bluuebunny/crossref_metadata_2025_split huggingface dataset:
The IKK-neutralizing compound Bay11 kills supereffector CD8 T cells by altering caspase-dependent activation-induced cell death
Authors: Lee Seung-Joo , Long Meixiao , Adler Adam J , Mittler Robert S , Vella Anthony T 
Published: October 2008

AbstractAntigen with dual costimulation through CD137 and CD134 induces powerful CD8 T cell responses. These effector T cells are endowed with an intrinsic survival program resulting in their accumulation in vivo, but the signaling components required for survival are unknown. We tested a cadre of pathway inhibitors and found one preclinical compound, Bay11-7082 (Bay11), which prevented survival. Even the γc cytokine family members IL-2, -4, -7, and -15 could not block death, nor could pretreatment with IL-7. We found that dual costimulation caused loading of phosphorylated IκBα (p-IκBα) and high basal levels of NF-κB activity in the effector CD8 T cells. Bay11 trumped both events by reducing the presence of p-IκBα and ensuing NF-κB activity. Not all pathways were impacted to this degree, however, as mitogen-mediated ERK phosphorylation was evident during NF-κB inhibition. Nonetheless, Bay11 blocked TCR-stimulated cytokine synthesis by rapidly accentuating activation-induced cell death through elicitation of a caspase-independent pathway. Thus, in effector CD8 T cells, Bay11 forces a dominant caspase-independent death signal that cannot be overcome by an intrinsic survival program nor by survival-inducing cytokines. Therefore, Bay11 may be a useful tool to deliberately kill death-resistant effector T cells for therapeutic benefit.
Sensitization by intratracheally injected dendritic cells is independent of antigen presentation by host antigen-presenting cells
Authors: Kuipers Harmjan , Soullié Thomas , Hammad Hamida , Willart Monique , Kool Mirjam , Hijdra Daniëlle , Hoogsteden Henk C , Lambrecht Bart N 
Published: October 2008

AbstractAdoptive transfer of antigen-pulsed dendritic cells (DC) in the airways of mice has been used as a model system for eosinophilic airway inflammation, which allows studying the DC-specific contribution of genes of interest or reagents to induced inflammation by genetically modifying DC or exposure of DC to compounds prior to injection in the airways. Antigen transfer and CD4+ T cell priming by endogenous antigen-presenting cells (APCs) may interfere with the correct interpretation of the data obtained in this model, however. We therefore examined antigen transfer and indirect CD4+ T cell priming by host APCs in this model system. Transfer of antigen between injected DC and host cells appeared to be minimal but could not be totally excluded. However, only direct antigen presentation by injected DC resulted in robust CD4+ T cell priming and eosinophilic airway inflammation. Thus, this adoptive transfer model is well suited to study the role of DC in eosinophilic airway inflammation.
Characterization of heat-up diesel oxidation catalysts through gas flow reactor and in-situ engine testing
Authors: Han M , Assanis D , Bohac S 
Published: October 2008

This study characterizes the performance of several diesel oxidation catalyst (DOC) formulations with respect to their ability to heat up engine exhaust for the purpose of regenerating a diesel particulate filter or desulphating a lean nitrogen oxide (NO x) trap. Platinum (Pt), platinum—palladium (Pt—Pd), and platinum—palladium+cerium oxide (Pt—Pd+CeO2) are characterized using gas flow reactor experiments and in-situ engine tests. The feed gas from conventional diesel combustion and the feed gas from low-temperature premixed charge compression ignition (PCI) combustion are compared. An in-cylinder post-injection strategy is used to add the chemical energy needed to support DOC exothermic reactions, and the effect of post-injection timing is studied. The effects of carbon monoxide (CO), hydrocarbon (HC), and oxygen (O2) partial pressures on light-off characteristics are also investigated. Reactor tests show that Pt—Pd exhibits the lowest light-off temperature, followed by Pt—Pd+CeO2 and then Pt, regardless of mixture composition and O2 concentration. In-situ engine tests demonstrate that PCI is superior to conventional combustion in increasing the exhaust gas temperature at the same post-fuel-injection quantity, but only if the exhaust gas temperature is high enough to oxidize HCs and CO in lieu of sufficient O2. However, PCI produces significant particulate matter (PM) as post-injection timing is retarded. To avoid an increase in PM emission, an alternative method to introduce fuel should be considered.
Effect of fuel properties on diesel spray development in extreme cold conditions
Authors: Payri R , Salvador F J , Gimeno J , Bracho G 
Published: October 2008

This paper presents an experimental and theoretical study with the purpose of quantifying and predicting the influence of fuel properties in extreme cold conditions on macroscopic diesel spray behaviour. The parameters studied were the fuel density and viscosity at different temperatures. Previous correlations available in the literature were analysed and extended in order to introduce the viscous term. A specific test rig that simulates the real engine in-cylinder air pressure and density was used. The fuel was injected from a convergent nozzle with eight holes at two injection pressures of 30MPa and 120MPa, two chamber densities of 23kg/m3 and 56kg/m3, and two temperatures of 255K (winter) and 298K (reference). In order to achieve cold conditions, the facility was introduced into a specialized climatic room with optical access, where the temperature and humidity were carefully controlled. The experimental results enabled the theoretical analysis that related the viscosity effect with the spray-tip penetration to be validated, obtaining high accuracy. The main conclusion of the paper is that fuel properties change significantly with the temperature in cold conditions, which affects the spray development, producing a shorter penetration in the transition stage. This phenomenon can be explained by a decrease in the fluid discharge coefficient in the outlet section of the hole as a result of the change in the fluid properties with the temperature.
Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants
Authors: Khalid J M , Oerton J , Cortina-Borja M , Andresen B S , Besley G , Dalton R N , Downing M , Green A , Henderson M , Leonard J , Dezateux C 
Published: October 2008

Objectives It has been suggested that homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disease of White ethnic origin but little is known regarding its ethnic distribution. We estimated ethnic-specific homozygous c.985A>G MCADD birth prevalence from a large-scale UK newborn screening study. Methods Homozygous c.985A>G MCADD cases were ascertained in six English newborn screening centres between 1 March 2004 and 28 February 2007 by screening approximately 1.1 million newborns using tandem mass spectrometry analysis of underivatised blood spot samples to quantitate octanoylcarnitine (C8). Follow-up biochemistry and mutation analyses for cases (mean triplicate C8 value ≥0.5 µmol/L) were reviewed to confirm diagnosis. Ethnicity was ascertained from clinician report and denominators from 2001 UK Census estimates of ethnic group of children less than one year. Results Sixty-four infants were c.985A>G MCADD homozygotes (overall prevalence 5.8 per 100,000 live births; 95% CI 4.4–7.2). Sixty (93%) were White, two (3%) were mixed/other and two were of unknown ethnic origin. No Asian or Black homozygotes were identified. Proportions of White, mixed/other, Asian and Black births in screening regions were estimated, yielding homozygous c.985A>G MCADD birth prevalence of 6.9 per 100,000 (95% CI 5.2–8.8) in White, and 95% CI estimates of 0–2.7 per 100,000 in Asian and 0–5.8 in Black populations. The c.985A>G carrier frequency in the White group was estimated at one in 65 (95% CI 1/74, 1/61) under Hardy–Weinberg conditions. Conclusion c.985A>G homozygous MCADD is not found in Black and Asian ethnic groups that have been screened at birth in England. This is consistent with the earlier published observations suggesting that MCADD due to the c.985A>G mutation is a disease of White ethnic origin.
Emerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer
Authors: Sardana Girish , Dowell Barry , Diamandis Eleftherios P 
Published: October 2008

Abstract
Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP.
Content: PSA is produced almost exclusively in the prostate, and abnormalities of this organ are frequently associated with increased serum concentrations. Because of PSA’s lack of specificity for CaP, however, many patients undergo unnecessary biopsies or treatments for benign or latent tumors, respectively. Thus, a more specific method of CaP detection is required to augment or replace screening with PSA. The focus recently has been on creating cost-effective assays for circulating protein biomarkers in the blood, but because of the heterogeneity of CaP, it has become clear that this effort will be a formidable challenge. Each marker will require proper validation to ensure clinical utility. Although much work has been done on variations of the PSA test (i.e., velocity, density, free vs bound, proisoforms) with limited usefulness, there are many emerging markers at various stages of development that show some promise for CaP diagnosis. These markers include kallikrein-related peptidase 2 (KLK2), early prostate cancer antigen (EPCA), PCA3, hepsin, prostate stem cell antigen, and α-methylacyl-CoA racemase (AMACR). We review biomarkers under investigation for the early diagnosis and management of prostate cancer.
Summary: It is hoped that the use of panels of markers can improve CaP diagnosis and prognosis and help predict the therapeutic response in CaP patients.
Tandem Mass Spectrometry for the Direct Assay of Lysosomal Enzymes in Dried Blood Spots: Application to Screening Newborns for Mucopolysaccharidosis I
Authors: Blanchard Sophie , Sadilek Martin , Scott C Ronald , Turecek Frantisek , Gelb Michael H 
Published: October 2008

Abstract
Background: Treatments now available for mucopolysaccharidosis I require early detection for optimum therapy. Therefore, we have developed an assay appropriate for newborn screening of the activity of the relevant enzyme, α-L-iduronidase.
Methods: We synthesized a new α-L-iduronidase substrate that can be used to assay the enzyme by use of tandem mass spectrometry together with an internal standard or by fluorometry. The assay uses a dried blood spot on a newborn screening card as the enzyme source. The assay protocol uses a simple liquid-liquid extraction step before mass spectrometry. We optimized enzyme reaction conditions and procedures for the assay, including the concentration of substrate, the reaction pH, the incubation time, and mass spectrometer operation. We also assessed inter- and intraassay imprecision.
Results: When the assay was tested on dried blood spots, the α-L-iduronidase activity measured for 5 patients with mucopolysaccharidosis I was well below the interval found for 10 randomly chosen newborns. Inter- and intraassay imprecision were &lt;10%. The synthesis of the α-L-iduronidase substrate is practical for use on a scale needed to support newborn screening demands.
Conclusions: This newly developed tandem mass spectrometry assay has the potential to be adopted for newborn screening of mucopolysaccharidosis I. This assay has advantages over a previously reported assay also developed in this laboratory and has the potential to be performed in a multiplex fashion to measure several lysosomal enzymes relevant to treatable lysosomal storage diseases.
A closer look at listening: interdisciplinarity and the varieties of languages employed in the conveyance of problem and solution
Authors: Chessin Laura , Garfin Gregg 
Published: October 2008

This paper explores the possibilities for incorporating into higher education graphic design pedagogy a more interdisciplinary and collaborative approach to all phases of problem solving, from project identification and framing to concept development and evaluation. In this paper, interdisciplinary
is explored from two approaches: a theoretical/methodological framework, and an applied case study. The theoretical foundation of this paper draws upon the progressive (and some would call, revolutionary) Reggio Emilia approach to early childhood education. More than just a tool for the classroom,
the RE Approach suggests to us a comprehensive view of education and community building that is truly interdisciplinary: incorporating current understandings about brain research and psychology with politics and philosophy.
The applied example provided is a case study of a charette presented
to graphic design students by a graphic designer and climatologist, providing students the opportunity to hear the languages of two very different disciplines: science and design. This paper provides a theoretical foundation for the framing, presentation and evaluation of a project based on
an interdisciplinary model, and concludes with both suggestions for further directions, and questions about limitations and possible conflicts.
Play Orbit: a play on the history of play
Authors: Punt Michael 
Published: October 2008

In 1969 Jasia Reichardt curated an exhibition at the Institute of Contemporary Art in London called Play Orbit. Although it has not achieved the landmark status of Reichardt's Cybernetic Serendipity, which was presented in London a year earlier, it caught the intellectual and artistic
mood of a newly emergent constituency of (largely British) artists who had benefited from a post-war revision of art education and a de-centring of intellectual energy away from the economic capitals.
It may be that Play Orbit will eventually be regarded in much the same way as Cybernetic
Serendipity that is, as a significant footnote in the history of contemporary art. By turning artists' attention to toys through this project, the categories of painting and sculpture dissolved and the Modernist imperative of the enduring observation that had informed the arts and letters
in a centred intellectual regime was seen for what it was: a colonial anachronism. The unapologetic relativism of play and the provisional truths of games coalesced in Play Orbit as confrontations to the essentialist materialism of the prevailing orthodoxy. In this sense Play Orbit, and its
extensive catalogue of images and essays, foreshadowed not only the critical style that followed the influence of Continental Theory in the mid 1970s but also anticipated the agenda of virtually all that has been written about games in the last decade. For all its apparent whimsy and reification
of idiosyncrasy, Play Orbit can now be seen as, above all, a constructively political intervention levered through the arts. For example, one of the more enduring and least contested impacts of the intellectual revisions of the last thirty years that Play Orbit foreshadowed is evident in the
practice of history not least the practice of history as a game to be played. This paper elaborates on these assertions and asks how games and games theory might be connected with their own political and intellectual history, and how contemporary artists who choose to benefit from the licence
that play endows might situate their work within what might be called Art Ludistory: a political play on the history of play.
Adaptive Differentiation of Quantitative Traits in the Globally Distributed Weed, Wild Radish (Raphanus raphanistrum)
Authors: Sahli Heather F , Conner Jeffrey K , Shaw Frank H , Howe Stephen , Lale Allison 
Published: October 2008

Abstract
Weedy species with wide geographical distributions may face strong selection to adapt to new environments, which can lead to adaptive genetic differentiation among populations. However, genetic drift, particularly due to founder effects, will also commonly result in differentiation in colonizing species. To test whether selection has contributed to trait divergence, we compared differentiation at eight microsatellite loci (measured as FST) to differentiation of quantitative floral and phenological traits (measured as QST) of wild radish (Raphanus raphanistrum) across populations from three continents. We sampled eight populations: seven naturalized populations and one from its native range. By comparing estimates of QST and FST, we found that petal size was the only floral trait that may have diverged more than expected due to drift alone, but inflorescence height, flowering time, and rosette formation have greatly diverged between the native and nonnative populations. Our results suggest the loss of a rosette and the evolution of early flowering time may have been the key adaptations enabling wild radish to become a major agricultural weed. Floral adaptation to different pollinators does not seem to have been as necessary for the success of wild radish in new environments.
Effects of Selection and Drift on G Matrix Evolution in a Heterogeneous Environment: A MultivariateQst–Fst Test With the Freshwater SnailGalba truncatula
Authors: Chapuis Elodie , Martin Guillaume , Goudet Jérôme 
Published: October 2008

AbstractUnraveling the effect of selection vs. drift on the evolution of quantitative traits is commonly achieved by one of two methods. Either one contrasts population differentiation estimates for genetic markers and quantitative traits (the Qst–Fst contrast) or multivariate methods are used to study the covariance between sets of traits. In particular, many studies have focused on the genetic variance–covariance matrix (the G matrix). However, both drift and selection can cause changes in G. To understand their joint effects, we recently combined the two methods into a single test (accompanying article by Martin et al.), which we apply here to a network of 16 natural populations of the freshwater snail Galba truncatula. Using this new neutrality test, extended to hierarchical population structures, we studied the multivariate equivalent of the Qst–Fst contrast for several life-history traits of G. truncatula. We found strong evidence of selection acting on multivariate phenotypes. Selection was homogeneous among populations within each habitat and heterogeneous between habitats. We found that the G matrices were relatively stable within each habitat, with proportionality between the among-populations (D) and the within-populations (G) covariance matrices. The effect of habitat heterogeneity is to break this proportionality because of selection for habitat-dependent optima. Individual-based simulations mimicking our empirical system confirmed that these patterns are expected under the selective regime inferred. We show that homogenizing selection can mimic some effect of drift on the G matrix (G and D almost proportional), but that incorporating information from molecular markers (multivariate Qst–Fst) allows disentangling the two effects.
Immediate Load and Esthetic Zone Considerations to Replace Maxillary Incisor Teeth Using a New Zirconia Implant Abutment in the Bone Grafted Anterior Maxilla
Authors: Lee Cameron Y. S. , Hasegawa Henry 
Published: October 2008

Abstract
The goal of this prospective clinical study is to evaluate a new all-ceramic implant abutment made from zirconium oxide during the immediate load of dental implants placed in the block grafted anterior maxilla. This new zirconia abutment gives the clinician the opportunity to provide the patient with an all-ceramic restorative system (abutment and crown) for an optimum esthetic result and a high level of patient satisfaction. A total of 9 hydroxyapatite-coated dental implants were surgically placed in 9 patients and were immediately loaded 5 to 7 days later with a custom composite provisional restoration that was placed out of functional occlusion. Each prefabricated, natural colored zirconia abutment was shaped and connected to the implant with a titanium screw. Provisional restorations were cemented to the zirconia abutment with the use of temporary cement. Twelve weeks later, the provisional restoration was replaced with an all-ceramic restoration. Over a 52-week observation period, no abutment fractures occurred, and no abutment screw loosening was observed. No implants failed. All 9 patients reported total satisfaction regarding esthetic quality of the all-ceramic restorative system (abutment and implant). Preliminary results of this clinical study indicate that this new zirconia abutment offers the clinician and the patient exceptional strength, optimal esthetics, and simplicity. It is of important clinical significance that use of this all-ceramic abutment eliminates the well-known disadvantages of metal abutments.
A path through the equivalence minefield
Authors: Eddy John W , Proctor Selene , Lambert Alice , Qureshi Sarah 
Published: October 2008

Entry to the General Medical Council specialist register via equivalence requires extensive evidence, based on specialty‐specific guidance.
Candidates who discuss their applications in advance with the Head of Specialist Registration at the RCOG have a higher chance of entering the register.
The curriculum vitae (CV) must be supported by validated documents.
Referees must take reasonable steps to verify information.

Learning objectives:

To understand the process of application to the Postgraduate Medical Education and Training Board.
To be aware of the evidence required.
To understand the pitfalls of writing a reference.

Ethical issues:

References should conform to the General Medical Council's good medical practice guidelines.
Patient data should not be included in the application.
Those signing off clinical practice or attendance at courses should have seen evidence of attendance or completion.

Please cite this article as: Eddy JW, Proctor S, Lambert A, Qureshi S. A path through the equivalence minefield. The Obstetrician & Gynaecologist 2008;10:257–262.