bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Rebound: Focusing on Someone New Helps Anxiously Attached Individuals Let Go of Ex-Partners
Authors: Spielmann Stephanie S. , MacDonald Geoff , Wilson Anne E.
Published: July 2009

The present research demonstrates that focusing on someone new may help anxiously attached individuals overcome attachment to an ex-romantic partner, suggesting one possible motive behind so-called rebound relationships. A correlational study revealed that the previously demonstrated link between anxious attachment and longing for an ex-partner was disrupted when anxiously attached individuals had new romantic partners. Two experiments demonstrated that this detachment from an ex can be induced by randomly assigning anxiously attached individuals to believe they will easily find a new partner (through bogus feedback in Study 2 and an ease of retrieval task in Study 3). This research suggests that for anxiously attached individuals, focusing on someone new can be an adaptive part of the breakup recovery process.
In Whose Interest Do We Work? Critical Comments of a Practitioner at the Fringes of the Liberation Paradigm
Authors: Lindorfer Simone
Published: July 2009

`De-ideologizing reality' is an urgent task within the psychology of liberation. Ignacio Martín-Baró characterized it as a process of conscientization that unmasks power interests underlying knowledge production, retrieves the `original experience of the people', and returns that experience in the form of `objective data'. In contemporary humanitarian trauma work in crisis areas, however, psychology often masks global power structures and further stigmatizes and alienates `victims' from their communities and their original experience. I draw upon my work as a psychologist, theologian and freelance consultant in the Great Lakes Region of Central Africa to analyse two case studies. I use these examples to analyse and critique the underlying power discourses implied in definitions of `victimhood' in humanitarian interventions and identify contradictions that challenge liberation thinking as well as demystify feminist agendas. I conclude by calling for a change of perspective and of professional attitudes that can be realized through engaging a de-ideologizing approach towards global psychosocial trauma interventions.
A relation between mass loss and life of incandescent filament lamps
Authors: Agrawal DC , Menon VJ
Published: July 2009

The thermodynamics of a radiating and evaporating tungsten filament having a hot-spot defect are examined theoretically. Assuming quasi-steady-states for the main and the hot-spot segments, the time profiles of their temperatures and radii are derived in closed form. Explicit relations among the fractional mass loss, failure time and defect size ratio are obtained and compared against approximate expressions used by Gluck and King7 and by Elenbaas.14 Numerical results computed for vacuum lamps support our theory.
Turning Access TM into a web-enabled secure information system for clinical trials
Authors: Dongquan Chen  , Chen Wei-Bang , Soong Mayhue , Soong Seng-Jaw , Orthner Helmuth F.
Published: July 2009

Background Organizations that have limited resources need to conduct clinical studies in a cost-effective, but secure way. Clinical data residing in various individual databases need to be easily accessed and secured. Although widely available, digital certification, encryption, and secure web server, have not been implemented as widely, partly due to a lack of understanding of needs and concerns over issues such as cost and difficulty in implementation.

Purpose The objective of this study was to test the possibility of centralizing various databases and to demonstrate ways of offering an alternative to a large-scale comprehensive and costly commercial product, especially for simple phase I and II trials, with reasonable convenience and security.

Methods We report a working procedure to transform and develop a standalone AccessTM database into a secure Web-based secure information system.

Results For data collection and reporting purposes, we centralized several individual databases; developed, and tested a web-based secure server using self-issued digital certificates.

Limitations The system lacks audit trails. The cost of development and maintenance may hinder its wide application.

Conclusions The clinical trial databases scattered in various departments of an institution could be centralized into a web-enabled secure information system. The limitations such as the lack of a calendar and audit trail can be partially addressed with additional programming. The centralized Web system may provide an alternative to a comprehensive clinical trial management system.
Development and Implementation of Clinical Trial Protocol Templates at the National Institute of Allergy and Infectious Diseases
Authors: Bridge Heather , Smolskis Mary , Bianchine Peter , Dixon Dennis O. , Kelly Grace , Herpin Betsey , Tavel Jorge ,   Protocol Template Working Group of the NIAID Clinical Research Subcommittee
Published: July 2009

Background A clinical research protocol document must reflect both sound scientific rationale as well as local, national and, when applicable, international regulatory and human subject protections requirements. These requirements originate from a variety of sources, undergo frequent revision and are subject to interpretation. Tools to assist clinical investigators in the production of clinical protocols could facilitate navigating these requirements and ultimately increase the efficiency of clinical research.

Purpose The National Institute of Allergy and Infectious Diseases (NIAID) developed templates for investigators to serve as the foundation for protocol development. These protocol templates are designed as tools to support investigators in developing clinical protocols.

Methods NIAID established a series of working groups to determine how to improve its capacity to conduct clinical research more efficiently and effectively. The Protocol Template Working Group was convened to determine what protocol templates currently existed within NIAID and whether standard NIAID protocol templates should be produced. After review and assessment of existing protocol documents and requirements, the group reached consensus about required and optional content, determined the format and identified methods for distribution as well as education of investigators in the use of these templates.

Results The templates were approved by the NIAID Executive Committee in 2006 and posted as part of the NIAID Clinical Research Toolkit [1] website for broad access. These documents require scheduled revisions to stay current with regulatory and policy changes.

Limitations The structure of any clinical protocol template, whether comprehensive or specific to a particular study phase, setting or design, affects how it is used by investigators. Each structure presents its own set of advantages and disadvantages. While useful, protocol templates are not stand-alone tools for creating an optimal protocol document, but must be complemented by institutional resources and support. Education and guidance of investigators in the appropriate use of templates is necessary to ensure a complete yet concise protocol document. Due to changing regulatory requirements, clinical protocol templates cannot become static, but require frequent revisions.
The reported experience of four women with intellectual disabilities receiving emergency psychiatric services in Canada
Authors: Lunsky Yona , Gracey Carolyn
Published: July 2009

Hospital emergency departments are not well prepared to meet the needs of individuals with intellectual disabilities. Negative experiences can be very traumatic, particularly when the emergency visit is because of a behavioural or psychiatric problem. A focus group study was conducted in 2005 in Toronto, Canada with four women with intellectual disabilities who had paid repeated visits to their local emergency department due to a psychiatric or behavioural crisis. These women spoke about not feeling respected, the trauma of being restrained physically or chemically, and about hospital staff not being comfortable working with women with intellectual disabilities. Clinical implications are discussed and recommendations are presented to improve the experience of women who require emergency services in the future.
Problems, problems
Authors: Shaw Susan
Published: July 2009

A learning disability discourse has developed over time and is driven by social policy and professional power. Landmark legislation such as the Disability Discrimination Act 1995 has promoted public accessibility for disabled and disenfranchised people. The social construction of difference and disability contributes to the ways people with learning disability are seen and described by others. Many professionals tell stories about their experiences of working with people who are learning disabled. Some stories construct the people with learning disabilities as heroic and tragic, but most construct them as problems to be solved. This qualitative study demonstrates that learning disability constructions in practice-based stories are not merely postcards from the past but indicators of the present and are a demonstration of the issues facing learning disability nurses. I argue that there are tensions in the way learning disability is constructed and ultimately communicated by learning disability nurses.
Using blended and guided technologies in a university course for scientist-practitioners
Authors: Roll-Pettersson Lise , Ala'I-Rosales Shahla
Published: July 2009

Although the incidence of autism spectrum disorders is increasing worldwide, there is a shortage of professionals trained to provide effective interventions. The article describes an advanced university course in Applied Behaviour Analysis (ABA) and autism tailored to meet the needs of Swedish professionals from multiple disciplines. The course implemented both blended-learning technologies (web, telecommunication, and in vivo) and guided-design (problem-solving) exercises to promote the scientist-practitioner model. Overall, students advanced their skills related to identifying extant scientific literature, choosing appropriate single-subject design evaluation methods, and critically analysing the effects of attempted interventions. Students rated the course as having high social validity and predicted the course content would positively affect their professional practice. The relevance of the course and future directions are discussed in the context of meeting the global need for effective autism intervention professionals.
Nicked β2-glycoprotein I binds angiostatin 4.5 (plasminogen kringle 1-5) and attenuates its antiangiogenic property
Authors: Nakagawa Hisako , Yasuda Shinsuke , Matsuura Eiji , Kobayashi Kazuko , Ieko Masahiro , Kataoka Hiroshi , Horita Tetsuya , Atsumi Tatsuya , Koike Takao
Published: July 2009

Angiostatin was first discovered as a plasminogen fragment with antitumor/antiangiogenic property. One of the angiostatin isoforms, that is, angiostatin 4.5 (AS4.5), consisting of plasminogen kringle 1 to 4 and a most part of kringle 5, is produced by autoproteolysis and present in human plasma. β2-glycoprotein I (β2GPI) is proteolytically cleaved by plasmin in its domain V (nicked β2GPI), resulting in binding to plasminogen. Antiangiogenic properties have been recently reported in nicked β2GPI as well as in intact β2GPI at higher concentrations. In the present study, we found significant binding of nicked β2GPI to AS4.5 (KD = 3.27 × 106 M−1). Via this binding, nicked β2GPI attenuates the antiangiogenic functions of AS4.5 in the proliferation of arterial/venous endothelial cells, in the extracellular matrix invasion and the tube formation of venous endothelial cells, and in vivo angiogenesis. In contrast, intact β2GPI does not bind to AS4.5 or inhibit its antiangiogenic activity. Thus, nicked β2GPI exerts dual effects on angiogenesis, that is, nicked β2GPI promotes angiogenesis in the presence of AS4.5, whereas nicked β2GPI inhibits angiogenesis at concentrations high enough to neutralize AS4.5. Our data suggest that plasmin-nicked β2GPI promotes angiogenesis by interacting with plasmin-generated AS4.5 in sites of increased fibrinolysis such as thrombus.
Interferon-γ–triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells
Authors: Jürgens Birgit , Hainz Ursula , Fuchs Dietmar , Felzmann Thomas , Heitger Andreas
Published: July 2009

The role of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in down-regulating human alloresponses has recently been controversially debated. We here demonstrate that human monocyte-derived dendritic cells (mDCs) can be endowed with sustained IDO competence in vitro by 48-hour activation with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). IFN-γ also amplified proinflammatory cytokine secretion during activation. Yet, on reculture after activation cytokine production ceased, whereas IDO enzymatic activity continued. Manipulation of tryptophan metabolism did not affect proinflammatory cytokine release, suggesting that IFN-γ triggers IDO activity and proinflammatory cytokine release as distinct cellular programs. IDO-competent DCs down-regulated allogeneic T-cell responses, but this IDO-mediated effect was overcome by slightly modifying cell culture conditions. Nevertheless, the CD4+CD25+ T-cell fraction stimulated by IDO-competent DCs displayed substantial suppressor activity. This suppressive activity (1) required allogeneic stimulation for its induction, (2) affected third-party T cells, and (3) was reduced by the IDO inhibitor methyl-thiohydantoin-tryptophan. It became also manifest when DC/T-cell cocultures were initiated with naive (CD4+CD25−CD45RA+) T cells, indicating the differentiation of adaptive regulatory T cells. Together, these findings suggest that IFN-γ triggered IDO competence in human mDCs constitutes a critical factor for endowing allogeneic T cells with regulatory activity.
The Odorant Binding Protein Gene Family from the Genome of Silkworm, Bombyx mori
Authors: Gong Da-Ping , Zhang Hui-Jie , Zhao Ping , Xia Qing-You , Xiang Zhong-Huai
Published: July 2009

Background

Chemosensory systems play key roles in the survival and reproductive success of insects. Insect chemoreception is mediated by two large and diverse gene superfamilies, chemoreceptors and odorant binding proteins (OBPs). OBPs are believed to transport hydrophobic odorants from the environment to the olfactory receptors.

Results

We identified a family of OBP-like genes in the silkworm genome and characterized their expression using oligonucleotide microarrays. A total of forty-four OBP genes were annotated, a number comparable to the 57 OBPs known fromAnopheles gambiaeand 51 fromDrosophila melanogaster. As seen in other fully sequenced insect genomes, most silkworm OBP genes are present in large clusters. We defined six subfamilies of OBPs, each of which shows lineage-specific expansion and diversification. EST data and OBP expression profiles from multiple larvae tissues of day three fifth instars demonstrated that many OBPs are expressed in chemosensory-specific tissues although some OBPs are expressed ubiquitously and others exclusively in non-chemosensory tissues. Some atypical OBPs are expressed throughout development. These results reveal that, although many OBPs are chemosensory-specific, others may have more general physiological roles.

Conclusion

Silkworms possess a number of OBPs genes similar to other insects. Their expression profiles suggest that many OBPs may be involved in olfaction and gustation as well as general carriers of hydrophobic molecules. The expansion of OBP gene subfamilies and sequence divergence indicate that the silkworm OBP family acquired functional diversity concurrently with functional constraints. Further investigation of the OBPs of the silkworm could give insights in the roles of OBPs in chemoreception.
DNA binding by Corynebacterium glutamicum TetR-type transcription regulator AmtR
Authors: Muhl Daniela , Jeßberger Nadja , Hasselt Kristin , Jardin Christophe , Sticht Heinrich , Burkovski Andreas
Published: July 2009

Background

The TetR family member AmtR is the central regulator of nitrogen starvation response in Corynebacterium glutamicum. While the AmtR regulon was physiologically characterized in great detail up to now, mechanistic questions of AmtR binding were not addressed. This study presents a characterization of functionally important amino acids in the DNA binding domain of AmtR and of crucial nucleotides in the AmtR recognition motif.

Results

Site-directed mutagenesis, the characterization of corresponding mutant proteins by gel retardation assays and surface plasmon resonance and molecular modelling revealed several amino acids, which are directly involved in DNA binding, while others have more structural function. Furthermore, we could show that the spacing of the binding motif half sites is crucial for repression of transcription by AmtR.

Conclusion

Although the DNA binding domain of TetR-type repressors is highly conserved and a core binding motif was identified for AmtR and TetR(D), the AmtR binding domain shows individual properties compared to other TetR proteins. Besides by distinct amino acids of AmtR, DNA binding is influenced by nucleotides not only of the conserved binding motif but also by spacing nucleotides in C. glutamicum.
Inappropriate medication use and risk of falls – A prospective study in a large community-dwelling elderly cohort
Authors: Berdot Sarah , Bertrand Marion , Dartigues Jean-François , Fourrier Annie , Tavernier Béatrice , Ritchie Karen , Alpérovitch Annick
Published: July 2009

Background

Explicit criteria for determining potentially inappropriate medication consumption in elderly were elaborated by Beers et al. These lists have been used worldwide to evaluate medical prescriptions but there is little epidemiologic evidence demonstrating negative consequences of inappropriate medication use. It has been reported that some drugs could increase the risk of falls, which are a frequent and serious problem in elderly population. We aimed to evaluate the association between the use of potentially inappropriate medications and the risk of falls.

Methods

The 3C Study is a multicentre prospective cohort study conducted in France with 4 years of follow-up. Non-institutionalized men and women aged 65 years or over (N = 6343) were randomly selected from electoral rolls. Data on socio-demographic, medical characteristics and medication use (based on self-reports and data from the national healthcare insurance) were collected. Use of inappropriate medication for elderly was defined from established criteria. Data about falls were collected at the two follow-up examinations (2 years and 4 years after baseline). The association between the exposure to inappropriate medications and the risk of falls was evaluated using multivariate models (Cox model and logistic regression).

Results

32% of subjects reported inappropriate medication use at baseline and 29% at least two of the three examinations; 22% had fallen 2 times or more during follow-up. Overall, inappropriate medication users had an increased risk of falling. This increase was mainly due to the use of long-acting benzodiazepines (adjusted odds ratio (OR) = 1.4, 95% confidence interval: [1.1–1.8], in both occasional and regular users), other inappropriate psychotropics (adjusted OR = 1.7 [1.7–2.7] in regular users), or medication with anticholinergic properties (adjusted OR = 1.6 [1.2–2.1] in regular users). Neither occasional, nor regular use of short- or intermediate-acting benzodiazepines was associated with an increased risk of falling. Further analysis in long-acting benzodiazepines users did not show any dose-effect relation between the number of prescriptions filled over a 3-year period and the risk of falling.

Conclusion

Our study showed that use of inappropriate medications was associated with an increased risk of falling in elderly persons. This increase was mainly due to long-acting benzodiazepines and other inappropriate psychotropics, and to medications with anticholinergic properties.
DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists
Authors: Navarro-Sarabia Federico , Ruiz-Montesinos Dolores , Hernandez Blanca , Navarro-Compán Victoria , Marsal Sara , Barcelo Mireia , Perez-Pampín Eva , Gómez-Reino Juan J
Published: July 2009

Introduction

No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one.

Methods

This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005. A database was created at the participating centres, with well-defined operational instructions. The main outcome variables were analyzed using parametric or non-parametric tests depending on the level of measurement and distribution of each variable.

Results

Mean (± SD) DAS-28 on starting the first, second and third TNF antagonist was 5.9 (± 2.0), 5.1 (± 1.5) and 6.1 (± 1.1). At the end of follow-up, it decreased to 3.3 (± 1.6; Δ = -2.6; p > 0.0001), 4.2 (± 1.5; Δ = -1.1; p = 0.0001) and 5.4 (± 1.7; Δ = -0.7; p = 0.06). For the first TNF antagonist, DAS-28-based EULAR response level was good in 42% and moderate in 33% of patients. The second TNF antagonist yielded a good response in 20% and no response in 53% of patients, while the third one yielded a good response in 28% and no response in 72%. Mean baseline HAQ on starting the first, second and third TNF antagonist was 1.61, 1.52 and 1.87, respectively. At the end of follow-up, it decreased to 1.12 (Δ = -0.49; p < 0.0001), 1.31 (Δ = -0.21, p = 0.004) and 1.75 (Δ = -0.12; p = 0.1), respectively. Sixty four percent of patients had a clinically important improvement in HAQ (defined as ≥ -0.22) with the first TNF antagonist and 46% with the second.

Conclusion

A clinically significant effect size was seen in less than half of RA patients cycling to a second TNF antagonist.
Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial
Authors: Ballard Kevin D , Bruno Richard S , Seip Richard L , Quann Erin E , Volk Brittanie M , Freidenreich Daniel J , Kawiecki Diana M , Kupchak Brian R , Chung Min-Yu , Kraemer William J , Volek Jeff S
Published: July 2009

Background

Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47) increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans.

Methods

A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10) and women (n = 10) (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2) participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47) or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD) and venous occlusion strain gauge plethysmography.

Results

Baseline peak FMD was not different for Placebo (7.7%) and NOP-47 (7.8%). Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively) whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P < 0.0001 for time × trial interaction). Baseline reactive hyperemia forearm blood flow was not different for placebo (27.2 ± 7.2%/min) and NOP-47 (27.3 ± 7.6%/min). Hyperemia blood flow measured 120 min post-ingestion (27.2 ± 7.8%/min) was unaffected by placebo whereas NOP-47 significantly increased hyperemia compared to baseline (29.9 ± 7.8%/min; P = 0.008 for time × trial interaction). Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25%) compared to NOP-47 (-18%).

Conclusion

These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.
Ovarian steroids regulate tachykinin and tachykinin receptor gene expression in the mouse uterus
Authors: Pinto Francisco M , Pintado C Oscar , Pennefather Jocelyn N , Patak Eva , Candenas Luz
Published: July 2009

Background

In the mouse uterus, pregnancy is accompanied by changes in tachykinin and tachykinin receptor gene expression and in the uterotonic effects of endogenous tachykinins. In this study we have investigated whether changes in tachykinin expression and responses are a result of changes in ovarian steroid levels.

Methods

We quantified the mRNAs of tachykinins and tachykinin receptors in uteri from ovariectomized mice and studied their regulation in response to estrogen and progesterone using real-time quantitative RT-PCR. Early (3 h) and late (24 h) responses to estrogen were evaluated and the participation of the estrogen receptors (ER), ERalpha and ERbeta, was analyzed by treating mice with propylpyrazole triol, a selective ERalpha agonist, or diarylpropionitrile, a selective agonist of ERbeta.

Results

All genes encoding tachykinins (Tac1, Tac2 and Tac4) and tachykinin receptors (Tacr1, Tacr2 and Tacr3) were expressed in uteri from ovariectomized mice. Estrogen increased Tac1 and Tacr1 mRNA after 3 h and decreased Tac1 and Tac4 expression after 24 h. Tac2 and Tacr3 mRNA levels were decreased by estrogen at both 3 and 24 h. Most effects of estrogen were also observed in animals treated with propylpyrazole triol. Progesterone treatment increased the levels of Tac2.

Conclusion

These results show that the expression of tachykinins and their receptors in the mouse uterus is tightly and differentially regulated by ovarian steroids. Estrogen effects are mainly mediated by ERalpha supporting an essential role for this estrogen receptor in the regulation of the tachykinergic system in the mouse uterus.
Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes
Authors: Hui Jerome HL , Raible Florian , Korchagina Natalia , Dray Nicolas , Samain Sylvie , Magdelenat Ghislaine , Jubin Claire , Segurens Béatrice , Balavoine Guillaume , Arendt Detlev , Ferrier David EK
Published: July 2009

Background

The ParaHox gene cluster is the evolutionary sister to the Hox cluster. Whilst the role of the Hox cluster in patterning the anterior-posterior axis of bilaterian animals is well established, and the organisation of vertebrate Hox clusters is intimately linked to gene regulation, much less is known about the more recently discovered ParaHox cluster. ParaHox gene clustering, and its relationship to expression, has only been described in deuterostomes. Conventional protostome models (Drosophila melanogaster and Caenorhabditis elegans) are secondarily derived with respect to ParaHox genes, suffering gene loss and cluster break-up.

Results

We provide the first evidence for ParaHox gene clustering from a less-derived protostome animal, the annelid Platynereis dumerilii. Clustering of these genes is thus not a sole preserve of the deuterostome lineage within Bilateria. This protostome ParaHox cluster is not entirely intact however, with Pdu-Cdx being on the opposite end of the same chromosome arm from Pdu-Gsx and Pdu-Xlox. From the genomic sequence around the P. dumerilii ParaHox genes the neighbouring genes are identified, compared with other taxa, and the ancestral arrangement deduced.

Conclusion

We relate the organisation of the ParaHox genes to their expression, and from comparisons with other taxa hypothesise that a relatively complex pattern of ParaHox gene expression existed in the protostome-deuterostome ancestor, which was secondarily simplified along several invertebrate lineages. Detailed comparisons of the gene content around the ParaHox genes enables the reconstruction of the genome surrounding the ParaHox cluster of the protostome-deuterostome ancestor, which existed over 550 million years ago.
Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-α, Oncostatin M and response to biologic therapies
Authors: Moran Ellen M , Mullan Ronan , McCormick Jennifer , Connolly Mary , Sullivan Owen , FitzGerald Oliver , Bresnihan Barry , Veale Douglas J , Fearon Ursula
Published: July 2009

Introduction

The aim of this study was to examine IL-17A in patients, following anti-TNF-α therapy and the effect of IL-17A on matrix turnover and cartilage degradation.

Methods

IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +/- TNF-α and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP/TIMP were assessed in patients pre/post biologic therapy.

Results

IL-17A levels were higher in RA vs osteoarthritis (OA)/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-α and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-α or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1/TIMP4, MMP3/TIMP1 and MMP3/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients.

Conclusions

IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.
Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions
Authors: MacArthur Stewart , Li Xiao-Yong , Li Jingyi , Brown James B , Chu Hou Cheng , Zeng Lucy , Grondona Brandi P , Hechmer Aaron , Simirenko Lisa , Keränen Soile VE , Knowles David W , Stapleton Mark , Bickel Peter , Biggin Mark D , Eisen Michael B
Published: July 2009

Background

We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional.

Results

Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of function and binding to thousands of genomic regions in vivo. Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis-regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors.

Conclusions

It is likely that the overlap in binding of biochemically and functionally unrelated transcription factors arises from the high concentrations of these proteins in nuclei, which, coupled with their broad DNA binding specificities, directs them to regions of open chromatin. We suggest that most animal transcription factors will be found to show a similar broad overlapping pattern of binding in vivo, with specificity achieved by modulating the amount, rather than the identity, of bound factor.
The effects of adding carbon nanotubes to the mechanical and tribological properties of a carbon fibre reinforced polyether ether ketone composite
Authors: Li J , Zhang L Q
Published: July 2009

The main objective of this article is to develop a high wear resistance carbon fibre (CF)-reinforced polyether ether ketone composite with the addition of multi-wall carbon nano-tubes (MWCNT). These compounds were well mixed in a Haake batch mixer and compounded polymers were fabricated into sheets of known thickness by compression moulding. Samples were tested for wear resistance with respect to different concentrations of fillers. Wear resistance of a composite with 20 wt% of CF increases when MWCNT was introduced. The worn surface features have been examined using a scanning electron microscope (SEM). Photomicrographs of the worn surfaces revealed higher wear resistance with the addition of carbon nanotubes. Also better interfacial adhesion between carbon and vinyl ester in a carbon-reinforced vinyl ester composite was observed.
First and second law analysis of a Stirling engine with imperfect regeneration and dead volume
Authors: Harrod J , Mago P J , Srinivasan K , Chamra L M
Published: July 2009

This article discusses the thermodynamic performance of an ideal Stirling cycle engine. This investigation uses the first law of thermodynamics to obtain trends of total heat addition, net work output, and thermal efficiency with varying dead volume percentage and regenerator effectiveness. Second law analysis is used to obtain trends for the total entropy generation of the cycle. In addition, the entropy generation of each component contributing to the Stirling cycle processes is considered. In particular, parametric studies of dead volume effects and regenerator effectiveness on Stirling engine performance are investigated. Finally, the thermodynamic availability of the system is assessed to determine theoretical second law efficiencies based on the useful exergy output of the cycle. Results indicate that a Stirling engine has high net work output and thermal efficiency for low dead volume percentages and high regenerator effectiveness. For example, compared to an engine with zero dead volume and perfect regeneration, an engine with 40 per cent dead volume and a regenerator effectiveness of 0.8 is shown to have ∼60 per cent less net work output and a 70 per cent smaller thermal efficiency. Additionally, this engine results in approximately nine times greater overall entropy generation and 55 per cent smaller second law efficiency.
An experimental study of leaning blades on the half-cone rotor of a squirrel cage fan
Authors: Nikkhoo M , Montazerin N , Damangir A , Samian R S
Published: July 2009

This article presents an improvement for the blade configuration of a squirrel cage fan. Numerical simulations have shown that a-2° lean angle applied to a half-cone rotor of+10° produces a higher efficiency. This is expected to be a result of blade alignment with the inlet stream. Performance curves in this article compare this new rotor with both a simple half cone of the same cone angle and a corresponding cylindrical rotor. The half-cone rotor with leaning blades had improved head coefficient and efficiency in the normal operating range, which is to the right of maximum head or efficiency points. The simple half-cone rotor had almost constant efficiency for all flow ranges, which is a very demanding feature for any fan. A study of velocity profiles inside the volute showed that maximum flow exited the rotor close to the cut-off. A leaning blade had negligible effect on radial and tangential components at this location but it changed the axial component. This was due to a movement of the vortex behind the inlet and a larger active region of the rotor blades.
Footprinting analysis of BWYV pseudoknot–ribosome complexes
Authors: Mazauric Marie-Hélène , Leroy Jean-Louis , Visscher Koen , Yoshizawa Satoko , Fourmy Dominique
Published: July 2009

Many viruses regulate translation of polycistronic mRNA using a −1 ribosomal frameshift induced by an RNA pseudoknot. When the ribosome encounters the pseudoknot barrier that resists unraveling, transient mRNA–tRNA dissociation at the decoding site, results in a shift of the reading frame. The eukaryotic frameshifting pseudoknot from the beet western yellow virus (BWYV) has been well characterized, both structurally and functionally. Here, we show that in order to obtain eukaryotic levels of frameshifting efficiencies using prokaryotic Escherichia coli ribosomes, which depend upon the structural integrity of the BWYV pseudoknot, it is necessary to shorten the mRNA spacer between the slippery sequence and the pseudoknot by 1 or 2 nucleotides (nt). Shortening of the spacer is likely to re-establish tension and/or ribosomal contacts that were otherwise lost with the smaller E. coli ribosomes. Chemical probing experiments for frameshifting and nonframeshifting BWYV constructs were performed to investigate the structural integrity of the pseudoknot confined locally at the mRNA entry site. These data, obtained in the pretranslocation state, show a compact overall pseudoknot structure, with changes in the conformation of nucleotides (i.e., increase in reactivity to chemical probes) that are first “hit” by the ribosomal helicase center. Interestingly, with the 1-nt shortened spacer, this increase of reactivity extends to a downstream nucleotide in the first base pair (bp) of stem 1, consistent with melting of this base pair. Thus, the 3 bp that will unfold upon translocation are different in both constructs with likely consequences on unfolding kinetics.
Tail Decay Rates in Double QBD Processes and Related Reflected Random Walks
Authors: Miyazawa Masakiyo
Published: July 2009

A double quasi-birth-and-death (QBD) process is the QBD process whose background process is a homogeneous birth-and-death process, which is a synonym of a skip-free random walk in the two-dimensional positive quadrant with homogeneous reflecting transitions at each boundary face. It is also a special case of a 0-partially homogenous chain introduced by Borovkov and Mogul'skii. Our main interest is in the tail decay behavior of the stationary distribution of the double QBD process in the coordinate directions and that of its marginal distributions. In particular, our problem is to get their rough and exact asymptotics from primitive modeling data. We first solve this problem using the matrix analytic method. We then revisit the problem for the 0-partially homogenous chain, refining existing results. We exemplify the decay rates for Jackson networks and their modifications.
Anglo-American anti-modernism: a transnational reading
Authors: Webb Andrew
Published: July 2009

This article identifies a revisionist critical tradition that argues for the existence of an indigenous English poetic line which, allied to a formally conservative poetry in the United States, forms an Anglo-American anti-modernist front. Central to this critical approach is the figure of Edward Thomas, whose work appears to demonstrate the continuity of traditional poetic form in the face of the historical cataclysm of World War One and the formal challenges of modernism, and whose literary relation with Robert Frost appears to exemplify an Anglo-American partnership in opposition to the modernist pairing of Ezra Pound and T.S. Eliot. By subjecting Thomas's work to a transnational analysis, this article reveals the ideologies which underlie this critical approach. It contends instead that Thomas should be read as a Welsh writer who opens English literature to modernist influences, and promotes writers from Ireland and the United States who are interested in re-appropriating the English language on behalf of their culturally dominated nations. As a case history in transnational modernism, this article thereby exposes the limitations of the Anglo-American anti-modernist critical tradition, showing in particular how, in anglicizing Britain and attempting to make anglophile American culture pre-eminent within the United States, it misses the literary significance of other national relations.
Fatigue Crack Growth Rates in Pipeline Steels Using Curved M(T) Specimens
Authors: Darcis Ph. P. , Treinen J. M. , McColskey J. D.
Published: July 2009

This study presents fatigue data for two different ferrite-pearlite pipeline steels. A fatigue crack growth test for full-thickness curved pipeline samples was developed using a middle tension (M(T)) specimen. Also, finite element analyses (FEAs) were carried out to show the M(T) curvature effects on the fatigue crack growth results. The two steels showed similar fatigue crack growth rate (da/dN) behavior. However, the ferrite-pearlite steel without banding had slightly better fatigue properties than the ferrite-pearlite banded steel. Uncertainty in the fatigue crack growth rates was analyzed by attributing all the fatigue scatter to the Paris law parameter C. The FEA based simulations, based on curved geometries, of the compliance relationship more accurately predicted both fatigue crack growth data and true crack lengths. Nevertheless, the ASTM E647-05 compliance relationship accurately predicted the crack length for the M(T) geometry, although its use leads to slightly conservative fatigue crack growth trends and a slight overestimation of the true final crack length.
Application of Computed Tomography in Manufacturing MetrologyAnwendung der Computer-Tomographie in der Fertigungsmesstechnik
Authors: Weckenmann Albert , Krämer Philipp
Published: July 2009

Since the development of X-ray Computed Tomography (CT) and its rapid acceptance in medical diagnostics, it became not only a powerful tool for non-destructive testing but was also adopted in manufacturing metrology in the last decade. CT offers new possibilities for coordinate measurements as it is possible to acquire a volumetric model of the entire workpiece with a single measurement at which analyses known from coordinate metrology such as estimation of geometric features or nominal/actual value comparisons can be performed. But with data sets generated by tomographic measurements it is as well possible to analyze the entire volume of the workpiece, so detection and analysis of conventionally not accessible features like defects (flaws, blow holes, bubbles) or wall thickness analyses with uncertainties in the micrometer range are possible.
High Speed 3-D Surface Profilometry using HSI Color Model and Trapezoidal Phase-Shifting MethodHochgeschwindigkeits-3D-Oberflächenprofilometrie mit HSI-Farbmodell und Trapez-Phasenverschiebungsmethode
Authors: Chen Liang-Chia , Nguyen Xuan-Loc , Shu Yao-Sheng
Published: July 2009

To achieve high-speed profilometry and avoid in-field vibration disturbances, high-speed 3-D surface profilometry using an innovative HSI color model and trapezoidal phase-shifting method has been developed to detect the morphology of measured objects at a high speed. By employing novel phase-shifting trapezoidal color fringe patterns, the method can reconstruct precise 3-D surface models by single one-shot image. Some industrial measurements were conducted to confirm that the measurement accuracy reached to 2.5% of the overall measurement range and the repeatability of 3.0% within ±3σ was achieved.
Process-Integrated Measurement of Aspherical SurfacesProzessintegrierte Vermessung asphärischer Oberflächen
Authors: Garbusi Eugenio , Pruss Christof , Osten Wolfgang
Published: July 2009

Aspheric lenses have become a synonym for high-performance optics. With an aspherical surface it is possible to correct a great number of aberrations in an optical system that otherwise would require a combination of several spherical ones. However the production of aspherical elements is substantially more complex as in the case of spherical ones because they require different production and measurement procedures. A flexible solution to the aspheric metrology problem without the use of additional compensation optics is presented.
Alguns hospedeiros reais de ectoparasitos do município de Caratinga, Minas Gerais, Brasil
Authors: Botelho José Ramiro , Linardi Pedro Marcos , Williams Paul , Nagem Ronaldo Luiz
Published: July 2009

Os autores determinaram os hospedeiros reais para seis espécies de ectoparasitos na região de Caratinga, Minas Gerais, sendo quatro espécies de ácaros e duas de pulgas, utilizando-se do índice de infestação e do coeficiente de associação interespecífico hospedeiro/ parasito.
New field observations on the competitive displacement between two species of planorbid snails inhabiting Northeastern Brasil
Authors: Barbosa F. S. , Costa D. P. Pereira da , Arruda F.
Published: July 2009

Observations reported in the present paper have shown that Biomphalaria glabrata is being gradually displaced by B. straminea in coastal areas of two counties on the state of Pernambuco, Brazil, confirming former observations made in the same region.
Leishmanioses tegumentares: aspectos clínicos e imunopatológicos
Authors: Grimaldi Júnior Gabriel
Published: July 2009

Foi visto nesta revisão que os parasitas do gênero Leishmania induzem uma variedade de respostas complexas nos hospedeiros vertebrados, efetuadas e/ou moduladas pelo seu sistema imunológico. Foi também salientado que o destino da Leishmania no interior de macrófagos depende de relações particulares parasito-hospedeiro, envolvendo não apenas as propriedades intrísecas do parasita, mas também as características, geneticamente determinadas, da cédula hospedeira ou das suas interações com outras células imunocompetentes. Atráves de uma revisão das evidências consubstanciando essesconceitos, os mesmos foram aplicados na descrição do espectro clínico e imunopatológico da doença humana, particularmente das leishmanioses cutâneas e mucocutâneas do Novo e do Velho Mundo. Finalmente, baseando-se nos resultados obtidos em modelos experimentais de leishmaniose cutânea, os quais reproduzem os achados das formas resolutiva e persistentes da doença humana, o autor apresenta uma análise esquemática da evolução das características histopatológicas das lesões leishmanióticas.
Notes on Amazonian Bittacidae (Mecoptera) with the descriptions of two new species
Authors: Penny Norman D. , Arias Jorge R.
Published: July 2009

New species of Issikiella and Nannobittacus are described and notes are presented on other Amazonian species of Mecoptera.
Immunogenetic and protective activity of an extract of Schistosoma mansoni
Authors: Tendler M. , Lima A. Oliveira , Pinto R. Magalhães , Cruz M. Queiroz , Brascher H. M. , Katz N.
Published: July 2009

The immunogenic and protective activity of an extract of S. mansoni, obtained by incubation of viable adult worms in buffered saline, was evaluated in rabbits and mice. Animal immunization with this extract resulted in the development of both humoral and cellular immune response. All immunized rabbits developed high levels (91 to 100%) of cytotoxic antibodies as determined by in vitro assays of cytotoxic activity of their sera against viable schistosomules. Immunized animals challenged with S. mansoni cercariae showed a lower parasite load than that of normal controls. Protective activity was 88.6% and 54.0% in immunized rabbits and mice, respectively.