bluuebunny/crossref_metadata_2025 huggingface dataset:
What did John `see and believe' in the tomb? Countless Easter sermons and many Bible commentators may have got it wrong
Authors: Meacham William
Published: March 2009

This article examines the varying interpretations of John 20:6—9. There is a 1,600-year division of opinion on the subject, with eminent figures in church history on opposing sides of the issue. Simply put, the two interpretations are (1) the mundane, that the evangelist believed what the women had said (the body was removed); or (2) the miraculous, that he believed Christ had risen from the dead. In the last two centuries, opinion has shifted significantly away from the mundane interpretation, due in part to a misunderstanding or mistranslation of the terms used for burial cloths. The author argues that the mundane is more consistent with the wording, the style of the gospel, and the relevant passages in Luke.
Shifts in Beliefs about Second Language Learning
Authors: Riley Paul A.
Published: March 2009

■ This article is based on a study which investigated the beliefs about English language learning of 661 first-year university students and their 34 English teachers at a Japanese university. The focus of the article is the shifts in reported student beliefs over a nine-month period of English study between two administrations of the Sakui and Gaies (1999) beliefs survey instrument. Beliefs are usually considered as resilient constructs, self-perpetuating in nature. In this study, however, significant differences were found in student responses to almost a quarter of the items on the questionnaire. Two student discussion groups were also formed which provided further evidence of shifts in student beliefs about language learning during the nine-month period of English study.
On the contrastive analysis of features in second language acquisition: uninterpretable gender on past participles in English—French processing
Authors: Dekydtspotter Laurent , Renaud Claire
Published: March 2009

Lardiere's discussion raises important questions about the use of features in second language (L2) acquisition. This response examines predictions for processing of a feature-valuing model vs. a frequency-sensitive, associative model in explaining the acquisition of French past participle agreement. Results from a reading-time experiment support the feature-valuing model.
The kids are alright … aren't they?
Authors: Duffield Nigel
Published: March 2009

In this commentary three aspects of the feature-based model that Lardiere assumes are discussed: the value of formalization in the investigation of second language acquisition, the extent to which native speakers converge on the same grammatical representations, and the length of time it takes to establish a mature native grammar. These factors need to be given serious consideration if the investigation of second language acquisition is to be successful.
How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale
Authors: Johansen PØ , Krebs TS
Published: March 2009

Abstract

Exposure therapy is known to be an effective treatment for anxiety disorders. Nevertheless, exposure is not used as much as it should be, and instead patients are often given supportive medications such as serotonin reuptake inhibitors (SSRIs) and benzodiazepines, which may even interfere with the extinction learning that is the aim of treatment. Given that randomized controlled trials are now investigating a few doses of ±3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) in combination with psychotherapy for treatment-resistant anxiety disorders, we would like to suggest the following three mechanisms for this potentially important new approach: 1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations. Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy. Further clinical and preclinical studies of the therapeutic value of MDMA are indicated.
Training Volunteers to Run Information Technologies
Authors: Evans Susan H. , Clarke Peter
Published: March 2009

Nonprofits are incorporating information technologies (ITs) into direct client services. Organizations may hesitate, however, to assign volunteers to operate these systems, for a variety of reasons. This article reports an experiment testing the capacity of two types of volunteers—“traditionals” (experienced in social services) and “beneficiaries” (from the ranks of the nonprofit’s clientele)—to use an IT for client services at two food pantries. The IT, Quick! Help for Meals, generates customized recipes and food-use tips about fresh vegetables. Results showed that both types of volunteers learned to operate the IT successfully. Traditionals’ use of the IT proved as effective as paid staff’s use in encouraging clients to consume more fresh vegetables. Beneficiaries’ use of the IT was not as effective in changing clients’ food use, compared to paid staff. Results of this case study should encourage nonprofits to experiment with assigning volunteers to operate ITs linked to client services.
Organo-Soluble Low CTE Polyimides and their Applications to Photosensitive Cover Layer Materials in Flexible Printed Circuit Boards
Authors: Ishii Junichi , Akamatsu Tadashi
Published: March 2009

A novel cover layer material for flexible printed circuit (FPC) applications was developed in this work. A high molecular weight of polyimide composed of four monomers, pyromellitic dianhydride (PMDA), 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), 2,2'-bis(trifluoromethyl)benzidine (TFMB) and 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane (BisApAf) was prepared by the one-pot polycondensation in N-methyl-2-pyrrolidone (NMP) without precipitation and gelation. The polyimide (PI) was highly soluble in various common organic solvents. Interestingly, the PI film formed by simple solution-casting of the PI solution had a low CTE value close to that of copper foil, therefore almost no curling of the PI/copper laminate was observed when the PI film was directly formed on a copper foil. The PI film also exhibited other combined properties, including a low CTE, a high Tg, high thermal stability, low water absorption, comparatively good transparency, the highest levels of non-flammability, good insulation properties and sufficient film flexibility. In addition, fine positive-tone patterns could be obtained from DNQ-containing PI with a sensitivity of 238 mJ cm-2. The results revealed that the present PI system is a promising candidate as a novel cover layer material.
Neonatal lupus in triplet pregnancy of a patient with undifferentiated connective tissue disease evolving to systemic lupus erythematosus
Authors: Demaestri M , Sciascia S , Kuzenko A , Bergia R , Barberis L , Lanza MG , Bertero MT
Published: March 2009

Pregnancy in patients suffering from undifferentiated connective tissue disease (UCTD) represents a risk situation for both the mother and the child. SSA/SSB autoantibodies can determine neonatal lupus (NL) in the foetus, regardless of the maternal disease. Furthermore, pregnancy increases the risk of flares and evolution to differentiated connective tissue disease (CTD). We report an uncommon case in which these complications occurred in a mother and in her foetuses. A 37-year-old woman affected by UCTD developed systemic lupus erythematosus (SLE) after her triplet pregnancy. The only manifestation of neonatal lupus we observed in the three newborns was SSA positivity associated with asymptomatic transient neutropenia.
Maternal and foetal outcomes in pregnant patients with active lupus nephritis
Authors: Wagner SJ , Craici I , Reed D , Norby S , Bailey K , Wiste HJ , Wood CM , Moder KG , Liang KP , Liang KV , Rose C , Rozkos T , Sitina M , Grande JP , Garovic VD
Published: March 2009

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria <0.5 mg/day and inactive urinary sediment. We identified 58 patients with 90 pregnancies. Compared with pregnancies in SLE patients without renal involvement ( n = 47), pregnancies in patients with active lupus nephritis ( n = 23) were associated with a higher incidence of maternal complications (57% vs 11%, P < 0.001), whereas those with quiescent lupus nephritis ( n = 20) were not (35% vs 11%, P = 0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs 40 gestational weeks, respectively ( P = 0.002) and were more likely to suffer foetal loss (35% vs 9%, P = 0.031). Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and foetal complications compared with pregnancies in SLE patients without renal involvement.
Development of lupus nephritis is associated with qualitative changes in the glomerular collagen IV matrix composition
Authors: Tveita AA , Ninomiya Y , Sado Y , Rekvig OP , Zykova SN
Published: March 2009

Lupus nephritis is associated with thickening of the glomerular extracellular membranes. Distribution of collagen IV α-chains in the glomerular basement membrane in kidneys of lupus-prone B/W mice has been examined in this study. The results are indicative of a qualitative change in the collagen IV matrix occurring around the time of development of proteinuria, with an embryonic α1/α2 isoform replacing the normal glomerular basement membrane (GBM). These changes mimic alterations seen in Alport syndrome and coincide with an increase in collagenolytic activity within the glomerulus. It has been hypothesized that alterations in collagen matrix synthesis represent compensatory responses to an increase in GBM proteolysis and could represent an important step in the pathogenesis of nephritis through the formation of a dysfunctional glomerular filter. Also, aberrations in the collagen matrix composition could contribute to the deposition of autoantibodies within the glomerulus.
Direct Optimal Vibration Control of a Piezoelastic Plate
Authors: Chellabi Abdelkader , Stepanenko Yury , Dost Sadik
Published: March 2009

An optimal control method for distributed parameter systems is developed and applied to active vibration control of a plate. Piezoelectric material is used as an actuator. The structural dynamics are modeled using the space—time assumed mode expansion technique (a Rayleigh—Ritz method applied to both time and space variables). In particular, the generalized coordinates (both mechanical and electrical) and all generalized forces are described in terms of expansion functions. Using Hamilton's law of varying action along with the space—time assumed mode expansion results in algebraic equations of motion. These are then used as the constraint equations in the optimal controller design. Using space—time expansion, the usual variational optimal control problem is transformed into an equivalent algebraic problem. Optimal solutions are then obtained in a closed form and the solution is global within the time period considered. The solution procedure does not lead to a Riccati equation as is the case in the conventional optimal control solutions. The direct optimal control problem of a vibrating plate is illustrated through simulations where a parametric study is undertaken to check the controller performance. This study shows that the developed optimal control method is simple and the structure—control interaction is an inherent property of the method.
Nonlinear Vibration Analysis of Clamped Skew Plates by a Variational Method
Authors: Das Debabrata , Sahoo Prasanta , Saha Kashinath
Published: March 2009

Nonlinear free vibration analysis of clamped isotropic skew plates has been presented. The large amplitude of vibration is imparted statically by subjecting the plate under uniform transverse pressure. The mathematical formulation is based on the variational principle in which the displacement fields are assumed as a combination of orthogonal polynomial or transcendental functions, each satisfying the corresponding boundary conditions of the plate. The large amplitude dynamic problem is addressed by solving the corresponding static problem first and subsequently with the resultant static displacement field, the dynamic problem is formulated. The vibration frequencies are obtained from the solution of a standard eigenvalue problem. Entire computational work is carried out in a normalized square domain obtained through an appropriate domain mapping technique. Results of the reduced problem revealed excellent agreement with other studies and a typical comparison of the actual problem is also carried out successfully. Results are furnished in dimensionless amplitude-frequency plane, in the form of backbone curves, and pictorial representations of some vibration mode shapes are made.
Burning Man at Google: a cultural infrastructure for new media production
Authors: Turner Fred
Published: March 2009

Every August for more than a decade, thousands of information technologists and other knowledge workers have trekked out into a barren stretch of alkali desert and built a temporary city devoted to art, technology and communal living: Burning Man. Drawing on extensive archival research, participant observation and interviews, this article explores the ways in which Burning Man's bohemian ethos supports new forms of production emerging in Silicon Valley and especially at Google. It shows how elements of the Burning Man world — including the building of a sociotechnical commons, participation in project-based artistic labor and the fusion of social and professional interaction — help to shape and legitimate the collaborative manufacturing processes driving the growth of Google and other firms. The article develops the notion that Burning Man serves as a key cultural infrastructure for the Bay Area's new media industries.
Wielding new media in Web 2.0: exploring the history of engagement with the collaborative construction of media products
Authors: Harrison Teresa M. , Barthel Brea
Published: March 2009

This article explores what is new about Web 2.0, the contemporary cutting-edge platform for web development, differentiating between what is celebrated in the discourse of Web 2.0 and what is genuinely novel about this phenomenon, which is users' propensity to construct content in the form of information and media products for the web environment. It argues that, from the perspective of theoretical treatments of the 'active audience', audiences or media users have created media content on a long-term and consistent historical basis for purposes related to radical and community movements.The article further considers expressive and aesthetic dimensions of Web 2.0 content construction through a discussion of three historical case studies of 'participatory public art' which, it is suggested, constitute a useful analogy for understanding similarly oriented Web 2.0 content construction. Finally, it proposes topics and questions that should figure prominently in research agendas addressing Web 2.0 phenomena in the future.
Underpinning the paradoxes in the artistic fields of MySpace: the problematization of values and popularity in convergence culture
Authors: Suhr Hiesun Cecilia
Published: March 2009

With the rise of participatory culture, social networking sites such as MySpace (www.myspace.com) provide a new outlet for the works of independent artists. The operation of participatory media is not autonomous because the opportunity of intersection with the mainstream media exists, hence the term 'convergence culture' coined by Henry Jenkins. Nonetheless, the critical question for this article pertains to the role of participatory media in consecrating artworks: are independent artists using participatory media simply to have their work viewed, or are they seeking mainstream media exposure? Does the mere act of gaining access to mainstream media result in the consecration of an artwork? How do musician labor on this site to gain value and legitimacy? Overall, this article argues that the blind valorization of the medium itself may inspire an indifferent attitude toward the underlying problems connected with the differing sets of values being negotiated in the participatory media.
Using digital cameras as quasi-spectral radiometers to study complex fenestration systems
Authors: Gayeski N. , Stokes E. , Andersen M.
Published: March 2009

This work discusses the use of digital cameras fitted with absorption filters as quasi-spectral radiometers. By filtering incident light into selected wavelength intervals, accurate estimates of radiances can be made for unknown spectra. This approach is being employed as part of a new video-projection goniophotometer to study the properties of angularly and spectrally selective complex fenestration systems. Complex fenestration systems are increasingly being used to distribute solar radiation purposefully in buildings. They can be utilized to optimize energy performance and enhance daylighting. Radiance estimates from calibrated digital cameras enable the assessment of quasi-spectral, bi-directional scattering distribution functions of total radiance transmitted or reflected by a fenestration system over desired wavelength intervals. A silicon and an indium gallium arsenide digital camera are used to enable measurements across a 380 to 1700 nm wavelength interval.
User attitudes toward tubular daylight guidance systems
Authors: Carter DJ , Al Marwaee M.
Published: March 2009

The study reports quantity and quality of daylight delivered by tubular daylight guidance systems in large open plan offices. The daylight contribution was of the order of 25% of total design workstation illuminance giving daylight penetration factors of between 0.5% and 1.3%. User views suggest that tubular daylight guidance systems were inferior to windows in delivery of both quantity and quality of daylight although satisfaction with some aspects improves with increased daylight penetration
``Worried all the time'': distress and the circumstances of everyday life among immigrant Australians with type 2 Diabetes
Authors: Manderson Lenore , Kokanovic Renata
Published: March 2009

People with diabetes commonly experience emotional distress and are often diagnosed with depression. To explore lay accounts of the conditions and social aspects of their co-occurrence, we draw on qualitative research conducted in metropolitan Melbourne, Australia. Data derive from in-depth interviews with men and women from Greek, Chinese, Indian and Pacific Island communities, all of which have a higher than average incidence of type 2 diabetes mellitus. Participants generally saw stress as a precursor to diabetes, influencing their ability to control symptoms. Yet they also emphasized that life adversities, trauma, disruption, and multiple losses caused distress and depression. Participants regarded diabetes as an illness that interrupted their ability to carry out everyday living tasks. This contributed to their social isolation and unsettled self-identity, resulting in feelings of personal inadequacy, loss and further distress. These themes were common across immigrant groups.
The Democratic Effects of the Internet, 1994—2003
Authors: Groshek Jacob
Published: March 2009

/ Since its inception and subsequent diffusion, the Internet has been lauded as a potent democratizing agent. Using macro-level panel data from 1994 to 2003, this study examined 152 countries and found that increased Internet diffusion was a meaningful predictor of more democratic regimes. This was shown to be most true in developed countries, where non-linear fixed effects regression models showed the highest coefficient estimates and largest observed associations. Consistent with media system dependency theory, greater effects were also demonstrated for countries that already were at least partially democratic where the Internet was more prevalent and thus more likely to fulfill a greater number of information functions. In addition, Internet diffusion and democracy demonstrated a positive, statistically significant relationship (but with a marginal observed association size) in developing countries where the average level of sociopolitical instability was much higher. The Internet therefore should not be employed as a modern `mobility multiplier' because of the strong associations and positive relationships it has shown with democracy but it should also not be ignored due to the democratic potential these results suggest.
Elaborating on systems thinking in health promotion practice
Authors: Naaldenberg Jenneken , Vaandrager Lenneke , Koelen Maria , Wagemakers Anne-Marie , Saan Hans , de Hoog Kees
Published: March 2009

Health and well-being are the result of a series of complex processes in which an individual interacts with other people and the environment. A systematic approach ensures incorporation of individual, ecological, social and political factors. However, interactions between these factors can be overlooked within a systematical approach. A systemic approach can provide additional information by incorporating interactions and communication. The opportunities of a systems thinking perspective for health promotion were investigated for this paper. Although others have also made attempts to explore systems thinking in the field of health promotion, the implications of systems thinking in practice need attention. Other fields such as agricultural extension studies, organizational studies and development studies provide useful experiences with the use of a systems thinking perspective in practice. Building on experiences from these fields, we give a theoretical background in which processes of social learning and innovation play an important role. From this background, we derive an overview of important concepts for the practical application of a systems thinking perspective. These concepts are the structure of the system, meanings attached to actions, and power relations between actors. To make these concepts more explicit and reduce the theoretical character of systems thinking, we use an illustration to elaborate on these concepts in practice. For this purpose, we describe a health promotion partnership in The Netherlands using the concepts structure, meaning and power relations. We show how a systems perspective increases insight in the functioning of a partnership and how this can facilitate processes of social learning and innovation. This article concludes by identifying future opportunities and challenges in adopting systems thinking for health promotion practice. A systems perspective towards health promotion can help projects reaching a more integral and sustainable approach in which the complex nature of health promotion processes is supported. Practical applications of systems thinking are necessary to adapt this perspective. (Global Health Promotion, 2009; 16 (1): pp. 39—47)
CEACAM1+ myeloid cells control angiogenesis in inflammation
Authors: Horst Andrea K. , Bickert Thomas , Brewig Nancy , Ludewig Peter , van Rooijen Nico , Schumacher Udo , Beauchemin Nicole , Ito Wulf D. , Fleischer Bernhard , Wagener Christoph , Ritter Uwe
Published: March 2009

Local inflammation during cutaneous leishmaniasis is accompanied by accumulation of CD11b+ cells at the site of the infection. A functional role for these monocytic cells in local angiogenesis in leishmaniasis has not been described so far. Here, we show that CD11b+ cells express high levels of the myeloid differentiation antigen carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). In experimental cutaneous leishmaniasis in C57BL/6 wild-type (B6.WT) and B6.Ceacam1−/− mice, we found that only B6.Ceacam1−/− mice develop edemas and exhibit impairment of both hemangiogenesis and lymphangiogenesis. Because CEACAM1 expression correlates with functional angiogenesis, we further analyzed the role of the CD11b+ population. In B6.Ceacam1−/− mice, we found systemic reduction of Ly-6Chigh/CD11bhigh monocyte precursors. To investigate whether CEACAM1+ myeloid cells are causally related to efficient angiogenesis, we used reverse bone marrow transplants (BMTs) to restore CEACAM1+ or CEACAM1− bone marrow in B6.Ceacam1−/− or B6.WT recipients, respectively. We found that angiogenesis was restored by CEACAM1+ BMT only. In addition, we observed reduced morphogenic potential of inflammatory cells in Matrigel implants in CEACAM1− backgrounds or after systemic depletion of CD11bhigh macrophages. Taken together, we show for the first time that CEACAM1+ myeloid cells are crucial for angiogenesis in inflammation.
JAK2V617F mutation for the early diagnosis of Ph− myeloproliferative neoplasms in patients with venous thromboembolism: a meta-analysis
Authors: Dentali Francesco , Squizzato Alessandro , Brivio Lorenza , Appio Lorena , Campiotti Leonardo , Crowther Mark , Grandi Anna Maria , Ageno Walter
Published: March 2009

Recent studies suggested that JAK2V617F mutation is frequent in patients with splanchnic vein thrombosis (SVT) but not in patients with other venous thromboembolic events (VTE). However, whether screening for the JAK2V617F mutation in VTE patients is justified remains unclear. Therefore, we performed a systematic review to assess the frequency of JAK2 mutation in VTE patients and the role of JAK2V617F mutation in the diagnosis of myeloproliferative neoplasms. MEDLINE and EMBASE databases were searched. Two reviewers independently performed study selection and extracted study characteristics. Pooled odds ratios of case-control studies and weighted mean proportion of the prevalence of JAK2V617F mutation of uncontrolled series were calculated. Twenty-four studies involving 3123 patients were included. Mean prevalence of JAK2 mutation was 32.7% (95% confidence interval, 25.5%-35.9%) in SVT patients. JAK2 mutation was associated with increased risk of SVT (odds ratio, 53.98; 95% confidence interval, 13.10-222.45). Mean prevalence of JAK2 mutation in other VTE patients was low (range, 0.88%-2.57%). Presence of JAK2V617F mutation in SVT patients was associated with a subsequent diagnosis of myeloproliferative neoplasm in many patients. JAK2 mutation is strongly associated with SVT, and routine screening of JAK2 mutation appears to be indicated in these patients.
GMFilter and SXTestPlate: software tools for improving the SNPlex™ genotyping system
Authors: Teuber Markus , Wenz Michael H , Schreiber Stefan , Franke Andre
Published: March 2009

Background

Genotyping of single-nucleotide polymorphisms (SNPs) is a fundamental technology in modern genetics. The SNPlex™ mid-throughput genotyping system (Applied Biosystems, Foster City, CA, USA) enables the multiplexed genotyping of up to 48 SNPs simultaneously in a single DNA sample. The high level of automation and the large amount of data produced in a high-throughput laboratory require advanced software tools for quality control and workflow management.

Results

We have developed two programs, which address two main aspects of quality control in a SNPlex™ genotyping environment: GMFilter improves the analysis of SNPlex™ plates by removing wells with a low overall signal intensity. It enables scientists to automatically process the raw data in a standardized way before analyzing a plate with the proprietary GeneMapper software from Applied Biosystems. SXTestPlate examines the genotype concordance of a SNPlex™ test plate, which was typed with a control SNP set. This program allows for regular quality control checks of a SNPlex™ genotyping platform. It is compatible to other genotyping methods as well.

Conclusion

GMFilter and SXTestPlate provide a valuable tool set for laboratories engaged in genotyping based on the SNPlex™ system. The programs enhance the analysis of SNPlex™ plates with the GeneMapper software and enable scientists to evaluate the performance of their genotyping platform.
Global comparative transcriptome analysis of cartilage formation in vivo
Authors: Cameron Trevor L , Belluoccio Daniele , Farlie Peter G , Brachvogel Bent , Bateman John F
Published: March 2009

Background

During vertebrate embryogenesis the initial stages of bone formation by endochondral ossification involve the aggregation and proliferation of mesenchymal cells into condensations. Continued growth of the condensations and differentiation of the mesenchymal cells into chondrocytes results in the formation of cartilage templates, or anlagen, which prefigure the shape of the future bones. The chondrocytes in the anlagen further differentiate by undergoing a complex sequence of maturation and hypertrophy, and are eventually replaced by mineralized bone. Regulation of the onset of chondrogenesis is incompletely understood, and would be informed by comprehensive analyses of in vivo gene expression.

Results

Tibial and fibular pre-condensed mesenchyme was microdissected from mouse hind limbs at 11.5 dpc, and the corresponding condensations at 12.5 dpc and cartilage anlagen at 13.5 dpc. Total RNA was isolated, and cRNA generated by linear amplification was interrogated using mouse whole genome microarrays. Differential expression was validated by quantitative PCR for Agc1, Bmp8a, Col2a1, Fgfr4, Foxa3, Gdf5, Klf2, Klf4, Lepre1, Ncad, Sox11, and Trpv4. Further, independent validation of the microarray data was achieved by in situ hybridization to analyse the expression of Lepre1, Pcdh8, Sox11, and Trpv4 from 11.5 dpc to 13.5 dpc during mouse hind limb development. We found significant differential expression of 931 genes during these early stages of chondrogenesis. Of these, 380 genes were down-regulated and 551 up-regulated. Our studies characterized the expression pattern of gene families previously associated with chondrogenesis, such as adhesion molecules, secreted signalling molecules, transcription factors, and extracellular matrix components. Gene ontology approaches identified 892 differentially expressed genes not previously identified during the initiation of chondrogenesis. These included several Bmp, Gdf, Wnt, Sox and Fox family members.

Conclusion

These data represent the first global gene expression profiling analysis of chondrogenic tissues during in vivo development. They identify genes for further study on their functional roles in chondrogenesis, and provide a comprehensive and important resource for future studies on cartilage development and disease.
Developmental and neurochemical features of cholinergic neurons in the murine cerebral cortex
Authors: Consonni Silvia , Leone Silvia , Becchetti Andrea , Amadeo Alida
Published: March 2009

Background

The existence and role of intrinsic cholinergic cells in the cerebral cortex is controversial, because of their variable localization and morphology in different mammalian species. We have applied choline acetyltransferase (ChAT) immunocytochemistry to study the distribution of cholinergic neurons in the murine cerebral cortex, in the adult and during postnatal development. For more precise neurochemical identification of these neurons, the possible colocalization of ChAT with different markers of cortical neuronal populations has been analyzed by confocal microscopy. This method was also used to verify the relationship between cholinergic cells and cortical microvessels.

Results

ChAT positive cells appeared at the end of the first postnatal week. Their density dramatically increased at the beginning of the second postnatal week, during which it remained higher than in perinatal and adult stages. In the adult neocortex, cholinergic neurons were particularly expressed in the somatosensory area, although their density was also significant in visual and auditory areas. ChAT positive cells tended to be scarce in other regions. They were mainly localized in the supragranular layers and displayed a fusiform/bipolar morphology.

The colocalization of ChAT with pyramidal neuron markers was negligible. On the other hand, more than half of the cholinergic neurons contained calretinin, but none of them expressed parvalbumin or calbindin. However, only a fraction of the ChAT positive cells during development and very few in adulthood turned out to be GABAergic, as judged from expression of GABA and its biosynthetic enzymes GAD67/65. Consistently, ChAT showed no localization with interneurons expressing green fluorescent protein under control of the GAD67 promoter in the adult neocortex. Finally, the cortical cholinergic cells often showed close association with the microvessel walls, as identified with the gliovascular marker aquaporin 4, supporting previous hypotheses on the role of cholinergic cells in modulating the cortical microcirculation.

Conclusion

Our results show that the development of the intracortical cholinergic system accompanies the cortical rearrangements during the second postnatal week, a crucial stage for the establishment of cortical cytoarchitecture and for synaptogenesis. Although intrinsic ChAT positive cells usually expressed calretinin, they displayed a variable GABAergic phenotype depending on marker and on cortical developmental stage.
Exploring the transcriptional landscape of plant circadian rhythms using genome tiling arrays
Authors: Hazen Samuel P , Naef Felix , Quisel Tom , Gendron Joshua M , Chen Huaming , Ecker Joseph R , Borevitz Justin O , Kay Steve A
Published: March 2009

Background

Organisms are able to anticipate changes in the daily environment with an internal oscillator know as the circadian clock. Transcription is an important mechanism in maintaining these oscillations. Here we explore, using whole genome tiling arrays, the extent of rhythmic expression patterns genome-wide, with an unbiased analysis of coding and noncoding regions of the Arabidopsis genome.

Results

As in previous studies, we detected a circadian rhythm for approximately 25% of the protein coding genes in the genome. With an unbiased interrogation of the genome, extensive rhythmic introns were detected predominantly in phase with adjacent rhythmic exons, creating a transcript that, if translated, would be expected to produce a truncated protein. In some cases, such as the MYB transcription factor AT2G20400, an intron was found to exhibit a circadian rhythm while the remainder of the transcript was otherwise arrhythmic. In addition to several known noncoding transcripts, including microRNA, trans-acting short interfering RNA, and small nucleolar RNA, greater than one thousand intergenic regions were detected as circadian clock regulated, many of which have no predicted function, either coding or noncoding. Nearly 7% of the protein coding genes produced rhythmic antisense transcripts, often for genes whose sense strand was not similarly rhythmic.

Conclusions

This study revealed widespread circadian clock regulation of the Arabidopsis genome extending well beyond the protein coding transcripts measured to date. This suggests a greater level of structural and temporal dynamics than previously known.
Widespread evidence for horizontal transfer of transposable elements across Drosophilagenomes
Authors: Bartolomé Carolina , Bello Xabier , Maside Xulio
Published: March 2009

Background

Horizontal transfer (HT) could play an important role in the long-term persistence of transposable elements (TEs) because it provides them with the possibility to avoid the checking effects of host-silencing mechanisms and natural selection, which would eventually drive their elimination from the genome. However, despite the increasing evidence for HT of TEs, its rate of occurrence among the TE pools of model eukaryotic organisms is still unknown.

Results

We have extracted and compared the nucleotide sequences of all potentially functional autonomous TEs present in the genomes of Drosophila melanogaster, D. simulans and D. yakuba - 1,436 insertions classified into 141 distinct families - and show that a large fraction of the families found in two or more species display levels of genetic divergence and within-species diversity that are significantly lower than expected by assuming copy-number equilibrium and vertical transmission, and consistent with a recent origin by HT. Long terminal repeat (LTR) retrotransposons form nearly 90% of the HT cases detected. HT footprints are also frequent among DNA transposons (40% of families compared) but rare among non-LTR retroelements (6%). Our results suggest a genomic rate of 0.04 HT events per family per million years between the three species studied, as well as significant variation between major classes of elements.

Conclusions

The genome-wide patterns of sequence diversity of the active autonomous TEs in the genomes of D. melanogaster, D. simulans and D. yakuba suggest that one-third of the TE families originated by recent HT between these species. This result emphasizes the important role of horizontal transmission in the natural history of Drosophila TEs.
Phase III Study of Gemcitabine Plus Docetaxel Compared With Capecitabine Plus Docetaxel for Anthracycline-Pretreated Patients With Metastatic Breast Cancer
Authors: Chan Stephen , Romieu Gilles , Huober Jens , Delozier Thierry , Tubiana-Hulin Michele , Schneeweiss Andreas , Lluch Ana , Llombart Antonio , du Bois Andreas , Kreienberg Rolf , Mayordomo Jose Ignacio , Antón Antonio , Harrison Mark , Jones Alison , Carrasco Eva , Vaury A. Thareau , Frimodt-Moller Bente , Fumoleau Pierre
Published: March 2009

Purpose

Patients with metastatic breast cancer who are pretreated with anthracyclines frequently receive taxane-based combinations. This phase III study compared the efficacy and safety of gemcitabine-docetaxel (GD) with capecitabine-docetaxel (CD) in advanced breast cancer.

Patients and Methods

Patients were randomly assigned to GD (G 1,000 mg/m2 days 1 and 8; D 75 mg/m2 day 1) or CD (C 1,250 mg/m2 twice daily days 1 through 14; D 75 mg/m2 day 1) every 21 days. Comparison of progression-free survival (PFS) was the primary objective.

Results

Patient characteristics were balanced between arms (N = 305). Median PFS was 8.05 months (95% CI, 6.60 to 8.71) for GD and 7.98 (95% CI, 6.93 to 8.77) for CD (log-rank P = .121). Overall response rate (ORR) was 32% in both arms, and overall survival (OS) was not different between arms (P = .983). Time to treatment failure (TTF; defined as discontinuation, progressive disease, death as a result of any cause, or the start of a new anticancer therapy) was superior in the GD arm (P = .059). Hematologic toxicity was similar in both arms, except for grades 3 to 4 leukopenia (GD, 78%; CD, 66%; P = .025) and transfusions (GD, 17%; CD, 7%; P = .0051). Grades 3 to 4 diarrhea, mucositis, and hand-and-foot syndrome were significantly higher in the CD arm. Fewer patients in the GD arm discontinued because of drug-related adverse events (13% v 27% in CD; P = .002).

Conclusion

No difference was observed between GD and CD arms in PFS, ORR, and OS. TTF was longer in the GD arm. These findings, combined with a nonhematologic toxicity profile that favors GD over approved doses of CD, suggest that gemcitabine may be a better option than capecitabine in combination with docetaxel in this clinical setting.
DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer
Authors: Iacobuzio-Donahue Christine A. , Fu Baojin , Yachida Shinichi , Luo Mingde , Abe Hisashi , Henderson Clark M. , Vilardell Felip , Wang Zheng , Keller Jesse W. , Banerjee Priya , Herman Joseph M. , Cameron John L. , Yeo Charles J. , Halushka Marc K. , Eshleman James R. , Raben Marian , Klein Alison P. , Hruban Ralph H. , Hidalgo Manuel , Laheru Daniel
Published: March 2009

Purpose

Contrary to the extensive data accumulated regarding pancreatic carcinogenesis, the clinical and molecular features characteristic of advanced stage (stage III and IV) disease are unknown. A comprehensive study of pancreatic cancers from patients who have succumbed to their disease has the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention.

Materials and Methods

Rapid autopsies were performed on 76 patients with documented pancreatic cancer. The histologic features of end stage disease were determined and correlated to the stage at initial diagnosis, patterns of failure (locally destructive v metastatic disease) and the status of the KRAS2, TP53, and DPC4 genes.

Results

At autopsy, 30% of patients died with locally destructive pancreatic cancer, and 70% died with widespread metastatic disease. These divergent patterns of failure found at autopsy (locally destructive v metastatic) were unrelated to clinical stage at initial presentation, treatment history, or histopathologic features. However, Dpc4 immunolabeling status of carcinoma tissues harvested at autopsy, a sensitive marker of DPC4 genetic status, was highly correlated with the presence of widespread metastasis but not with locally destructive tumors (P = .007).

Conclusion

Pancreatic cancers are represented by distinct genetic subtypes with significantly different patterns of failure. Determinations of DPC4 status at initial diagnosis may be of value in stratifying patients into treatment regimens related to local control versus systemic therapy.
Online Quality Control, Hyperfractionated Radiotherapy Alone and Reduced Boost Volume for Standard Risk Medulloblastoma: Long-Term Results of MSFOP 98
Authors: Carrie Christian , Grill Jacques , Figarella-Branger Dominique , Bernier Valerie , Padovani Laetitia , Habrand Jean Louis , Benhassel Mohamed , Mege Martine , Mahé Marc , Quetin Philippe , Maire Jean Philippe , Baron Marie Helene , Clavere Pierre , Chapet Sophie , Maingon Philippe , Alapetite Claire , Claude Line , Laprie Anne , Dussart Sophie
Published: March 2009

Purpose

To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance.

Patients and Methods

Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Société Française d'Oncologie Pédiatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales.

Results

After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, −1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline.

Conclusion

HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.
Health Care System and Socioeconomic Factors Associated With Variance in Use of Sentinel Lymph Node Biopsy for Melanoma in the United States
Authors: Bilimoria Karl Y. , Balch Charles M. , Wayne Jeffrey D. , Chang David C. , Palis Bryan E. , Dy Sydney M. , Lange Julie R.
Published: March 2009

Purpose

Guidelines recommend sentinel lymph node biopsy (SLNB) for patients with clinical stage IB/II melanomas, but not clinical stage IA melanoma. This study examines factors associated with SLNB use for clinically node-negative melanoma.

Methods

Patients diagnosed with clinically node-negative invasive melanoma in 2004 and 2005 were identified from the National Cancer Data Base. Regression models were developed to assess the association of clinicopathologic (sex, age, race/ethnicity, comorbidities, T stage), socioeconomic (insurance status, educational level, income), and hospital (hospital type, geographic area) factors with SLNB use.

Results

A total of 16,598 patients were identified: 8,073 patients with clinical stage IA and 8,525 patients with clinical stage IB/II melanoma. For clinical stage IB/II melanoma, SLNB use was reported in 48.7% of patients. Patients with clinical stage IB/II melanoma were less likely to undergo SLNB if they were older than 75 years; had T1b tumors, no tumor ulceration, or head/neck or truncal lesions; were covered by Medicaid or Medicare; or lived in the Northeast, South, or West census regions. SLNB use was reported in 13.3% of patients with clinical stage IA melanoma and was more likely in patients who were younger than 56 years or lived in the Mountain or Pacific census regions. Patients treated at National Comprehensive Cancer Network–or National Cancer Institute–designated hospitals were most likely to undergo SLNB in adherence with national consensus guidelines.

Conclusion

SLNB use was associated with clinicopathologic factors but also with health system factors, including type of insurance, geographic area, and hospital type. These findings have implications for provider education and health policy.
Consolidation Therapy With Low-Dose Thalidomide and Prednisolone Prolongs the Survival of Multiple Myeloma Patients Undergoing a Single Autologous Stem-Cell Transplantation Procedure
Authors: Spencer Andrew , Prince H. Miles , Roberts Andrew W. , Prosser Ian W. , Bradstock Kenneth F. , Coyle Luke , Gill Devinder S. , Horvath Noemi , Reynolds John , Kennedy Nola
Published: March 2009

Purpose

Thalidomide is effective in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). However, the role of thalidomide in the post-autologous stem cell transplantation (ASCT) context remains unclear. This study assessed whether the addition of thalidomide consolidation following ASCT would improve the durability of responses achieved and overall survival.

Patients and Methods

Between January 2002 and March 2005, 269 patients with newly diagnosed MM who achieved disease stabilization or better with conventional induction chemotherapy received a single high-dose melphalan conditioned ASCT. Post-ASCT, 129 patients were randomly assigned to receive indefinite prednisolone maintenance therapy (control group) and 114 to receive the same in addition to 12 months of thalidomide consolidation (thalidomide group). The primary study end points were progression-free survival (PFS) and overall survival (OS). The secondary end point was tolerability.

Results

After a median follow-up of 3 years, the postrandomization 3-year PFS rates were 42% and 23% (P < .001; hazard ratio [HR], 0.5; 95% CI, 0.35 to 0.71) and the OS rates were 86% and 75% (P = .004; HR, 0.41; 95% CI, 0.22 to 0.76) in the thalidomide and control groups, respectively. There was no difference in survival between groups 12 months after disease progression (79% v 77%; P = .237). Neurological toxicities were more common in the thalidomide arm but there were no differences between arms for thromboembolic events.

Conclusion

Consolidation therapy with 12 months of thalidomide combined with prednisolone prolongs survival when used after a single high-dose therapy supported ASCT in patients with newly diagnosed MM. Furthermore, thalidomide consolidation therapy did not adversely impact on survival in the subsequent salvage setting.