bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas‐Cooled Fast Reactor: A Historical Overview and Future Outlook
Authors: van Rooijen W. F. G.
Published: July 2009

A review is given of developments in the area of Gas‐Cooled Fast Reactors (GCFR) in the period from roughly 1960 until 1980. During that period, the GCFR concept was expected to increase the breeding gain, the thermal efficiency of a nuclear power plant, and alleviate some of the problems associated with liquid metal coolants. During this period, the GCFR concept was found to be more challenging than liquid‐metal‐cooled reactors, and none were ever constructed. In the second part of the paper, we provide an overview of the investigations on GCFR since the year 2000, when the Generation IV Initiative rekindled interest in this reactor type. The new GCFR concepts focus primarily on sustainable nuclear power, with very efficient resource use, minimum waste, and a very strong focus on (passive) safety. An overview is presented of the main design characteristics of these Gen IV GCFRs, and a literature list is provided to guide the interested reader towards more detailed publications.
Myeloid-Related Protein-8/14 Is Critical for the Biological Response to Vascular Injury
Authors: Croce Kevin , Gao Huiyun , Wang Yunmei , Mooroka Toshifumi , Sakuma Masashi , Shi Can , Sukhova Galina K. , Packard René R.S. , Hogg Nancy , Libby Peter , Simon Daniel I.
Published: July 2009

Background—

Myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) are members of the S100 family of calcium-modulated proteins that regulate myeloid cell function and control inflammation, in part, through activation of Toll-like receptor-4 and the receptor for advanced glycation end products. A transcriptional profiling approach in patients with acute coronary syndromes identified MRP-14 as a novel predictor of myocardial infarction. Further studies demonstrated that elevated plasma levels of MRP-8/14 heterodimer predict increased risk of first and recurrent cardiovascular events. Beyond its serving as a risk marker, whether MRP-8/14 participates directly in vascular inflammation and disease remains unclear.

Methods and Results—

We evaluated vascular inflammation in wild-type and
MRP-14
–deficient (
MRP-14
−/−
) mice that lack MRP-8/14 complexes with experimental arterial injury, vasculitis, or atherosclerosis. After femoral artery wire injury,
MRP-14
−/−
mice had significant reductions in leukocyte accumulation, cellular proliferation, and neointimal formation compared with wild-type mice. In a cytokine-induced local Shwartzman-like reaction that produces thrombohemorrhagic vasculitis,
MRP-14
−/−
mice had significant reductions in neutrophil accumulation, lesion severity, and hemorrhagic area. In response to high-fat feeding, mice doubly deficient in apolipoprotein E and MRP-8/14 complexes had attenuation in atherosclerotic lesion area and in macrophage accumulation in plaques compared with mice deficient in apolipoprotein E alone.

Conclusion—

This study demonstrates that MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.
Effects of Fixed-Dose Isosorbide Dinitrate/Hydralazine on Diastolic Function and Exercise Capacity in Hypertension-Induced Diastolic Heart Failure
Authors: Wilson Richard M. , De Silva Deepa S. , Sato Kaori , Izumiya Yasuhiro , Sam Flora
Published: July 2009

Hypertension-induced diastolic heart failure accounts for a large proportion of all heart failure presentations. Hypertension also induces left ventricular (LV) hypertrophy. Fixed-dose isosorbide dinitrate/hydralazine (HISDN) decreased mortality in human systolic heart failure but it is unknown whether it improves maladaptive myocardial remodeling. We sought to test the hypothesis that chronic HISDN modulates LV hypertrophy and myocardial remodeling in hypertension-induced diastolic heart failure. FVB mice underwent either saline (n=18) or aldosterone (n=28) infusion. All underwent uninephrectomy and drank 1% salt water for 4 weeks. Mice were randomized after surgery to regular chow or chow containing HISDN (isosorbide dinitrate: 26 mg/kg per day; hydralazine: 50 mg/kg per day) for 4 weeks. Aldosterone infusion increased tail-cuff blood pressure (161±3 mm Hg) versus saline-infused mice (129±2 mm Hg). Aldosterone induced LV hypertrophy versus saline-infused mice (LV:body weight ratio: 4.2±0.1 versus 3.6±0.1 mg/g). HISDN attenuated the aldosterone-induced increased in systolic blood pressure (137±5 mm Hg) and also lowered blood pressure in saline-infused mice (114±2 mm Hg). However, HISDN did not cause LV hypertrophy regression in aldosterone-infused mice. Aldosterone increased LV end-diastolic dimensions that were not attenuated by HISDN. Similarly, neither aldosterone infusion nor HISDN affected LV end-systolic dimensions. LV ejection fraction and wet:dry lung ratio were not different between aldosterone-untreated and aldosterone-HISDN mice. However, mitral Doppler E/A ratio (a measure of diastolic function), exercise capacity, and plasma soluble vascular cell adhesion molecule 1 levels were improved in aldosterone-HISDN hearts. In conclusion, fixed-dose HISDN improved hypertension, diastolic function, and exercise capacity and reduced soluble vascular cell adhesion molecule 1 levels. There were no reductions in LV hypertrophy, cardiac fibrosis, or pulmonary congestion. These functional improvements are likely related to extracardiac effects, such as effects on the vasculature.
Sexual size dimorphism, diet, and reproductive biology of the Afro-Asian Sand Snake, Psammophis schokari (Psammophiidae)
Authors: Cottone Amanda , Bauer Aaron
Published: July 2009

We measured and dissected 226 museum specimens of Psammophis schokari (Schokari Sand Snake), a widespread, common “whipsnake” occurring in North Africa and southwest Asia. Three aspects of its ecology were investigated: sexual size dimorphism (SSD), diet, and reproductive biology. There was no significant SSD in mean body size or shape for the traits measured. The species is an opportunistic feeder, but preys predominately on lizards. Males and females exhibit their highest levels of sexual activity in synchrony and exhibit prenuptial spermiogenesis and a Type 1 vitellogenic cycle, respectively. Mating occurs at the end of the rainy season and clutch sizes are small. These findings from a Northern Hemisphere temperate sand snake are consistent with previous results for both tropical and south temperate Psammophis. These traits thus appear to be highly conserved within the genus and also exhibit convergence with respect to unrelated colubroid “whipsnakes”.
Taking Root in the Sunshine State
Authors: Proffitt Jennifer M. , Opel Andy , Gaccione Joseph
Published: July 2009

This paper explores the emergence of the media reform movement in the state of Florida in 2008. Focusing on the development of a statewide coalition, the paper details the tensions between local and national policy agendas, the barriers faced by local activists as they attempt to build support for the concept of media reform in their communities, and the diversity of interests represented under the banner of media reform. This case study also reveals an ideological bias toward the left among the movement activists currently working in Florida, signaling a need to harness the broad-based dissatisfaction that exists across the political spectrum.
Efficient Servants of Pluralism or Marginalized Media Policy Tools?
Authors: Ots Mart
Published: July 2009

For more than 30 years, Sweden’s media policy has relied on positive incentives to promote diversity. That is, competition law has rarely been used to prevent dominant newspapers from acquiring smaller ones, but rather press subsidies have been used to increase survival rates and promote independence among the latter. Internationally, the broad trend toward concentration in newspaper markets has been of concern to policy makers, and the Swedish model has attracted considerable interest as a possible path to a more heterogeneous media landscape. However, over the last decade, ownership distribution on the newspaper market has started to change at an accelerating pace, and Swedish media policy stands at a crossroad—to increase reliance on subsidies or to make way for something new. The arising questions regarding how to reshape media policy have several parallels to the ongoing international debate. This case study explores the performance of subsidies from the perspective of pluralism and discusses alternative political responses and future policy directions.
FMLA Protection Recently Expanded to Military Families: Qualifying Exigency and Servicemember Family Leave
Authors: Martin Sarah B.
Published: July 2009

Employers must promptly incorporate changes required by new amendments into workplace policies, practices, forms and training.
An Interview With Alan J. Hovestadt: AAMFT Past President and Long-Time Marriage and Family Counselor Educator
Authors: Juhnke Gerald A. , Sunich Michael F. , Coll Kenneth M. , Lebron-Striker Maritza
Published: July 2009

Alan J. Hovestadt, EdD, is the immediate past president of the 24,000 member American Association for Marriage and Family Therapy (AAMFT) and a long-time IAMFC member who served as an IAMFC founding board member when American Counseling Association (ACA) first granted International Association of Marriage and Family Counselors (IAMFC) divisional status. Recently, Dr. Hovestadt was one of seven recipients of the prestigious American Counseling Association's Presidential Award and was honored at the 2008 ACA Conference in Honolulu, Hawaii. Given Dr. Hovestadt's prominence within both AAMFT and IAMFC and his long-time marriage and family counselor educator identity, the authors' believed that an interview with Dr. Hovestadt would be of significant interest to The Family Journal readerships. Thus, Dr. Hovestadt graciously participated in an interview with Drs. Ken Coll, Michael Sunich, and Gerald Juhnke on November 20, 2007. In the interview below, Dr. Hovestadt responds to questions related to his (a) AAMFT Presidency experiences and accomplishments, (b) perceptions related to professionals aligning themselves either with AAMFT or IAMFC, (c) thoughts related to pressing legislative concerns that would be of specific interest to IAMFC members and The Family Journal readership, (d) perceptions related to marriage and family training changes, and (e) advice for those seeing to become counselor educators with specialization in couples, marriage, and family counseling.
Borderline Personality Disorder and Sexuality
Authors: Wiederman Michael W. , Sansone Randy A.
Published: July 2009

From its earliest conception, borderline personality disorder (BPD) has been said to entail problematic issues related to sexuality. It is surprising, then, that relatively little research has been conducted on sexuality among this group of mental health clients, and that such research has been limited with regard to samples and measures of sexuality. In this article, we provide an overview of BPD as well as the existing research on sexuality among these clients. We then provide some possible explanations for these research findings and conclude with considerations for counselors when working with clients who exhibit BPD symptoms.
Effect of Inhibition of Neuropathy Target Esterase in Mouse Nervous Tissues In Vitro on Phosphatidylcholine and Lysophosphatidylcholine Homeostasis
Authors: Hou Wei-Yuan , Long Ding-Xin , Wu Yi-Jun
Published: July 2009

Neuropathy target esterase has been shown to be a lysophospholipase in mouse. The authors investigate the effect of neuropathy target esterase inhibition in mouse nervous tissues in vitro on the homeostasis of phosphatidylcholine and lysophosphatidylcholine by treating the homogenates with tri-ortho-cresyl phosphate, paraoxon, paraoxon plus mipafox, and phenylmethylsulfonyl fluoride. The activity of neuropathy target esterase is significantly inhibited by phenylmethylsulfonyl fluoride and paraoxon plus mipafox but not by paraoxon alone. Tri-ortho-cresyl phosphate slightly but significantly inhibits neuropathy target esterase activity in brain. The levels of phosphatidylcholine and lysophosphatidylcholine in all 3 nervous tissues are not obviously altered after treatment with tri-ortho-cresyl phosphate, paraoxon, or paraoxon plus mipafox. However, phosphatidylcholine and lysophosphatidylcholine levels are clearly enhanced by phenylmethylsulfonyl fluoride. It is concluded that inhibition of neuropathy target esterase in mouse nervous tissues is not enough to disrupt the homeostasis of phosphatidylcholine and lysophosphatidylcholine and that the upregulation by phenylmethylsulfonyl fluoride may be the consequence of combined inhibition of neuropathy target esterase and other phospholipases.
The Politics of Pleasure Talk in 18th-Century Europe
Authors: Cook Alexander
Published: July 2009

This article provides an analysis of the role played by competing conceptions of pleasure in European cultural politics during the 18th century. Beginning with the `onanism' panic, which gripped western Europe in 1712, and with the apparent paradox that new concern about masturbation developed at a time when the pursuit of pleasure was increasingly legitimized in intellectual discourse, this article suggests that the panic can be understood as part of a wider process. This was a process in which a legitimization of pleasure was accompanied by a series of battles to define the concept in more socially useful ways. These battles can be traced across a range of literary fields from theology and aesthetics to physiology and political and moral theory.
Wikipedia leeches? The promotion of traffic through a collaborative web format
Authors: Langlois Ganaele , Elmer Greg
Published: July 2009

This article investigates the circulation of Wikipedia entries on the web in an effort to determine the integration of its collaborative model into existing proprietary web formats. In particular it details the use of Wikipedia content as 'tags' or information that is used to increase traffic to webpages through search engine results. Consequently, the article discusses the need to develop theoretical models that provide for an understanding of both content and form on the web, particularly as formatted by open-source legal frameworks.
Thermal Performance of a Building Envelope - A Probabilistic Approach
Authors: Pietrzyk Krystyna
Published: July 2009

A probabilistic model of the thermal performance of a building envelope is proposed. The model predicts the probability density function of the heat loss over a specified period of time on the basis of the design parameters of the house, climatic characteristics of the site as well as the air change rate due to mechanical or natural ventilation. Reliability of the heat loss performance of the building envelope components exposed to various climatic conditions is analyzed, and the probability of excessive heat loss is quantified. Different design options are considered. They involve a dynamic wall strategy and various types of building ventilation.
What Race Do They Represent and Does Mine Have Anything to Do with It? Perceived Racial Categories of Anime Characters
Authors: Lu Amy Shirong
Published: July 2009

Is the intended race of anime characters distinguishable because of their facial features or are they too `international' to tell? This study addressed this question empirically by comparing the intended racial categories of static frontal portraits of 341 anime characters randomly selected from anime produced between 1958 and 2005 with the perceptions of 1,046 raters. Results showed that, although the race of more than half of the anime characters was originally designed to be Asian and only a small fraction were intended to be Caucasian, many were perceived as Caucasian by the largely Caucasian raters. Response patterns also indicated `Own Race Projection (ORP)', i.e. perceivers frequently perceived anime characters to be of their own racial group. Implications for anime's international dissemination are discussed.
Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells
Authors: Mason Mike J , Fan Guoping , Plath Kathrin , Zhou Qing , Horvath Steve
Published: July 2009

Background

Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes.

Results

We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation.

Conclusion

Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology.
Selection of reliable reference genes for gene expression studies in peach using real-time PCR
Authors: Tong Zhaoguo , Gao Zhihong , Wang Fei , Zhou Jun , Zhang Zhen
Published: July 2009

Background

RT-qPCR is a preferred method for rapid and reliable quantification of gene expression studies. Appropriate application of RT-qPCR in such studies requires the use of reference gene(s) as an internal control to normalize mRNA levels between different samples for an exact comparison of gene expression level. However, recent studies have shown that no single reference gene is universal for all experiments. Thus, the identification of high quality reference gene(s) is of paramount importance for the interpretation of data generated by RT-qPCR. Only a few studies on reference genes have been done in plants and none in peach (Prunus persica L. Batsch). Therefore, the present study was conducted to identify suitable reference gene(s) for normalization of gene expression in peach.

Results

In this work, eleven reference genes were investigated in different peach samples using RT-qPCR with SYBR green. These genes are: actin 2/7 (ACT), cyclophilin (CYP2), RNA polymerase II (RP II), phospholipase A2 (PLA2), ribosomal protein L13 (RPL13), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S ribosomal RNA (18S rRNA), tubblin beta (TUB), tubblin alpha (TUA), translation elongation factor 2 (TEF2) and ubiquitin 10 (UBQ10). All eleven reference genes displayed a wide range of Cq values in all samples, indicating that they expressed variably. The stability of these genes except for RPL13 was determined by three different descriptive statistics, geNorm, NormFinder and BestKeeper, which produced highly comparable results.

Conclusion

Our study demonstrates that expression stability varied greatly between genes studied in peach. Based on the results from geNorm, NormFinder and BestKeeper analyses, for all the sample pools analyzed, TEF2, UBQ10 and RP II were found to be the most suitable reference genes with a very high statistical reliability, and TEF2 and RP II for the other sample series, while 18S rRNA, RPL13 and PLA2 were unsuitable as internal controls. GAPDH and ACT also performed poorly and were less stable in our analysis. To achieve accurate comparison of levels of gene expression, two or more reference genes must be used for data normalization. The combinations of TEF2/UBQ10/RP II and TEF2/RP II were suggested for use in all samples and subsets, respectively.
Identification of an extensive gene cluster among a family of PPOs in Trifolium pratense L. (red clover) using a large insert BAC library
Authors: Winters Ana , Heywood Sue , Farrar Kerrie , Donnison Iain , Thomas Ann , Webb K Judith
Published: July 2009

Background

Polyphenol oxidase (PPO) activity in plants is a trait with potential economic, agricultural and environmental impact. In relation to the food industry, PPO-induced browning causes unacceptable discolouration in fruit and vegetables: from an agriculture perspective, PPO can protect plants against pathogens and environmental stress, improve ruminant growth by increasing nitrogen absorption and decreasing nitrogen loss to the environment through the animal's urine. The high PPO legume, red clover, has a significant economic and environmental role in sustaining low-input organic and conventional farms. Molecular markers for a range of important agricultural traits are being developed for red clover and improved knowledge of PPO genes and their structure will facilitate molecular breeding.

Results

A bacterial artificial chromosome (BAC) library comprising 26,016 BAC clones with an average 135 Kb insert size, was constructed from Trifolium pratense L. (red clover), a diploid legume with a haploid genome size of 440–637 Mb. Library coverage of 6–8 genome equivalents ensured good representation of genes: the library was screened for polyphenol oxidase (PPO) genes.

Two single copy PPO genes, PPO4 and PPO5, were identified to add to a family of three, previously reported, paralogous genes (PPO1–PPO3). Multiple PPO1 copies were identified and characterised revealing a subfamily comprising three variants PPO1/2, PPO1/4 and PPO1/5. Six PPO genes clustered within the genome: four separate BAC clones could be assembled onto a predicted 190–510 Kb single BAC contig.

Conclusion

A PPO gene family in red clover resides as a cluster of at least 6 genes. Three of these genes have high homology, suggesting a more recent evolutionary event. This PPO cluster covers a longer region of the genome than clusters detected in rice or previously reported in tomato. Full-length coding sequences from PPO4, PPO5, PPO1/5 and PPO1/4 will facilitate functional studies and provide genetic markers for plant breeding.
Association study between vitamin D receptor gene polymorphisms and asthma in the chinese han population: a case-control study
Authors: Saadi Ahlem , Gao Guimin , Li Huaichen , Wei Chunhua , Gong Yaoqin , Liu Qiji
Published: July 2009

Background

Modulation of the immune system is one of the principal roles of Vitamin D, for which the effects are exerted via the vitamin D receptor (VDR). Importantly, variants in the VDR gene have been susceptible in the past to raise the risk of asthma in several populations. These effects of VDR allelic markers remain speculative in the Chinese Han population.

Results

A case-control study of 1090 individuals including 567 asthmatic patients was realized on five SNPs within the VDR gene. Only rs7975232 (ApaI) marker showed a significant association with asthma (P = 0.009). Haplotype analysis of the five VDR polymorphisms showed a significant association with asthma (global-p value = 0.012).

Conclusion

Although the susceptibility of VDR gene variants with asthma could not be confirmed for all SNPs tested in this study, the significant association obtained for rs7975232 provides evidence for a previously unknown report about the Chinese Han population and may raise the susceptibility of VDR to be a candidate gene for asthma.
Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer
Authors: Hong Yong Sang , Cho Hyeon Jin , Kim Sun Young , Jung Kyung Hae , Park Ji Won , Choi Hyo Seong , Oh Jae Hwan , Kim Byung Chang , Sohn Dae Kyung , Kim Dae Yong , Chang Hee Jin
Published: July 2009

Background

Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment.

Methods

Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area.

Results

The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival.

Conclusion

Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.
Establishment and characterization of pleomorphic adenoma cell systems: an in-vitro demonstration of carcinomas arising secondarily from adenomas in the salivary gland
Authors: Maruyama Satoshi , Cheng Jun , Shingaki Susumu , Tamura Takashi , Asakawa Shuichi , Minoshima Shinsei , Shimizu Yoshiko , Shimizu Nobuyoshi , Saku Takashi
Published: July 2009

Background

Among the salivary gland carcinomas, carcinoma in pleomorphic adenoma has been regarded as a representative carcinoma type which arises secondarily in the background of a pre-existent benign pleomorphic adenoma. It is still poorly understood how and which benign pleomorphic adenoma cells transform into its malignant form, carcinoma ex pleomorphic adenoma.

Methods

We have established five cell systems from a benign pleomorphic adenoma of the parotid gland of a 61-year-old woman. They were characterized by immunofluorescence, classical cytogenetics, p53 gene mutational analysis, fluorescence in-situ hybridization, and histopathological and immunohistochemical examinations of their xenografts, to demonstrate their potency of secondary transformation.

Results

We established and characterized five cell systems (designated as SM-AP1 to SM-AP5) from a benign pleomorphic adenoma of the parotid gland. SM-AP1 to SM-AP3 showed polygonal cell shapes while SM-AP4 and SM-AP5 were spindle-shaped. SM-AP1-3 cells were immunopositive for keratin only, indicating their duct-epithelial or squamous cell differentiation, while SM-AP4/5 cells were positive for both keratin and S-100 protein, indicating their myoepithelial cell differentiation. Chromosome analyses showed numeral abnormalities such as 5n ploidies and various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9;13)(p13.3;q12.3) was shared by all five of the cell systems. In addition, they all had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which resulted in generation of its nonsense gene product. Transplanted cells in nude mice formed subcutaneous tumors, which had histological features of squamous cell carcinoma with apparent keratinizing tendencies. In addition, they had ductal arrangements or plasmacytoid appearances of tumor cells and myxoid or hyaline stromata, indicating some characteristics of pleomorphic adenoma.

Conclusion

This study demonstrates in vitro that certain cell types from pleomorphic adenoma are able to clone and survive over a long term and develop subcutaneous tumors in nude mice. The histological features of squamous cell carcinoma from the transplanted cell systems in nude mice might suggest a secondary onset of malignancy from a pre-existing benign adenoma.
A qualitative study to assess school nurses' views on vaccinating 12–13 year old school girls against human papillomavirus without parental consent
Authors: Stretch Rebecca , McCann Rosemary , Roberts Stephen A , Elton Peter , Baxter David , Brabin Loretta
Published: July 2009

Background

In the UK, parental consent for the routine vaccination of 12–13 year olds schoolgirls against human papillomavirus (HPV) is recommended, although legally girls may be able to consent themselves. As part of a vaccine study conducted ahead of the National HPV Vaccine Programme we sought the views of school nurses on vaccinating girls who did not have parental consent.

Methods

HPV vaccination was offered to all 12 year old girls attending schools in two Primary Care Trusts in Greater Manchester. At the end of the study semi-structured, tape-recorded interviews were conducted with school nurses who had delivered the vaccine (Cervarix™). The interview template was based on concepts derived from the Theory of Planned Behaviour. Transcripts were analysed thematically in order to understand school nurses' intentions to implement vaccination based on an assessment of Gillick competency.

Results

School nurses knew how to assess the competency of under-16s but were still unwilling to vaccinate if parents had refused permission. If parents had not returned the consent form, school nurses were willing to contact parents, and also to negotiate with parents who had refused consent. They seemed unaware that parental involvement required the child's consent to avoid breaking confidentiality. Nurses' attitudes were influenced by the young appearance and age of the school year group rather than an individual's level of maturity. They were also confused about the legal guidelines governing consent. School nurses acknowledged the child's right to vaccination and strongly supported prevention of HPV infection but ultimately believed that it was the parents' right to give consent. Most were themselves parents and shared other parents' concerns about the vaccine's novelty and unknown long-term side effects. Rather than vaccinate without parental consent, school nurses would defer vaccination.

Conclusion

Health providers have a duty of care to girls for whom no parental consent for HPV vaccination has been given, and in the UK, this includes conducting, and acting upon, an assessment of the maturity and competence of an adolescent minor. To facilitate this, policies, training and support structures for health providers should be implemented.
Efficient, chemoselective synthesis of immunomicelles using single-domain antibodies with a C-terminal thioester
Authors: Reulen Sanne WA , van Baal Ingrid , Raats Jos MH , Merkx Maarten
Published: July 2009

Background

Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL). However, current methods to generate antibody fragments with C-terminal thioesters require cumbersome refolding procedures, effectively preventing application of NCL for antibody-mediated targeting and molecular imaging.

Results

Targeting to the periplasm of E. coli allowed efficient production of correctly-folded single-domain antibody (sdAb)-intein fusions proteins. On column purification and 2-mercapthoethanesulfonic acid (MESNA)-induced cleavage yielded single-domain antibodies with a reactive C-terminal MESNA thioester in good yields. These thioester-functionalized single-domain antibodies allowed synthesis of immunomicelles via native chemical ligation in a single step.

Conclusion

A novel procedure was developed to obtain soluble, well-folded single-domain antibodies with reactive C-terminal thioesters in good yields. These proteins are promising building blocks for the chemoselective functionalization via NCL of a broad range of nanoparticle scaffolds, including micelles, liposomes and dendrimers.
A novel bacterial isolate Stenotrophomonas maltophilia as living factory for synthesis of gold nanoparticles
Authors: Nangia Yogesh , Wangoo Nishima , Goyal Nisha , Shekhawat G , Suri C Raman
Published: July 2009

Background

The synthesis of gold nanoparticles (GNPs) has received considerable attention with their potential applications in various life sciences related applications. Recently, there has been tremendous excitement in the study of nanoparticles synthesis by using some natural biological system, which has led to the development of various biomimetic approaches for the growth of advanced nanomaterials. In the present study, we have demonstrated the synthesis of gold nanoparticles by a novel bacterial strain isolated from a site near the famous gold mines in India. A promising mechanism for the biosynthesis of GNPs by this strain and their stabilization via charge capping was investigated.

Results

A bacterial isolate capable of gold nanoparticle synthesis was isolated and identified as a novel strain of Stenotrophomonas malophilia (AuRed02) based on its morphology and an analysis of its 16S rDNA gene sequence. After 8 hrs of incubation, monodisperse preparation of gold nanoparticles was obtained. Gold nanoparticles were characterized and found to be of ~40 nm size. Electrophoresis, Zeta potential and FTIR measurements confirmed that the particles are capped with negatively charged phosphate groups from NADP rendering them stable in aqueous medium.

Conclusion

The process of synthesis of well-dispersed nanoparticles using a novel microorganism isolated from the gold enriched soil sample has been reported in this study, leading to the development of an easy bioprocess for synthesis of GNPs. This is the first study in which an extensive characterization of the indigenous bacterium isolated from the actual gold enriched soil was conducted. Promising mechanism for the biosynthesis of GNPs by the strain and their stabilization via charge capping is suggested, which involves an NADPH-dependent reductase enzyme that reduces Au3+ to Au0 through electron shuttle enzymatic metal reduction process.
Changes in smoking prevalence among first- and second-generation Turkish migrants in Germany – an analysis of the 2005 Microcensus
Authors: Reeske Anna , Spallek Jacob , Razum Oliver
Published: July 2009

Background

Compared to the majority population of a host country, migrants tend to have different health risks and health behaviour. We have hypothesised that these differences diminish with time passed since migration. We tested this hypothesis by examining smoking behaviour among Turkish migrants and their children born in Germany (second-generation migrants), stratified by educational level and, for the first generation, length of residence.

Methods

We estimated the prevalence of smoking based on the representative 2005 Mikrozensus, an annual survey including 1% of Germany's households. The 2005 Microcensus was the first to provide information that makes it possible to differentiate between first- and second-generation Turkish migrants. In total, 12,288 Turkish migrants and 421,635 native-born Germans were included in our study. The unit non-response is generally low (about 6% in 2005) because participation in the Microcensus is obligatory.

Results

We found the prevalence of smoking in second-generation male Turkish migrants to be lower than in the first-generation group: 47.0% of first-generation Turkish migrants with a high level of education were smokers, in contrast to only 37.6% in the second generation. Within the German reference population, 29.9% were smokers. The percentage of Turkish women in our sample who smoked was generally smaller, but was not significantly lower in the second generation. In fact, the prevalence of smoking was highest among Turkish women of the second generation with a low level of education (40.9%), similar to younger second-generation German women with the same level of education.

Conclusion

We present the first representative data on changes in the prevalence of a risk factor for many chronic diseases among Turkish migrants in Germany. Male Turkish migrants (with a high level of education) showed a decrease over the generations while smoking prevalences of female Turkish migrants increased. In the second generation, prevalences partly converged with those of the German reference population or were even higher. Our hypothesis – that migration can be interpreted as a "health transition" – was thus partly confirmed.
Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b
Authors: Samalecos Annemarie , Reimann Katja , Wittmann Stefanie , Schulte Heinrich M , Brosens Jan J , Bamberger Ana-Maria , Gellersen Birgit
Published: July 2009

Background

Coordinated differentiation of the endometrial compartments in the second half of the menstrual cycle is a prerequisite for the establishment of pregnancy. Endometrial stromal cells (ESC) decidualize under the influence of ovarian progesterone to accommodate implantation of the blastocyst and support establishment of the placenta. Studies into the mechanisms of decidualization are often hampered by the lack of primary ESC. Here we describe a novel immortalized human ESC line.

Methods

Primary ESC were immortalized by the transduction of telomerase. The resultant cell line, termed St-T1b, was characterized for its morphological and biochemical properties by immunocytochemistry, RT-PCR and immunoblotting. Its progestational response was tested using progesterone and medroxyprogesterone acetate with and without 8-Br-cAMP, an established inducer of decidualization in vitro.

Results

St-T1b were positive for the fibroblast markers vimentin and CD90 and negative for the epithelial marker cytokeratin-7. They acquired a decidual phenotype indistinguishable from primary ESC in response to cAMP stimulation. The decidual response was characterized by transcriptional activation of marker genes, such as PRL, IGFBP1, and FOXO1, and enhanced protein levels of the tumor suppressor p53 and the metastasis suppressor KAI1 (CD82). Progestins alone had no effect on St-T1b cells, but medroxyprogesterone acetate greatly enhanced the cAMP-stimulated expression of IGFBP-1 after 3 and 7 days. Progesterone, albeit more weakly, also augmented the cAMP-induced IGFBP-1 production but only after 7 days of treatment. The cell line remained stable in continuous culture for more than 150 passages.

Conclusion

St-T1b express the appropriate phenotypic ESC markers and their decidual response closely mimics that of primary cultures. Decidualization is efficiently induced by cAMP analog and enhanced by medroxyprogesterone acetate, and, to a lesser extent, by natural progesterone. St-T1b cells therefore serve as a useful model for primary ESC.
KSP inhibitor ARRY-520 as a substitute for Paclitaxel in Type I ovarian cancer cells
Authors: Kim Ki Hyung , Xie Yanhua , Tytler Ewan M , Woessner Richard , Mor Gil , Alvero Ayesha B
Published: July 2009

Background

We previously described a sub-population of epithelial ovarian cancer (EOC) cells with a functional TLR-4/MyD88/NF-κB pathway (Type I EOC cells), which confers the capacity to respond to Paclitaxel, a known TLR-4 ligand, by enhancing NF-κB activity and upregulating cytokine secretion – events that are known to promote tumor progression. It is therefore important to distinguish those patients that should not receive Paclitaxel; it is also important to identify alternative chemotherapy options that would benefit this sub-group of patients. The objective of this study is to determine if the KSP inhibitor, ARRY-520, can be a substitute for Paclitaxel in patients with Type I EOC.

Methods

EOC cells isolated from either ascites or tumor tissue were treated with increasing concentrations of ARRY-520 or Paclitaxel and cell viability determined. Activation of the apoptotic pathway was determined using Western blot analysis. Mitochondrial integrity was quantified using JC1 dye. Cytokine profiling was performed from supernatants using xMAP technology. NF-κB activity was measured using a Luciferase reporter system.In vivoactivity was determined using a subcutaneous xenograft mouse model.

Results

ARRY-520 and Paclitaxel exhibited the same cytotoxic effect on Type I and II cells. The GI50at 48 h for Type II EOC cells was 0.0015 μM and 0.2 μM for ARRY-520 and Paclitaxel, respectively. For Type I EOC cells, the GI50at 48 h was > 3 μM and >20 μM for ARRY-520 and Paclitaxel, respectively. Decrease in the number of viable cells was accompanied by mitochondrial depolarization and caspase activation. Unlike Paclitaxel, ARRY-520 did not induce NF-κB activation, did not enhance cytokine secretion, nor induce ERK phosphorylation in Type I EOC cells.

Conclusion

Administration of Paclitaxel to patients with high percentage Type I cancer cells could have detrimental effects due to Paclitaxel-induced enhancement of NF-κB and ERK activities, and cytokine production (e.g. IL-6), which promote chemoresistance and tumor progression. ARRY-520 has similar anti-tumor activity in EOC cells as that of Paclitaxel. However, unlike Paclitaxel, it does not induce these pro-tumor effects in Type I cells. Therefore, the KSP inhibitor ARRY-520 may represent an alternative to Paclitaxel in this subgroup of EOC patients.
A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre
Authors: Navarro Pablo , Chantalat Sophie , Foglio Mario , Chureau Corinne , Vigneau Sébastien , Clerc Philippe , Avner Philip , Rougeulle Claire
Published: July 2009

Background

Delimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (Xic), theXistlocus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).

Results

We describe here that developmentally regulated transcription ofTsix, a crucial non-coding antisense toXist, is required to block the spreading of the H3K27me3 domain to the adjacent H3K4me2-richXistregion. Analyses of a series of distinctTsixmutations suggest that the underlying mechanism involves the RNA Polymerase II accumulating at theTsix3'-end. Furthermore, we report additional unexpected long-range effects ofTsixon the distal sub-region of theXic, involved inXic-Xictrans-interactions.

Conclusion

These data point toward a role for transcription of non-coding RNAs as a developmental strategy for the establishment of functionally distinct domains within the mammalian genome.
Colorectal Cancer Risk Perception on the Basis of Genetic Test Results in Individuals at Risk for Lynch Syndrome
Authors: Grover Shilpa , Stoffel Elena M. , Mercado Rowena C. , Ford Beth M. , Kohlman Wendy K. , Shannon Kristen M. , Conrad Peggy G. , Blanco Amie M. , Terdiman Jonathan P. , Gruber Stephen B. , Chung Daniel C. , Syngal Sapna
Published: July 2009

Purpose

Lynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk.

Patients and Methods

A total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses.

Results

Of the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as “high” or “very high” compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome–associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased.

Conclusion

Patients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk.
Risk-Stratified Therapy and the Intensive Use of Cytarabine Improves the Outcome in Childhood Acute Myeloid Leukemia: The AML99 Trial From the Japanese Childhood AML Cooperative Study Group
Authors: Tsukimoto Ichiro , Tawa Akio , Horibe Keizo , Tabuchi Ken , Kigasawa Hisato , Tsuchida Masahiro , Yabe Hiromasa , Nakayama Hideki , Kudo Kazuko , Kobayashi Ryoji , Hamamoto Kazuko , Imaizumi Masue , Morimoto Akira , Tsuchiya Shigeru , Hanada Ryoji
Published: July 2009

Purpose

To improve the prognosis in children with newly diagnosed acute myeloid leukemia (AML) by introducing a dose-dense intensive chemotherapy regimen and an appropriate risk stratification system.

Patients and Methods

Two hundred forty children with de novo AML were treated with continuous cytarabine-based induction therapy and stratified to three risk groups based on the initial treatment response, age, and WBC at diagnosis and cytogenetics. All of the patients were treated with intensive consolidation chemotherapy including three or four courses of high-dose cytarabine. Allogeneic hematopoietic stem-cell transplantation (HSCT) was indicated for only the intermediate-risk patients with matched related donors and for all the high-risk subsets.

Results

Two hundred twenty-seven children (94.6%) achieved a complete remission (CR). Four children demonstrated induction death. The median follow-up of the live patients was 55 months (range, 37 to 73 months). The 5-year overall survival of all 240 children was 75.6% (95% CI, 70.3% to 81.4%) and event-free survival was 61.6% (95% CI, 55.8% to 68.1%). The 5-year disease-free survival in each risk group were 71.3% (95% CI, 63.4% to 80.2%) in the low-risk group (n = 112), 59.8% (95% CI, 50.6% to 70.7%) in the intermediate-risk group (n = 92), and 56.5% (95% CI, 39.5% to 80.9%) in the high-risk group (n = 23). Eight children died during the first CR, including four after HSCT.

Conclusion

A high survival rate, 75.6% at 5 years, was achieved for childhood with de novo AML in the AML99 trial. The treatment strategy was well tolerated with only 1.7% induction death rate and 3.5% remission death rate. Low-risk children were successfully treated with chemotherapy alone.