequency, for cancelling vibrations. Numerical simulation is employed as the basic tool to investigate the system and to carry out parameter studies. The stability of the system is determined by calculating the eigenvalues of the state transition matrix. Robustness of the proposed methods for vibration cancelling is discussed with respect to various aspects.
Adaptive Multiple-surface Sliding Control of Hydraulic Active Suspension Systems Based on the Function Approximation Technique
Authors: Chen P. C. , Huang A. C.
Published: April 2005

In this paper we propose an adaptive multiple-surface sliding controller (AMSSC) to control a non-autonomous quarter-car suspension system with hydraulic actuator. Due to the spring nonlinearities, the system property becomes asymmetric under the system’s own weight. Besides, because precise parameters of practical systems are hard to obtain, the system uncertainties should be dealt with. In this paper, these uncertainties are assumed to be lumped into three unknown functions such that the system model has both matched and mismatched uncertainties. Because the bounds of some of time-varying uncertainties are unavailable, traditional adaptive schemes or robust strategies are infeasible. To deal with this problem, a function approximation based adaptive multiple-surface sliding controller (AMSSC) is proposed in this paper. The multiple-surface sliding controller (MSSC) is used to cope with mismatched uncertainties while the function approximation technique is used to represent those uncertainties as finite combinations of basis functions. Adaptive laws for the approximating series can thus be derived based on the Lyapunov-like approach to ensure the closed-loop stability. Convergent performance of tracking errors can be obtained to improve the ride quality. Because the state measurements of the unsprung mass are lumped into the uncertainties, there is no need to feed back these signals with the proposed method. Therefore, the hardware structure can be simplified in the actual implementation. Computer simulations are performed to verify the effectiveness of the proposed strategy.
Optimal Vibration Control of a Model Frame Structure Using Piezoceramic Sensors and Actuators
Authors: Sethi V. , Song G.
Published: April 2005

This research concerns the active vibration control of a three-story model structural frame by using piezoceramics smart materials, in particular lead zirconate titanate (PZT), in the form of patches. These PZT patches are surface-bonded on the structure and function as actuators and sensors. To assist the control design, system identification is first performed. To excite the frame for identification purposes, a sweep sinusoidal input is used to drive the PZT actuator patches, and then a sixth-order state space model with a fit of 90% is identified to represent the dynamics of the first three modes of the model structural frame. A full-state linear quadratic regulator (LQR) controller is designed using the identified model. To achieve the full state feedback, an observer is designed based on the identified model. The LQR controller along with the observer is implemented to actively control the vibration of the model frame structures and is experimentally verified effective in the simultaneous suppression of vibrations at the first three modes.
Determination of the Depolymerisation Kinetics of Amylose, Amylopectin and Maltodextrin by Aspergillus niger Glucoamylase Using a 2-p-toluidinylnaphthalene-6-sulfonate/Flow-injection Analysis System with Fluorimetric Detection
Authors: Batlle N. , Carbonell J. V. , Sendra J. M.
Published: April 2005

This work describes the determination of depolymerisation kinetics of amylose, amylopectin and maltodextrin by Aspergillus niger glucoamylase using a flow-injection analysis system with fluorimetric detection and 2- p-toluidinylnaphthalene-2-sulfonate as the fluorescent probe. Experimental data corresponding to the time evolution of the concentration of detectable substrate were fitted to a single exponential decay curve in the case of amylose (linear substrate) and to a double exponential decay curve in the case of amylopectin and maltodextrin (ramified substrates). For all the substrates assayed, the depolymerisation rates at time zero correlated well with the initial substrate and enzyme concentrations through the Michaelis-Menten hyperbola. Therefore, this methodology allowed the determination of glucoamylase activity using any of these substrates. The determined value of the enzymic constant K m was lower for amylose than for amylopectin and maltodextrin, thus reflecting the higher difficulty of glucoamylase to hydrolyse the (1,6) when compared to the (1,4) linkages. In contrast, the values obtained for the rate constant k3 were very similar for all the substrates assayed.
Party Cohesion and Policy-Making in Russia
Authors: Chaisty Paul
Published: April 2005

Most commentators agree that a consolidated party system has not emerged in Russia since the collapse of communism. At the same time, Russian parties within parliament have become more cohesive. Recent analysis of Russian legislative politics has concentrated on the electoral foundations of party cohesion, but the results are mixed. Alternative explanations of cohesion that focus on the policy-shaping incentives commanded by parties have received less attention. This article attempts to fill the gap by assessing the evidence for party effects on policy at different stages of the legislative process. Focusing on legislative results in the sphere of economic policy, party effects in two venues of legislative decision-making are examined: the Duma Council and legislative committees. The article contends that the provision of policy benefits provides a weak explanation for party cohesion in Russia. Other explanations, such as presidential strategy and intra-party arrangements, are proposed as alternative avenues of research.
Recently Introduced Policy Instruments and Intervention Theories
Authors: Kautto Petrus , Similä Jukka
Published: April 2005

Evaluation of recently introduced policy instruments (RIPIs) is especially problematic, because only some effects have occurred, and information on them is imperfect. Policy makers and the public at large are, however, particularly interested in early evaluations. This article examines problems with the retrospective evaluation of RIPIs, and explores the advantages of using intervention theories in these evaluations. Two case studies from the field of environmental policy instruments are used as examples. It is argued that when evidence on final outcomes is largely unavailable, an intervention theory is a useful tool to overcome information problems. By using intervention theories, it is possible to identify observable prerequisites that precede intended, but not yet occurred, outcomes.
Motives for the Adoption of Protective Health Behaviours for Men and Women: An Evaluation of the Psychosocial-Appraisal Health Model
Authors: Ho Robert , Davidson Graham , Ghea Vanessa
Published: April 2005

The present study has been designed to: (1) evaluate the adequacy of a psychosocial-appraisal health model posited to explain the decision-making processes associated with the intention as well as the (non)practice of protective behaviours; and (2) test for sex differences in the hypothesized structural relations (both direct and indirect) between the model’s exogenous (psychosocial) and endogenous (cognitive appraisal) factors in representing the way health decisions are made. Results obtained from path analysis ( N = 1269) provided overall support for the ‘fit’ of the hypothesized health model. The implications of the findings with regard to differences in male and female health status are discussed.
A Qualitative Analysis of Psychological Processes Mediating Quality of Life Impairments in Chronic Daily Headache
Authors: Tenhunen Katri , Elander James
Published: April 2005

Quality of life impairments are greater in chronic daily headache (CDH) than in episodic headache conditions like migraine. This qualitative interview study aimed to identify psychological processes associated with quality of life impairments among individuals meeting diagnostic criteria for CDH. Grounded theory analysis showed that perceived loss of control was the central experience mediating the impact of CDH on quality of life. The results provide explanations for previous quantitative findings about quality of life impairments in CDH, and could inform interventions to reduce the impact of CDH. Further research could also examine the roles played by perceived control in the onset and development of CDH, including possible links with pre-emptive analgesic use.
Is Gay Parenting Bad for Kids? Responding to the ‘Very Idea of Difference’ in Research on Lesbian and Gay Parents
Authors: Hicks Stephen
Published: April 2005

This article examines the claim that children of lesbians and gay men are different to those of heterosexuals, particularly in their gender and sexual identity. The author considers two examples, a UK Christian discourse opposed to all forms of lesbian and gay parenting and a US liberal equality approach, represented by the work of Stacey and Biblarz (2001). Both, the author argues, treat difference as a thing acquired by children. This article examines and disputes the ways in which this idea of difference is achieved, and proposes that treating gender and sexuality as measurable outcomes is highly problematic. The author argues for research that asks how contemporary discourses of sexuality actually maintain the very idea that lesbian and gay families are different.
Welfare Moms and the Two Grooms: The Concurrent Promotion and Restriction of Marriage in US Public Policy
Authors: Cahill Sean
Published: April 2005

Since the mid-1990s political and religious conservatives and reactionaries have constructed two seemingly contradictory threats to the American body politic: poor, presumably heterosexual, single mothers who fail to marry, and same-sex couples, presumed to be economically privileged, who seek to marry. Ironically, welfare reformers in 1996 portrayed single mothers and cohabiting unmarried couples as selfish for not getting married, and today these same politicians and pundits denounce gay and lesbian couples as self-indulgent for seeking to get married. They are also attacking gay and lesbian parenting, and lesbian parenting in particular, as being ‘as bad’ for children as single mother parenting. In both discourses about women on welfare and gay and lesbian people, a central theme emerges: bad individual sexual choices are the key causes of the problems poor women and gay people face, not flawed public policy and social stigma.
Contested Heteronormativities: Discourses of Fatherhood among Lesbian Parents in Sweden and Ireland
Authors: Ryan-Flood Róisín
Published: April 2005

This article explores discourses of fatherhood among lesbian parents in Sweden and Ireland, based on interviews with 68 participants. Swedish lesbian parents generally expressed a strong preference for a known donor who would play an active parenting role. In contrast, Irish participants usually chose an uninvolved donor, but nonetheless one whose identity was known, albeit usually only to the lesbian parents. The significance of biology to kinship was both destabilized and reinforced, while gender and parenting discourses were also reinvented in complex ways. Reproductive decision-making among lesbian parents reflects hegemonic discourses of fatherhood in both countries. The ways that these discourses are subverted and reinscribed reveals the situatedness of lesbian parents in national contexts, where the ‘Other’ is deeply embedded in local discourses.
Accessing Medicalized Donor Sperm in the US and Britain: An Historical Narrative
Authors: Barney Sandra
Published: April 2005

Extensive public debate has been held recently about the rights of British lesbians to access medically prepared donor sperm. Public statements by the head of the Human Fertilisation and Embryology Authority (HFEA) indicate that this agency may be preparing to reconsider its objections to the acquisition of donor sperm by lesbians. By examining the evolution of sperm banking in the United States and Britain, this essay considers the consequences of open market versus state control over medicalized sperm for lesbians. It argues that sexuality alone does not determine the ability of lesbians to access sperm under either system and that officially ending the discriminatory practices of the HFEA may not guarantee access for all lesbians.
the culture of a home visit in early intervention
Authors: Brorson Kent
Published: April 2005

This article uses data from an ethnographic study that examined the delivery of home-based services in early intervention. Participants were families with an infant or toddler with special needs, and professionals providing early intervention services to these and other families. The study examined an early intervention program that uses primarily a transdisciplinary approach to home-based service delivery. Perspectives on the delivery of services were elicited by ethnographic interviewing, participant observation of home visits, and the review of program structure, artifacts, and documents to determine what makes this program effective in the delivery of services. The data revealed that effectiveness of service delivery is dependent upon professionals creating a cultural environment that is similar in all homes during home visits. The discussion addresses the difficulty in defining and then implementing a family-centered service delivery model that takes individual differences into account.
Reflection
Authors: Koch Tina , Mann Susan , Kralik Debbie , van Loon Antonia M.
Published: April 2005

In this paper, four researchers describe reflection as a component of a participatory action research cycle. We draw on our experiences and learning while undertaking three research inquiries. In the first inquiry we listen and respond to the voices of Australian Aboriginal people who live with diabetes and we share an alternate story, where fear is turned into courage, as told by these Elders. The second inquiry involves email communications with women and men who live with a chronic illness and gives a facilitator’s reflections. And the third study is a capacity building process with women who have experienced child sexual abuse. These women have used/misused alcohol, licit/illicit substances, or gambling, which has contributed to their homelessness. Confronted by many of life’s obstacles, we gain a glimmer of hope as women describe the way in which they use the participatory process to make sense of their lives.

It is argued that reflection occupies a central place is participatory action research cycles of ‘look, think and act’. ‘Look, think and act’ processes are appealing precisely because they are meaningful to research participants in their everyday lives. When these processes are internalised as modus operandi, they can be sustained throughout one’s life as a strategy for building capacity or ‘moving on’. ‘Moving on’ or transition is the theoretical focus that holds these inquiries together.
The inclusion of bias in reflective and reflexive research
Authors: Mantzoukas Stefanos
Published: April 2005

In this paper I explore the relationship between bias, research and reflective studies. I argue that bias is not by definition counterproductive for research studies, and that biased studies do not necessarily constitute invalid research. Hence, I commence by discussing how the concept of bias and its relationship to knowledge production has developed within the history of science and how it has evolved during the twentieth century by drawing on the work of Ayer, Popper and Wittgenstein. I go on to argue that bias cannot sincerely be excluded from the research process, irrelevant of paradigm, and that the presupposition of excluding bias from research studies is based upon historical and ideological assumptions that, once pushed to their logical conclusion, do not hold ground. Nonetheless, I consider that research studies deriving from positivist or post-positivist paradigms will need to continue to strive for the elimination or minimisation of bias, because these are the fundamental rules of these paradigms. However, for non-positivist studies, which utilise reflection to reveal the researcher’s bias, the paradigmatic rules require that these biases should be included rather than excluded from the study. Thus, the article concludes by suggesting that such studies are reflexive studies which are valid only if the researcher’s bias is fully incorporated and becomes transparent throughout the study.
Integrating qualitative and quantitative research methods
Authors: Kinn Sue , Curzio Joan
Published: April 2005

There are a growing number of authors arguing the case for integrating qualitative and quantitative research methods within research projects. A study was carried out to identify the amount of published work integrating qualitative and quantitative research methods and to assess the quality of the outcomes of studies purporting to use both methods. Electronic searches of the health literature and critical appraisal of a random sample of papers retrieved was undertaken as well as a hand search of five journals. Over one-quarter (130, or 27%) of the papers from the electronic searches were theoretical discussions about the merits of mixing research methods, 22% (110) were papers purporting to have used mixed methodologies. Critical appraisal of the sample papers showed the qualitative and quantitative elements varied. Where the results of the different parts of the study were integrated, the outcomes from the research were more convincing than they might otherwise have been. Other papers had little discussion about the balance or integration of the different types of results. Hand searching revealed very few mixed method papers. Further work is required to refine and develop ways to mix methods to generate the evidence required to support practice.
Implementing the Rock Challenge
Authors: Salmon Debra , Orme Judy , Kimberlee Richard , Jones Matthew , Murphy Simon
Published: April 2005

This paper presents the qualitative process findings from an evaluation of a school-based performing arts programme, ‘Rock Challenge’. Rock Challenge aims to promote healthy life styles ‘by building resilience amongst young people involved’. The research aimed to capture the experiences and perceptions of young people’s involvement in the programme, particularly in relation to the concept of the ‘drug-free high’, support offered throughout the programme and participants’ response to Rock Challenge as a drug-prevention initiative. Findings from the study suggest young people felt very positive about their involvement and, in particular, valued the skills and experiences associated with organising a performance, team-working, developing confidence, friendship, fun and excitement. The excitement felt during dance rehearsals and the live performance was associated with the concept of a ‘drug-free high’, feeling good in the absence of drugs and alcohol, and was seen as a key benefit of the programme. While support from teachers and families was perceived as high, difficulties were identified in the recruitment of males and students vulnerable to substance misuse and recommendations are made for improvement. The health promotion opportunities for school nurses and other public health practitioners and personal, social and health education co-ordinators are highlighted.
A New High-Performance mVLDPE
Authors: Halley Richard W. , Malakoff Alan M.
Published: April 2005

Metallocene polyethylenes are well known for providing superior toughness, heat sealing, and clarity when compared to the conventional polyethylenes. Their unique attributes have been employed for over a decade in the manufacture of many different types of blown and cast films for numerous end-use applications. A new family of very low density metallocene polyethylenes, defined here as mVLDPE, exhibits outstanding toughness and surprising heat seal and hot tack performance. Both monolayer and coex blown film studies have demonstrated that the unique properties of these mVLDPEs can be used to produce high-performance films for a wide variety of packaging applications. Selected data from these studies are used to demonstrate that the properties of these mVLDPEs are superior to those of conventional very low density polyethylenes (VLDPEs), linear low density polyethylenes (LLDPEs), metallocene linear low density polyethylenes (mLLDPEs), and ethylene vinyl acetate copolymers (EVAs).
Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype
Authors: Renkl Andreas C. , Wussler Julia , Ahrens Thomas , Thoma Käthe , Kon Shigeyuki , Uede Toshimitsu , Martin Stefan F. , Simon Jan C. , Weiss Johannes M.
Published: April 2005

Osteopontin (OPN) has been shown to have T helper 1 (Th1) cytokine functions in cell-mediated immunity. Deficiency of OPN is linked to a reduced Th1 immune response in autoimmunity, infectious disease, and delayed-type allergy. Dendritic cells (DCs) are central for the induction of T-cell–mediated immunity, when initially flexible DCs are instructed by priming signals and tissue-derived factors to adopt Th1, Th2, or regulatory T-cell–inducing phenotypes. Although OPN influences the cytokine secretion of T cells and macrophages, its effects on DC polarization remain an important missing link in the understanding of OPN functions in Th1 immunity. Here we demonstrate that OPN promotes the emigration of human DCs from the epidermis and functionally activates myeloid-type DCs, augmenting their expression of HLA-DR, costimulatory, and adhesion molecules. OPN induces their Th1-promoting tumor necrosis factor α (TNF-α) and interleukin-12 (IL-12) secretion, and enhances their allostimulatory capacity. In mixed lymphocyte reactions (MLRs), OPN stimulates IL-12 secretion by DCs, inducing elevated interferon-γ (IFN-γ) production by T cells. Naive Th cells stimulated by OPN-activated DCs show a Th1-polarized cytokine production. Our findings identify OPN as an important tissue-derived factor that DCs encounter when traveling from peripheral sites of activation to secondary lymphatic organs, which induces DC maturation toward a Th1-promoting phenotype.
Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance
Authors: Rajkumar S. Vincent , Kyle Robert A. , Therneau Terry M. , Melton L. Joseph , Bradwell Arthur R. , Clark Raynell J. , Larson Dirk R. , Plevak Matthew F. , Dispenzieri Angela , Katzmann Jerry A.
Published: April 2005

We hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio < 0.26 or > 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P < .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non–immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (≥ 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).
The use of time-resolved fluorescence imaging in the study of protein kinase C localisation in cells
Authors: Stubbs Christopher D , Botchway Stanley W , Slater Simon J , Parker Anthony W
Published: April 2005

Background

Two-photon-excitation fluorescence lifetime imaging (2P-FLIM) was used to investigate the association of protein kinase C alpha (PKCα) with caveolin in CHO cells. PKCα is found widely in the cytoplasm and nucleus in most cells. Upon activation, as a result of increased intracellular Ca2+ and production of DAG, through G-protein coupled-phospholipase C signalling, PKC translocates to a variety of regions in the cell where it phosphorylates and interacts with many signalling pathways. Due to its wide distribution, discerning a particular interaction from others within the cell is extremely difficult

Results

Fluorescence energy transfer (FRET), between GFP-PKCα and DsRed-caveolin, was used to investigate the interaction between caveolin and PKC, an aspect of signalling that is poorly understood. Using 2P-FLIM measurements, the lifetime of GFP was found to decrease (quench) in certain regions of the cell from ~2.2 ns to ~1.5 ns when the GFP and DsRed were sufficiently close for FRET to occur. This only occurred when intracellular Ca2+ increased or in the presence of phorbol ester, and was an indication of PKC and caveolin co-localisation under these conditions. In the case of phorbol ester stimulated PKC translocation, as commonly used to model PKC activation, three PKC areas could be delineated. These included PKCα that was not associated with caveolin in the nucleus and cytoplasm, PKCα associated with caveolin in the cytoplasm/perinuclear regions and probably in endosomes, and PKC in the peripheral regions of the cell, possibly indirectly interacting with caveolin.

Conclusion

Based on the extent of lifetime quenching observed, the results are consistent with a direct interaction between PKCα and caveolin in the endosomes, and possibly an indirect interaction in the peripheral regions of the cell. The results show that 2P-FLIM-FRET imaging offers an approach that can provide information not only confirming the occurrence of specific protein-protein interactions but where they occur within the cell.
Strain-specific differences in Neisseria gonorrhoeae associated with the phase variable gene repertoire
Authors: Jordan Philip W , Snyder Lori AS , Saunders Nigel J
Published: April 2005

Background

There are several differences associated with the behaviour of the four main experimental Neisseria gonorrhoeae strains, FA1090, FA19, MS11, and F62. Although there is data concerning the gene complements of these strains, the reasons for the behavioural differences are currently unknown. Phase variation is a mechanism that occurs commonly within the Neisseria spp. and leads to switching of genes ON and OFF. This mechanism may provide a means for strains to express different combinations of genes, and differences in the strain-specific repertoire of phase variable genes may underlie the strain differences.

Results

By genome comparison of the four publicly available neisserial genomes a revised list of 64 genes was created that have the potential to be phase variable in N. gonorrhoeae, excluding the opa and pilC genes. Amplification and sequencing of the repeat-containing regions of these genes allowed determination of the presence of the potentially unstable repeats and the ON/OFF expression state of these genes. 35 of the 64 genes show differences in the composition or length of the repeats, of which 28 are likely to be associated with phase variation. Two genes were expressed differentially between strains causing disseminated infection and uncomplicated gonorrhoea. Further study of one of these in a range of clinical isolates showed this association to be due to sample size and is not maintained in a larger sample.

Conclusion

The results provide us with more evidence as to which genes identified through comparative genomics are indeed phase variable. The study indicates that there are large differences between these four N. gonorrhoeae strains in terms of gene expression during in vitro growth. It does not, however, identify any clear patterns by which previously reported behavioural differences can be correlated with the phase variable gene repertoire.
Lack of association between Chlamydia Pneumoniae serology and endothelial dysfunction of coronary arteries
Authors: Ferrari Markus , Werner Gerald S , Richartz Barbara M , Oehme Albrecht , Straube Eberhard , Figulla Hans R
Published: April 2005

Background

Recent publications brought up the hypothesis that an infection with Chlamydia Pneumoniae (CP) might be a major cause of coronary artery disease (CAD). Therefore, we investigated whether endothelial dysfunction (ED) as a precursor of atherosclerosis might be detectable in patients with previous infection with CP but without angiographic evidence of CAD.

Methods

We included 16 patients (6 male / 10 female) of 52 consecutive patients with normal coronary angiography who had typical angina pectoris and pathologic findings in the stress test. Exclusion criteria were: active smoker, elevated cholesterol, hypertension, age > 65 years, diabetes mellitus, treatment with ACE-inhibitors, or known CAD. Blood sample analysis for serum titer against CP (aCP-IgG) was performed after coronary angiography. We looked for endothelial dysfunction analyzing the diameter of the left anterior descending coronary artery (LAD) before and after acetylcholine (ACh) i. c. Quantitative analysis of luminal diameter (LD) was performed in at least two planes during baseline conditions and after ACh for 2 minutes in dosages of 7.2 μg/min and 36 μg/min with an infusion speed of 2 ml/min. Using Doppler guide wire, the coronary flow velocity was measured continuously in the LAD. The coronary flow velocity reserve (CFVR) was measured after 20 μg adenosine i. c.

Results

10 patients had an elevated aCP-IgG (> 1:8). 6 patients with negative titers (aCP-IgG ≤ 1:8) served as control (CTRL). Both groups were comparable in age, gender, angina class, results of non-invasive stress-test and the baseline values of LD and flow. In the CP positive group 3 patients (30%) did not show an increase of LD after ACh as evidence of ED. In the CTRL group 4 patients (67 %) had ED. There was no association between aCP-IgG and changes of coronary blood flow after ACh. All patients showed normal CFVR (3.0 ± 0.27) irrespective of their aCP-IgG values.

Conclusion

In patients with typical symptoms of coronary ischemia but without angiographically visible CAD and absence of other factors affecting the endothelial function, a previous infection with CP is not associated with endothelial dysfunction.
Diabetes (db/db) mutation-induced endometrial epithelial lipoapoptosis: Ultrastructural and cytochemical analysis of reproductive tract atrophy
Authors: Garris David R
Published: April 2005

Background

The diabetes (db/db) mutation in C57BL/KsJ mice promotes a progressive cytolipidemia within the endometrial epithelial (EE) layer of the female reproductive tract which results in premature cellular and organ atrophy. The current studies focus on the ultrastructural and cytochemical changes which promote nuclear apoptosis and cytostructural disruption following the expression of endometrial hypercytolipidemia which promotes diabetes-associated organoinvolution and manifest infertility.

Methods

Control (normal:+/+) and diabetes (db/db) genotype groups were prepared for high resolution light microscopic analysis of cytolipidemia and nuclear apoptosis (TUNEL-labeled 3'-DNA fragmentation) indices and compared to the transmission electron (TEM) microscopic analysis of endometrial tissue samples collected from 8–16 week-old groups.

Results

Compared to controls, db/db mutation expression induced a dramatic increase in EE cytolipid vacuole volume and density within the epithelial endometrial layer. TEM analysis revealed that cytolipid vacuole accumulations initially aggregated at the baso-polar regions of UEE cells in response to the systemic hyperglycemic/hypertriglyceridemic conditions which characterized the (db/db) groups. Progressive cytoplasmic movement of the lipid pools into perinuclear compartments of affected EE cells induced nuclear isolation from organelles that were displaced towards peripheral cytoplasmic compartments. Cytochemical analysis of lipid vacuole accumulations indicated attraction towards, and incorporation within, the nuclear envelope of hyperlipidemic cells. Co-localization of nuclear apoptotic 3'-DNA fragments within identified hyperlipidemic EE cells was coincident with the cytochemical and ultrastructural identification of lipid penetration through the nuclear envelope in db/db mutants.

Conclusion

These results are the first cytochemical indication that the metabolic disturbances in db/db mutants which promote hypercytolipidemia are coincident with lipoapoptosis-induced nuclear dissolution, as denoted by DNA fragmentation analysis. The lipidemia-induced alterations in intracellular organelle and nuclear architectures suggests that the metabolic disturbances in glucose and lipid metabolic cascades in diabetes (db/db) mutants disrupts cytointegrity, culminating in nuclear disregulation (as indicated by lipoapoptosis) and eventual premature reproductive tract organoinvolution and resultant, manifest, reproductive sterility.
The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT): rationale, design and methodology
Authors:   The Complications of Age-Related Macular Degeneration Prevention Trial study group
Published: April 2005

Background The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) is a randomized clinical trial to evaluate whether prophylactic laser treatment to the retina can prevent the complications of the advanced stage of Age-Related Macular Degeneration (AMD), the leading cause of irreversible blindness.

Methods CAPT is conducted in 23 clinical centers and in three central resource centers. The primary outcome measure is change in visual acuity; secondary outcomes include the incidence of complications of AMD, changes in other measures of visual functioning and vision-related quality of life. In total, 1052 patients with two high-risk eyes were enrolled. One eye was randomized to receive laser treatment and the other eye to observation. All patients were treated immediately after randomization and again at 12 months, dependent on clinical status. All patients are followed via study visits and telephone calls for a minimum of five years. Study visit procedures include established tests of visual function conducted by examiners masked to the treatment assignment of each eye, a biomicroscopic examination by CAPTophthalmologists, and photographs of each eye taken according to protocol and assessed by masked graders in a centralized Photograph Reading Center.

Results This paper describes the CAPT study, including study rationale, operational structure, and measures implemented to ensure standardization of assessments, adherence to protocol, quality assurance, and maintaining follow-up. Several features related to study design and procedures that are specific to CAPT are highlighted, including clinic selection and judgements regarding patient eligibility.

Conclusions An intervention that can reduce the risk of advanced AMD by 30% in the eyes of people with two high-risk eyes may halve the rate of bilateral blindness from AMD. It would also yield substantial savings in expenditures devoted to treating advanced AMD and the disability it causes, and enhance the quality of life for people at risk.
Using clinical trials as a condition of coverage: lessons from the National Emphysema Treatment Trial
Authors: Carino Tanisha , Sheingold Steven , Tunis Sean
Published: April 2005

In making evidence-based coverage decisions, The Centers for Medicare & Medicaid Services (CMS) often must balance the need for rigorous evaluation of medical technologies with the public's demand for rapid access to new services. During the mid-1990s, this dilemma was apparent with regard to a promising, yet unproven, new procedure for emphysema patients known as lung volume reduction surgery (LVRS). In a unique decision, CMS provided coverage for LVRS only under the protocol of the National Emphysema Treatment Trial (NETT), which it cosponsored with the National Heart, Lung, and Blood Institute. The CMS has recently revised its coverage policy for LVRS based on the results of the NETT. This paper provides a history and rationale for CMS's approach to paying for LVRS. It also discusses lessons learned from the NETT experience and potential implications for future collaborations between health plans and the clinical research enterprise that would provide better information for coverage treatment decisions.
The Salk Polio Vaccine Trial of 1954: risks, randomization and public involvement in research
Authors: Dawson Liza
Published: April 2005

The year 2004 marks the ”ftieth anniversary of the celebrated 1954 Salk polio vaccine trial. This enormous clinical trial, involving 1.8 million children, was carried out with the co-operation and assistance of hundreds of thousands of lay volunteers, along with medical professionals and local health departments throughout the USA. While the trial was an impressive public health achievement, ”rmly establishing the ef”cacy of the killed virus vaccine and paving the way for eradication of the disease, it was not without controversy. This article recounts the story of this important early clinical trial and how the social and political conditions at the time affected its planning and execution.
Treatment effects monitoring committees and early stopping in large clinical trials
Authors: Kiri Antariksha , Tonascia Susan , Meinert Curtis L
Published: April 2005

Background Treatment effects monitoring is a process carried out over the course of a trial to determine whether it should continue unaltered. The purpose of monitoring is to protect persons enrolled from harm, caused either by exposure to an ineffective or harmful treatment or failure to provide a better treatment. The aim of this paper is to characterize treatment effects monitoring committees (TEMCs) as extant in published trials and to examine the effect of their presence on the premature stopping of a trial.

Methods Trials published in 1990–1995 in the Annals of Internal Medicine, Archives of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, New England Journal of Medicine or Controlled Clinical Trials were identi”ed via MEDLINE (4279 publications). Abstracts were screened to include only trials with parallel treatment designs and sample sizes of ¶200, reducing the set to 661 papers. Those papers were then read, reducing the set to 562 after exclusion of papers not reporting trial results. The results that follow come from a review of these 562 published papers and from the responses to two questionnaires. The ”rst was mailed to the corresponding author, and the second to the chair of the monitoring body or other contact as provided by the author in response to the ”rst questionnaire.

Results Less than half (48%) of the 562 trials had TEMCs. Factors having a positive univariate relationship with the presence of a TEMC include National Institutes of Health (NIH) sponsorship, larger sample size, multicentered, longer data collection and follow-up, and mortality as an outcome. Most of the early stops occurred in trials with TEMCs (66 out of 78). The odds ratios for early stopping for trials with TEMCs versus those without TEMCs was 4.4 (CI: 2.3–8.5).

Conclusions The evidence suggests that early stopping is associated with the presence of a TEMC, but a substantial number of trial reports do not mention the presence of a TEMC even when one was used to stop a trial early.
Computer-assisted analysis of filopod formation and the role of myosin II heavy chain phosphorylation inDictyostelium
Authors: Heid Paul J. , Geiger Jeremy , Wessels Deborah , Voss Edward , Soll David R.
Published: April 2005

To investigate the role played by filopodia in the motility and chemotaxis of amoeboid cells, a computer-assisted 3D reconstruction and motion analysis system, DIAS 4.0, has been developed. Reconstruction at short time intervals of Dictyostelium amoebae migrating in buffer or in response to chemotactic signals, revealed that the great majority of filopodia form on pseudopodia, not on the cell body; that filopodia on the cell body originate primarily on pseudopodia and relocate; and that filopodia on the uropod are longer and more stable than those located on other portions of the cell. When adjusting direction through lateral pseudopod formation in a spatial gradient of chemoattractant, the temporal and spatial dynamics of lateral pseudopodia suggest that filopodia may be involved in stabilizing pseudopodia on the substratum while the decision is being made by a cell either to turn into a pseudopodium formed in the correct direction (up the gradient) or to retract a pseudopodium formed in the wrong direction (down the gradient). Experiments in which amoebae were treated with high concentrations of chemoattractant further revealed that receptor occupancy plays a role both in filopod formation and retraction. As phosphorylation-dephosphorylation of myosin II heavy chain (MHC) plays a role in lateral pseudopod formation, turning and chemotaxis, the temporal and spatial dynamics of filopod formation were analyzed in MHC phosphorylation mutants. These studies revealed that MHC phosphorylation-dephosphorylation plays a role in the regulation of filopod formation during cell migration in buffer and during chemotaxis. The computer-assisted technology described here for reconstructing filopodia at short time intervals in living cells, therefore provides a new tool for investigating the role filopodia play in the motility and chemotaxis of amoeboid cells.
CD95 capping is ROCK-dependent and dispensable for apoptosis
Authors: Söderström Thomas S. , Nyberg Sofia D. , Eriksson John E.
Published: April 2005

Upon engagement, the CD95 receptor is rapidly clustered into cellular `caps'. This receptor capping is one of the first events to take place following activation and it has been proposed to be important for the initiation of apoptotic signaling. As the biological roles of CD95 capping are still elusive, we explored in detail the role of capping in induction of apoptosis in lymphocytes. CD95 capping was shown to be uncoupled from apoptosis, as apoptosis could occur in the absence of CD95 capping and, vice versa, capping could occur without inducing apoptosis. CD95 capping occurred concomitantly with reorganization of the actin cytoskeleton and aggregation of lipid rafts. While inhibition of actin polymerization and caspase-8 activity had cell type-specific effects on capping in type I and type II cells, the rapid CD95-mediated cellular polarization, as visualized by the orchestrated reorganization of CD95, F-actin and lipid rafts, was shown to be dependent on signaling by Rho kinase (ROCK) in both cell types, however, by distinct activation mechanisms in the respective cell type. CD95 activated RhoA exclusively in the type II cell, whereas ROCK activation was caspase-dependent in the type I cell. Taken together, our results imply that CD95 capping and the subsequent cellular polarization is a ROCK signaling-regulated process that does not correlate with the induction of apoptosis, but is more likely to be involved in the emerging non-apoptotic functions of CD95.
Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats
Authors: Conlee K M , Stephens M L , Rowan A N , King L A
Published: April 2005

Carbon dioxide (CO2) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO2 as a euthanasia agent.
Multiple in vivo passages enhance the ability of a clinical Helicobacter pylori isolate to colonize the stomach of Mongolian gerbils and to induce gastritis
Authors: Bleich A , Köhn I , Glage S , Beil W , Wagner S , Mähler M
Published: April 2005

The Mongolian gerbil is an excellent animal model for Helicobacter pylori-induced gastritis in humans. In this study, initially low colonization rates of the H. pylori strains ATCC 43504, SS1, or HP87 inoculated into gerbils caused difficulties in establishing this model. In order to increase the colonization ability and pathogenicity, the clinical HP87 isolate was selected for adaptation to the gerbil stomach by multiple in vivo passages through gerbils. Development of gastritis was examined histologically at 4–52 weeks after infection. The proportion of gerbils which tested positive for H. pylori by culture at four weeks after inoculation gradually increased from 11.1% of gerbils inoculated with HP87 without prior in vivo passage (P0) to 100% of gerbils inoculated with HP87 with seven in vivo passages (P7). In addition, adaptation of HP87 resulted in more severe histopathological changes. Gerbils infected with adapted HP87 (P7) exhibited severe infiltration by monomorphonuclear and polymorphonuclear leukocytes in the mucosa, submucosa, and subserosa of the gastric antrum, as well as epithelial changes consisting of hyperplasia, erosion, and ulceration. Histopathological changes increased in severity from four to 52 weeks after infection. Adaptation of HP87 during its passages through gerbils could be due to genetic changes in bacterial colonization factors. Identification of these changes might be useful to understand the underlying mechanism of gastric adaptation and pathogenesis of H. pylori.